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Biomedical subjects

J P Frindik

Publications and source records attributed to J P Frindik.

15 recordsLinked to original sources
PubMed1999

Effects of recombinant human growth hormone on height and skeletal maturation in growth hormone-deficient children with and without severe pretreatment bone age delay.

UNLABELLED: The relative effects of growth hormone (GH) on GH-deficient (GHD) children with and without severely delayed skeletal maturation prior to treatment are unclear. METHODS: Pre-pubertal GHD children enrolled in the National Cooperative Growth Study were divided into two groups: severe pretreatment BA delay (BA Z-score </=-2, group 1) and mild to moderate delay (BA Z-score between -2 and 0, group 2). BA Z-scores (BAZ), height Z-scores and predicted adult height (PAH) Z-scores at pubertal onset were determined after initiation of recombinant human GH (rhGH) therapy. RESULTS: Height Z-scores increased from baseline to the start of puberty in both groups (group 1: mean difference of +0.99, males and +1.02, females; group 2: +0.68, males and +0.75, females). Mean BAZ also increased in all group 1 children (+1.62, males and +1.08, females) with no corresponding change in mean BAZ in group 2. PAH Z-scores increased in both groups. There was no evidence of undue advance in BA since mean BAZ remained well below zero in group 1 and was unchanged in group 2. CONCLUSION: rhGH has a beneficial effect on growth in prepubertal GHD children at all levels of pretreatment BA delay.

Adult↗
PubMed1999

Adult height in growth hormone deficiency: historical perspective and examples from the national cooperative growth study.

There are few historical data on final or adult heights after the completion of long-term growth hormone (GH) therapy in children with GH deficiency (GHD). Adult height has been defined as that achieved at chronologic ages ranging from 18 to 30 years, at bone ages >/=13 years (girls) and >/=15 years (boys), at growth velocities </=1 to 2 cm per 6 to 12 months, at the "cessation of growth," at "1 year after the completion of pubertal development," and that at which patients are either "satisfied with their height" or have attained an "accept adult stature." Without GH treatment, children with GHD have a mean adult height standard deviation score of -4.7 (range, -6. 1 to -3.9). After treatment, the standard deviation score range from -4.7 to -1.2 (pituitary GH [pitGH] 2-4 times a week) and from -1.4 to -0.5 (recombinant human [rhGH] GH 3 times a week to daily) in women and from -3.6 to -1.1 (pitGH) and from -1.3 to -0.7 (rhGH) in men. Because there is no uniformly applied definition of adult height, comparisons are difficult, but historical data suggest that posttreatment heights are greater with rhGH than with pitGH. Using the National Cooperative Growth Study database, we found that the criteria used to define adult height affected the apparent outcome. When chronologic age >/=20 years for men and >/=18 years for women was the only criterion, 27% of patients grew >/=5 cm after having reached this age. Adding the requirement of advanced puberty before adult height could be considered to have been attained reduced the proportion of those who later grew >/=5 cm to <10%, but also decreased the number of patients available for analysis. A combination of criteria for adult height (chronologic and bone age >/=16 years for boys and >/=14 years for girls plus advanced puberty plus growth rate of <2 cm per year) left only 1% of patients with later growth of >/=5 cm.

Adult↗
PubMed1996

Hypothalamic-hypophyseal dysgenesis as a neuroimaging correlate of pituitary hormone deficiency in anophthalmia.

PURPOSE: To document the association of neurohypophyseal dysgenesis with hypopituitarism in a child with primary bilateral anophthalmia. METHODS: An infant with bilateral anophthalmia underwent magnetic resonance imaging and endocrinologic evaluation. RESULTS: Magnetic resonance imaging showed dysgenesis confined to the hypothalamus and hypophyseal stalk. Endocrinologic testing showed low serum cortisol and pituitary gonadotropin levels. CONCLUSION: Magnetic resonance imaging can help predict which children with anophthalmia will have endocrinologic deficiencies.

Abnormalities, Multiple↗
PubMed1994

Lipids and apolipoproteins in growth hormone-deficient children during treatment.

The role of growth hormone (GH) in regulating the transport of plasma lipoproteins has not been clearly defined, but past studies suggest that GH may influence cholesterol levels. This protocol was designed to evaluate possible changes in lipid and apolipoprotein status in GH-deficient children and children with neurosecretory dysfunction (NS) before GH therapy and at intervals after GH therapy was started. Twenty children with classic GH deficiency were evaluated, and 28% were hyperlipidemic at the onset of the study. Seven children were evaluated in the NS group, and only one (14%) showed an elevated total cholesterol (TC) greater than 200 mg/dL. The mean TC for all the GH-deficient children was elevated above the normal range, but not for the NS group. The mean apolipoprotein (apo) C-III level and its heparin-precipitated fraction (HP) were also elevated in the GH-deficient group, but only the apo C-III HP was elevated in the NS group. A standard replacement dose of recombinant methionyl GH was used, and therapy had no significant effect on TC or triglyceride (TG) levels. Apo C-III HP, a marker of hypertriglyceridemia, increased after the start of therapy, but no other lipoprotein levels changed significantly in the GH-deficient group. No changes were seen with treatment in the NS group. The longitudinal design of this study allowed demonstration of the later changes in the apolipoproteins and the presence of a distinct subset of patients with both GH deficiency and hypercholesterolemia. This study supports the role of GH in modulating lipid metabolism.

Adolescent↗
PubMed1993

Clinical and biochemical correlates of growth associated with short-term administration of methionyl growth hormone.

Twenty newly diagnosed growth hormone-deficient children (19 males) were randomized to receive methionyl growth hormone (0.3 mg/kg/week) in subcutaneous doses divided daily (n = 12) or 3 times per week (TIW). With the initial dose and at 4-6 weeks after beginning therapy, procollagen type III propeptide (PIIIP) concentrations were determined. Growth velocities were calculated before and at 1, 3, and 6 months after beginning the therapy. Pretreatment growth velocities were 3.66 +/- (SD) 1.45 and 3.79 +/- 0.55 cm/year for the daily and TIW groups, respectively. At 1, 3, and 6 months mean growth velocities increased to 17.2, 10.2, and 9.5 cm/year for the daily group and 9.8, 6.8, and 7.6 cm/year for the TIW group, with differences between groups significant (p < 0.05) at 1 and 3 months. PIIIP concentrations increased significantly (p < 0.05) over 1 month in both groups, from 11.3 to 18.8 ng/ml and from 10.0 to 12.0 ng/ml in the daily and TIW groups, respectively. In addition PIIIP concentrations were significantly higher (p < 0.05) in the daily group at 1 month. A significant correlation was found between PIIIP concentrations at 1 month and the growth velocity at 1 (r = 0.47), 3 (r = 0.60), and 6 (r = 0.67) months. Pretreatment growth velocity was weakly correlated with posttreatment growth velocity at both 1 (r = -0.45) and 3 (r = -0.42) months. We conclude that (1) growth hormone is more effective when administered daily, (2) pretreatment growth velocity and PIIIP plasma concentration at 1 month correlate with 1 month growth velocity, and (3) PIIIP at 1 month provides a good evaluation of 6 months' response to methionyl growth hormone therapy.

Adolescent↗
PubMed1991

Effect of metabolic control on serum protein concentrations in diabetes.

Serum albumin, transferrin, transthyretin (prealbumin), and retinol binding protein concentrations were determined in 74 children with insulin-dependent diabetes mellitus before and after a 10-day camp session during which blood glucose concentrations were controlled. Initial concentrations of albumin and transferrin in the subjects were not different from those in 21 children and adults without diabetes, and did not change during the study period. Transthyretin and retinol binding protein concentrations were lower in subjects with diabetes than in the control population, and increased from 182 +/- 49 mg/l and 42.5 +/- 13.4 mg/l to 232 +/- 71 mg/l and 47.2 +/- 13.5 mg/l, respectively. We observed correlations between the changes in transferrin, transthyretin, and retinol binding protein. Although reductions in glycated albumin and transferrin indicated improvement in blood glucose control, there was no correlation between changes in the glycated markers and the concentrations of serum transport proteins. Thus, serum protein concentrations were influenced by the metabolic control of diabetes, but did not directly reflect blood glucose.

Adolescent↗
PubMed1991

Single and multiple dose pharmacokinetics of methionyl growth hormone in children with idiopathic growth hormone deficiency.

The pharmacokinetics (PK) of methionyl GH (metGH) were characterized in 20 newly diagnosed GH-deficient children (19 males; 12.9 +/- 3.3 yr old; initial height, 138.8 +/- 16.2 cm; weight, 32.1 +/- 13.1 kg) after the first dose (FD) of metGH and again after 4-5 weeks of multiple dosing (MD). All subjects received a total metGH dose of 0.3 mg/kg.week by sc administration, but were randomized to receive the drug daily (D; n = 12; dose, 0.043 mg/kg) or three times per week (TIW; n = 8; dose, 0.1 mg/kg). After drug administration, repeated blood samples (n = 14) were obtained over a 10-h period. Concentrations of metGH from each sample were determined using a monoclonal antibody radiometric assay (range of linearity, 0.5-40.0 ng/ml; coefficient of variation, less than 4%). Plasma concentration vs. time data were curve fit using a nonlinear weighted least squares algorithm which permitted calculation of the following PK parameters (mean +/- SEM; FD vs. MD group): elimination rate constant (0.23 +/- 0.04 vs. 0.25 +/- 0.04 h-1), absorption rate constant (0.43 +/- 0.05 vs. 0.48 +/- 0.04 h-1), elimination half-life (t1/2; 3.01 vs. 2.77 h), total plasma clearance (CL/F; 0.32 +/- 0.02 vs. 0.54 +/- 0.09 L/h.kg), and apparent volume of distribution (VDss/F; 2.2 +/- 0.14 vs. 3.15 +/- 0.28 L/kg). Both the CL/F and VDss/F of metGH were significantly greater when data from the entire study population were compared on the basis of FD vs. MD administration. With the exception of a larger VDss/F in subjects who received daily (3.6 +/- 0.4 L/kg) vs. TIW metGH (2.4 +/- 0.2 L/kg), no significant differences were found for the PK parameters between the D and TIW dosing groups. In all subjects, absorption of metGH was slow, with an average time to reach maximum concentration (Tmax) of 4.4 h and an absorption t1/2 that ranged from 1.4-1.8 h. Proportionality was also found between the dose and the area under the plasma concentration vs. time curve, suggesting dose-independent PK of metGH. Our data demonstrate that the PK of metGH after sc administration to children are markedly different from those previously reported in adults and, also, do not vary as a consequence of dosing schedule (i.e. D vs. TIW). The apparent increase in CL/F and VDss/F for met GH with multiple dosing may reflect concentration-dependent changes in plasma binding of the drug or, alternatively, represent the effect of increased body mass on the pharmacokinetics of GH.

Adolescent↗
PubMed1991

Glomerulopathy in patient with Donohue syndrome (leprechaunism).

OBJECTIVE: To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. RESEARCH DESIGN AND METHODS: The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. RESULTS: On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. CONCLUSIONS: This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen.

Adolescent↗
PubMed1986

Decreased cyclic guanosine 3',5' monophosphate and guanylate cyclase activity in leprechaunism: evidence for a postreceptor defect.

Patients with leprechaunism have hyperinsulinemia and extreme insulin resistance. The mechanism of the insulin resistance has not been delineated. To examine postreceptor events in this unusual syndrome we have assayed the enzyme guanylate cyclase [E.C.4.6.12], which is modulated by insulin, and the concentration of the intracellular messenger cyclic GMP in liver from two children with leprechaunism and extreme insulin resistance. Both patients exhibited down regulation of the red blood cell insulin receptors, but normal insulin receptor binding to Ebstein-Barr transformed IM-9 lymphocytes and monocytes. There was no evidence of antireceptor or antiinsulin antibodies. Activity of liver guanylate cyclase expressed as pmol/mg protein/10 min incubation in the soluble and particulate fractions were, respectively, Ark-1 133 +/- 18, 25 +/- 6; Ark-2 129 +/- 17, 23 +/- 8; control children (six average) 287 +/- 16, 55 +/- 9. The concentration of cyclic GMP was also 50% lower (0.08 +/- 0.03 in Ark-1 and 0.07 +/- 0.04 in Ark-2), compared to 0.19 +/- 0.07 pmol/mg protein/min in the control livers. There was no change in adenylate cyclase activity in children with leprechaunism versus the control children. These data suggest an abnormality of a postreceptor event in this rare genetic disease. These data, however, do not rule out that in some cases of leprechaunism a receptor binding abnormality may be the primary defect. We speculate that a defect in insulin action distal to plasma membrane receptor binding may be etiological in this unusual syndrome.

Abnormalities, Multiple↗
PubMedDate not supplied

Comparison of Visidex and Chemstrip bG with Beckman Glucose Analyzer determination of blood glucose.

Chemical test strips for estimating blood glucose have been shown to be reliable, rapid, and convenient when properly used. This study compares a new product, the Ames Visidex (Miles Laboratories, Elkhart, Indiana), and an established product, the Bio-Dynamics Chemstrip bG (Boehringer-Mannheim, Indianapolis, Indiana) with plasma glucose as measured by standard laboratory methods. Determination of blood glucose by visual inspection of both chemical strips gave an estimation of true plasma glucose in the hypoglycemic and euglycemic ranges. Both strips were reliable in predicting those values that were hyperglycemic (greater than 180 mg/dl).

Blood Glucose↗
PubMedDate not supplied

Effective use of magnetic resonance imaging in the assessment of children with possible growth hormone deficiency.

OBJECTIVE: To present our experience with diagnosis of growth hormone (GH) deficiency in children and to determine which patients are most likely to benefit from magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed medical records of pediatric patients who underwent assessment for possible GH deficiency during a 6-year period and correlated clinical variables, stimulated GH responses, and MRI findings. RESULTS: Of 100 children who failed outpatient GH screening tests, 14 were classified as at risk for hypothalamic pituitary defects, and 86 were considered not at risk, having short stature only. Patients were further stratified by age, sex, growth variables, maximal GH response to provocative testing, and MRI findings. A significant relationship existed between the presence of risk factors, maximal GH of <5 mg/L, and sellar defects. With no risk factors, MRI scans showed normal findings in 15 of 17 patients with maximal GH of <5 mg/L, in 33 of 34 patients with GH between 5 and 10 mg/L, and in all 35 patients with GH of >10 mg/L. Abnormal MRI findings included posterior pituitary ectopy, decreased pituitary size, absent midline central nervous system structures, enlarged infundibulum, and hamartoma. In one child with a 4-year history of growth failure and a maximal GH of 3.5 mg/L, craniopharyngioma was diagnosed. CONCLUSION: MRI scans should be obtained in any child with multiple pituitary hormone deficiencies, hypoglycemia, ophthalmologic anomalies, low-stimulated GH, or acquired growth failure. Otherwise asymptomatic children with growth delay and maximal GH of >10 mg/L do not need routine MRI screening. Such a strategy could result in substantial cost savings.

Journal Article↗