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Biomedical subjects

N G Greger

Publications and source records attributed to N G Greger.

13 recordsLinked to original sources
PubMed1999

Whole body bone mass and body composition in a girl with achondroplasia, at ages 9 through 12.

A 9-yr-old white female with achondroplasia was one of a group of 773 children who were recruited for a study of the accumulation of whole body skeletal mass during four annual measurements. Measurements of bone, fat, and lean mass were obtained with a Hologic 1000W instrument. The following variables are used to compare the subject with the 130 healthy white girls who participated in the study: bone mineral content (BMC), bone mineral density (BMD), and bone mineral apparent density (BMAD). Ratios of BMC to weight or BMC to height, and BMD to weight or height, were also calculated. We found that the BMC of the subject was lower when compared to the reference group, but the ratios of BMC to weight or BMC to height were similar in both. BMD was also lower in the patient, but, when expressed in relation to height and weight, the ratios were similar or slightly higher in the case. BMAD was higher in the subject with achondroplasia at all ages. The subject had a lower percentage fat and higher percentage lean mass than the reference children. We conclude that the accumulation of bone mass in this subject with achondroplasia is appropriate for her reduced body size.

Achondroplasia↗
PubMed1996

Anabolic effect of biosynthetic growth hormone in cystic fibrosis patients.

The purpose of this study was to determine whether GH treatment of cystic fibrosis (CF) patients can result in an anabolic effect, i.e., increased weight gain, improved growth rate, nitrogen retention, and improved pulmonary function. Nine prepubertal endocrinologically normal CF patients (3 girls, 6 boys; chronological age (CA) 5.5-9.8 years, and bone age (BA) 4.5-9.0 years), received recombinant human growth hormone (rhGH) 0.3 mg/kg/week subcutaneously for a period of 12 months (N = 8) or 9 months (N = 1). Normal glucose tolerance was determined before treatment. Pulmonary function studies and anthropometric measurements were done every 3 months. Thyroid status, somatomedin C (SmC), BA, and routine chemistries were evaluated every 6 months. The pretreatment growth velocity averaged 5.7 +/- 0.3 (SE) cm/year and significantly increased to 7.8 +/- 0.4 (SE) cm/year during therapy, (P < 0.01). Standard deviation scores (SDS) for height significantly increased during rhGH therapy as compared with pretreatment, (P < 0.05). Weight of the patients during rhGH therapy did not significantly change during or after rhGH therapy. After therapy, all patients showed a significant increase in arm muscle area (AMA) and a significant decrement in arm fat area (AFA) (P < 0.01). Net nitrogen anabolism was negative in all subjects before therapy but became more positive in five patients during rhGH therapy. Three patients achieved positive nitrogen retention. SmC values significantly increased from a mean value of 0.62 +/- 0.1 (SE) U/ml to 1.6 +/- 0.6 (SE) U/ml after therapy. BA advanced 1.0 +/- 0.1 SE per year after treatment. Of the seven patients able to perform adequate pulmonary function testing, improvement occurred in FVC, FEV1.0, and PEFR in 5, 5, and 4 patients, respectively, but these changes did not reach statistical significance. We conclude that biosynthetic rhGH therapy had a significant anabolic effect in CF patients as shown by increased growth velocity, SmC values, increased protein and decreased fet stores, and a positive or less negative net nitrogen retention in five of the patients.

Body Height↗
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↗
PubMed1990

High-density lipoprotein response to 5-alpha-dihydrotestosterone and testosterone in Macaca fascicularis: a hormone-responsive primate model for the study of atherosclerosis.

A decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease, occurs during puberty in males. Previous studies have shown this decrease with testosterone (T) therapy for adolescent males, but the mechanism of this effect is unknown and has not been studied in a non-human primate. Two adult male monkeys (Macaca fascicularis) were studied to determine simultaneous changes in plasma androgens and HDL-C during the phases precastration (Ci); postcastration (Cx); Cx and T therapy; Cx and dihydrotestosterone (DHT) therapy; and T and 5-alpha-reductase inhibitor therapy (4-MA). After castration, the HDL-C concentrations increased significantly in both animals (monkey A, 57.0 +/- 1.8 mg/dL SE to 66.6 +/- 2.2, P less than .005; monkey B, 62.9 +/- 1.6 to 80.2 +/- 1.7, P less than .001). T-propionate treatment produced a significant decrease in HDL-C (monkey A, 48.0 +/- 5.0, P less than .01; monkey B, 43.5 +/- 0.5, P less than .001), which was similar to HDL-C reductions seen when treated with a nonaromatizeable androgen, DHT-propionate (monkey A, 47.5 +/- 1.5, P less than .005; monkey B, 44.5 +/- 3.5, P less than .001). T and the 5-alpha-reductase inhibitor therapy did not increase HDL-C from the levels with T therapy alone (monkey A, 55.7 +/- 1.9, NS; monkey B, 57.3 +/- 0.3, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha Reductase Inhibitors↗
PubMed1990

Reduced bone mineral in patients with eating disorders.

Bone mineral measurements of the forearm and spine were made in 63 patients under treatment in the Eating Disorders Program of the University of Nebraska Medical Center, 26 with anorexia nervosa (AN), 11 with bulimia nervosa (BU) and 26 with features of both AN and BU (AN/BU). Comparison was made with a group of 211 normal women of similar age. Spinal bone mineral content (BMC) of L2-4 was 45.1 +/- 5.7 g in the normals, 38.0 +/- 7.5 in the AN's, 40.3 +/- 6.6 g in the AN/BU's and 44.4 +/- 6.9 g in the BU's. The AN and AN/BU averages were both significantly different from normal (p less than 0.0005), but the BU average was not. BMC was correlated with body weight in each group and weakly correlated with age in the patients under age 30 in the AN and AN/BU groups combined. Forearm bone mineral measurements in the AN's and AN/BU's were also significantly lower than normal, but the differences were not as great as for the spine. We conclude that bone mineral is reduced in these patients, severely in some of them, and that reduced body weight plays a role. Menstrual disturbances, inhibition of growth and development, and malnutrition remain open as causal factors. Potential for recovery from reduced bone mineral was not demonstrated in this study.

Adult↗
PubMed1987

Dihydrotestosterone heptanoate: synthesis, pharmacokinetics, and effects on hypothalamic-pituitary-testicular function.

Dihydrotestosterone heptanoate (DHT-hp), a seven-carbon fatty acid ester of DHT, was synthesized, and its pharmacokinetics and effects on hypothalamic-pituitary-testicular function were determined in men and pubertal boys. Plasma DHT levels markedly increased 24 h after im injection of DHT-hp, reached their peak during the first week, and fell to baseline levels after 4-6 weeks. An estimated 43-55% of DHT-hp was converted to DHT 4-6 weeks after injection. Plasma testosterone, estradiol, LH, and FSH levels decreased by 4 days after DHT-hp injection, were lowest during the second week, and returned to baseline values after 4-6 weeks. The LH and FSH responses to GnRH were diminished by chronic administration of DHT-hp to pubertal boys at 3-week intervals for 15 weeks. The affinity of DHT-hp was 100 times less than the affinity of DHT for the human androgen receptor, and no affinity for the estrogen receptor in breast tissue could be demonstrated. Since DHT is a nonaromatizable androgen, and neither DHT nor DHT-hp binds readily to the estrogen receptor, suppression of LH and FSH secretion by this drug probably occurs via an androgen-dependent mechanism. Receptor binding and pharmacokinetic data indicate that unesterified DHT is the active principle. DHT-hp is a useful derivative of DHT, since prompt, predictable, and sustained rises in DHT occur after its administration.

Adult↗
PubMed1986

Central diabetes insipidus. 22 years' experience.

The etiology of diabetes insipidus (DI) was determined in 73 children evaluated from 1962 through 1983. Intracranial tumors produced DI in 34 children, but 27 of these 34 children developed DI only after excision of the tumor. Diabetes insipidus occurred in ten children with intracranial birth defects, eight with severe central nervous system infections, and six with histiocytosis. Six had other causes. No etiology was detected in nine. Division of the cases into two time periods (1962 through 1972 and 1973 through 1983) revealed a decrease in the frequency of idiopathic DI (26.7% to 8.6%), an increase in the frequency of intracranial birth defects (0% to 17.3%), and an increase in the frequency of severe central nervous system infections (0% to 13.8%). Significant changes in therapy for DI have occurred during these 22 years. Use of desmopressin acetate has facilitated treatment of this complex management problem.

Brain Neoplasms↗
PubMed1984

Cytosol androgen receptor (AR) in human skin fibroblasts: characterization of the binding reaction and differentiation from androgen binding molecules of lower affinity.

Androgen binding was studied in cytosol of human fibroblasts at 4 degrees C. When 5 alpha-dihydrotestosterone (DHT) was the ligand, a curvilinear Scatchard plot was seen, which was resolved into two components: I the androgen receptor (AR), Kd = 0.12-0.44 nM, and II a low affinity species, Kd = 6.3-28 nM. The same cytosol demonstrated only type I binding for 3H-methyltrienolone (MTr), Kd = 0.10-0.40 nM. The AR, i.e., 3H-MTr binding activity, eluted at 440,000 d by gel filtration chromatography in pre-labeling and post-labeling experiments. When the ligand was 3H-DHT, binding activity in the 10,000-45,000 d range was seen in addition to AR. Thus, saturable nonreceptor steroid binding was seen for DHT but not for MTr. The latter is the preferred ligand for the study of the AR in this system.

Binding, Competitive↗