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Biomedical subjects

F L Culler

Publications and source records attributed to F L Culler.

At least 19 recordsLinked to original sources
PubMed1999

Preservation of growth hormone secretion in response to growth hormone-releasing peptide-2 during prednisone therapy.

Children who require long-term glucocorticoid treatment often demonstrate poor growth. Growth hormone (GH) secretion is decreased during glucocorticoid treatment, and this decrease may be due to a relative excess of the hypothalamic hormone somatostatin (SRIF). GH-releasing peptide-2 (GHRP-2) is a GH secretagogue that acts via multiple mechanisms at multiple sites. One of its proposed mechanisms is the ability to bypass SRIF blockade of GH secretion. We measured the ability of GHRP-2 to release GH before and during prednisone therapy (20 mg orally three times daily for 4 days). The degree of preservation of GH secretion and the pattern of GH release in response to GHRP-2 were compared with those observed in response to arginine, a known SRIF inhibitor. GH release in response to GHRP-2 and arginine was measured in the same eight subjects before and during prednisone therapy. Before prednisone, peak GH levels in response to arginine and GHRP-2 were 8.8 +/- 2.8 and 80.8 +/- 21.2 microg/L. During prednisone therapy, the peak GH level in response to arginine and to GHRP-2 was 20.1 +/- 8.3 and 71.3 +/- 18.4 microg/L, respectively. The difference in peak values before and after prednisone was not significant. The time to the peak GH level during prednisone therapy occurred sooner for both arginine and GHRP-2. The pattern of GH release to arginine and to GHRP-2 was not identical, and the mean area under the curve for GH release to GHRP-2 decreased significantly with steroid treatment (P = .04), suggesting that GHRP-2 acts by mechanisms additional to the removal of SRIF inhibition. GHRP-2 elicited a 10-fold greater GH response than arginine at baseline, and the GH response was threefold greater versus arginine even in the face of prednisone therapy. GH release occurred earlier for both arginine and GHRP-2 during steroid treatment. We propose that this may suggest an increased storage phenomenon due to the blockade of GH secretion by glucocorticoids and then a sudden release with SRIF inhibition. If GHRP-2 can indeed counteract the inhibitory effect of glucocorticoids on GH secretion, then a new form of therapy may be available to support growth in children who must receive long-term steroid treatment.

Adult↗
PubMed1997

Predictors of change in insulin sensitivity during glucocorticoid treatment.

Glucocorticoid induced alterations in carbohydrate metabolism can result in hyperglycemia. We evaluated changes in carbohydrate metabolism produced by four days of prednisone (20 mg PO TID) measuring insulin sensitivity, basal glucose, basal insulin and first phase insulin release (FPIR). We correlated these measures of carbohydrate metabolism with changes in free fatty acids and lactate levels both of which have been reported to be possible mediators of insulin sensitivity. Insulin sensitivity decreased by 64% (p = 0.002), basal insulin levels increased 50% (p = 0.026), FPIR tripled (p = 0.064) while fasting glucose levels increased significantly but remained normal. Basal FFAs levels increased (p = 0.045) while lactate levels did not change significantly, and neither predicted changes in SI. Basal levels of SI and FPIR were found to be independent predictors of change in insulin sensitivity and together explained 83% of the change in insulin sensitivity produced by short term treatment with prednisone.

Adult↗
PubMed1993

Preservation of somatostatin secretion in cystic fibrosis patients with diabetes.

Immunohistochemical studies of pancreatic tissue from patients with cystic fibrosis associated with diabetes mellitus (CFDM) show increased numbers of somatostatin secreting delta cells. To look for a possible functional correlate to this finding basal and arginine stimulated plasma somatostatin and serum C peptide concentrations in eight insulin treated patients with cystic fibrosis and eight normal male controls were measured. Mean basal somatostatin concentrations were not different in the two groups. Mean peak somatostatin concentrations were significantly higher in the group with CFDM: 11.60 pmol/l v 7.14 pmol/l in controls. Mean peak C peptide concentrations were significantly lower in the group with cystic fibrosis: 0.89 nmol/l v 4.27 nmol/l in controls. This observation provides a physiological correlate to the pathological finding of increased somatostatin content in pancreatic tissue from patients with CFDM. Selective preservation of somatostatin secretion in patients with cystic fibrosis may further complicate pancreatic endocrine insufficiencies through paracrine inhibition of insulin and glucagon secretion.

Adult↗
PubMed1993

Effect of hypersomatostatinemia on growth hormone secretion in cystic fibrosis patients with diabetes.

We have recently shown that hypersomatostatinemia is a feature of cystic fibrosis (CF) when these patients have CF-associated pancreatogenic diabetes mellitus (CFDM). To address the possibility that patients with CFDM might have suppressed pituitary growth hormone (GH) release as a result of increased plasma somatostatin, GH secretion in 8 CFDM patients and 8 normal male controls was studied using a standard arginine infusion stimulus. Concentrations of the GH-dependent peptides, insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) were also measured. We found that mean GH concentrations in the CFDM group were significantly increased (p < 0.05) rather than decreased at the 30-min (12.3 +/- 3.6 vs. 3.8 +/- 1.9 ng/ml), 45-min (15.4 +/- 2.9 vs. 6.1 +/- 2.3 ng/ml) and 60-min (13.2 +/- 2.3 vs. 6.2 +/- 2.2 ng/ml) time points of study. Mean GH area under the curve (633 +/- 128 vs. 249 +/- 107 ng/ml) was also significantly greater (p < 0.05) in the CFDM group. Despite higher GH levels in the CFDM patients, their IGF-I and IGFBP-3 concentrations were low. We conclude that plasma somatostatin elevations in the CFDM group are not of sufficient magnitude to suppress pituitary GH release. Decreased levels of growth mediating peptides in the relatively malnourished CF subjects suggest a pattern of malnutrition-induced GH resistance which may contribute to poor weight and height gain.

Adult↗
PubMed1991

Double vagina, cardiac, pulmonary, and other genital malformations with 46,XY karyotype.

We have studied two unrelated genetic males with a novel constellation of genital, cardiac, and pulmonary malformations. The genital abnormalities consisted of a true double vagina, retention of Müllerian structures, and undervirilization of the external genitalia. Both infants had complex cyanotic congenital heart defects, hypoplastic right lungs, anomalous pulmonary venous return, and abnormalities of the diaphragm. One patient had rhabdomyomatous dysplasia of the lungs. The cause of this malformation pattern is unknown. There was no family history of similar defects, no consanguinity, no known exposure to teratogens, and no chromosome abnormality. The retention of Müllerian structures and undervirilization of male genitalia in these cases could be the result of failure in production of adequate amounts of testosterone and Müllerian inhibitory factor at appropriate times in gestation. Because the developing human vagina is at no stage a duplicate structure, a double vagina cannot be the result of arrested genital differentiation. The unusual occurrence of a true double vagina should lead to careful pulmonary and cardiac evaluation.

Abnormalities, Multiple↗
PubMed1991

Internalizing and externalizing symptoms and attributional style in youth with diabetes.

The psychiatric functioning of 28 youths with insulin-dependent diabetes mellitus was examined. Measures of psychological functioning were related to age at onset, duration of diabetes, and metabolic control, as assessed by HgbAlC. Children diagnosed with insulin-dependent diabetes mellitus at a later age were considered by teachers to have more behavioral problems. Children who had better metabolic control tended to hold themselves responsible for negative events. It is worthwhile to develop interventions to teach diabetic children a realistic balance between taking appropriate responsibility for controllable negative events without taking undue blame for uncontrollable negative events associated with the disease.

Adaptation, Psychological↗
PubMed1988

Comparison of the acute metabolic effects of 22,000-dalton and 20,000-dalton growth hormone in human subjects.

The acute metabolic effects of 20,000-dalton human growth hormone (hGH20K) in man have not previously been tested. We compared changes in concentrations of free fatty acids (FFA), glucose, and insulin in nine growth hormone deficient children following injection of 22,000-dalton intact human growth hormone (hGH22K) and the smaller variant, hGH20K. There was a significant decline (37%) in the mean FFA concentration from baseline to 1/2 hour post-injection and from baseline to 1 hour post-injection (36%) in the children given hGH22K, but no such decline was seen after injection of hGH20K. No significant differences in mean insulin or glucose concentrations were noted between the two treatment groups, and glucose and insulin concentrations did not acutely change after injection of either hormone. The results of this study indicate that hGH20K has a diminished activity for suppression of FFA as compared to hGH22K. This suggests that GH residues 32-46, missing in hGH20K, constitute all or part of the region of hGH22K producing this response, or that the different primary structures of the two hormones result in tertiary structural differences and altered biological activity.

Adolescent↗
PubMed1988

Inhibition by prednisone of growth hormone (GH) response to GH-releasing hormone in normal men.

Glucocorticoids increase GHRH-stimulated GH secretion when added in vitro to cultured monkey, rat, and human pituitary cells and when injected in vivo into anesthetized rats. Yet, in man glucocorticoids inhibit linear growth and GH secretion. To clarify this apparent disparity and to determine if glucocorticoid stimulation can augment GH release in man after direct pituitary stimulation with GHRH, we administered 1 microgram/kg GHRH dosage to seven normal men before and after a 4-day course of prednisone (20 mg, orally, three times daily). The second GHRH test was done 12 h after the last dose of prednisone was given. Prednisone significantly inhibited the mean maximal increase in serum GH after GHRH treatment [20.7 +/- 4.5 (+/- SE) vs. 6.3 +/- 2.4 micrograms/L; P less than 0.01] as well as the GH value obtained by summing and averaging the individual means of the 15, 30, 45, 60, 75, and 90 min serum GH concentrations (11.1 +/- 1.2 vs. 4.3 +/- 0.9 micrograms/L; P less than 0.05). The mean serum insulin-like growth factor I and plasma glucose concentrations were not significantly altered by prednisone administration. These results together with previous in vitro findings imply that glucocorticoid-induced inhibition of GH secretion in man does not occur at the level of the pituitary gland, but, rather, at the hypothalamus or above.

Adrenocortical Hyperfunction↗
PubMed1987

An in vivo model for study of the angiogenic effects of basic fibroblast growth factor.

We have investigated the angiogenic effects of basic fibroblast growth factor following its implantation in slow release beads under the kidney capsule. The presence of basic fibroblast growth factor in the subcapsular space induced a marked angiogenic response maximal at 1 microgram dose per kidney. Histological examination at the site of treatment failed to reveal evidence of an inflammatory response, thus supporting the observation that basic fibroblast growth factor alone can stimulate in vivo neovascularization. Beads pretreated with saline or with human growth hormone had no angiogenic effect. Because of the readily accessible location in the retroperitoneal space, the ease of drug delivery, and the marked vascular proliferation seen in response to FGF, our results suggest that the kidney capsule is an excellent model for study of the physiological role played by FGF and related peptides in promoting angiogenesis in vivo.

Animals↗
PubMed1986

Growth hormone deficiency in the Rothmund-Thomson syndrome.

We describe the first proven occurrence of growth hormone deficiency in an individual with the Rothmund-Thomson syndrome. This was suspected because of the patient's severely retarded growth and bone age and her failure to respond normally to growth hormone stimulation testing with l-DOPA, arginine, and growth hormone releasing factor. In addition, we have briefly reviewed other genetic and malformation syndromes that have been found associated with growth hormone deficiency. We recommend that growth hormone deficiency be considered in these syndromes, especially when the growth failure is more marked than expected.

Arginine↗
PubMed1986

Release of the 22,000- and the 20,000-dalton variants of growth hormone in vivo and in vitro by human anterior pituitary cells.

Using a combination of polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and immunoblotting with antihuman GH (anti-hGH) serum, we quantitatively and independently measured the major 22,000-dalton form of hGH (hGH22K) and the 20,000-dalton form (hGH20K). This technique was equally effective in assaying cell culture media or human sera. We studied isolated human pituitary cell cultures during a 16-day incubation period with and without stimulation by GH-releasing hormone (GHRH). Under basal conditions, the cells released 2.83 +/- 0.24 (+/- SEM) microgram hGH22K/ml . day and 0.67 +/- 0.17 microgram hGH20K/ml . day. GHRH (10(-8) M) treatment resulted in stimulation of both hGH22K and hGH20K by 24 h. We also measured both hGH22K and hGH20K in the sera of normal subjects before and after an iv bolus injection of 100 micrograms GHRH. hGH20K increased as did hGH22K. Peak concentrations of both variants occurred 45 min after GHRH administration. The results of this study indicate that the combination of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting is an accurate and effective means of separately assaying hGH22K and hGH20K. We also demonstrated that primary monolayer cultures of human pituitary cells are an excellent model system for study of the secretion of these two hGH variants.

Adult↗
PubMed1985

Imparied calcitonin secretion in patients with Williams syndrome.

Williams syndrome is associated with neonatal hypercalcemia of unclear pathogenesis. To learn more about the hormonal control of calcium metabolism in patients with Williams syndrome, we studied five such children, with intravenous calcium and parathyroid hormone infusions as provocative stimuli. These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion, compared with a group of seven normal children. No abnormalities of vitamin D metabolite concentrations were found, either before or after parathyroid hormone stimulation. Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.

Calcitonin↗
PubMed1985

Identification of gonadotropin-releasing hormone in neurons of a hypothalamic hamartoma in a boy with precocious puberty.

We have studied a 3 1/12-year-old boy who presented with a hypothalamic mass and precocious puberty. His history suggested a course of isosexual precocity progressing from birth. Gelastic seizures also began at an early age. Endocrine evaluation revealed normal thyroid-stimulating hormone and growth hormone secretion, elevated basal and stimulated prolactin concentrations, and luteinizing hormone responses to sequential intravenous injections of gonadotropin-releasing hormone (GnRH) that were pubertal in pattern and magnitude. A needle biopsy of the mass recovered tissue that contained neurons histologically similar to those found in the normal hypothalamus, and the mass was characterized as a hypothalamic hamartoma. Immunohistochemical staining of this tissue with anti-GnRH antiserum demonstrated positive staining for GnRH immunoreactivity in neurons. This suggests a neurosecretory pathogenesis for the precocious puberty found in patients with hamartomas in the hypothalamic region.

Biopsy, Needle↗