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Biomedical subjects

G P August

Publications and source records attributed to G P August.

At least 19 recordsLinked to original sources
PubMed2001

Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control.

PURPOSE: Progress has been made in the treatment of medulloblastoma, the most common childhood malignant brain tumor: However, many long-term survivors will have posttherapy growth hormone insufficiency with resultant linear growth retardation. Growth hormone replacement therapy (GHRT) may significantly improve growth, but there is often reluctance to initiate GHRT because of concerns of an increased likelihood of tumor relapse. PATIENTS AND METHODS: This study retrospectively reviewed the use of GHRT for survivors of medulloblastoma in 11 neuro-oncology centers in North America who received initial treatment for disease between 1980 and 1993 to determine its impact on disease control. A Landmark analysis was used to evaluate the relative risk of relapse in surviving patients. RESULTS: Five hundred forty-five consecutive patients less than 15 years of age at diagnosis were identified. Six-year progression-free survival (mean +/- SD) was 40% +/- 5% in children less than 3 years of age at diagnosis compared with 59% +/- 3% for older patients. Older patients with total or near-total resections (P = .003) and localized disease at diagnosis (P < .0001) had the highest likelihood of survival. One hundred seventy patients (33% +/- 3% of the cohort) received GHRT. GHRT use varied widely among institutions, ranging from 5% to 73%. GHRT was begun a mean of 3.9 years after diagnosis, later in children younger than 3 years at diagnosis (5.4 years). By Landmark analyses, for those surviving 2, 3, and 5 years after diagnosis, there was no evidence that GHRT increased the rate of disease relapse. CONCLUSION: This large retrospective review demonstrates that GHRT is underutilized in survivors of medulloblastoma and is used relatively late in the course of the illness. GHRT is not associated with an increased likelihood of disease relapse.

Adolescent↗
PubMed2000

Survey of clinical practice: growth hormone use during illness.

Prior to the 1999 National Cooperative Growth Study (NCGS) meeting, a postal card survey was conducted of the NCGS investigators about their current practices regarding continuation of growth hormone (GH) therapy during intercurrent illnesses. The survey results were subsequently compared with responses to the same questions obtained from NCGS investigators who attended lectures at the NCGS meeting describing the physiology and effects of GH in critically ill patients. Comparing results from the two surveys, there were no observed differences in the responses with respect to practices relative to the intercurrent illnesses treated at home. The percentage of NCGS investigators who indicated that they would stop GH treatment during more serious illnesses was greater following attendance at the lectures.

Comorbidity↗
PubMed1998

Adult height in children with growth hormone deficiency who are treated with biosynthetic growth hormone: the National Cooperative Growth Study experience.

OBJECTIVE: To determine whether the height gain during puberty in children with growth hormone deficiency (GHD) who are treated with biosynthetic growth hormone (GH) is similar to that in otherwise healthy children with delayed bone ages and whether the height standard deviation score (SDS), which began to increase before puberty, continues to increase during puberty. METHODS: The inclusion criteria included a diagnosis of idiopathic GHD, prepubertal on enrollment in the National Cooperative Growth Study, and spontaneous onset of puberty, as defined by Tanner stage 2 breast development in girls and a testicular volume of at least 3 mL in boys. Near-adult height was judged to have been attained in the subjects who had reached a chronologic age of at least 18 years (females) or 20 years (males) or had reached at least pubertal stage 4 and a chronologic age of at least 14 years (females) or 16 years (males). These subjects constituted group 1. Group 2 was a subgroup of these subjects who met a more stringent criterion for near-adult height; in addition to meeting the above criteria, they had to have attained a bone age of at least 14 years (females) or 16 years (males). RESULTS: Group 1 consisted of 480 males and 194 females. Group 2 consisted of 153 males and 105 females. In the subjects in group 1, the Tanner pubertal stage 2 was 14.1 +/- 1.5 years in males and 12.6 +/- 1.6 years in females; the bone age at this stage was 11. 9 +/- 1.5 years in males and 10.6 +/- 1.5 years in females; and the height SDS was -2.1 +/- 0.9 in males and -2.4 +/- 0.9 in females. The total height gained during puberty was 22.4 +/- 7.9 cm in males and 17.4 +/- 6.3 cm in females; the percentage of adult height gained during puberty was 13.3% +/- 4.6% in males and 11.3% +/- 4.0% in females; the near-adult height SDS was -1.3 +/- 1.0 in males and -1.6 +/- 0.9 in females; and the target adult height SDS was -0.4 +/- 0.8 in males and -0.5 +/- 0.7 in females. The growth characteristics in the subjects in group 2 were of similar magnitude. In both groups, there was a significant negative correlation between age at the onset of Tanner stage 2 and both the total height gained during puberty and the percentage of adult height gained. CONCLUSIONS: The growth characteristics of these subjects were similar to those reported in normal children and in previous reports of the pubertal growth in smaller populations of children with GHD. The height SDS increased in these subjects during puberty, but the target adult height SDS was not attained. This is a strong argument for early diagnosis and treatment in children with GHD to optimize prepubertal growth.

Adult↗
PubMed1993

Factors predicting the response to growth hormone (GH) therapy in prepubertal children with GH deficiency.

To identify factors influencing the response to GH therapy, we used a multiple regression model to analyze data from 632 naive prepubertal children with GH deficiency (GHD). There were 523 children with idiopathic and 109 children with organic GHD. They were treated with the same preparation of biosynthetic methionyl GH (somatrem, Protropin) for at least 1 yr. In children with idiopathic GHD, six variables predicted 40% of the response to treatment. They were (listed in relative importance, all P < 0.0001): age, log maximum GH, weight adjusted for height, dosing schedule, dose, and midparental height. Three variables, pretreatment growth rate, log maximum GH, and age, predicted 20% of the GH response in children with organic GHD. When data for all children were analyzed using analysis of covariance, children with idiopathic GHD grew better than those with organic GHD (mean +/- SD, 9.2 +/- 2.4 vs. 8.8 +/- 2.6 cm/yr; P < 0.0001). The children (both organic and idiopathic GHD) who did not respond well to treatment were younger and thinner than those who did. Early diagnosis and initiation of therapy should be beneficial to ultimate height attainment. The best response to GH therapy should be in young children with severe idiopathic GHD who receive daily weight-adjusted doses. The use of GH daily in higher doses would be expected to be most beneficial in older children with acquired and/or less severe GHD or in children who are underweight for height.

Aging↗
PubMed1992

Solitary thyroid nodules in 71 children and adolescents.

Seventy-one children and adolescents with a solitary nodule of the thyroid gland were seen over a 27-year period and all had their nodules removed surgically. All of the patients had preoperative thyroid scintiscans, 55 of which showed a cold nodule. The most common cause of solitary thyroid nodules was follicular adenoma. Fourteen of the 55 cold nodules were malignant (25.5%) while no malignancies were present in warm or hot nodules. Available diagnostic methods for attempting differentiation of benign from malignant solitary nodules are reviewed and recommendations to their clinical management as derived from our experience are presented.

Adolescent↗
PubMed1990

Growth hormone treatment in the United States: demographic and diagnostic features of 2331 children.

Demographic, diagnostic, and baseline clinical data were collected for a large cohort (N = 2331) of children who started treatment with biosynthetic human growth hormone (GH) between October 1985 and October 1987. Eighty-one percent met classic criteria for GH deficiency and were classified as having idiopathic GH deficiency (59%), organic GH deficiency (18%), or septo-optic dysplasia (4%). The remaining 19.8% had short stature of varied causes. Height standard deviation score at diagnosis, maximum GH response to stimulation, and heights of parents were examined according to gender, race, age at diagnosis, and previous treatment history. The predominance of boys in all subgroups except septooptic dysplasia, and the observation that girls with idiopathic GH deficiency were comparatively shorter than boys at diagnosis, suggest ascertainment bias. Black children with idiopathic GH deficiency were shorter than white children at diagnosis, and their low overall representation (6.0%) compared with their percentage in the at-risk population (12.9%) also suggest ascertainment bias among races. These data provide a profile of GH deficiency as it is currently defined and expose possible inherent biases in the diagnostic process. Now that GH supply is no longer limited, criteria for its use should be formulated to avoid apparent underascertainment or late diagnosis of GH deficiency in girls and black children.

Adolescent↗
PubMed1986

Clinical studies with recombinant-DNA-derived methionyl human growth hormone in growth hormone deficient children.

Thirty-six children with growth hormone deficiency were treated for up to 48 months with methionyl human growth hormone (hGH) synthesised by DNA recombinant methods. The growth rate for these children increased from 3.2 +/- 1.1 cm/yr to 10.5 +/- 2.2 cm/yr (mean +/- SD). This was similar to the effect of pituitary hGH in ten GH deficient children, 3.8 +/- 1.0 to 10.1 +/- 1.1 cm/yr. Serum somatomedin C rose from 0.26 +/- 0.23 U/ml to 0.79 +/- 0.53 U/ml after 6 months of methionyl-hGH therapy, similar to the effect of pituitary hGH. The incidence of antibody formation to methionyl-hGH was higher than that observed with pituitary hGH (Kabi) but poor growth was observed only in the one patient on methionyl-hGH who acquired high-titre high-binding-capacity antibodies to hGH. No consistent changes in levels of antibodies to Escherichia coli proteins were detected. No other allergic manifestations or systemic side-effects were demonstrable.

Adolescent↗
PubMed1984

Growth hormone neurosecretory dysfunction. A treatable cause of short stature.

Pulsatile growth hormone (GH) secretion was assessed in a subgroup of short children to determine whether they had GH secretory abnormalities, and these results were compared with those of normal and GH-deficient children. This subgroup of children was defined as having GH neurosecretory dysfunction and met the following criteria: height, less than first percentile; growth velocity, 4 cm/yr or less; bone age, two or more years behind chronological age, normal findings from provocative GH tests (peak, greater than or equal to 10 ng/mL), low somatomedin-C level, and abnormal 24-hour GH secretory patterns. When compared with controls, both children with GH neurosecretory dysfunction and GH-deficient patients had a significant decrease in parameters relating to the total GH secretion during the 24-hour period. As with GH-deficient children, the group with GH neurosecretory dysfunction more than doubled their growth velocity after replacement therapy with exogenous human GH during the first year of treatment. As a result of these detailed studies on pulsatile GH secretion, we suggest that there is a spectrum of GH secretory abnormalities from absolute deficiency to an intermittent irregularity in GH secretion.

Adolescent↗
PubMed1984

Pygmy mouse fibroblasts in tissue culture: evaluation of multiplication stimulating activity (MSA) receptors and growth responses to MSA.

The pygmy mouse has been proposed as a model for growth hormone resistance; it has normal serum somatomedin levels and does not respond to growth hormone treatment. In order to determine if the growth impairment is caused by a defect in somatomedin binding or in postreceptor action of somatomedin we compared fibroblasts derived from pygmy mice with those from normal appearing littermates. Using multiplication-stimulating activity (MSA) as a model somatomedin we found a normal Ka of binding to the cell surface MSA receptor but a significantly increased number of MSA receptors on the fibroblasts derived from pygmy mice. Studies of thymidine incorporation into DNA failed to demonstrate a difference between pygmy and normal fibroblasts in their responses to MSA alone, but there was a significantly greater thymidine incorporation into the DNA of normal fibroblasts when both competence factor (platelet-derived growth factor) and progression factors (somatomedins and growth hormone deficient platelet-poor plasma) were present in the test medium. On the other hand, cell proliferation studies did not demonstrate a consistent difference in the growth rate of normal versus pygmy fibroblasts. The data support the conclusion that the imparied growth of the pygmy mouse in vivo may be caused by factors which lie outside of the growth hormone-somatomedin pathway.

Animals↗
PubMed1983

Purification of an insulin-like growth factor II receptor from rat chondrosarcoma cells.

An insulin-like growth factor II (IGF-II) receptor was purified from rat chondrosarcoma cells by Triton X-100 solubilization of a 100,000 X g membrane preparation and affinity chromatography on a multiplication-stimulating activity (MSA)-Sepharose column. Analysis of the purified receptor by sodium dodecyl sulfate-gel electrophoresis and silver staining showed a major band of Mr = 210,000 (Mr = 250,000 after reduction with dithiothreitol). When 125I-MSA was chemically cross-linked to the purified receptor and analyzed by sodium dodecyl sulfate-gel electrophoresis (with and without dithiothreitol) and autoradiography, the radioactive bands coincided with the Mr = 210,000 and 250,000 bands identified by silver staining. The purified receptor also appeared to contain an Mr = less than 68,000 species identified by silver staining in addition to the Mr = 250,000 binding component. IGF-I, IGF-II, and MSA-II inhibited binding of 125I-MSA to the purified receptor with the same relative potency as for binding to the intact chondrosarcoma cell (IGF-II greater than MSA-II greater than IGF-I), and insulin did not inhibit binding. The association constant (K alpha) for MSA-II binding to the purified receptor was 2 X 10(9) M-1. The purified receptor bound to concanavalin A-Sepharose and wheat germ lectin-Sepharose columns and was eluted with alpha-methyl-D-mannoside and N-acetyl-D-glucosamine, respectively, showing that the receptor is a glycoprotein.

Animals↗
PubMed1982

Solitary thyroid nodules in children and adolescents.

Thirty-nine children and adolescents with a solitary nodule of the thyroid gland were seen over a 16-yr period and 35 had their nodules removed surgically. All of the patients had preoperative thyroid scintiscans, of which 27 showed a cold nodule. The most common cause of solitary thyroid nodules was follicular adenoma. Five of the 27 cold nodules were malignant (18.5%) while no malignancies were present in the warm or hot nodules. Available diagnostic methods of attempting differentiation of benign from malignant solitary nodules are reviewed and an approach to the clinical management of such nodules as derived from our experience is presented.

Adenoma↗
PubMed1980

Computerized tomography in the evaluation of isosexual precocity.

Clinical and laboratory observations were made in three children with isosexual precocity. None of the patients showed abnormalities in neurological or visual-field examinations although one patient had arrested hydrocephalus and a head circumference greater than the 98th percentile for her age and another patient had a history of seizures. Roentgenograms of the skull were normal in all patients. Cranial computerized tomography (CT) identified a lesion in each patient. We believe that craniel CT should be performed in any patient with isosexual precocity in whom a specific cause is not evident or in whom a cerebral cause is suggested even though the patient may be otherwise normal. Cranial CT is a safe, accurate, and noninvasive technique.

Brain Diseases↗
PubMed1980

Prenatal diagnosis of congenital adrenal hyperplasia.

In patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, the concentrations of the cortisol precursor 17-alpha hydroxyprogesterone (17-OHP) and its metabolite delta 4-androstenedione (delta 4 A) are increased. CAH was diagnosed in twins by measurement of 17-OHP and delta 4 A concentrations in amniotic fluid obtained by amniocentesis from both amniotic cavities at 17 weeks' gestation. Both prenatal karyotypes were 46,XX. Spontaneous labor and delivery of 2 nonviable fetuses with genital masculinization occurred at 26 weeks' gestation. It is concluded that delta 4 A measurement, like 17-OHP quantitation, is valuable in the prenatal diagnosis of CAH; that both methods appear useful in prediction of CAH in twin fetuses; and that abnormal adrenal-mediated masculinization in female CAH is well established before the end of the second trimester.

Adrenal Hyperplasia, Congenital↗