Search PubMed⌕ Search

Biomedical subjects

W S Cutfield

Publications and source records attributed to W S Cutfield.

24 records · Page 2Linked to original sources

Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure. The International Board of the Kabi Pharmacia International Growth Study.

To assess the role of growth hormone in fetal and infant growth, we analyzed the pretreatment data on 52 patients with a diagnosis of congenital growth hormone deficiency before 2 years of age, obtained from the Kabi Pharmacia International Growth Study. These infants had reduced birth-length standard deviation scores, an excess of birth weight relative to length, and progressive growth failure. We conclude that congenital growth hormone deficiency may cause impaired growth in utero and early infancy, and that growth hormone plays an important role in perinatal and infantile growth.

Analysis of Variance↗

Diminished growth hormone-binding protein in children with insulin-dependent diabetes mellitus.

Two distinct GH-binding proteins (GHBP) are present in circulation in the human. The major GHBP (high affinity GHBP) is homologous to the extracellular portion of the GH receptor and the concentration of this protein in circulation may reflect the status of the GH receptor in the tissues. To gain information about the concentration of GHBPs in children with insulin-dependent diabetes mellitus (IDDM), we measured GHBP in the serum of 46 children with IDDM and compared it to that in 53 healthy control subjects matched for age and sexual maturity. The total GHBP concentration in the group of pubertal and postpubertal IDDM patients was lower than that measured in the control group (mean +/- SEM: 7.8 +/- 0.4 vs. 9.0 +/- 0.5%, P = 0.05). The diabetic children in stages II to IV of puberty had a lower GHBP level compared to their healthy controls (7.6 +/- 0.4 vs. 9.1 +/- 0.5%, P = 0.02), whereas the difference between the diabetic and control group of postpubertal children was not statistically different (8.3 +/- 0.7 vs. 9.7 +/- 0.7%, P = 0.1). In a randomly selected subset of eight patients and eight controls, the concentration of the individual GHBPs (i.e. high affinity and low affinity (GHBP) was estimated by gel chromatography. There was no difference in the low affinity GHBP between the two groups (9.9 +/- 0.6% vs. 9.9 +/- 0.4%), but the high affinity GHBP was less in the diabetic group than in the control group (10.5 +/- 0.9 vs. 15.6 +/- 1.0%, P less than 0.01). In the diabetic group, there was no correlation between the GHBP levels and age, duration of diabetes, hemoglobin A1, or insulin dose. We conclude that in IDDM there is less of the high affinity GHBP, suggesting a decrease in the number of GH receptors in these patients. This decrease may contribute to GH resistance manifesting as decreased insulin-like growth factor-I levels despite high GH levels in patients with IDDM.

Adolescent↗

Evaluation of a pen injector system for growth hormone treatment.

The increasing use of human growth hormone (hGH) treatment has resulted in the introduction of a number of alternative delivery systems to conventional syringe and needle administration. We examined patients' evaluation of a new delivery system, the Kabipen (Kabi-Vitrum). We also assessed the accuracy of hGH delivery by the Kabipen. Of the 77 survey respondents 13 had used only the Kabipen, 14 the syringe only, and 50 had used both systems. Altogether 46 (92%) of those who had used both systems preferred the Kabipen. Children over 10 years were more likely to self administer hGH with the Kabipen (64%) than syringe (25%). Patient instructions, convenience of use, and comfort of use were rated better for the Kabipen than syringe. With a dose setting of 2 units the Kabipen delivered a mean (SD) of 1.997 (0.073) units with 102.5% recovery from a unit cartridge. In summary the Kabipen is an accurate device clearly preferred by the majority of hGH recipients surveyed.

Child↗

Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. Its role in fetal macrosomia.

BACKGROUND AND METHODS: Fetal macrosomia occurs despite nearly normal maternal blood glucose levels in women with diabetes treated with insulin. We examined the hypothesis that it may be caused by insulin transferred as an insulin-antibody complex from the mother to her fetus. We adapted and validated a method based on high-performance liquid chromatography and used it to quantitate insulin in small volumes (0.5 to 1.0 ml) of cord serum from 51 infants born to mothers with insulin-dependent diabetes mellitus. RESULTS: In mothers receiving only human insulin (n = 6), only human insulin was detected in cord serum. Of the remaining 45 infants, whose mothers received animal insulin during pregnancy, 28 (group 1) had levels of animal (bovine or porcine) insulin (mean [+/- SE], 707 +/- 163 pmol per liter) that constituted 27.4 +/- 2.5 percent of the total insulin concentration (2393 +/- 500 pmol per liter) measured in the cord serum. The cord-serum insulin concentration in the remaining 17 infants (group 2), in whom only human insulin was detected (381 +/- 56 pmol per liter), was only 15 percent of that in group 1 (P less than 0.001). There was a significant correlation between the maternal and the cord-serum concentrations of anti-insulin antibody and the concentration of animal insulin in the baby (r = 0.77, P less than 0.01, and r = 0.76, P less than 0.001, respectively), suggesting that the animal insulin was transferred as an insulin-antibody complex. In group 1 the mean concentration of animal insulin in cord serum was higher in the 12 infants with macrosomia than in the 16 infants without the condition (1113 +/- 321 vs. 402 +/- 110 pmol per liter; P less than 0.05), and the concentration of animal insulin in cord serum correlated with birth weight (r = 0.39, P less than 0.05). The maternal glycosylated hemoglobin values and the incidence of respiratory distress syndrome were similar in groups 1 and 2. CONCLUSIONS: Considerable amounts of antibody-bound insulin are transferred from mother to fetus during pregnancy in some women with insulin-dependent diabetes mellitus; the extent of transfer correlates with the maternal concentration of anti-insulin antibody. The correlation between macrosomia and the concentrations of animal insulin in cord serum indicates that the transferred insulin has biologic activity and suggests that the formation of antibody to insulin in the mother is a determinant of fetal outcome independent of maternal blood glucose levels.

Adult↗

The modified minimal model: application to measurement of insulin sensitivity in children.

The modified minimal model (MMM), a recently introduced method that assesses insulin sensitivity (SI) by a computed mathematical analysis of the relation between the change in insulin and glucose clearance after a bolus of iv glucose, followed 20 min later by a bolus of tolbutamide, has been standardized in adults, but this method has not been validated in children. We performed an abbreviated 90-min MMM test in 50 children who were siblings of patients with insulin-dependent diabetes mellitus and 7 healthy adult volunteers and compared the results to the standard 180-min MMM test in 11 of these subjects. The cohort consisted of 29 prepubertal children [16 males and 13 females; 8.7 +/- 2.0 (mean +/- SEM) yr old]; 16 pubertal children defined as less than 17 yr of age and Tanner stage 2-5 (8 males and 8 females; 13.4 +/- 1.8 yr old), and 12 postpubertal subjects (7 males and 5 females; 18.2 +/- 0.9 yr old), with no significant difference in the weight for length index (WLI) among the 3 groups and with sera of all subjects negative for islet cell antibodies and insulin autoantibodies. The test procedure consisted of 3 baseline blood samples over 30 min, followed at zero time by 0.3 g/kg 25% dextrose infused iv over 1 min and an iv injection of tolbutamide (5 mg/kg) 20 min later; sequential blood samples for glucose and insulin measurements were withdrawn from zero time until completion 90 or 180 min later. In the 11 subjects who underwent both the standard and the abbreviated tests, there was no significant difference between the SI estimated by the 2 methods provided that glucose and insulin values were interpolated at 180 min during the computer calculations of the abbreviated test. Using the 90-min abbreviated test, the SI of the pubertal subjects (2.92 +/- 0.45) was markedly less than that of the prepubertal subjects (6.57 +/- 0.45; P = 0.0001). While the postpubertal group value of 4.63 +/- 0.86 was significantly higher than that of the pubertal group (P = 0.0001), the pre- and postpubertal groups remained significantly different (P = 0.0001). The 10 obese subjects with WLI greater than 120% had a lower SI (3.5 +/- 0.53) than the 47 nonobese subjects with WLI less than 120% (SI = 5.48 +/- 0.42; P less than 0.04), and there was a negative correlation between SI and WLI. None of the study subjects experienced symptomatic hypoglycemia during the test.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Factors predictive of response to growth hormone therapy in Turner's syndrome.

In Turner's syndrome there is marked heterogeneity of growth response to growth hormone (GH) therapy. The study aim was to identify pretreatment factors that influence response to GH therapy. The 70 subjects recruited were prepubertal, had not received sex steroids and had received 28 units/m2/week of GH for > or = 1 year. Pretreatment variables associated with the greatest improvement in height SDS (r2 = 0.58) were weight for length index (p = 0.0001), target height (p = 0.004), bone age delay (p = 0.008) and age (p = 0.04). In conclusion, during two years of GH therapy the best growth response occurred in girls who were younger, heavier, had a delayed bone age and tall parents. Height SDS as a continuous variable is the most effective measure of growth when considering pretreatment factors that may influence response to GH therapy.

Adolescent↗