Biomedical subjects
Publications and source records attributed to S Castells.
Hypocalcemia can be devastating if unrecognized. Neuromuscular dysfunction occurs in severe cases. A review and an update on the topic may assist general pediatricians. The authors provide a general overview of pathogenesis and management of hypocalcemia in children.
We describe a patient with leukemia in remission for 7 years who developed growth hormone (GH) deficiency and was treated with recombinant human growth hormone (rhGH). We compare her growth with that of patients from the National Cooperative Growth Study (NCGS) database, 145 with leukemia in remission and 725 with idiopathic growth hormone deficiency (IGHD) on treatment with rhGH. We also review the literature on the risk of relapse of leukemia in similar patients. The patients with leukemia in remission from the NCGS database had a significantly lower change of mean height standard deviation score than that of IGHD patients in the first, second, and third year of rhGH treatment. The relapse rate of leukemia in patients treated with rhGH is between 0.8% and 2%. Starting rhGH therapy in patients with leukemia in remission and with GH deficiency at an adequate dosage and without undue delay would improve their growth response. Such therapy does not appear to increase the risk of leukemia.
The present study was conducted to determine the extent of insulin deficiency and glucagon excess in the hyperglycemia of type 2 diabetes in children. The incidence of type 2 diabetes mellitus in children and adolescents has increased substantially over the past several years. Because insulin and glucagon action both regulate blood glucose concentration, we studied their responses to mixed meals in children with type 2 diabetes. Subjects were 24 patients with type 2 diabetes compared with 24 controls, aged 9--20 yr (predominantly African-Americans), matched for body mass index and sexual maturation. All of those with diabetes were negative for antibodies to glutamic acid decarboxylase. Plasma glucose, glucagon, and serum C-peptide concentrations were measured at 0, 30, 60, 90, and 120 min after a mixed liquid meal (Sustacal) ingestion (7 mL/kg body weight; maximum, 360 mL). The area under the curve (AUC) was calculated by trapezoidal estimation. The incremental C-peptide (Delta CP) in response to the mixed meal was calculated (peak -- fasting C-peptide). The plasma glucose AUC was significantly greater in patients than in controls (mean +/- SEM, 1231 +/- 138 vs. 591 +/- 13 mmol/L x min; P < 0.001). The Delta CP was significantly lower in those with diabetes than in controls (1168 +/- 162 vs. 1814 +/- 222 pmol/L; P < 0.02). Glucagon responses did not differ between the two groups. Hyperglycemia is known to inhibit glucagon secretion. Therefore, our patients with substantial hyperglycemia would be expected to have decreased glucagon responses compared with controls and are thus relatively hyperglucagonemic. Patients were divided into poorly and well controlled subgroups (glycosylated hemoglobin A(1c), > or =7.2% and <7.2%, respectively). There were no significant differences in the Delta CP and glucagon responses between these two subgroups. We next analyzed the data in terms of duration of diabetes (long term, > or =1 yr; short term, <1 yr). The CP was significantly lower in long- vs. short-term patients (768 +/- 232 vs. 1407 +/- 199 pmol/L; P < 0.05). The plasma glucagon AUC was significantly higher in the long- vs. short-term patients (9029 +/- 976 vs. 6074 +/- 291 ng/L x min; P < 0.001). Hemoglobin A(1c) did not differ between long- vs. short-term patients. Our results indicate that relative hypoinsulinemia and hyperglucagonemia represent the pancreatic beta- and alpha-cell dysfunctions in children with type 2 diabetes. The severity of both beta- and alpha-cell dysfunctions appears to be determined by the duration of diabetes.
The authors report an 18-year-old girl with HIV infection who developed new-onset insulin-dependent diabetes mellitus (IDDM) in association with anemia. IDDM among patients with HIV infection has been infrequently reported and suggested to be caused by different etiologies. Susceptibility to autoimmune diseases, such as IDDM, has been associated functionally with two members of a newly described multigene family called PERB11. In this patient, the progression of hyperglycemia associated with a rapid increase in insulin requirement is suggestive of insulin resistance.
A substitution of arginine for glycine at amino acid position 154 of the alpha 1(I) collagen chain was found in a father and his three children. The phenotype of the patients includes manifestations of types I and III/IV osteogenesis imperfecta, but appears to be milder than that of the previously described two unrelated patients that had the identical mutation in the alpha 1(I) collagen chain. The variability in the phenotype raises the possibility of epistatic loci or environmental effects on expression of the disorder.
More than 150 mutations in the genes for type I procollagen have been found in unrelated patients with osteogenesis imperfecta (OI), but mutations have been difficult to define in many patients with the mildest forms of the disease. Here, we have used robotically automated sequencing of the cDNAs for type I procollagen to screen for mutations in 12 patients suspected of having nonlethal OI (types I, III, and IV). Single base mutations that changed codons for obligate glycine residues were found in seven of the patients. Altogether, we analyzed 4,379 bp of sequences of both alleles of the pro alpha 1 (I) collagen (8,758 bp of allelic sequences) and 4,200 bp of sequences of both alleles of the pro alpha 2(I) collagen (8,400 bp of allelic) from each patient.
We have found that some children with Down's syndrome (DS) have growth retardation secondary to growth hormone (GH) deficiency. To test the hypothesis that hypothalamic dysfunction is the primary cause for GH deficiency and growth retardation, hypothalamic-pituitary responses of serum GH concentrations to levodopa and clonidine as well as pituitary responses in serum GH concentrations to growth-hormone-releasing hormone (GHRH) were analysed in 14 prepubertal children with DS. Levodopa and clonidine were given, and blood was drawn for determining serum GH levels. Seven prepubertal control children had both levodopa and clonidine tests done. The delta serum GH during levodopa was 5.7 +/- 6.3 ng ml-1 in DS and 13.1 +/- 9.8 ng ml-1 in controls. The delta serum GH during clonidine administration was 3.0 +/- 3.2 ng ml-1 in DS and 17.3 +/- 5.6 ng ml-1 in controls. Children with DS had a significantly lower response to levodopa and clonidine, compared with controls by the Mann-Whitney U-test (P < 0.03 and P < 0.009, respectively). Growth-hormone-releasing hormone was given at 1 microgram kg-1 i.v. bolus and bloods for GH were drawn at-15, 0, 15, 30, 60, 90 and 120 min in 14 subjects with DS and 24 normal controls, both groups prepubertal. The mean delta serum GH concentration in DS was 53.6 +/- 38.3 ng ml-1, and it was 35.6 +/- 25.1 ng ml-1 in controls with P < 0.23 non-significant by the Mann-Whitney U-test. These results indicate that levodopa and clonidine (drugs stimulating hypothalamic GHRH release and secondary pituitary GH release in normal individuals) do not stimulate GH release in DS. Furthermore, normal GH response to GHRH in DS indicates normal pituitary function (normal somatotroph response to GHRH) and supports hypothalamic dysfunction in DS.
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Down's syndrome (DS) children have been reported to have severe postnatal growth arrest and microcephaly. To determine if growth hormone (GH) deficiency plays a role in growth retardation in DS, 20 children were studied. The subjects (13 boys, 7 girls) were aged between 15 months and 13.9 years, had a height SDS ranging from -1.19 to -5.48, weight SDS ranging from -0.21 to -4.58, head circumference SDS ranging from -0.40 to -6.6, and a skeletal age ranging from 0.9 to 4.6 SD below the mean for normal children of same age and sex. GH was evaluated by levodopa (125 mg up to 15 kg, and 250 mg between 15-30 kg), clonidine (0.15 mg m-2) stimulation tests and hGH secretory patterns by the integrated 24 h. GH concentration (IC-GH) using a constant withdrawal pump with continuous blood collection every 30 min. The serum concentrations were: TSH, 0.7-8.0 mIU ml-1 (0.2-5.5); T4, 6.6-14.3 micrograms dl-1 (5-12); T3, 95-254 ng dl-1 (85-185); LH, less than 2.0-8.3 mIU ml-1 (less than 3); FSH, less than 1.3-7.2 mIU ml-1 (less than 3); testosterone, less than 30 ng dl-1 (5-35); estradiol, less than 5 ng dl-1 (less than 5-25); prolactin, 35.7-2.9 (F: 5-25; m 5-15); and somatomedin-C (Sm-C), 0.14-1.98 U ml-1 (0.08-5.90) (normal values in brackets). Peak serum GH after levodopa and clonidine was found to be below 10 ng ml-1 for both stimulatory tests in seven out of the 20 children studied. Twelve children showed a disparity between levodopa and clonidine testing. Of the 12 children, peak serum GH after levodopa was found to be below 10 ng ml-1 in five children; and peak serum GH after clonidine was found to be below 10 ng ml-1 in six. One child had a clonidine peak increase in serum GH concentration exactly 10 ng ml-1, but had a 12 h IC-GH of 1.5 ng ml-1 (N greater than 3.2). Two children with peak GH after clonidine above 10 ng ml-1 had a 24 h IC-GH of 0.7 and 1.3 ng ml-1. A fourth child who had peak GH concentrations above 10 ng ml-1 with levodopa and clonidine had a 12 h IC-GH of 0.5 ng ml-1.(ABSTRACT TRUNCATED AT 400 WORDS)
The effect of recombinant human growth hormone on children with Down syndrome who had growth retardation and microcephaly was examined. Thirteen children with trisomy 21 without congenital heart disease who were short for age (-1.19 to -3.5 standard deviation score) and microcephalic (-1.58 to -6.60 standard deviation score) were given recombinant human growth hormone, 0.1 mg/kg subcutaneously, 3 days a week for 1 year. Before treatment, peak serum growth hormone concentrations were less than 10 micrograms/L after levodopa and clonidine stimulation tests in five patients, after clonidine in three patients, and after levodopa in three patients. Three patients had nocturnal integrated growth hormone concentrations of 0.5, 1.5 and 0.65 micrograms/L, respectively. The mean growth rate before treatment was 5.4 +/- 1.6 cm/yr and increased to 12.2 +/- 3.2 cm/yr (p less than 0.001) after 12 months of recombinant human growth hormone treatment. The mean head circumference standard deviation score before treatment was -3.1 +/- 1.3 and increased to -2.3 +/- 1.2 (p less than 0.001) at 12 months. Bone age before and 1 year after treatment increased in correspondence with chronologic age. Plasma hemoglobin A1c concentration was normal during treatment with recombinant human growth hormone. The mean plasma concentrations of insulin-like growth factor I at baseline and at 12 months were 0.54 +/- 0.19 U/ml and 1.25 +/- 0.97 U/ml, respectively (p less than 0.02). We conclude that recombinant human growth hormone therapy can result in a significant increase in annual growth rate and head circumference in children with Down syndrome, without significant side effects.
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Adolescents with insulin-dependent diabetes mellitus (IDDM) have a rate of noncompliance in our clinic of approximately 20% despite all of the usual measures aimed at securing compliance. Seven IDDM patients ranging in age from 11 to 19 years were managed in our clinic with all of our usual modalities, but all remained in long-term poor control during the 6 months immediately prior to the study. To ensure that each patient would serve as his/her own control, no changes were made in his/her management other than the addition of hypnosis. Six of the seven patients were followed for more than 6 months. No changes were made in insulin, diet, or exercise as prescribed. Posttreatment, the average HgbA1C dropped from 13.2% to 9.7%, and the average fasting blood sugar from 426 mg/dl to 149 mg/dl, values which are consistent with good compliance.
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A 1.6-yr-old Hispanic boy with sparse hair, muscle weakness, severe growth retardation, and rickets was found to have hypocalcemia, secondary hyperparathyroidism, and high circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels. One year of treatment with a high dose of 1,25-(OH)2D3 (20 micrograms, orally, daily) resulted in marked subjective and radiological improvement; there was a parallel improvement in serum calcium, phosphorus, PTH, alkaline phosphatase, and osteocalcin concentrations. Soluble extracts from cultured skin fibroblasts did not bind [3H]1,25-(OH)2D3 using standard methods. To evaluate the possibility of receptors with abnormally low affinity, we tested for binding with [3H]1,25-(OH)2D3 concentrations higher than those usually used. In one experiment, there was a suggestion of low affinity binding. Hormone receptors with abnormally low affinity for 1,25-(OH)2D may explain this patients resistance to 1,25-(OH)2D. Therapy to maintain extremely high serum 1,25-(OH)2D3 concentrations markedly improved mineral homoeostasis, but did not affect the hair disorder.
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Spinal somatosensory evoked potentials to stimulation of the peroneal nerves in the popliteal fossa were recorded from 46 insulin-dependent neurologically normal patients with juvenile diabetes. Conduction velocities of these potentials were determined over proximal peroneal nerve, cauda equina, and spinal cord and were compared with those obtained from 46 age-matched control subjects. Mean values for overall spinal conduction velocity (L3-C7 spines) and conduction velocity over rostral spinal cord (T6-C7 spines) and peroneal nerve-cauda equina (stimulus to L3 spine) were lower in the diabetic group (p less than 0.001). Peripheral nerve conduction velocity alone was slow in 5 patients, and spinal conduction velocity was slow in 8; in 2 patients both peripheral and spinal velocities were slow. This study suggests that in addition to impairment of peripheral nerve function, patients with juvenile diabetes without clinical evidence of neurological involvement can have a defect in spinal afferent transmission.
This article reviews our current knowledge on the effects of diabetes mellitus on thyroid function at the level of the pituitary-thyroid-peripheral tissue axis and attempts to determine its clinical importance.