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Biomedical subjects

G E Richards

Publications and source records attributed to G E Richards.

At least 19 recordsLinked to original sources

Effectiveness of a rural pediatric diabetes management program.

BACKGROUND: Children with type 1 diabetes living in rural areas may have limited access to specialty diabetes care compared to children living in urban areas. To address this issue, providers have developed outreach services in which specialists travel periodically to rural communities. OBJECTIVE: To determine whether the care of children with type 1 diabetes treated by pediatric endocrinologists in a rural outpatient clinic is comparable to the care of children treated in an urban medical center by the same diabetes team. METHODS: We carried out a retrospective cohort study comparing the number of patient visits with physicians, behavioral specialists, and dietitians and the frequency of hemoglobin A1c (HbA1c) measurements over a 12-month period treated in a rural clinic with a matched group treated in an urban children's hospital clinic. RESULTS: We found that urban patients (n = 38) were more likely to complete four visits per year compared to a matched group (n = 19) at the rural clinic (55.3% vs. 15.8%; p < 0.004), were significantly more likely than those in the rural clinic to have had four HbA1c measurements per year (55.3% vs. 21.1%; p < 0.014), and more likely to have had an assessment by a behavioral specialist (31.6% vs. 0%). Children at the rural clinic site were more likely to have had a visit with a nutritionist during the year (89.5% vs. 36.8%; p < 0.005). CONCLUSION: We conclude that diabetes care provided using a rural outreach model closely approximates, but does not entirely duplicate, care provided in the urban setting.

Child↗

Obesity in Auckland school children: a comparison of the body mass index and percentage body fat as the diagnostic criterion.

OBJECTIVES: First, to determine obesity rates in Auckland school children according to their ethnic group using two different criteria: the body mass index (BMI) and percentage body fat (PBF) derived from bioelectrical impedance analysis (BIA). Second to examine the relationship between BMI and body composition across ethnic groups to determine if BMI references from European children accurately reflect obesity in other ethnic groups. DESIGN: A total of 2273 Auckland school children, aged 5-10.9 y had their height, weight and bioelectrical impedance measured. Using these measurements, each child's BMI, fat free mass, fat mass and PBF were derived. RESULTS: In all 14.3% of children were obese using the recommended definition of obesity (BMI) greater than the 95th percentile). There was no clinically significant difference in the relationship between BMI and body composition in different ethnic groups. Obesity rates varied with ethnicity (P<0.0001) and were higher in Pacific Island (24.1%) and Maori (15.8%) than in European children (8.6%). Obesity rates also varied with age (P<0.03), with the highest rates in older children. PBF levels were higher in females than males (P<0.0001). Using a definition of obesity based on percentage body fat (PBF>30%), obesity rates were higher in all ethnic groups. CONCLUSIONS: Obesity rates are high in Auckland school children and there are clear differences in obesity rates in different ethnic groups. If BMI criteria are used to define obesity in our population, we recommend the same standards be used for children of all ethnicities.

Age Factors↗

Androgen regulation of growth hormone binding protein.

Male puberty is associated with elevated plasma concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I), as well as accelerated linear growth. These effects can be reproduced by administration of testosterone (T). To further elucidate the mechanisms underlying pubertal growth, we treated 14 boys with delayed puberty and short stature with either T (n = 7) or 5alpha-dihydrotestosterone (DHT) (n = 7) and compared the effect on plasma concentrations of GH, IGF-I, and GH binding protein (GHBP). Before treatment and after either three or four doses of T enanthate or DHT heptanoate, mean 12-hour GH concentration (8 AM to 8 PM) and plasma IGF-I, T, DHT, and GHBP levels were measured, and height velocity (HV) was measured over this interval. T treatment resulted in an increase of mean GH from 3.3 to 12.0 microg/L (P < .005) and of IGF-I from 22.3 to 45.4 nmol/L (P < .01). During treatment, HV was 11.0 +/- 1.1 cm/yr, consistent with normal pubertal growth, and plasma T was 22.5 +/- 5.3 nmol/L. GHBP decreased in this group from 937 to 521 pmol/L (P < .025). DHT treatment resulted in a small decrease of mean GH from 4.3 to 2.9 microg/L (P < .025) and of IGF-I from 29.4 to 27.2 nmol/L (nonsignificant [NS]). During treatment, HV was 9.3 +/- 1.1, not significantly different from the HV obtained with T treatment, and plasma DHT was 24.2 nmol/L at 1 week and 29.2 at 2 weeks postinjection. Likewise, there was a decrease in GHBP from 928 to 698 pmol/L (P < .025). The decline in GHBP with T treatment was apparently due to an androgen receptor-dependent mechanism, since the same effect was seen during treatment with the nonaromatizable androgen, DHT. This effect is opposite to the normal chronological trend upward for GHBP, which occurs from infancy into midpuberty. Factors determining the upward trend are not known, but are evidently independent of the plasma concentration of sex hormones and GH. The increase in IGF-I in response to T treatment despite a moderate decline in GHBP (and possibly GH receptor) levels is most likely due to the large increase in GH, which may override a modest decrease in GHBP/GH receptor.

Adolescent↗

A simplified gonadotrophin-releasing hormone test for precocious puberty.

BACKGROUND AND OBJECTIVE: The gonadotrophin-releasing hormone (GnRH) test is important for the evaluation of children with disorders of puberty. Traditionally, the test determines the peak LH and the peak FSH responses from 5 to 8 blood samples, which makes it cumbersome and costly. We suspected that the test could be simplified to require fewer hormonal measurements. DESIGN: A retrospective clinical study. PATIENTS: Subjects were 44 girls and 7 boys with signs of precocious puberty, of whom 39 were diagnosed as definite central precocious puberty. Fifty-five diagnostic tests and 39 tests for suppression during GnRH-analogue treatment were reviewed. MEASUREMENTS: LH and FSH were measured in serum samples obtained during a standard GnRH test. PARAMETERS: LH and FSH responses and the LH:FSH ratio at 30, 45 and 60 minutes, and the respective peak levels. For each parameter, the sensitivities and specificities were estimated and the receiver operating characteristic curve was constructed. RESULTS: The receiver operating characteristic curves for the LH responses at 30, 45 and 60 minutes and peak, were similar and showed high specificities and sensitivities for the diagnosis of central precocious puberty. A single LH cut-off (15 IU/I) had diagnostic sensitivity > 90% and specificity > 80% for LH concentrations at 30, 45 or 60 minutes and peak, and sensitivity > 90% to detect suppression. Calculations of the LH:FSH ratio did not improve the diagnostic accuracy of the GnRH test achieved by LH alone. CONCLUSIONS: A single LH determination 30 minutes after GnRH administration is as useful as the peak LH; FSH measurements are unnecessary for the differential diagnosis of central precocious puberty. We propose that for the diagnosis of central precocious puberty and for treatment monitoring, the GnRH test to be simplified to LH measurement in a single blood sample at 30 minutes.

Child↗

Different sites of photodamage in chilling-sensitive (sorghum) and chilling-resistant (barley and wheat) plants.

The electron transport chain was affected to varying degrees by high light intensity at low temperature in different crop plants. The PS II was found to be the sensitive site while PS I showed very little change in its activity. Photoinhibition affected the oxidizing side of PS II in all three plants. However, the site of inhibition was different in chilling-sensitive and chilling-resistant plants. In sorghum, the water splitting reaction was damaged while in barley and wheat the damage occurred in the reaction centre itself. It appears that photoinhibition may affect different sites within the PS II in chilling-resistant and sensitive plants.

Cold Temperature↗

Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty.

The purpose of this study was to investigate the roles of androgenic and estrogenic mechanisms in the stimulation of structural growth and plasma GH in male puberty. To resolve these two possible mechanisms, we compared the effect of two androgens in the treatment of constitutional delay in growth and adolescence: an aromatizable androgen, testosterone (T), and a nonaromatizable androgen, dihydrotestosterone (DHT). Nine adolescent males, Tanner stage 1 or 2, were studied before and during treatment with T enanthate (group A) or DHT heptanoate (group B). After 2.5 months of treatment, the height velocity (HV) was 12.6 +/- 2.8 cm/yr (n = 3) in group A and 8.9 +/- 1.7 cm/yr (n = 6) in group B, both within the range of peak HV for pubertal males. In group A, the integrated concentration of GH (ICGH) increased from 3.12 +/- 0.90 to 13.67 +/- 6.0 micrograms/L (P < 0.05), and plasma insulin-like growth factor-I (IGFI) increased from 126.7 +/- 2.5 to 350.3 +/- 20.3 micrograms/L (P < 0.01); plasma T increased from 0.8 +/- 0.5 to 33.8 +/- 11.0 nmol/L (P < 0.001), and the LH response to LHRH decreased from 27.6 +/- 10.7 to 5.9 +/- 2.5 IU/L (P = NS). In group B, ICGH decreased from 4.32 +/- 0.61 to 2.39 +/- 0.42 (P < 0.025), and IGF-I decreased from 218.3 +/- 39.2 to 184.0 +/- 15.8 (P = NS). Plasma T increased from 2.0 +/- 0.5 to 2.7 +/- 0.8 (P = NS), and the LH response to LHRH decreased from 45.7 +/- 14.5 to 10.7 +/- 5.8 (P < 0.05). To further evaluate the mechanism of the effect of DHT on plasma GH, seven male subjects with adolescent gynecomastia were treated with DHT heptanoate, and their responses were studied at 1 week and 3.5 months. ICGH decreased in conjunction with a decrease in the integrated T concentration (r = -0.77; P < 0.001) and to a slight degree with decreasing plasma estradiol (r = -0.39; P < 0.2). Plasma IGF-I did not show a significant change in the subjects with gynecomastia. Thus, the increase in GH at puberty in males appears to be due to an estrogen-dependent mechanism. The suppressive effect of DHT on GH secretion may be due to either suppression of estradiol production or a direct effect. Acceleration of HV into the peak pubertal range by DHT without an increase in plasma GH suggests that an increase in GH is not necessary for the pubertal growth spurt.

Adolescent↗

The effect of thyroidectomy on growth hormone regulation in the ovine fetus.

To test the hypothesis that growth hormone gene messenger RNA abundance in the fetus is subject to the same effects of thyroid hormone previously demonstrated in other situations, we evaluated the effect of thyroidectomy on pituitary GH mRNA content at three gestational ages in the ovine fetus. One of each twin pair of fetal lambs underwent thyroidectomy at 90, 100 or 110 days gestation. Fetal pituitaries were collected 25-30 days later. Plasma GH and IGF-I were measured as well as pituitary GH mRNA content. Serum growth hormone in the thyroidectomy group was less than in the control twins (129.8 vs 187.6 micrograms/l, P = 0.0. GH mRNA was likewise decreased in pituitaries of thyroidectomy fetuses compared to controls (1.01 vs 1.80 units, P = 0.0006). Serum IGF-I and body weight were similar in the thyroidectomy and control twins. We conclude that the ovine fetus in the final trimester of gestation exhibits effects of thyroid hormone on serum GH and mRNA abundance similar to those seen in postnatal animals.

Actins↗

Relation between nocturnal melatonin profile and hormonal markers of puberty in humans.

We examined the relation between nocturnal melatonin and hormonal markers of puberty in 57 normal children and adolescents and 39 subjects with disorders of pubertal onset. Melatonin was measured in hourly blood samples drawn overnight by constant withdrawal. Basal 08.00 h plasma testosterone, estradiol and LH, and the peak LH response to LHRH administration were determined. There were no significant correlations between testosterone, estradiol, basal LH and peak LH and melatonin peak (r = -0.18, -0.22, -0.02, -0.12, respectively) or melatonin peak time (r = 0.12, -0.01, -0.02, 0.07 respectively). The results were not affected significantly by sex, diagnosis or age. A comparison of subjects grouped by peak LH < 15 U/l (most likely prepubertal; n = 40) and peak LH > 30 U/l (most likely pubertal; n = 34) showed no significant differences in melatonin peak (160.5 +/- 59.3 vs. 146.6 +/- 50.9 pg/ml; t = 1.09; p > 0.05) or melatonin peak time (1.8 +/- 1.7 vs. 2.5 +/- 1.7 h; t = -1.79; p > 0.05). Although a pineal-puberty relation cannot be excluded, the results do not support the hypothesis that melatonin restrains the hypothalamic-pituitary-gonadal axis during childhood.

Adolescent↗

Long-term prospective evaluation of offspring of diabetic mothers.

We have suggested that altered maternal metabolism may affect the subsequent anthropometric and neuropsychological development of children who were in utero during disturbances in maternal fuel economy. This study reports the physical growth through 8 yr of age and the neuropsychological development through 4 yr of age in offspring of diabetic mothers (ODM). At birth, 50% of infants had weights greater than 90th percentile for gestational age. By 12 mo, length and weight were similar to the general population. Height remained normal until 7 yr of age, when it became slightly greater than average. After 5 yr of age, relative weight increased dramatically, and by 8 yr of age, half of the ODM had weights greater than 90th percentile. This childhood obesity in ODM is correlated with maternal prepregnant weight and independently with amniotic fluid insulin at 32-38 wk gestation. The Brazelton Neonatal Behavioral Assessment Scale (BNBAS) was administered to 185 newborn ODM. Significant correlations were found between poorer second- and third-trimester glycemic regulation and lower scores in three of four newborn BNBAS dimensions. The Stanford-Binet Intelligence Scale was measured in 102 ODM at 4 yr of age. We found an inverse correlation between childhood IQ and second- and third-trimester maternal lipid metabolism (serum free fatty acids and beta-hydroxybutyrate). This correlation is not explained by adverse perinatal events, socioeconomic status, maternal IQ, ethnicity, or diabetes type. These long-range associations between altered maternal metabolism and childhood growth and development continue to support Freinkel's hypothesis of fuel-mediated teratogenesis.

Aging↗

The ontogeny of [3H]5-hydroxytryptamine binding in the lamb: effects of in vivo thyroidectomy.

The effects of congenital hypothyroidism in the late gestation ovine fetus include changes in serotonin concentrations in specific brain areas. To investigate possible ontogenic patterns of changes in 5-HT receptor function, we studied the binding characteristics of [3H]5-HT in the midbrain, hypothalamus and cerebral cortex in the late gestation ovine fetus and young lamb. We compared the binding characteristics of control fetuses to those of thyroidectomized fetuses, with or without thyroxine replacement therapy. In each of the areas examined, age-dependent changes in the receptor density (Bmax) for [3H]5-HT was observed. In cerebral cortex, Bmax was constant from 120 days gestation through the early neonatal period and increased significantly only at 25-30 days after birth. In hypothalamus, [3H]5-HT binding density decreased late in gestation (140-145 days) with a return after birth to values comparable to those at 120-125 and 130-135 days gestation. The midbrain also exhibited a significant age-dependent pattern of altered receptor density with a decrease in the 130-135 and 140-145 day gestational age groups compared to both younger and older lambs. In contrast, the affinity constant (Kd) for [3H]5-HT did not change over the ages evaluated in cerebral cortex or hypothalamus. In the midbrain, however, there was a significant increase in Kd at 1-5 days after birth compared to all other age groups. The ability of fetal thyroidectomy, with or without thyroxine replacement therapy, to alter patterns of [3H]5-HT binding was also tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Changes in selected brain neurotransmitters and their metabolites in the lamb after thyroidectomy during the last two trimesters of gestation or the early neonatal period.

To evaluate in a development context the effect of congenital hypothyroidism on concentrations of the neurotransmitters norepinephrine, dopamine, and serotonin (5HT) in selected brain areas of the ovine fetus, we studied the effect of thyroidectomy at three ages on the concentrations of these neurotransmitters and their major metabolites, homovanillic acid and 5-hydroxyindoleacetic acid. Fetuses underwent thyroidectomy at 90-95 or 105-115 d gestation (term = 147-150 d) or 1-5 d after birth. Approximately 25 d after thyroidectomy, at d 120-125 or 130-135 of gestation or 25-30 d after birth, respectively, the ewes were killed and fetal brains removed. Neurotransmitters and their metabolites were measured by HPLC with electrochemical detection. Thyroidectomy in the 2nd trimester increased 5HT in five brain areas: anterior hypothalamus, dorsal medial hypothalamus, pons, medulla, and cerebellum. Thyroidectomy in the 3rd trimester increased 5HT in the pons and medulla, increased norepinephrine in the dorsal medial hypothalamus and pons, and increased homovanillic acid in the posterior hypothalamus. Thyroidectomy in the newborn period decreased NE in the anterior hypothalamus, ventral medial hypothalamus, and midbrain, decreased 5-hydroxyindoleactic acid in the posterior hypothalamus, lateral hypothalamus, dorsal medial hypothalamus, and ventral medial hypothalamus, and decreased homovanillic acid in the dorsal medial hypothalamus and ventral medial hypothalamus. From these data we conclude the following: 1) Hypothyroidism causes changes in neurotransmitter concentrations only in selected brain areas of the ovine fetus, rather than causing generalized and similar changes in all brain areas; and 2) 5HT 5-hydroxyindoleacetic acid concentrations are affected more often than the other neurotransmitters evaluated, perhaps because the 5HT neurotransmitter system is developing at these times.

Animals↗

Expanded ontogeny of neurotransmitters and their metabolites in the brains of fetal and newborn lambs.

To evaluate the ontogeny of the brain neurotransmitters norepinephrine, dopamine, serotonin and the metabolites hydroxyindoleacetic acid and homovanillic acid, we measured these neurotransmitters in 10 brain areas at three ages in fetal sheep and two ages in newborn lambs. Norepinephrine exhibited an increase only at 25-30 days after birth in the midbrain, lateral hypothalamus, dorsal medial hypothalamus and ventral medial hypothalamus. Dopamine concentration was very low and did not change over the ages examined. Homovanillic acid decreased after 125 days in the cerebellum, but this change is probably not biologically meaningful, since there were no statistically significant changes in homovanillic acid in other brain areas. Serotonin increased at 25-30 days after birth in the ventral medial hypothalamus, but changes in other brain areas were not significant. Hydroxyindoleacetic acid reached its greatest concentration at 1-5 days after birth in nine of the ten brain areas examined. Thus we conclude that the serotonin system is undergoing more change in the last third of gestation and first month of extrauterine life than the norepinephrine or dopamine systems.

Animals↗

The effects of hydrocortisone on lung structure in fetal lambs.

The effect of cortisol infusion on fetal lung development was studied in lambs. Changes were compared with those of control groups of saline-infused fetuses of the same age (day 132) and normal late gestation fetuses (142 +/- 4.6 days). Cortisol was infused into five fetal lambs at 129 days of gestation at a rate of 17.0 mg/day. Four fetuses were delivered by hysterotomy at the onset of labour-like uterine activity (58 +/- 3 h). In cortisol-infused fetuses the concentration of cortisol in fetal plasma and tracheal fluid rose to levels similar to those in normal fetuses during the last week of gestation. Progesterone concentration in maternal plasma declined at about 48 h after the start of treatment. Cortisol-infused lambs showed increases in fixed lung volume, specific lung volume, absolute volume of both parenchyma and non-parenchyma and the proportion of the parenchyma which was potential airspace and a decrease in the proportion of parenchyma. For cortisol-infused lambs Type II cell size and the abundance of lamellar bodies, and the volume fraction of cell occupied by the nucleus were similar to the 142 day group, whereas Golgi apparatus and RER were closer to age matched saline-infused (day 132) controls. Glycogen content was midway between the two control groups. We conclude that infusion of cortisol for about 60 h at physiological levels, beginning at 0.85 of gestation, accelerates many, but not all aspects of pulmonary parenchymal maturation, expressed in terms either of morphogenesis of the gas exchange area or differentiation of Type II alveolar cells.

Adrenal Glands↗

Evoked potentials show early and delayed abnormalities in children with congenital hypothyroidism.

To evaluate the effect of congenital hypothyroidism (CH) on nervous system development, we performed evoked potential studies on 7 CH infants at 3-8 weeks of age before treatment and at four months or more after treatment began. All infants were screened using filter paper determination of T4 and TSH, confirmed by serum specimen determinations. These infants had serum TSH concentrations greater than 100 microU/ml (normal less than 7), and the serum T4 range was 4.1-8.5 micrograms/dl. All had thyroid tissue on 99Tc scan; five had ectopic thyroid tissue, and two had a thyroid gland in the normal location. Four older CH children were tested after 3-6 years of treatment. Brainstem auditory evoked potentials (BAEP) were abnormal in three of the 7 infants and showed bilateral conduction delays in caudal brainstem regions. The BAEP became normal after 6 months of thyroxine treatment. Visual evoked potentials (VEP) were abnormally delayed and had an immature pattern in the four patients tested at four weeks of age. At age 8 weeks, even in untreated patients, the VEP was normal and remained so. Somatosensory evoked potentials (SSEP) were normal at the time of diagnosis. However, seven patients tested after at least five months of therapy had prolonged central conduction times. We conclude that infants with relatively mild CH (serum T4 values greater than 4 micrograms/dl at 3-8 weeks of age) have evidence of delayed visual system maturation that becomes normal even without treatment and of abnormal caudal brainstem development that resolves slowly with replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

Effect of growth hormone on the glomerular filtration response to a protein meal.

The role of dietary protein intake in the pathogenesis of progressive renal disease has been recently reexamined. Studies of both animal and humans with chronic renal disease have shown that restriction of dietary protein may slow the progression of the decline in renal function. This occurs because of a decrease in intraglomerular blood flow and pressure. The mechanism of this phenomenon is not known. The effect of protein intake on renal function is thought to be hormonally mediated. Since growth hormone can increase renal blood flow as well as GFR, we tested the hypothesis that the presence of growth hormone is necessary for the increase in glomerular filtration rate (GFR) seen after the ingestion of a protein meal. We evaluated the change in GFR after a standardized mixed protein meal in 13 patients with growth hormone deficiency. Neither basal creatinine clearance after an overnight fast (76 +/- 17 ml/min/m2; mean +/- SD) nor maximum increment after a 50 g/m2 protein meal (33 +/- 11 ml/min/m2) differed in these growth hormone-deficient patients from 16 normals controls (76 +/- 18 and 30 +/- 15 ml/min/m2, respectively). Twelve hours after an injection of exogenous growth hormone, 0.06 mg/kg up to a maximum of 5 mg, the GFR response to a protein meal did not differ from the pretreatment response (77 +/- 19 and 32 +/- 17 ml/min/m2, respectively). We conclude that the presence of physiologic amounts of growth hormone is not necessary for the GFR response to a standard protein meal.

Adolescent↗