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Biomedical subjects

A L Ogilvy-Stuart

Publications and source records attributed to A L Ogilvy-Stuart.

At least 19 recordsLinked to original sources
PubMed2005

The continuous glucose monitoring sensor in neonatal intensive care.

OBJECTIVE: To determine the feasibility of continuous glucose monitoring in the very low birthweight baby requiring intensive care, as these infants are known to be at high risk of abnormalities of glucose control. METHOD: Sixteen babies were studied from within 24 hours of delivery and for up to seven days. RESULTS: The subcutaneous glucose sensors were well tolerated and readings were comparable to those on near patient whole blood monitoring devices. CONCLUSION: Continuous glucose monitoring is practical in neonates, giving detailed information about glucose control.

Biosensing Techniques↗
PubMed2002

Neonatal thyroid disorders.

Hypothyroxinaemia, which is common in the preterm infant, and thyrotoxicosis, which is rare, are important neonatal thyroid disorders. Their causes and treatment are discussed.

Breast Feeding↗
PubMed2001

Hypoglycemia and resistance to ketoacidosis in a subject without functional insulin receptors.

Humans with congenital absence of the islets of Langerhans and mice rendered null for the insulin receptor rapidly develop severe hyperglycemia and ketoacidosis and, if untreated, die in the early neonatal period. In contrast, children with homozygous or compound heterozygous mutations of the insulin receptor gene, although hyperglycemic postprandially, survive for many months without developing ketoacidosis. Paradoxically, they often develop hypoglycemia. The rarity of the condition and the difficulties of undertaking metabolic studies in ill infants have limited the physiological information that might explain the clinical features. We studied a boy with Donohue's syndrome who represents a further example of the null phenotype, with two different and novel nonsense mutations in the alpha-subunit of the receptor. He survived for 8 months without developing ketoacidosis, and fasting hypoglycemia was a frequent problem. Despite the complete absence of insulin receptors, evidence for persistent insulin-like effects on fat and liver was seen; fasting plasma beta-hydroxybutyrate and nonesterified fatty acid levels were low, fell further during the early postprandial period, and failed to rise in response to hypoglycemia. The inverse relationships between plasma insulin and insulin-like growth factor-binding protein-1 levels were maintained, suggesting persistent hepatic effects of insulin. GH levels measured over a 6.5-h period were low throughout. Thus, the differences between congenital insulin deficiency vs. insulin receptor deficiency in humans may be explained by persistent insulinomimetic activity of the grossly elevated plasma insulin presumably being mediated through the type 1 insulin-like growth factor receptor. As GH plays a critical role in the regulation of ketogenesis during insulinopenia in humans, but not in rodents, this may contribute to the distinct phenotype of human vs. mouse insulin receptor knockouts.

3-Hydroxybutyric Acid↗
PubMed1998

Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn.

The relationship between GH, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin may be critical to the understanding of variation in early growth, especially in the small for gestational age (SGA) baby. To investigate these relationships, we have undertaken 12-h hormone profiles in 26 babies (13 SGA) at a median of 4.5 days of age. GH levels were measured every 10 min; insulin and IGFBP-1 were measured every 20 min. Mean levels of these hormones and IGF-I levels (from a single sample) were related to size at birth. The GH data were analyzed by Pulsar and time series analysis to characterize hormone pulsatility and relationship with feeds. IGF-I levels correlated with birth weight and length (r2 = 0.47; P = 0.004, and r2 = 0.5; P = 0.0005, respectively, after allowing for gestation), whereas mean GH levels were negatively related to birth size (r2 = -0.18; P = 0.04 and r2 = -0.2; P = 0.03 for weight and length, respectively). No direct relationship between mean GH levels and IGF-I was identified. IGF-I levels were higher in appropriate for gestational age (AGA; mean +/- SD, 82+/-61 ng/mL) than in SGA (34+/-22 ng/mL; P = 0.03) babies. Baseline (mean +/- SD, 25.9+/-11.9), mean (33.9+/-14.0), and peak (45.0+/-18.1 microg/L) GH levels were higher in SGA than in AGA babies [17.1+/-8.2 (P = 0.04), 22.5+/-10.4 (P = 0.03), and 30.7+/-15.4 microg/L (P = 0.04), respectively]. Mean IGFBP-1 levels were also higher in SGA than AGA babies (157.4+/-90.7 vs. 62.7+/-43.8 ng/mL; P = 0.01). A positive correlation was identified between changes in insulin and coincident pulses of GH (r = 0.147; P < 0.01), whereas there was an inverse relationship between insulin and IGFBP-1, with a lag time 120 min (r = -0.33; P < 0.0001). In conclusion, these studies indicate that the GH-IGF-I axis is closely related to feeding in the newborn. In SGA babies, low IGF-I and elevated IGFBP-1 reflect the slow growth, but elevated GH and rapid GH pulsatility may be a signal for lipolysis.

Eating↗
PubMed1997

Treatment of radiation-induced growth hormone deficiency with growth hormone-releasing hormone.

UNLABELLED: In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth. OBJECTIVE: We have aimed to determine the efficacy and safety of growth hormone-releasing hormone (GHRH) (1-29)-NH2 given as a twice daily subcutaneous injection in the treatment of growth failure in children with radiation-induced GH deficiency. DESIGN: A multicentre study comparing growth before and after 1 year of treatment with GHRH (1-29)-NH2, 15 micrograms/kg twice daily, by subcutaneous injection in children with radiation-induced GH deficiency. On completion of the study year all children were treated with GH (0.5 U/kg/week) and growth parameters were documented over the next year. PATIENTS: Nine children (six boys) with radiation-induced GH deficiency following cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant from the hypothalamic-pituitary axis (n = 8) or prophylaxis against central nervous system leukaemia (n = 1) were studied. All were prepubertal when the study commenced, which was at least 2 years from radiotherapy. MEASUREMENTS: Anthropometry and pubertal staging were carried out at 3-monthly intervals and bone age estimations at 6-monthly intervals (TW2 method). Pretreatment standing height velocities were compared with values during the year of GHRH treatment and then after the first year of GH therapy. In those that had received craniospinal irradiation, a change in leg-length Standard deviation score (SDS) was noted before and after GHRH therapy. Changes in skin-fold thickness and bone age during the GHRH study year were documented. Adverse events and 3-monthly measurements of clinical chemistry, haematology, lipid profile and thyroid function were recorded. RESULTS: There was a significant increase in height velocity from 3.3 (SD 1.1) cm/year before treatment, to 6.0 (SDS 1.5) cm/year after 1 year of GHRH treatment (P = 0.004). GHRH maintained or improved the leg length SDS in children who had received craniospinal irradiation. Bone age increased by a mean of 1.1 years/chronological year during treatment with GHRH. Subsequent height velocity during 1 year of GH therapy was 7.5 (SD 1.5)cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse events that could be attributed to GHRH therapy. One child went into puberty during the GHRH study year and three were pubertal during the first year of GH therapy. CONCLUSION: In cranially irradiated children, GHRH was effective in increasing growth velocity but this was less than that seen in response to GH therapy, although it matched that in children with isolated idiopathic GH deficiency treated with the same dose and schedule of GHRH administration.

Age Determination by Skeleton↗
PubMed1997

The use of an automated microsampling system for the characterization of growth hormone pulsatility in newborn babies.

To overcome the difficulties of studying hormone pulsatility in the newborn, we have developed an automated microsampling system that permits the measurement of hormones in small prediluted samples of blood (40 microL) taken at 10-min intervals over 12 h. The system has been validated in adult volunteers, and the error attributable to the dilution was <4%. Using this method in 10 preterm babies, we have been able to describe pulsatile changes in GH and have demonstrated a clear postprandial elevation in GH levels peaking 60 min after a feed. Fourier transform analysis indicated a pulse periodicity of 180 min in babies who were appropriate for gestational age (n = 6), but faster, co-dominant pulse periodicities of 90-100 and 140 min in babies who were small for gestational age (weight and length below the 10th centile) (n = 4). There was no significant difference between mean, peak, and baseline GH levels between the two groups.

Adult↗
PubMed1995

High incidence of obesity in young adults after treatment of acute lymphoblastic leukemia in childhood.

To determine whether obesity complicated the treatment of childhood acute lymphoblastic leukemia, we studied the body mass index (BMI) of 63 female when and 51 male patients from the time of diagnosis of acute lymphoblastic leukemia to the time when final height was attained. The BMI z score was calculated for each patient at diagnosis, at end of treatment, and at attainment of final height. Obesity at attainment of final height was defined as a BMI greater than the 85th percentile of the normal reference population. At final height 23 of 51 male (45%) and 30 of 63 female patients (47%) were obese. Girls became obese between diagnosis and the end of chemotherapy (p = 0.02), after which they had no further increase, indicating that chemotherapy may have played a role in their obesity. Boys had a progressive and gradual increase in BMI z score through to attainment of final height. Obesity did not appear to be associated with growth hormone insufficiency, disproportionate growth, or abnormal timing of puberty. We conclude that approximately half the survivors of leukemia in childhood become obese young adults. Many of those treated with the more recent regimens studied are still only in their mid or preteen years and should be advised regarding a more active lifestyle and a healthy diet in an attempt to reduce the incidence of obesity.

Adolescent↗
PubMed1995

Effect of chemotherapy on growth.

Growth restriction has been demonstrated clearly following the treatment of childhood malignancies, even in the absence of irradiation to the hypothalamic-pituitary axis. The use of CT and spinal irradiation in the original treatment of brain tumours has a marked effect on growth. This effect is most profound in children who have received both treatments and cannot be overcome using GH therapy at conventional doses.

Adolescent↗
PubMed1995

Growth and puberty after growth hormone treatment after irradiation for brain tumours.

The impact of treatment with either cranial or craniospinal irradiation with or without cytotoxic chemotherapy for a brain tumour distant from the hypothalamic-pituitary axis was assessed in 29 children who had reached final height. All had received growth hormone treatment for radiation induced growth hormone deficiency. Final height, segmental growth during puberty, and duration of puberty were studied. Both craniospinal irradiation and the use of chemotherapy resulted in a significant and equal reduction in final height; this effect in those children who received both craniospinal irradiation and chemotherapy was additive. The degree of height loss was related to the age at irradiation, the most profound effect on final height occurring in the youngest at irradiation. The mean duration of puberty from G2-G4/B2-B4 (1.97 years) was not significantly different from the duration of puberty in normal children. Growth hormone increases growth velocity in children with radiation induced growth hormone deficiency but their final height is significantly less than their mid-parental height. The use of spinal irradiation and chemotherapy in the original treatment of brain tumours has a marked effect on growth which is not overcome with the use of growth hormone treatment in current doses. Early puberty of normal duration contributes to poor growth.

Adolescent↗
PubMed1995

Safety of growth hormone after treatment of a childhood malignancy.

The use of growth hormone therapy in children with radiation-induced growth hormone (GH) deficiency is widely accepted, but the safety of this mitogenic hormone, particularly in children previously treated for cancer, continues to cause concern. A variety of malignant tumours have been induced in animals exposed to supraphysiological doses of GH, whereas hypophysectomised animals appear protected from carcinogen-induced neoplasms. Growth hormone and insulin-like growth factor-1 have been shown to stimulate both proliferation and transformation of normal and leukaemic human lymphocytes in vitro when used in supraphysiological doses. Despite the theoretical arguments, there is no evidence of an increased risk of tumour recurrence following GH therapy in replacement dosage in children previously treated for a malignancy.

Animals↗
PubMed1994

Radiation and neuroregulatory control of growth hormone secretion.

OBJECTIVE: Cranial irradiation frequently results in growth hormone (GH) deficiency. Patients with radiation-induced GH deficiency usually remain responsive to exogenous growth hormone releasing hormone, implying radiation damages the hypothalamus rather than the pituitary. Little is known about the effect of cranial irradiation on the neuroendocrine control of GH secretion. This study was to determine the effect of cranial irradiation on somatostatin tone. DESIGN: Somatostatin tone was examined by manipulating cholinergic tone in young adults with radiation-induced GH deficiency and a control population. Each individual underwent three separate studies: the GH response to 100 micrograms GHRH-(1-29)-NH2 was assessed alone, and 60 minutes after pyridostigmine or pirenzepine. PATIENTS: Eight young male adults with radiation induced GH deficiency following treatment in childhood for a brain tumour or acute lymphoblastic leukaemia, and ten healthy adult men were studied. MEASUREMENTS: Serum growth hormone was measured at 15-minute intervals throughout each of the three study periods. RESULTS: One of 10 controls and four of eight irradiated subjects had a peak GH level to GHRH analogue of less than 20 mU/l. After pretreatment with pyridostigmine, all subjects except one irradiated subject had a peak GH level of greater than 20 mU/l. Pretreatment with pyridostigmine and pirenzepine significantly modified the GH response to GHRH analogue within both groups (P < 0.0005). Pretreatment with pyridostigmine significantly enhanced the GH response to GHRH analogue (median (range) area under the curve, 9029 (1956-20940) mU/l/min in controls vs 1970 (628-3608) mU/l/min in the irradiated group) compared with GHRH analogue alone (1953 (512-16140) mU/l/min in control group vs 997 (266-3488) mU/l/min in the irradiated group). Pretreatment with pirenzepine significantly attenuated the GH response to GHRH analogue (552 (64-1274) mU/l/min in controls vs 305 (134-2726) mU/l/min in irradiated group). Between the groups there was no significant difference in GH area under the curve (AUC) after GHRH analogue alone. There was a significantly (P = 0.0014) greater increment of GH secretion after pyridostigmine and GHRH analogue compared with GHRH analogue alone (difference in AUC of pyridostigmine+GHRH analogue and GHRH analogue alone 6348 (696-12856) mU/l controls vs 542 (120-1340) mU/l in the irradiated group) and significantly (P = 0.033) greater suppression of GH secretion after pirenzepine and GHRH analogue compared with GHRH analogue alone (difference in AUC of GHRH analogue alone and pirenzepine+GHRH analogue 1644 (222-15205) mU/l in controls vs 479 (469-1623) mU/l in the irradiated group) in the control population compared with those who had received cranial irradiation in childhood. CONCLUSIONS: These data suggest that cranial irradiation reduces but does not abolish somatostatin (SRIH) tone and also reduces endogenous GHRH secretion. Although SRIH tone is reduced, it can be increased by cholinergic manipulation and is therefore not irreversibly fixed. This has possible implications if GHRH analogues were used to treat children with radiation induced GH deficiency.

Adult↗
PubMed1994

Cranial irradiation and early puberty.

Low doses of cranial irradiation (18-24 gray) employed in the management of acute lymphoblastic leukemia may cause early or precocious puberty, predominantly in girls. To determine whether this sexual dichotomy exists at higher irradiation doses (25-47 gray), the onset of puberty was identified in 46 GH-deficient children (30 males) previously irradiated for a brain tumor not involving the hypothalamic-pituitary axis and compared with the normal pubertal standards of Marshall and Tanner. Age at irradiation was at least 2 SD below the mean age of pubertal onset in normal children. There was a significant linear association between age at irradiation and age at onset of puberty. The onset of puberty occurred at an early age in both sexes (mean, 8.51 yr in girls and 9.21 yr in boys plus 0.29 yr for every year of age at irradiation). For example, the estimated age at onset of puberty in a boy irradiated at 2 yr of age would be 9.79 yr, and that for a boy irradiated at 9 yr of age would be 11.82 yr. In the context of GH deficiency, which is usually associated with a delay in the onset of puberty, this is abnormal. At each age of irradiation, the estimated age at the onset of puberty was approximately 0.7 yr earlier in girls than boys. A similar trend was seen for bone age, which was abnormally early at the time of pubertal onset (mean, 7.39 yr in girls and 8.66 yr in boys plus 0.25 yr for every year of age at the time of irradiation). At the doses of irradiation employed in the treatment of brain tumors, radiation-induced early puberty is not restricted to girls. The clinical consequence of early puberty in the management of poor growth associated with radiation-induced GH deficiency is to foreshorten the time available for treatment with GH.

Age Factors↗
PubMed1993

Effect of radiation on the human reproductive system.

Irradiation may have a profound effect on reproductive function. The schedule of the delivered irradiation (total dose, number of fractions, and duration) is an important determinant of the radiobiological effect on the tissues involved and varies among different tissues and organs. Irradiation to the central nervous system may affect the timing of the onset of puberty, result in hyperprolactinemia, or cause gonadotropin deficiency if the hypothalamic-pituitary axis is involved in the radiation field. Direct irradiation to the testis will, in lower doses, affect the germinal epithelium: doses of irradiation greater than 0.35 Gy cause aspermia, which may be reversible. The time taken for recovery increases with larger doses; however, with doses in excess of 2 Gy aspermia may be permanent. At higher radiation doses (> 15 Gy), Leydig cell function will also be affected. In addition to radiation dose, the vulnerability of the testis is dependent on the age at irradiation and the pubertal status of the male. In the female, the response of the ovary to the effects of irradiation varies with age as well as dose, and separation of ovarian dysfunction into hormonal and fertility effects is not clearcut. An ovarian dose of 4 Gy may cause a 30% incidence of sterility in young women, but 100% sterility in women over 40 years of age. Pelvic irradiation may also have a profound effect on the uterus, with arrested growth in the prepubertal girl, and failure of uterine expansion during pregnancy with subsequent miscarriages and premature labor.

Adolescent↗
PubMed1992

Growth hormone and tumour recurrence.

OBJECTIVE: To determine whether using growth hormone to treat radiation induced growth hormone deficiency causes tumour recurrence. DESIGN: Comparison of tumour recurrence rates in children treated with growth hormone for radiation induced deficiency and an untreated population. Computed tomograms from children with brain tumours were reviewed when starting growth hormone and subsequently. SETTING: North West region. PATIENTS: 207 children treated for brain tumour, 47 of whom received growth hormone and 161 children with acute lymphoblastic leukaemia 15 of whom received growth hormone. MAIN OUTCOME MEASURES: Tumour recurrence and changes in appearances on computed tomography. RESULTS: Among children with brain tumour, five (11%) who received growth hormone had recurrences compared with 42 (26%) who did not receive growth hormone. Also adjusting for other variables that might affect tumour recurrence the estimated relative risk of recurrence was 0.82 (95% confidence interval 0.28 to 2.37). The only child with acute lymphoblastic leukaemia who relapsed while taking growth hormone had relapsed previously before starting treatment. Two of the five children with brain tumours who relapsed had abnormal appearances on computed tomography when growth hormone was started. 14 other children who remained relapse free and had follow up computed tomography showed no deterioration in radiological appearance during treatment. CONCLUSIONS: In this population growth hormone did not increase the risk of tumour recurrence but continued surveillance is essential. Abnormal results on computed tomography are not a contraindication to treatment with growth hormone.

Adolescent↗
PubMed1992

Irradiation-induced growth failure.

GH deficiency, skeletal disproportion and early or precocious puberty may complicate irradiation to the head or axial skeleton in childhood. Certain cohorts of children are at particular risk, including those irradiated for brain tumours and various haematological malignancies. Both GH deficiency and impaired spinal growth may result in short stature, whereas the occurrence of early puberty in association with GH deficiency reduces the time available for GH therapy. The age of the child at irradiation is critical in that, in younger children, the central nervous system is more radiosensitive, the severity of the subsequent skeletal disproportion is greatest and the onset of puberty earliest. It is the very young craniospinally-irradiated child who is most at risk of extreme short stature.

Age Factors↗