Biomedical subjects
Publications and source records attributed to C J Kelnar.
A 10 year old girl with hypertrichosis associated with primary hypothyroidism that resolved after 6 months' replacement treatment with thyroxine is reported. It is important to consider the diagnosis of hypothyroidism in children with abnormal hairiness or distribution of body hair.
Twenty four-hour urine samples have been collected 6 monthly for 18 months from 127 normal boys aged between 7.5 and 17 years. Urinary steroid metabolites have been measured by gas-liquid chromatography and ratios of steroid metabolites used to draw conclusions about likely enzymic activities at each step in the adrenal biosynthetic pathway. DHA excretion rose throughout the study, especially between 7.5 and 11 years. Metabolites of cortisol and corticosterone did not increase when related to surface area. During adrenarche there were changes consistent with a decrease in 3 beta-hydroxysteroid dehydrogenase activity, a slight rise in 17 alpha hydroxylase activity, a marked rise in 17,20 lyase activity, and a fall in 11 beta hydroxylase activity. These data are compatible with the hypothesis that a small reduction in the ability to synthesize cortisol requires a marginal increase in the secretion of ACTH and/or other CRF-induced peptides to maintain cortisol production rate. ACTH itself or a dexamethasone-suppressible CRF-induced peptide would in such a case control the growth of the zona reticularis at adrenarche, which thus appears to be primarily an adrenal event.
7 patients aged 16-25 years with hypogonadotrophic hypogonadism have been treated with 100 micrograms of a synthetic gonadotrophin-releasing hormone intranasal spray (HOE 766) on alternate days. In 1 patient, after an encouraging initial response there was a rapid decline in gonadotrophin responsiveness. 3 patients failed to show biochemical or clinical effects of treatment. 3 cases showed continuing responsiveness of gonadotrophin sex steroid levels to treatment for periods between 8 and 11 months.
A 12-year-old boy developed renal wasting of magnesium, calcium, and potassium, with secondary hypomagnesaemia, hypocalcaemia, and hypokalaaemia (without hyperaldosteronism) after treatment with 14 400 mg gentamicin over 4 months. Gentamicin should not be given for prolonged courses if less toxic antibiotics are suitable. If it used, plasma magnesium, calcium, and potassium levels should be monitored during and after treatment.
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Knemometry is an accurate and non-invasive method of quantifying lower leg length changes. It reveals multiple fluctuations in leg length velocity over a short period of measurement, and on the basis of this it has been proposed that short-term growth is saltatory rather than a continuous phenomenon. The technical error (TE) of the technique which is generally employed, and which is subject to observer bias, ranges from 0.09 to 0.16 mm. This study was undertaken to compare the original method (OM) to a modified technique which involved measuring from a baseline value of which the operator was not aware; this technique is referred to as the random zero method (RM). Over a period of 10 months, 58 subjects were measured on 413 occasions. Overall, median TE in the RM group at 0.15 mm (P5-0, P95-0.65) was higher than the median TE in the OM group at 0.11 mm (P5-0, P95-0.37). However, the median TE over the last 3 months of 0.15 mm (P5-0.05, P95-0.87) was lower than the TE in the preceding 4 months of 0.20 mm (P5-0, P95-0.55) (WSR, p = 0.04) pointing towards the presence of an operator learning curve. The random zero method is a simple modification of the original method. It reduces observer bias but leads to a higher TE, which could explain some of the fluctuations seen between frequent knemometric measurements. Some knowledge of the length of the training period is important in the design of new studies involving knemometry; our data suggest that there should be a learning period of about 4 months if knemometry is performed as often as quoted above.
As the knemometer is increasingly being used to study changes in lower leg length in conditions associated with weight changes it is important to clearly delineate the relationship between these two variables. Lower leg length and weight were measured in 26 children and nine adults including one pregnant woman. There was a weak but positive relationship between lower leg length and weight fluctuation in children. Daily fluctuations in weight as well as lower leg length were higher in women than men; median lower leg length fluctuation: women, 0.16 mm (P5-0, P95-0.7); men, 0.1 mm (P5-0, P95-0.48) p approximately 0.02, Wilcoxon signed-rank test. Median weight fluctuation: women 0.15 kg (P5-0, P95-0.54); men, 0.1 kg (P5-0, P95-0.5) p = 0.94 (Wilcoxon signed-rank test). Sustained weight gain in pregnancy led to a reduction in lower leg length followed by an increase which was coincident with the appearance of dependent oedema. Lower leg length changes are likely to be positively related to changes in weight when the latter are only modest in magnitude. However, greater sustained increases in weight are likely to have an opposite effect on lower leg length due to direct compression of the lower leg. Due consideration of weight is essential in longitudinal studies of lower leg length changes, especially in conditions which are associated with significant changes in weight.
In order to identify metabolic cues involved in the control of onset of male human puberty, 70 pre- and peri-pubertal boys, aged 9.21 +/- 0.03 years at the start of the study, had their lean body mass (LBM), basal metabolic rate (BMR) and total daily energy expenditure (TDEE) measured at 6-monthly intervals on three occasions each. Hormonal pubertal activity was assessed by measuring early morning salivary testosterone (ST) at each assessment. A subgroup of 44 boys, who first showed an increase in ST at their third assessment, was identified. In the general population at this stage of development, and in the overall 70 boys studied here, BMR/LBM decreases significantly with age (from 0.185 +/- 0.001 to 0.180 +/- 0.001 MJ/day per kg over 6 months, p < 0.01, ANOVA), since both are increasing, but LBM at a greater rate than BMR. The 'imminently pubertal' group of 44 boys showed no decrease in the ratio BMR/LBM (0.182 +/- 0.001 MJ/day per kg) during the 6 months between their first two assessments despite the normal increase in LBM, indicating that BMR rises at a similar rate to LBM during this specific period of development. This observation supports the hypothesis that energy balance plays an important role during the events leading up to the onset of puberty and subsequent fertility.
This study tests the hypothesis that equations to predict basal metabolic rate (BMR) of adolescent boys may be made more accurate by using a measure of pubertal maturity (testicular volume, TV). Eighty-six male volunteers aged 11.8-13.7 years were studied. There was a wide range of pubertal development within the subject group, ranging from mean TV of 3 to 22.5 ml. BMR was found to correlate more highly with TV (r = 0.519) than height (r = 0.425) or age (r = 0.272). BMR predicted using the World Health Organization equations (based on height and weight) were significantly higher than measured BMR in early pubertal boys (TV < or = 4 ml, BMR (measured) = 5.04 +/- 0.17, BMR (predicted) = 6.14 +/- 0.15 MJ/day, p < 0.001, Student's t-test). The results provide evidence that measurement of testicular volume may increase the accuracy of equations for the prediction of BMR of adolescent boys.
A high prevalence of obesity in survivors of acute lymphoblastic leukemia (ALL) has been described, but genetic and social influence in obesity has not been analyzed in this group of patients. The authors studied a population of 33 long-term (25 females, 8 males) in first remission who had reached their final height. All patients received cranial irradiation as part of their central nervous system (CNS)-directed therapy and no patient received growth hormone. The body mass index (BMI: weight/height2) of patients and their biological parents was calculated and submitted to statistical analysis. Obesity was defined as BMI greater than the 85th centile. No excessive obesity was found among the males at final height. Fifty-six percent of the females were obese. In this group of 14 obese female survivors 59% had obese mother, but only 14% had obese fathers. The results indicate a significant maternal predisposition to obesity.
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The lower leg length velocity (LLLV) of 14 children with a median age of 4.5 yr who were undergoing chemotherapy (CT) for acute lymphoblastic leukaemia (ALL) was studied for a median duration of 56 weeks (range 14-112). Nine children were studied over the first 6 months, six over the first year, four over the full 2-year course and nine children over the 3 months before and after the end of CT. Over the first month of CT, during induction, median LLLV was 0 mm/wk (P5, P95: -1.6, 0.11); during the fourth month of CT, at the end of CNS-directed therapy, there was a significant rise to 0.38 mm/wk (P5, P95: -0.04, 0.81; p = 0.01, WSR). In the children measured following the end of CT, median LLLV rose from 0.46 mm/wk (P5, P95: -0.02, 0.79) in month 23 to 0.84 mm/wk (P5, P95: 0.72, 1.12) (p = 0.03). There was a positive relationship between neutrophil count and LLLV during continuation chemotherapy (r = 0.4, p = 0.0002); median LLLV was 0.2 mm/ wk (P5, P95: -0.15, 0.5) when the neutrophil count was less than 1 x 10(9)/l and 0.65 mm/wk (P5, P95: 0.1, 1.0) (p = 0.01) when the count was above 1 x 10(9)/l. No significant differences in LLLV were observed between children randomised to different UKALLXI regimens. Intensive chemotherapy for ALL adversely affects lower leg growth. Growth was subnormal during the first few weeks of chemotherapy, but was comparable to healthy children during CNS directed and continuation therapy. There was a significant relationship between growth velocity and neutrophil count during continuation chemotherapy. On discontinuation of chemotherapy there was a further acceleration in lower leg length velocity to supranormal levels ("catch-up" growth).
Biochemical markers of bone and collagen turnover have been found to be a valuable adjunct to measurements of bone mineral density in post-menopausal women in whom they appear to be independent predictors of osteoporosis and fracture risk. In children, they have been less extensively studied but have begun to find a similar complementary role in a number of disorders affecting bone turnover and growth. Although they may give helpful information in their reflection of recent bone turnover and growth in various disorders, their principal value appears to be in giving an early and sensitive indication of response to treatment, before changes in either height velocity or bone mineral density can be accurately determined. This review discusses the use and limitations of these markers in children, the clinical conditions in which they have been studied and their potential value in monitoring either beneficial or adverse effects of treatment on bone turnover and growth.
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