Biomedical subjects
Publications and source records attributed to P C Hughes.
Body proportion was studied in Turner's syndrome by measurement of standing an sitting heights in relation to chronological and bone age. The mean standard deviation score for standing height was -3.8. Disproportionate growth of the legs was not a major determinant of short stature, either before or after oestrogen replacement.
Male rats were undernourished for one of three periods of time during suckling. They were subjected to undernutrition from birth to 8 days post-partum, birth to 15 days or birth to 22 days. The growth of the humerus, radius, femur and tibia was followed radiographically during the undernutrition and recovery periods. It was found that the lengths of these bones in animals undernourished from birth to 8 days were able to recover completely, while after the two longer periods of undernutrition, the animals were unable to recover. The results are not in complete agreement with those of previous workers and it is suggested that this may be due to differing rates of growth and maturation between the animals used in different studies.
It would appear from these results that no simple relationship exists between the ability of the animal to achieve complete catch-up and the degree to which it has fallen behind controls, the maturity of the region at the time the insult is applied, or the relationship of the insult to the timing of the peak growth velocity. The findings of Widdowson and McCance [1963], that postweaning undernutrition has far less serious consequences than preweaning undernutrition, are, however, confirmed. The age of the animal at the time that the insult is applied and the degree to which it falls behind controls would both seem to make a contribution to the eventual catch-up, older animals being better able than younger ones to recover fully from the same degree of deficit. The results show that different regions of the skeleton respond differently to periods of undernutrition, both in the degree to which they fall behind control values and in their ability to achieve complete catch-up. The potential for catch-up is known to vary, depending on the state of cell multiplication at the time that the insult is applied [Enesco and LeBlond, 1962; Winick and Noble, 1965, 1966] and periods of undernutrition are known to result in a disturbance in the structure of cartilage [Silberberg, 1968; Dearden and Espinosa, 1974; Dearden and Mosier, 1974]. Presumably the results presented here reflect differences in the various cartilages of the regions being examined, complete catch-up being impossible in some regions due to permanent abnormalities of structure and/or function having been induced.
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Seven first-grade children with conduct disorders and/or hyperactivity attended full-day sessions at a laboratory school classroom. During an 8-week period, the classroom lighting conditions alternated at the end of each week. During odd-numbered weeks, the classroom was illuminated by a standard cool-white fluorescent system. On even-numbered weeks, illumination was a daylight-simulating fluorescent system of equal footcandles with controls for purported soft X rays and radio frequency (RF). There were no effects of lighting conditions on hyperactive behavior as assessed by (a) independent observations of task orientation or (b) ratings of activity level. A Critical Flicker Fusion (CFF) measure, a reported indicator of visual-sensory fatigue, indicated that the daylight-simulating condition was associated with a decreasing CFF across weeks.
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The growth of the rat calf muscle has been followed radiographically during neonatal undernutrition and subsequent catch-up. The following observations were made: (1) The mean calf muscle width of rats reared in litters of 16 was 20% less than that of those reared in litters of 8. (2) There was no significant difference between the sexes in the degree of growth retardation brought about by suckling the pups in large litters. (3) By the end of the experiment, females had caught up in both muscle width and muscle length, the males had caught up in muscle length (identical to tibia length) but not in muscle width. (4) In male pups during undernutrition the muscle diameter was greater than in normally fed animals of the same weight (but younger). This difference was not seen in females. (5) During recovery, until a weight of about 160 g was reached, the muscle width of the neonatally undernourished rats of both sexes was less than controls of the same body weight.
In rats whose growth was restricted by rearing in large litters the skull was less affected than the spine and the brain case less than the face. No sex difference was apparent during undernutrition but on subsequent rehabilitation females had caught up to controls in four out of five skull measurements within 4 weeks and by the end of the experiment the skulls of the neonatally undernourished females were the same size and shape as the controls. In the case of males, however, the skull of the undernourished rats never attained the same width as the controls.
The growth of the skull of the rat was longitudinally from 23 to 140 day PC from radiographs. Four measurements were made on each animal at each age studied. The velocity graphs of these measurements showed that for two, namely neurocranium length and bizygomatic width, the peak rate of growth occurred before birth. Viscerocranium length and neurocranium width showed peak rates after birth. Males became significantly larger than females in each of the absolute measurements studied, but in cranial index and facial index there were no significant differences between the sexes. Both these indices showed strain differences when compared to the results obtained by other workers.
The widths of muscle and fat in the upper arm and calf have been measured radiologically before treatment and at intervals of 1, 3. 6 and 12 months during administration of human growth hormone in 41 pre-pubertal patients with "isolated" growth hormone deficiency and in 22 patients with multiple deficiencies following gross CNS lesions. Height was also measured. The curves of response of muscle and fat on the one hand and height on the other were strikingly dissimilar. A very rapid increase of muscle took place in the first month; but after 6 months the increments had fallen to normal values for size and bone age. Decrements in fat followed the same pattern. Height, however, showed a smaller increment in the first month than in the period 1 to 3 months in the "isolated" deficiency cases, and much slower fall back towards normal. The first-year height increment was not at all correlated with the first-month height increment in the "isolated" deficiency cases, though it had a correlation coefficient of 0.46 with the first-month muscle increment. Nine cases of short stature not due to GH deficiency were similarly studied. There was considerable overlap between deficient and non-deficient in all responses in the first 3 months, though children in the top half of the responder's distribution could be distinguished. A 1-month radiological test of responses to hGH in doubtful cases is proposed, using in all only 40 IU of hormone. It is emphasised that a small response of muscle and fat may occur in cases who do nevertheless respond in height to hGH administration; a large response in muscle and fat, however, is indivative that treatment will be effective, though it does not well predict the precise amount of height that may be gained.
The growth of the calf muscle of the rat has been examined using a non-destructive,, radiological procedure. The growth was followed longitudinally in one set of rats from 3-228 days of age. A second group containing 165 animals was examined cross sectionally. In these animals the weight as well as the width of the muscle was recorded. It was concluded that growth of the calf muscle in width is more complex than the grwoth of the tibia, as a second growth peak was seen between 28 days and 35 days in the muscle but not in the tibia. It was observed that in animals greater than 150g body weight the muscle radiological shadow of the female was greater than that of the male, but this difference was not seen in muscle weight. The relationship between muscle size and muscle weight was not uniform: if the lightest animals were excluded then a logarithmic relation appeared, and if the heaviest animals were excluded, a cube relation was found. Variation in weight was always greater than in width, and it was concluded that muscle width could not be used for accurate estimation of muscle weight.
We have followed the growth of stature, sitting height, skinfolds, muscle widths measured radiologically, and skeletal maturity in growth hormone-deficient patients in whom hGH was given and withheld in alternating three-month periods throughout puberty (referred to as "off-hGH" and "on-hGH" periods). Six boys and four girls had true isolated GH deficiency and developed puberty spontaneously. Two boys had gonadotrophin deficiency plus GH deficiency, and five boys had multiple deficiencies; in these boys the signs of puberty were induced by hormone treatment. Boys with true isolated deficiency grew about two-thirds as much in height in the off-hGH periods as in the on-hGH periods; their total gain in height during the adolescent spurt would have been about 20 cm, instead of 30 cm, if hGH had been discontinued at the beginning of puberty. The effect of hGH was entirely on growth in leg-length, however, which virtually ceased during the off-hGH periods. Growth in sitting height altered little when hGH was withdrawn. Growth in limb muscles, however, was GH dependent throughout puberty; during the majority of periods when hGH was withheld, muscle was actually lost; this occurred in the boys who were receiving large doses of testosterone as well as in those producing their own normal amounts. Subcutaneous fat diminished when hGH was given and increased when it was withdrawn; this occurred independently of administration of testosterone. There was little evidence that growth of pubic and axillary hair progressed faster during on-hGH periods, except perhaps in patients with multiple deficiencies. There was some evidence, however, that bone age progressed less rapidly during on-hGH periods than during off-hGH periods in the patients with isolated deficiency. The results in the girls agreed with those in boys so far as stature was concerned, but the relationship with sitting height and leg length appeared to be different; the reasons for this are discussed. We conclude that all children with GH deficiency should continue on treatment with hGH throughout puberty, ideally until growth ceases.
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Catch-up in body weight, nose-rump length and tail length has been examined in male rats. At birth, pups from several females were pooled and reallocated to provide litters of 16 pups. In group 1, the number was reduced to 8 at day 8, in group 2 on day 15, group 3 were raised in large litters until weaning. Animals reared in litters of 8 were termed controls. All animals were weaned at 22 days, placed two to a cage and provided with food and water ad libitum. They were examined at intervals to day 120. Animals rehabilitated at 8 days had caught up in body weight and 97% of the length of controls on day 120. Rats rehabilitated on day 22 were 88% of the body weight and 97% of the body length of the controls at 120 days. None of the experimental groups achieved the same tail length as the controls. It was concluded that the data do not support the "time tally" mechanism of catch-up growth. This may be due to early timing of the experiment or an oversimplification of the mechanism. It was also concluded that catch-up following neonatal undernutrition in rats is greatly influenced by the normal growth pattern.
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