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Biomedical subjects

R D Milner

Publications and source records attributed to R D Milner.

At least 91 records · Page 5Linked to original sources

Growth hormone deficiency presenting under age 2 years.

Twenty nine (1.8%) of a national cohort of 1600 patients with growth hormone deficiency presented before the age of 2 years. Sixteen of the 29 presented before 6 months of age--11 with symptomatic hypoglycaemia, four with failure to thrive, and one with obesity. Hypoglycaemia was persistent and difficult to control until growth hormone treatment was started. Ten of the 11 hypoglycaemic patients had multiple pituitary hormone deficiencies compared with two of the remaining five. Thirteen children presented between 6 months and 2 years of age; 12 had failure to thrive and one had spontaneous hypoglycaemia. Twelve of the 29 were boys and all but one of these had microgenitalia . Growth hormone deficiency should be considered in the differential diagnosis of infants presenting with refractory hypoglycaemia and in boys with failure to thrive and microgenitalia .

Age Factors↗

Reduced plasma somatomedin activity and costal cartilage sulfate incorporation activity during experimental growth retardation in the fetal rat.

In this study, the experimental model of Wigglesworth was used to limit the maternal blood supply to the rat fetus and induce intrauterine growth retardation. The associated changes in plasma somatomedin activity, insulin, glucose, and cartilage metabolic activity are reported. The mean body weight (+/- SEM) of 108 fetuses in ligated uterine horns was significantly lower than that of 146 control fetuses (ligated, 2820 +/- 50 mg; control, 3180 +/- 50 mg; p less than 0.001), as was mean nose-tail tip length (ligated, 55.6 +/- 0.4 mm; control, 59.4 +/- 0.3 mm; p less than 0.001) and mean liver weight (ligated, 222 +/- 5 mg; control, 274 +/- 5 mg; p less than 0.001). The uptake of [35S]sulfate by fetal costal cartilage in basal culture medium was significantly lower in growth-retarded fetuses than in controls. Plasma somatomedin activity measured by fetal rat cartilage bioassay was significantly lower in growth-retarded than in control fetuses (p less than 0.001). The growth-retarded fetuses were relatively hypoinsulinemic and hypoglycemic compared to control animals. These studies suggest that nutrient supply may become a limiting factor in the release of insulin and the circulating levels of somatomedin activity in the rat fetus, and hence in its growth.

Animals↗

Somatomedin activity in tracheal fluid from the newborn infant.

Somatomedin activity was determined by porcine cartilage bioassay and somatomedin-C RIA in matched samples of tracheal fluid (TF), amniotic fluid (AF), and cord (CP) and maternal plasma collected during the delivery of normal infants of 36-40 weeks gestation. Somatomedin levels determined by both assay systems were significantly greater in TF than in AF [TF, 0.40 +/- 0.04 (+/- SE) U/ml; AF, 0.20 +/- 0.02 U/ml by bioassay in 11 infants; TF, 0.25 +/- 0.04 U/ml; AF, 0.18 +/- 0.03 U/ml, by RIA in 6 infants; P less than 0.005]. When chromatographed on Bio-Gel P10 at pH 3.5, the major part of the somatomedin immunoreactivity from both TF and CP eluted in the same position as iodinated somatomedin-C (mol wt, 7600). Somatomedin activity recovered after chromatography of TF and CP increased the incorporation of radiothymidine by growth-restricted human fetal fibroblasts in vitro. Maternal plasma contained 2.49 U/ml radioimmunoassayable somatomedin-C, a value higher than that in the nonpregnant adult. The results suggest that the human fetal lung contributes somatomedin to TF and raises the possibility that these peptides are involved in lung growth or maturation.

Amniotic Fluid↗

Effect of glucose on insulin biosynthesis and beta cell ultrastructure in cultured fetal rat pancreas.

Pancreatic rudiments from 14-day fetal rats were cultured whole for 8 days in medium containing 5.5 or 16.5 mmol glucose/l (1G or 3G medium). Rudiments grown in 3G medium (3G cells) contained more DNA and insulin than those grown in 1G medium (1G cells) but there was no alteration in the insulin/DNA ratio or the fractional area of the rudiment occupied by insulin-containing cells. Morphometric analysis of ultrastructure revealed that the beta cells grown in 3G medium were smaller and had smaller nuclei than those grown in 1G medium. The size of exocrine cell nuclei in 1G or 3G medium was similar. Insulin granules occupied a greater proportion of the cytoplasmic volume in rudiments grown in 3G medium although the mean absolute volume of insulin granules per cell grown in 1G and 3G media was similar. Hence the residual cytoplasmic volume (cell--nucleus and granules) of 3G cells was less than that of 1G cells. Insulin granules from 3G cells had smaller granule sacs and cores than those from 1G cells. It is concluded that glucose stimulates the growth of rat fetal pancreas in vitro and has important effects on beta cell ultrastructure.

Animals↗

Platelet-derived growth factor and multiplication-stimulating activity II, but not multiplication-stimulating activity III-2, stimulate [3H]thymidine and [35S]sulphate incorporation by fetal rat costal cartilage in vitro.

The actions of partially purified porcine platelet-derived growth factor (PDGF) and highly purified multiplication-stimulating activity (MSA) II and MSA III-2, which are somatomedins, were investigated on the incorporation of [3H]thymidine and [35S]sulphate by fetal rat costal cartilage in vitro. This was compared with their effects in the presence of 1% fetal calf serum (FCS) on the uptake of thymidine by growth-arrested fetal rat fibroblasts. Platelet-derived growth factor at concentrations of 0.21-21 micrograms/l enhanced the incorporation of both isotopes by fetal cartilage in the presence of 1% FCS, but had an inconsistent action on thymidine uptake and no significant action on sulphate uptake in serum-free medium. Platelet-derived growth factor promoted thymidine uptake by growth-arrested, isolated fetal rat fibroblasts. Multiplication-stimulating activity II (10-100 micrograms/l) stimulated the uptake of thymidine and sulphate by fetal cartilage in medium containing 1% FCS but had no consistent action in serum-free medium, although MSA II and PDGF had a synergistic effect on thymidine uptake in the absence of serum. Multiplication-stimulating activity III-2 had no consistent action on thymidine or sulphate incorporation by fetal cartilage in either serum-free or serum-supplemented medium. However, the same preparation of MSA III-2 stimulated the uptake of [3H]thymidine into fetal rat fibroblasts with a half-maximal response at a concentration of 5-10 micrograms/l. The results identify PDGF as a possible mitogenic agent for fetal rat connective tissues in vitro and show a differential sensitivity of fetal cartilage to MSA peptides.

Animals↗

Factors affecting the peak expiratory flow rate in children.

Standing height and peak expiratory flow rate (PEFR) were measured in 339 British schoolchildren aged 7-16 years. Enquiry was made into a past history of wheeze or atopy, a family history of asthma or atopy, or a cold within the preceding 2 weeks. A strong correlation was found between PEFR and height, expressed by the equation PEFR = 5.640 Ht - 472.5 (r = 0.89). Neither a recent cold nor a positive personal or family history of wheeze or atopy had any significant effect on the regression equation. Sex was also unimportant. Further examination of the data revealed that age had an effect on peak expiratory flow rate independent of height. The effect of age was linear in girls and curvilinear in boys. Five hundred and sixty-nine Greek schoolchildren were also studied and similar age effects were found on the regression of peak expiratory flow rate on height. The implication of these findings is that any population study of peak expiratory flow rates in children should ensure a normal age distribution at each height interval. Significant error in the prediction of the PEFR will result if the effect of age is ignored, particularly in pubertal boys.

Adolescent↗

A controlled trial of a high dietary fibre intake in pregnancy--effects on plasma glucose and insulin levels.

Non-obese women in the second half of pregnancy were randomised into a control group receiving standard dietary advice and a group advised to make high fibre whole-food substitutions in their diets at every opportunity. Glucose and insulin profiles were performed over 24-h periods at 29 and 35 weeks gestation when the diets were equivalent in available carbohydrate, protein and fat, but the control group ingested 12.4 g dietary fibre/24 h and the high fibre group 51.4 g/24 h. Glucose homeostasis was similar in both groups but there was a significant attenuation of post-prandial insulin secretion in the high fibre group. It is suggested that the characteristic post-prandial peaks of plasma insulin observed in Western pregnant women are an unphysiological response to dietary fibre depletion.

Blood Glucose↗

Abdominal nocardiosis in a Sudanese girl.

A Sudanese girl became desperately ill with liver and kidney abscesses due to Nocardia asteroides. She did not have pulmonary or cutaneous infection. She recovered after surgical drainage of the abscesses and prolonged treatment with intravenous amikacin and high dosage cotrimoxazole and sulphadimidine. After recovery normal neutrophil function, cell-mediated and humoral immunity were demonstrated.

Abscess↗

Unexpectedly high peak expiratory flow rates in normal Greek children.

Peak expiratory flow rate (PEFR) and standing height (Ht) were measured in 522 healthy Greek children aged 7-16 years. The regression equation of PEFR on height in centimetres was PEFR = 5.34 Ht--380.8. This demonstrated markedly higher values for PEFR in Greek children compared to previously published data from other countries. A sample of 339 British children was examined similarly. The regression equation of PEFR on height in centimetres was PEFR = 5.64 Ht--472.5. This was similar to previously published data. No cause for this discrepancy was found after close examination of population sampling, measurement error or calibration error in the Greek study. It is therefore concluded that Greek children appear to have an unexpectedly high PEFR for height.

Adolescent↗

The preterm infant: breast or bottle?

The long term survival of preterm infants has greatly improved in the last decade. Clinicians have consequently been able to concentrate more on their optimal nutrition and this has led to a controversy regarding the best milk for these infants. Current theory and practice suggests that the fastest growth and the best energy retention is obtained if a highly modified preterm formula milk is used. Banked mature human breast milk appears nutritionally inadequate and has no proven advantages. The use of fresh mothers' own milk merits further investigation, although its widespread use will usually be impractical.

Editorial↗

Upper intestinal bacterial flora during transpyloric feeding.

Samples from the pharynx, stomach, duodenum or jejunum, and faeces were collected on 7 days between 1st and 28th day from neonates weighing less than 1.5 kg at birth who were fed by transpyloric tube. These were cultured on selective and non-selective media, and the results were expressed in a semi-quantitative manner. The number of bacterial species and the density of their growth increased with the patient's age; this was particularly noticeable with Gram-negative bacteria and the ratio of Gram-negative to Gram-positive organisms increased steadily in specimens from all sites with increasing age. The upper small intestine was more heavily colonised than the stomach early in life and the microflora present was predominantly faecal in nature. The species isolated from all sites were mainly aerobes or facultative anaerobes; strict anaerobes did not form a significant proportion of the microflora in these infants. Necrotising enterocolitis developed only after heavy jejunal colonisation with Gram-negative bacilli.

Bacteria↗

Response to TRH in suspected hypopituitarism.

A retrospective analysis was made of 405 thyrotrophin-releasing hormone (TRH) stimulation tests on children who were successful applicants for growth hormone (GH) therapy in the UK between 1977 and 1981 inclusive. Thyroid-stimulating hormone (TSH) responses to TRH were divided into normal and those indicating pituitary or hypothalamic disease on the basis of criteria which eliminated variation in TSH assay between laboratories. Among children known to be hypothyroid 93% had abnormal TRH stimulation tests, but 35% of those children who were clinically euthyroid and who had normal serum thyroxin levels also had abnormal TSH responses to TRH. Abnormal TRH tests in the latter group were most common in euthyroid children who had GH deficiency with clearly defined aetiology and least common in those with idiopathic GH deficiency. Further work is required to clarify the interpretation of an abnormal TRH stimulation test in this group of children, but until this is done, such patients should be kept under regular review with respect to thyroid function.

Adolescent↗

Height and lymphoblastic leukaemia.

Two hundred and thirty six children with untreated lymphoblastic leukaemia were compared for height with the normal population by calculation of their mean standard deviation score. As a group, they proved to be significantly taller (P less than 0.0001), which gives support to the theory that growth hormone or a somatomedin may be involved in the development of the disease.

Body Height↗

Clinical pharmacology of netilmicin in the newborn.

The plasma peak, trough, and peak-trough concentrations of netilmicin given to preterm and term infants were measured after different regimens to determine which dosage would provide satisfactory peak and trough concentrations. In infants aged less than 7 days, dosage regimens of 3.0 or 2.5 mg/kg every 12 hours gave satisfactory peak levels (range 5.2-12.0 micrograms/ml) but troughs were above the desirable maximum level of 3 micrograms/ml in more than half the preterm infants. Subsequently a dosage regimen of 3.0 mg/kg immediately followed by 2.0 mg/kg every 12 hours resulted in trough levels that exceeded 3 micrograms/ml in only 2 of 25 preterm determinations and never in term infants, yet gave satisfactory peak levels (range 4.5-7.4 micrograms/ml). In preterm infants aged 4 to 7 weeks a dosage of 3 mg/kg every 8 hours gave satisfactory peak and trough levels.

Body Weight↗

Somatomedin activity and cartilage [35S]sulphate incorporation in the growth-retarded neonatal rat.

Plasma somatomedin activity, cartilage metabolism and the levels of insulin and growth hormone were studied during relative neonatal malnutrition in the rat, produced by the small and large litter method. In growth-retarded rats reduced somatomedin activity and raised growth hormone concentration were found. Neither basal cartilage activity nor cartilage responsiveness to somatomedin was altered in the growth-retarded animals.

Animals↗