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Biomedical subjects

D A Price

Publications and source records attributed to D A Price.

At least 199 records · Page 11Linked to original sources

Congenital hypothyroidism: increased incidence in Asian families.

Screening in the North West health region of England showed a significantly higher incidence of congenital hypothyroidism in Asian families--1/918 compared with 1/3391 in non-Asians. This could only in part be explained by consanguinity. No differences were found in birth order, season of birth, gestational age, or birth weight between normal infants and those with congenital hypothyroidism. There was a significantly higher incidence of additional congenital abnormalities (9%) and a significantly increased mortality (5%) in infants with congenital hypothyroidism compared with unaffected infants.

Asia↗

Management of idiopathic growth hormone deficient patients during puberty.

Boys with idiopathic GH deficiency, treated with hGH and entering spontaneous puberty, have an onset of puberty and peak height velocity (PHV) at a late chronological age but normal bone age. PHV occurs at G3 with testicular volumes of 6-12 ml. The size of PHV and the height gain after G2 are similar to those of a normal delayed adolescent. In contrast, idiopathic GH deficient girls have an onset of puberty and PHV nearer to a normal chronological age and at an early bone age. PHV occurs at B2 and its size and the height gain after B2 are similar to those of normal girls. The length of time of pubertal growth is shorter in both GH deficient boys and girls. Very late induction of puberty in idiopathic GH deficient boys results in psychosocial damage and in bodily disproportion. It is suggested that induction of puberty be considered no later than 14.5 years in boys and 13.5 years in girls with the use of low-dose sex steroids. The decision to induce puberty should be taken to avoid psychosocial problems and be independent of proof of associated gonadotrophin deficiency. In GH deficient girls with early puberty, therapies to delay puberty may be considered. There are theoretical grounds for increasing the GH dose given during puberty, but present dose-response studies fail to include controls for important biological variables and are so far inconclusive. Cost-effectiveness is an important consideration. Increasing the frequency of injections probably improves the growth effect for a given dose of GH.

Adolescent↗

FMRFamide peptides in Helisoma: identification and physiological actions at a peripheral synapse.

Previous reports have demonstrated powerful neuromodulatory actions of the molluscan tetrapeptide FMRFamide in both the central and peripheral nervous systems of the freshwater snail Helisoma. The present study was designed to examine both the nature of the FMRFamide-like peptides in Helisoma and to define their physiological actions at a peripheral synapse. We report that, as determined by HPLC/RIA and mass spectrometry, Helisoma contains both FMRFamide and 2 of its analogs, FLRFamide and GDPFLRFamide. Whereas whole animals contain about 100 pmol/gm of these peptides, they were enriched in the nervous system (3000 pmol/gm) and in a peripheral target organ, the salivary glands (500 pmol/gm). For histochemical and physiological studies we examined the salivary glands, which are known to be innervated by neuron 4 of the buccal ganglion. We confirmed the presence of FMRFamide-like fibers on the salivary gland by immunohistochemistry using a polyclonal antiserum. These fibers appear to be largely derived from somata located in the central ring ganglia. For physiological tests we examined the neuron 4-gland synapse, at which presynaptic action potentials normally evoke a suprathreshold EPSP in gland cells. Bath application of FMRFamide, FLRFamide, or GDPFLRFamide at micromolar concentration to a buccal ganglia/salivary gland preparation completely suppressed spontaneous rhythmic activity. The sites of action of these peptides were examined by iontophoretic application of FMRFamide to neuron 4 or the salivary gland. Application of the peptide to the soma of neuron 4 caused a hyperpolarization that suppressed spontaneously generated action potentials. When applied to the salivary gland, FMRFamide caused a hyperpolarization that reduced the EPSPs evoked by neuron 4 to below spike threshold. The latter observation implies a postsynaptic locus of action for FMRFamide, and this possibility was tested by direct depolarization of the gland with iontophoresis of ACh (the putative transmitter of neuron 4). Such depolarizations were also reduced by FMRFamide. We conclude that Helisoma contains FMRFamide and 2 of its analogs, these peptides being enriched in the nervous system and salivary glands. Furthermore, these peptides can suppress activation of the salivary glands by actions both directly on gland cells and on the effector neuron.

Animals↗

Studies on the growth of the fetal sheep. Effects of surgical reduction in placental size, or experimental manipulation of uterine blood flow on plasma sulphation promoting activity and on the concentration of insulin-like growth factors I and II.

The effect of long- and short-term manipulations of uterine blood flow on fetal plasma levels of IGF-I and -II have been studied in sheep at days 125-139 of pregnancy and compared with those in near term rats and guinea pig. The primary objective is to show that both long- and short-term reduction of uterine blood flow is associated with increase in the fetal plasma concentration of IGF-II while that of IGF-I falls. In the pregnant sheep long-term depression of utero-placental blood flow was caused by surgical reduction in placental mass (carunclectomy) prior to conception. This reduced fetal weight to 2.42 +/- 0.49 kg (SD) compared with 3.41 +/- 0.46 in controls; the respective values for uterine blood flow being 1694 +/- 558 and 913 +/- 324 ml/min respectively. This was associated with a fall in fetal plasma IGF-I concentration from 22.6 +/- 3.4 ng/ml to 14.9 +/- 1.31 ng/ml and a rise in IGF-II from 1952 +/- 284 ng/ml to 3360 +/- 914 ng/ml respectively. Similar changes in the plasma concentrations of IGF peptides were observed in fetal rats and guinea pigs in response to uterine artery ligation. Short-term reduction (60 min) of the uterine blood flow was caused either by compression of the common uterine artery to depress flow from 1491 +/- 375 to 648 +/- 216 ml/min or through intraarterial infusion of adrenaline at 35 ug/min to lower flow from 1628 +/- 339 to 1195 +/- 128 ml/min. Such falls in uterine blood flow had no significant effect on fetal plasma IGF-I levels but increased IGF-II levels by 30 to 60%.

Animals↗

Does growth hormone cause relapse of brain tumours?

Tumour relapse rates in 14 patients with medulloblastoma, 8 with glioma, 2 with ependymoma, 6 with leukaemia, and 1 with T-cell lymphoma who received growth hormone (GH) treatment for growth failure secondary to cranial irradiation were compared with rates among patients treated with radical radiotherapy for the same types of tumour. Five relapses (in 5 patients) occurred (1 optic nerve glioma, 2 medulloblastomas, and 2 ependymomas), three during and two after completion of GH treatment. Patients with medulloblastoma and ependymoma who relapsed were older at tumour diagnosis, underweight at the start of GH therapy, and entered puberty later than similar relapse-free patients. The late relapse rate of medulloblastoma and glioma was unaltered by GH therapy. Ependymoma carries a poor prognosis, and of the 4 late survivors, the 2 who received GH relapsed. No leukaemic relapse has been associated with GH treatment. The findings indicate that GH therapy does not increase the relapse rate of medulloblastoma, glioma, and leukaemia.

Adolescent↗

Plasma growth hormone (GH) responses to growth hormone releasing factor (hp GRF 1-44) in familial GH deficiency.

In four children with familial GH deficiency peak and integrated GH responses to an acute intravenous bolus of hp GRF 1-44 were lower than in 18 children with non-familial idiopathic GH deficiency and in 5 children with structural hypothalamic abnormalities. It is possible that the familial forms of GH deficiency described may be due to absence or biological inactivity of endogenous GRF or possibly GRF receptor or post receptor abnormalities.

Adolescent↗

Growth hormone state after completion of treatment with growth hormone.

After completion of treatment with growth hormone (GH) 19 patients with isolated 'idiopathic' GH deficiency and 15 with post-irradiation GH deficiency underwent retesting of GH secretion with an insulin tolerance test or an arginine stimulation test, or both. Patients with post-irradiation GH deficiency comprised 13 patients with central nervous system tumours distant from the hypothalamo-pituitary axis and two with acute lymphoblastic leukaemia, who had received cranial or craniospinal irradiation. All 15 patients with post-irradiation GH deficiency remained GH deficient (peak GH response less than 7 mU/l (n = 10) and 7-15 mU/l (n = 5)). Of the 19 retested patients with idiopathic GH deficiency, however, five (26%) had peak GH responses of greater than 15 mU/l (regarded now as transient or false idiopathic GH deficiency) and were indistinguishable from the remainder (permanent or true idiopathic GH deficiency, peak GH responses less than 7 mU/l (n = 12) and 7-15 mU/l (n = 2)), by pretreatment anthropometry and post-treatment height standard deviation score, but had a lower first year height velocity (mean (SD) velocity 5.6 (0.5) cm/year for false idiopathic deficiency v 8.7 (1.75) cm/year for true idiopathic deficiency, p less than 0.01) and height increment on treatment (mean (SD) increment 2.2 (1.5) cm/year for false idiopathic deficiency v 5.2 (2.3) cm/year for true idiopathic deficiency, p less than 0.05). By current practices two patients with false idiopathic deficiency may have been distinguished by sex steroid priming. Thus post-irradiation GH deficiency seems to be permanent, but errors in diagnosis in idiopathic GH deficiency are common.

Adolescent↗

United Kingdom multicentre clinical trial of somatrem.

In a multicentre clinical trial 54 children aged 4.0 to 17.3 years, who had growth hormone deficiency that had not previously been treated, were given biosynthetic methionyl growth hormone (somatrem) 4 units three times a week by subcutaneous or intramuscular injection for one year. Height was measured every three months for at least one year before and during treatment. Forty two patients responded to treatment with an increase in growth of greater than 1.5 cm/year. The remaining 12 who grew more slowly were less obviously short and had a higher pretreatment growth than those who responded. The three who responded and the one who did not had undergone therapeutic spinal irradiation before starting the drug. If a whole year's pretreatment growth rate of less than 5 cm/year had been used as a diagnostic criterion the prediction of those who responded would have slightly improved. About two thirds of the patients developed antibodies against growth hormone and Escherichia coli protein; these were, however, of low and fluctuating titre and binding capacity, and did not influence the response to treatment. No adverse side effects were encountered. We conclude that somatrem is a safe and effective alternative to pituitary growth hormone.

Adolescent↗

Seasonal variation of glycosylated haemoglobin.

Retrospective analysis of glycosylated haemoglobin concentrations in a diabetic outpatient clinic over three and a half years showed a small seasonal variation in the mean value with a peak in mid February and a nadir in mid August.

Adolescent↗

The role of growth hormone in stunted head growth after cranial irradiation.

The head sizes of 38 patients, growth hormone (GH) deficient following craniospinal (n = 26) or cranial irradiation (n = 12), have been assessed before (n = 38) and on completion of GH therapy (n = 15) or at the end of a similar period of observation without GH (n = 7). These results were compared to the change in head size seen in idiopathic GH deficiency following GH therapy (n = 14). Before GH therapy, the latter had small heads [mean occipitofrontal circumference SD score (SDS) -1], which were relatively large compared to the height deficit [height SDS (CA) -4.7], and they exhibited catch-up growth with GH (delta occipitofrontal circumference SDS + 0.7, final occipitofrontal circumference SDS -0.2). In contrast, over a similar period all patients, who previously had received cranial irradiation in the dosage range 2700-4750 centi-Geigy, irrespective of the radiation schedule or GH treatment, showed a decrease in occipitofrontal circumference SDS (mean delta -0.9), a significant difference to the expected head growth of normal children over a similar period (p less than 0.01). We have noted that restricted head growth occurs in the years following cranial irradiation and is unaffected by GH therapy. Earlier work has shown that cranial irradiation may impair intelligence. The exact relationship between intellectual impairment and stunted head growth remains to be determined.

Adolescent↗

Localization of FMRFamide-like peptides in the snail Helix aspersa.

The distribution of FMRFamide-like material in the gastropod mollusc, Helix aspersa, was studied by radioimmunoassay (RIA) and immunocytochemistry. Most of the RIA activity was concentrated in the central nervous system, the male reproductive tract, the tentacles and the posterior digestive system (Table 1). The density of FMRFamidergic perikarya, nerves and nerve varicosities in the muscle tissue of all these regions, as indicated immunocytochemically (Fig. 2), was well correlated with the distribution as determined by RIA. Gel chromatography of each extract resolved two peaks of FMRFamide-like immunoreactivity (Fig. 3). The first of these was further analysed by high-pressure liquid chromatography (HPLC), and the components included two major immunoreactive peaks identifiable, both by their retention times and their effects on the radula protractor muscle of Busycon contrarium, as the known peptides FMRFamide and pQDPFLRFamide (Figs 4-6). The second peak from gel chromatography gave only a single peak, distinct from that of FMRFamide and pQDPFLRFamide, in two HPLC systems (Fig. 7), but it did not behave like a competitive ligand in the FMRFamide RIA. Moreover, its immunoreactivity, unlike any peptides we tested, was not affected by carboxypeptidase Y (Fig. 8), and it was not active on the radula protractor muscle. Thus, it is certainly not an FMRFamide-like peptide. We conclude that Helix aspersa contains at least two FMRFamide-like peptides, FMRFamide and pQDPFLRFamide. These peptides appear to act both as neurohormones and as neurotransmitters or modulators in the central ganglia, reproductive, digestive, muscular and circulatory systems.

Animals↗

Studies on the growth of the fetal guinea pig. Changes in the plasma concentration of sulphation-promoting activity and of insulin-like growth factors during gestation.

Plasma sulphation-promoting activity, insulin-like growth factors (IGF)-I and -II and insulin concentrations have been measured in the developing guinea. Sulphation-promoting activity fell progressively from midgestation to term in a manner that correlated fairly closely with the decline in the fractional rate of body and liver growth. The changes in plasma concentrations of IGF-I, & -II were quite different, both being substantially higher than fetal plasma insulin concentration. IGF-I, like insulin, plasma concentration rose between 35 and 50 days, then declined as term approached. These changes correlated with phases of lipid, DNA and RNA synthesis, but not of glycogen synthesis in the fetal liver. Fetal Plasma IGF-II concentration was comparatively low until about 55 days gestation then rose sharply, at the time that large quantities of glycogen are deposited in the fetal liver and myelation is initiated in the fetal brain, to achieve very high levels by 60-63 days then declining as term approaches. Plasma IGF-I and -II, measured by radioimmunoassay and radioreceptor assay respectively, showed the same cross-reactivity or binding characteristics as peptides in human or rat plasma. On separation by hplc IGF-I consisted of two major fractions and IGF-II of one. This picture was the same if the peptides were from fetal or adult plasma. There was no evidence of a distinctly fetal class of IGF. Plasma IGF-I and -II concentrations did not correlate with changes in fetal size or fractional rate of growth.

Animals↗