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Biomedical subjects

D A Price

Publications and source records attributed to D A Price.

At least 127 records · Page 7Linked to original sources
PubMed1996

Model of normal prepubertal growth.

Growth over the short term is a highly complex non-linear process. Contrasting models of short term growth have been proposed which include periodic growth cycles versus abrupt growth spurts with intervening growth arrest ('saltation and stasis'). The variability of short term growth has been characterised from a study of 46 healthy prepubertal children measured three times a week over one academic year using a combination of descriptive statistical approaches and regression modelling. Growth in childhood over one year is represented by a biphasic process comprising three to six unpredictable growth spurts, each of mean length 56 days (range 13-155 days), separated by periods of stasis (less than or equal to 0.05 cm height increment over more than seven days), each lasting a mean of 18 days (range 8-52 days) and accounting for at least 20% of the period of observation. This is superimposed on strong seasonal trends in growth with a declining growth rate over the autumn months reaching a nadir in midwinter, followed by a growth spurt in the spring. Human growth over short periods is therefore a discontinuous, irregular, and unpredictable process.

Anthropometry↗
PubMed1996

Spontaneous adult height in patients with idiopathic short stature.

This paper is a review of studies investigating adult height achieved by patients with idiopathic short stature. In all of these studies, final height SDS was increased compared with height SDS at presentation, but mean adult height usually fell short of target height. Prediction of adult height was inaccurate, varied with the method used and was imprecise. There was little objective evidence of a negative psychosocial impact of short stature, although patients did perceive the disadvantages of short stature.

Adult↗
PubMed1996

Insulin-like growth factor binding protein-3 generation: an index of growth hormone insensitivity.

GH insensitivity may be an inherited condition or may arise as a consequence of disease of malnutrition. Laron syndrome is the most severe form of GH insensitivity, arising from an absent or defective GH receptor. Less severe forms of GH insensitivity, however, may exist, resulting in short stature but in few other features of Laron syndrome. We have identified a heterogeneous group of children with short stature and either high basal (> 10 mU/L) or high peak GH levels (> 40 mU/L) on GH provocation testing, to examine biochemical markers of GH sensitivity. These children received 4 d of GH (0.1 U/kg) and the increment in IGF-I, IGF binding protein (BP)-3, and GHBP was determined. Eight GHD children, commencing GH therapy, were recruited as positive controls. The two groups could not be differentiated by age, height SDS (SD score), height velocity SDS, or body mass index. IGF-I and IGFBP-3 generation were correlated in all children (delta SDS IGF-I versus delta SDS IGFBP-3, r = 0.49, p = 0.03). Neither basal GHBP levels or the increment in GHBP were predictive of the IGF-I or IGFBP-3 response to GH. The GHI group had a significantly reduced IGFBP-3 response to stimulation with 4 d of GH (median percent increment in IGFBP-3, 26%, versus 72% in the GHD group, P = 0.03); their IGF-I response to GH was also reduced (median % increment in IGF-I 75% versus 144% in the GH deficient group), but this did not achieve significance, p = 0.06. In all children, the percentage rise or delta SDS in both IGF-I and IGFBP-3 inversely correlated with the GH peak obtained on provocation testing, the latter being the most significant determinant of GH peak. We propose that the "IGF generation test", in particular IGFBP-3 generation, can be used in the investigation of partial GH insensitivity. Further work, however, is required to establish diagnostic criteria for partial GH insensitivity.

Adolescent↗
PubMed1996

Infradian rhythms in urinary growth hormone excretion.

All studies of urinary GH excretion in normal and disordered growth have revealed marked day to day (infradian) variation. We used serial overnight urinary GH estimations as an indirect measure of endogenous GH secretion in eight normal prepubertal children (aged 3.6-7.3 yr) over 90-365 days to determine whether longer term rhythms in GH output could exist. This study constitutes a first step in examining the potential relationship between GH excretion and growth. Urinary GH was measured by immunoradiometric assay after dialysis, expressed as the total amount excreted (nanograms per night) or as the GH/creatinine ratio (nanograms per mmol), and assessed by pulse counting techniques and time-series analysis. Variability in urinary GH excretion (median coefficient of variation, 46%) was significantly greater than creatinine (median coefficient of variation, 25%; P = 0.003). Additionally, there was marked month by month variation in baseline urinary GH in all children. High frequency pulses of urinary GH were defined in all children, with periods between 3-5 days. In the two children followed for 7 months or more, time-series analysis was also undertaken on urinary GH data divided into weekly series. This revealed significant rhythms present at 2.6 and 4.1 weeks. There were, therefore, three components to urinary GH excretion: long term basal fluctuation (over months), short term pulses (over days), and intermediate rhythms (over weeks). Further work is required to establish the relationship between these patterns of GH excretion and short term growth.

Child↗
PubMed1996

The peptide pQFYRFamide is encoded on the FMRFamide precursor of the snail Helix aspersa but does not activate the FMRFamide-gated sodium current.

The complete sequence of the FMRFamide precursor cDNA from Helix aspersa is reported here. Since the 5' end of this cDNA is identical to that of the precursor that encodes the heptapeptide analogs of FLRFamide, the two transcripts are probably derived by alternative RNA splicing. A novel pentapeptide, Glp-Phe-Tyr-Arg-Phe-NH2 (pQFYRFamide), predicted from the cDNA sequence, was purified from extracts of H. aspersa ganglia and identified by mass spectroscopy. Partial gene sequences for the FMRFamide precursors of two closely related pulmonate species-Cepaea nemoralis and Polydontes acutangula-were also determined and compared with the cDNA sequence of H. aspersa and a partial gene sequence previously determined from H. pomatia. Not only are the FMRFamide-related sequences and proteolytic processing sites conserved, but the linear arrangement of these landmarks is also retained. Synthetic pQFYRFamide has some effects on the isolated heart and on neuronal potassium currents in H. aspersa that are similar to those of FMRFamide, but it does not activate the neuronal FMRFamide-gated sodium channel.

Amino Acid Sequence↗
PubMed1995

Ultrasonographic measurement of the dividing membrane in twin pregnancy during the second and third trimesters: a reproducibility study.

OBJECTIVE: Our purpose was to examine the reproducibility of intertwin membrane thickness measurements used to predict chorionicity in twin pregnancies. STUDY DESIGN: Twenty-seven twin pregnancies were scanned with high-resolution ultrasonography on 52 occasions during the second and third trimesters. Two observers, blind to other criteria of chorionicity, measured the dividing membrane twice in five different sites (total measurements 1040). The data were log-transformed and the coefficient of repeatability calculated as a measure of intraobserver variability. Interobserver variability was estimated by the Bland and Altman 95% limits of agreement. Random variation was assessed with the restricted maximum likelihood procedure in Genstat. RESULTS: The overall estimate of the coefficient of repeatability was 2.14, indicating that 95% of repeated measurements would be expected to be within 114% of each other. Measurements taken close to the placenta (up to 3 cm) were the most repeatable and displayed no bias when repeated. Coefficients of repeatability at this site ranged from 1.42 to 1.91, with no evidence of consistent differences between monochorionic and dichorionic twins. Gestational age was not significantly associated with membrane thickness for any of the models. The pregnancy type x subject x observer and pregnancy type x subject x site interactions were statistically significant (p < 0.001 and p < 0.005, respectively), implying that interobserver variability depends on the subject being measured, the site of sampling, and chorionicity. CONCLUSION: Ultrasonographic measurement of membrane thickness has high intraobserver and interobserver variability in the second and third trimesters. Our findings provide an explanation for the suboptimal accuracy reported with this method in determining chorionicity in the second and third trimesters.

Chorion↗
PubMed1995

Reversible AIDS-related sclerosing cholangitis.

Although hepatobiliary involvement is common in the acquired immunodeficiency syndrome, it infrequently leads to biliary tract abnormalities. We describe a 39-year-old man with human immunodeficiency virus infection and no previous acquired immunodeficiency syndrome-defining illnesses, who presented with malaise, right upper quadrant pain, lymphadenopathy and cholestasis. An endoscopic retrograde cholangiopancreatography demonstrated sclerosing cholangitis due to disseminated B-cell nonHodgkin's lymphoma. Following chemotherapy, his symptoms and signs rapidly improved, so that 1 month later his endoscopic retrograde cholangiopancreatography had returned entirely to normal.

Adult↗
PubMed1995

Volume sensitive hypertension and the digoxin-like factor. Reversal by a Fab directed against digoxin in DOCA-salt hypertensive rats.

Although volume and vasoconstriction have been considered polar elements in a useful pathogenetic hypertension model, many observations suggest that vasoconstriction is involved in volume-dependent hypertension, reflecting the effect of a digitalis-like factor. To examine that possibility, we assessed the depressor responses to Digibind, an antibody Fab directed against digoxin, in a volume-dependent model--DOCA-salt-induced hypertension in rats. Digibind (10 mg/kg, intravenously) induced a gradual blood pressure fall over 2 h that was sustained for 4 h (P < .001). Blood pressure did not fall with Digibind when DOCA was administered without salt or a high-salt intake was provided without DOCA. The intracellular sodium content of the rat aorta, measured by atomic absorption spectroscopy after cold choline wash, was increased in the DOCA-high-salt rats (23.3 +/- 2.7 mEq/L) compared to control rats (12.1 +/- 0.8 mEq/L; P < .001). Aorta sodium content, in parallel with blood pressure, was not increased either by dietary salt supplementation without DOCA, or by DOCA with a low-salt diet. Sodium pump activity was measured as 86Rb uptake into vascular smooth muscle (VSM). Both ouabain-sensitive and ouabain-resistant 86Rb uptake were significantly higher in VSM from DOCA-high-salt animals (P < .01). Despite its effectiveness in reducing blood pressure in this model, Digibind influenced neither VSM sodium content nor 86Rb uptake. The results are consistent with a role for a circulating digitalis-like factor in this volume-dependent model, but events at the VSM level are complex.

Animals↗
PubMed1995

Final height after long-term growth hormone treatment in Turner syndrome. European Study Group.

OBJECTIVES: To study final height after long-term growth hormone (GH) treatment in girls with Turner syndrome (TS). PATIENTS: One hundred fifty three patients with TS, participating in five European trials, were included. They started GH treatment in 1987-1989 at an age of 10 years or older. Mean age at start of treatment ranged between 11.7 and 14.6 years among countries and mean bone age between 9.4 and 11.8 years. Fourteen girls were lost to follow-up, leaving 139 for analysis. Most girls have now attained final height (FH), defined as a linear growth velocity (GV) of 4 mm/yr or less, measured over at least 6 months (group 1, n = 56), or near-FH, defined as a GV of 5 to 9 mm/yr (group 2, n = 22). Sixty-one girls were still growing 10 mm/yr or more. METHODS AND MAIN RESULTS: At the last measurement, mean (SD) height was 150.7 (4.9) cm in group 1 and 148.5 (5.1) cm in group 2. The differences between FH and projected final height based on extrapolation of the initial height-standard deviation score on Turner syndrome reference values, were 2.9 (3.8) and 3.0 (3.3) cm, respectively. The mean gain over the Bayley-Pinneau prediction of FH was 3.3 (3.9) cm in both groups. No significant differences between countries were found. The range of gains over projected height (-4.7 to 12.1 cm) was large, and 25% of gains were 5 cm or more. Gain over initial projection was strongly related to initial growth delay and to growth response during the first 2 years of treatment. A logistic regression model is presented that predicts gain of more than 5 cm with a positive predictive value of 62% and a negative predictive value of 84%. CONCLUSIONS: Long-term GH treatment in girls with TS, starting treatment at a relatively advanced age ( > 10 years) resulted in a modest mean gain in FH of 3 cm, with wide interindividual variation.

Adolescent↗
PubMed1995

Adrenal function following topical steroid treatment in children with atopic dermatitis.

Adrenal suppression is a potential complication of topical corticosteroid treatment in atopic dermatitis. We used a low-dose adrenocorticotrophic hormone (ACTH) test (500 ng/1.73 m2) to detect subtle changes in adrenal glucocorticoid function in 14 prepubertal children with moderate or severe atopic dermatitis affecting 16-90% (median 58%) of the body surface area. All had received regular treatment with mild potency BNF (British National Formulary) classification topical corticosteroid ointments (hydrocortisone 48.7-223.2 mg/m2 body surface area/day; median 134.2) for 3-10 years (median 6.5 years). Nine children had also intermittently used moderate potency preparations. However, none had been treated with corticosteroids by any other route in the preceding 6 months. Fourteen prepubertal children with constitutional short stature, without atopic disease, served as controls. The basal, peak, increment and area-under-curve in plasma cortisol concentrations in children with atopic dermatitis were not significantly different from controls, indicating normal adrenal sensitivity to low-dose ACTH. However, the peak in plasma cortisol occurred earlier in children with atopic dermatitis (median 17.5 min) than in controls (median 25 min) (P = 0.02). In addition, there was a significant inverse relationship between time to peak and extent of atopic dermatitis (rs = -0.52; P < 0.05), but not topical steroid treatment dose or score in children with atopic dermatitis. These findings indicate accelerated adrenal responsiveness to ACTH in children with atopic dermatitis, which is independent of treatment. Mild to moderately potent topical corticosteroid ointments in these doses did not suppress adrenal glucocorticoid function in this sample of children with atopic dermatitis.

Administration, Topical↗
PubMed1995

Family functioning: a correlate of diabetic control?

Poor diabetic control was found in nearly 50% of adolescents attending two paediatric clinics. Adolescents with well and poorly controlled diabetes differed in reported parental involvement in their diabetic regime. There was little association between glycaemic control and family functioning using the McMaster Family Assessment Device (FAD) whether rated by adolescent or a parent. Neither did sufferers with diabetes differ from families of matched community controls according to the FAD overall though the families of well controlled diabetics were more likely than the other two groups to score themselves in the unhealthy range on the subscale of global functioning.

Adolescent↗
PubMed1995

Nocturnal urinary growth hormone excretion in growth hormone-deficient children on and off growth hormone treatment.

Non-compliance has been reported as a major issue in growth hormone (GH) therapy. We explored the use of urinary GH (uGH) measurements to monitor the GH treatment of 18 children (aged 5-16 years) diagnosed as GH deficient on the basis of history, phenotype, auxology and peak GH concentration during 2 provocation tests of < 15 mU/l. Each child collected 5 consecutive overnight urine samples while on GH replacement schedules, then discontinued treatment for 2 days and collected a further 5 urine samples. The mean mass of uGH excreted on treatment (8.6 ng, range 3.6-13.0 ng) was significantly greater than that off treatment (1.2 ng, range 0.6-2.7 np; p < 0.01). All uGH values on treatment exceeded the mean nocturnal uGH excretion of normal age- and sex-matched children. The clear distinction between uGH levels on and off GH treatment indicates that uGH measurement would determine whether two or more GH injections had been missed. A series of uGH estimates over a 2-week period may provide a realistic perspective on injection frequency.

Adolescent↗
PubMed1995

Urinary insulin-like-growth factor I in normal children: relationship to age, pubertal status and urinary growth hormone.

Authentic insulin-like growth factor 1 (IGF-I) can be detected in human urine at one thousandth of the serum level, with which it correlates closely. The aim of this study was to establish the normal range of urinary IGF-I (uIGF-I) in relation to age, sex, and pubertal status, and to define the relationship between uIGF-I and urinary growth hormone (uGH). IGF-I was measured by RIA after acid extraction of IGF-I binding protein, and separation by gel chromatography in 302 healthy children (149 boys and 153 girls) in whom uGH had already been measured. The mean amount of uIGF-I excreted each night ranged from 17.5 ng (males) and 14.9 ng (females) at pubertal stage I (PS 1), to a peak of 66.8 ng (males) at PS 4, and 55.8 ng (females) at PS 3, coinciding with peak uGH excretion. Highly significant correlations were found between uGH and uIGF-I both before and during puberty (P < 0.01). These findings extend the range of non-invasive investigation available in growth disorders and physiological studies.

Adolescent↗
PubMed1994

Morphological changes of neural and vascular peptides in human skin suction blister injury.

Suction blister injury is an experimental model for the investigation of the possible derangement of dermal/epidermal interaction in injury. An extensive fibre network can be stained in skin using antisera to the pan-neuronal marker protein gene product 9.5 (PGP) and the sensory neuropeptide calcitonin gene-related peptide (CGRP), while microvessels are identifiable with antisera to the endothelial marker von Willebrand's factor (vWf) and the peptide endothelin (ET). To investigate the possible involvement of superficial cutaneous innervation and microcirculation during the repair process in injury, human skin biopsies taken at different times after suction blister injury were investigated by quantitative immunohistochemistry. Neural and endothelial changes were seen in both edge and blister areas. PGP- and CGRP-immunoreactive nerves showed an increase in both areas compared with control skin up to 6 h after injury, followed by a decrease which lasted until 72 h. This was followed by a gradual increase of both nerve types starting from the blister edge and lasting up to 8 days after injury when the values were similar to controls. Similarly, in the blister area of the skin, vWF-immunoreactive capillaries showed statistically significant increases between 0 and 6 h after injury, followed by a decrease at 12 and 18 h which was maintained up to 72 h. ET-1 immunoreactivity showed a similar, although more variable, pattern of changes. At the blister edge from 23 h onwards, both vWf and ET-1 immunoreactivities showed a second increase from the edge of the blister spreading towards the centre of the blister ahead of the nerve increase. This lasted up to 8 days, when vWf immunoreactivity showed a statistically significant increase compared with control skin. Generally the numerical increase observed at early time points was accompanied by a strong staining intensity, which reverted to a normal staining intensity at later time points. These results suggest that there is a reactive process for all immunoreactive elements in the early stages of injury, followed by changes indicative of neuronal and endothelial damage (depletion phase) and the subsequent repair process. The repair started with re-epidermalization from the blister edge, followed by revascularization and, lastly, by reinnervation of the tissue. These results indicate a close relationship between epidermis, blood vessels, and nerve fibres during the healing process which follows suction blister injury.

Calcitonin Gene-Related Peptide↗