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Biomedical subjects

N J Shaw

Publications and source records attributed to N J Shaw.

At least 37 records · Page 2Linked to original sources
PubMed2004

Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing's syndrome due to primary nodular adrenocortical hyperplasia.

BACKGROUND: Primary nodular adrenocortical hyperplasia (PNAH) is a well recognized, but infrequently studied cause of paediatric Cushing's syndrome (CS). OBJECTIVE: To assess presentation, diagnosis, radiological imaging, treatment and molecular analysis of patients with childhood-onset CS due to PNAH. PATIENTS: Four males and two females (median age 12.9 years, range 10.9-16.9 years) were studied. RESULTS: All had growth failure (mean height SDS -1.2; range -2.5-0.0), weight gain [mean body mass index (BMI) SDS 3.5; range 2.5-4.6] and clinical virilization, while five had hypertension [mean systolic blood pressure (SBP) 130 mmHg, diastolic blood pressure (DBP) 83 mmHg]. One patient had generalized lentigines, one had a tibial chondromyxomatous cyst and two had facial freckling. One patient had a family history of primary nodular adrenocortical disease. The diagnosis of CS was based on elevation of sleeping midnight serum cortisol and urinary free cortisol excretion, and impaired suppression of cortisol on both low- and high-dose dexamethasone suppression tests (DST). All patients had undetectable plasma ACTH with absent responses of both plasma ACTH and serum cortisol to an intravenous (i.v.) corticotrophin-releasing hormone (CRH) test. Computed tomography or magnetic resonance imaging showed normal or small adrenals, with nodules in two patients. All patients underwent bilateral adrenalectomy, performed by open (n = 2) or laparoscopic surgery (n = 4) at a mean of 0.4 years (range 0.2-0.8 years) from diagnosis. Hypercortisolaemia was treated preoperatively by metyrapone alone 0.50-0.75 g/day (n = 4), metyrapone 0.75-1.50 g/day + o'p'DDD/mitotane 1-2 g/day (n = 1), or ketoconazole (n = 1). Adrenal histology showed nodular cortical hyperplasia with shrinkage of intervening cortical tissue and pigmentation, present in four patients. Molecular analysis of the type 1-alpha regulatory subunit of protein kinase A (PRKAR1A) gene revealed a novel germline mutation in one patient. Postadrenalectomy, three patients, had catch-up growth with height velocities increasing from 3.0, 3.9 and 2.5-8.9, 8.3 and 9.0 cm/years, respectively. All six are well at a follow-up (mean 4.0 years; range 0.5-10.8 years). CONCLUSIONS: PNAH was associated with cushingoid features, virilization and hypertension with a lack of cortisol suppression on high DST, undetectable plasma ACTH and absent cortisol and ACTH responses to CRH. Adrenals were normal or small on imaging. PRKAR1A gene analysis may be helpful in the assessment of these patients.

Adolescent↗
PubMed2004

Health care utilisation of prematurely born, preschool children related to hospitalisation for RSV infection.

BACKGROUND: In prematurely born infants with chronic lung disease (CLD), RSV hospitalisation is associated with increased health service utilisation and costs in the first two years after birth. AIMS: To determine whether RSV hospitalisation in the first two years was associated with chronic respiratory morbidity during the preschool years in prematurely born children who had had CLD. METHODS: Retrospective review of readmissions, outpatient attendances, and community care in years 2-4 and, at age 5 years, assessment of the children's respiratory status and their health related quality of life. Comparison was made of the results of children who had had at least one hospitalisation in the first two years after birth for RSV infection (RSV group) to those of the rest of the cohort. Participants were 190 of an original cohort of 235 infants with CLD and a median gestational age 27 (range 22-33) weeks. RESULTS: The 33 children in the RSV group, compared to the rest of the cohort, had a greater duration of hospital stay and more outpatient appointments. The RSV group had required more prescriptions for all treatments and respiratory medications, and more had used an inhaler. The cost of care of the RSV group was higher (median 2630 pounds sterling [4000 Euros, US4800 dollars], range 124-18,091 pounds sterling versus 1360 pounds sterling [2500 Euros, US3000 dollars], range 5-18 929 pounds sterling ) and their health related quality of life was lower. CONCLUSION: In prematurely born children who had developed CLD, RSV hospitalisation in the first two years was associated with chronic respiratory morbidity and increased cost of care.

Ambulatory Care↗
PubMed2004

Comparison of continuation or cessation of growth hormone (GH) therapy on body composition and metabolic status in adolescents with severe GH deficiency at completion of linear growth.

Although GH replacement improves the features of GH deficiency (GHD) in adults, it has yet to be established whether cessation of GH at completion of childhood growth results in adverse consequences for the adolescent with GHD. Effects of continuation or cessation of GH on body composition, insulin sensitivity, and lipid levels were studied in 24 adolescents (13 males, 11 females, aged 17.0 +/- 0.3, yr, mean +/- se, puberty stage 4 or 5) in whom height velocity was less than 2 cm/yr. Provocative testing confirmed severe GHD [peak GH < 9 mU/liter (3 microg/liter)] in all cases and was followed by a lead-in period of 3 months during which the pediatric dose of GH continued unchanged. Baseline investigations were then performed using dual-energy x-ray absorptiometry (body composition), lipid measurements, and assessment of insulin sensitivity by both homeostasis model assessment and a short insulin tolerance test. Twelve patients remained on GH (0.35 U/kg.wk), and 12 patients ceased GH treatment. The groups were followed up in parallel with repeat observations made after 6 and 12 months. No endocrine differences were evident between the groups at baseline. GH cessation resulted in a reduction of serum IGF-I Z score [-1.62 +/- 0.29, baseline vs. -2.52 +/- 0.12, 6 months (P < 0.05) vs. -2.52 +/- 0.10, 12 months (P < 0.01)] but values remained unchanged in those continuing GH replacement. Lean body mass increased by 2.5 +/- 0.5 kg ( approximately 6%) over 12 months in those receiving GH but was unchanged after GH discontinuation. Cessation of GH resulted in increased insulin sensitivity [short insulin tolerance test, 153 +/- 22 micromol/liter.min, baseline vs. 187 +/- 20, 6 months (P < 0.05) vs. 204 +/- 14, 12 months (P = 0.05)], but no significant change was seen during 12 months of GH continuation. Lipid levels remained unaltered in both groups. Continuation of GH at completion of linear growth resulted in ongoing accrual of lean body mass (LBM), whereas skeletal muscle mass remained static after GH cessation in these adolescents with GHD. This divergence of gain in LBM is of potential importance because increases in LBM occur as a feature of healthy late adolescent development. GH is a major mediator of insulin sensitivity, independent of body composition in adolescents. Further studies are required to determine whether discontinuation of GH in the adolescent with severe GHD once linear growth is complete results in long-term irreversible adverse physical and metabolic consequences and to determine conclusively the benefits of continuing GH therapy.

Adolescent↗
PubMed2003

Bone density and body composition in children with growth hormone insensitivity syndrome receiving recombinant IGF-I.

OBJECTIVE: There are few reports of the metabolic action of insulin-like growth factor 1 (IGF-I) in vivo. Growth hormone insensitivity syndrome is a good model to examine the effects of IGF-I deficiency. This study was designed to assess body composition and bone density in children with growth hormone insensitivity syndrome before and after receiving treatment with recombinant IGF-I. DESIGN: A prospective longitudinal study. PATIENTS: Four prepubertal boys age 6.1-9.8 years with short stature due to growth hormone insensitivity syndrome. MEASUREMENTS: Assessment of body fat by skinfold thickness measurements and dual energy X-ray absorptiometry (DXA) was made during the first 6 months of recombinant IGF-I treatment. Assessment of lumbar spine bone density by DXA was performed prior to IGF-I treatment and during the subsequent five years. RESULTS: Each child showed a significant reduction in fat mass (0.26-1.22 kg) after 6 weeks of IGF-I treatment. Bone density prior to treatment was reduced in comparison to age-matched controls but calculated volumetric bone density was within the normal range. Volumetric bone density progressively improved over the 5-year treatment period. CONCLUSIONS: Children with growth hormone insensitivity syndrome exhibit a metabolic response to IGF-I within 6 weeks analogous to that seen in GH-deficient children receiving GH. Bone density when corrected for body size is within normal limits and demonstrates a response to IGF-I, confirming the anabolic action on bone.

Absorptiometry, Photon↗
PubMed2003

The effect of cessation of growth hormone (GH) therapy on bone mineral accretion in GH-deficient adolescents at the completion of linear growth.

In many countries, treatment of childhood-onset GH deficiency (GHD) with GH ceases when linear growth is complete. Peak bone mass occurs several years after the completion of linear growth. Given that GH has important anabolic actions on bone, discontinuation of GH therapy at the completion of linear growth may have adverse consequences for the attainment of peak bone mass in adolescent GHD patients. In this United Kingdom multicenter study, 24 adolescents (13 males, mean age 17.0 +/- 1.4 yr, SD) with severe GHD were randomized to discontinue or continue GH (0.35 IU/kg x wk) at the completion of linear growth. Whole body bone mineral content (BMC) and lumbar spine bone mineral density were assessed by dual-energy x-ray absorptiometry at baseline and then at 6-month intervals for 1 yr. Markers of bone remodeling (serum bone-specific alkaline phosphatase and urinary deoxypyridinoline) were measured at the same time points. In patients who continued GH (GH+), median BMC increased by 3.8% (interquartile range, 2.6, 5.9, P < 0.001) at 6 months; and by 6.0% (3.7-9.1, P < 0.001) at 12 months. In patients who discontinued GH (GH-) median BMC was unchanged at 6 and 12 months (+1.9%, -0.4-4.2, P = 0.9; and +2.4%, 0.4-4.9, P = 0.5, respectively, median, interquartile range). The differences in median change in BMC between the two groups at 6 and 12 months was marginally significant (P = 0.085 and 0.074, respectively). Mean lumbar spine bone mineral density increased by 4.7 (95% confidence interval, 1.0, 8.2) at 12 months in patients continuing GH (P = 0.01), but the mean change was not statistically significant change in patients who discontinued GH [+2.7% (95% confidence interval, -0.8, +6.2)]. These preliminary data suggest that, in adolescent patients with severe GHD, discontinuation of GH at completion of growth may limit the attainment of peak bone mass in this patient group. This may predispose to clinically significant osteopenia in later adult life.

Adolescent↗
PubMed2003

Distribution analysis of vitamin D highlights differences in population subgroups: preliminary observations from a pilot study in UK adults.

There is no consensus between Authors on the definition of a replete or deficient vitamin D state. Our aim was to describe a suitable method that could be used to compare vitamin D data in subject groups with small or large numbers. Two hundred and forty indigenous asymptomatic, non-pregnant adult subjects recruited from a single-consultation outpatient attendance with normal biochemistry, represented a sample of our inner city district population. 25-hydroxyvitamin D (25,OHD3) levels were measured to illustrate the effects of season, sex and ethnic group on vitamin D levels and subjected to distribution analysis. This method quantifies as a percentage the distribution of 25,OHD3 concentrations (observed concentration, OC) in pooled group data. The data can be expressed as distribution frequency domains or cumulative frequency ogives (0-100%) or transformed into discrete linear probits, amenable to regression analysis. An estimate of the OC50 (mid-point) and upper (either OC75 or OC95) or lower (either OC25 or OC5) range or at any other frequency between subject groups can be compared. A marked difference in 25,OHD3 levels between Asian and non-Asian asymptomatic adult subjects was seen during both seasons. 25,OHD3 deficiency was defined as at or below the OC25 for the non-Asian group (for both sexes: winter < 13.36 ng/ml, summer <13.38 ng/ml). The majority of Asians of both sexes were 25,OHD3 deficient (winter 94%, summer 82%). The distribution analysis provides an easy technique to compare 25,OHD3 status of different subject groups, allowing the description of populations using either longitudinal or cross-sectional data. This method may offer a way of describing 25,OHD3 deficiency between observers worldwide.

Adolescent↗
PubMed2002

Home oxygen status and rehospitalisation and primary care requirements of infants with chronic lung disease.

OBJECTIVES: To determine whether the rehospitalisation and primary care requirements of infants with chronic lung disease (CLD) during the first two years after birth were influenced by a requirement for supplementary oxygen after discharge from the neonatal intensive care unit. METHODS: Review of records from both the hospital and general practitioner. PATIENTS: 235 infants, median gestational age 27 (range 22-31) weeks, 88 of whom were receiving supplementary oxygen when discharged home. RESULTS: Overall, the infants required a median of 2 (range 0-20) admissions per patient, 8 (0-41) outpatient attendances, 13 (0-76) contacts with the general practitioner, and 17 (0-169) consultations with other primary healthcare professionals. The home oxygen patients required significantly more and longer admissions (p < 0.01) and more outpatient attendances (p < 0.05). The total cost of care per infant of the home oxygen group was greater (p < 0.001); this reflected higher costs for hospital stay (p < 0.01), total inpatient care (p < 0.01), and primary care drugs (p < 0.01). CONCLUSION: Despite routine use of antenatal steroids and postnatal surfactant, certain patients with CLD, particularly those who receive home oxygen treatment, show high rates of utilisation of health service resources after discharge from the neonatal care unit.

Analysis of Variance↗
PubMed2002

Vitamin D deficiency in UK Asian families: activating a new concern.

Vitamin D has steroid hormonal effects which can produce clinical symptoms and signs unrelated to calcium homoeostasis. Its deficiency has been implicated as a risk factor for diabetes, ischaemic heart disease, and tuberculosis in Asians. In this review, the incidence, aetiology, prevention, and treatment of symptomatic vitamin D deficiency in childhood are considered. A renewed public health campaign is required in the UK to address the continuing problem of vitamin D deficiency in Asian families.

Asia↗
PubMed2002

A parent completed questionnaire to describe the patterns of wheezing and other respiratory symptoms in infants and preschool children.

AIM: To develop a standardised and validated respiratory symptom questionnaire for use in epidemiological or follow up studies in infants and preschool children. METHODOLOGY: After initial design and development, the questionnaire was administered to two cohorts of subjects, one recruited from a respiratory clinic and the other from a postnatal ward. The two cohorts then repeated the questionnaire, two weeks apart. The qualities of the questionnaire were assessed. RESULTS: Response rate to the initial questionnaire was 100% for the clinic based cohort and 64% for postnatally recruited families (total number of subjects 114). Questions showed good to moderate short term reliability (weighted kappa scores 0.47-0.7; average correct classification rates 0.74-0.91). Four domain concept scores showed excellent internal consistency (Cronbach alpha scores 0.87-0.95). Using principal component factor analysis, four new domains were devised showing acceptable construct validity and internal consistency. Criterion validity was assessed using a respiratory physician based diagnosis of asthma (RPBDA) as the gold standard for comparison. All eight scales in the questionnaire could significantly distinguish between infants with RPBDA and well or mildly symptomatic subjects. CONCLUSION: We have developed a practical, acceptable questionnaire with eight concept domains for use in infants and preschool children. The questionnaire has strong construct validity and internal consistency with good short term reliability of questions. More detailed study of criterion validity and the responsiveness of the questionnaire is required using a larger population and including children with the different phenotypes of wheezy illness.

Child, Preschool↗
PubMed2001

Continuous enteral feeding impairs gallbladder emptying in infants.

OBJECTIVE: The objective was to test the hypothesis that continuous enteral feeding impairs gallbladder emptying in infants. STUDY DESIGN: A prospective crossover study was performed in 15 infants: (1) bolus enteral feeds were given in phase A, (2) a continuous milk feed was given for 3 days in phase B, and (3) bolus feeds were resumed in phase C. The gallbladder was studied with ultrasonography in phase A, on days 1 and 3 of phase B, and at the start and on days 2 and 4 of phase C. RESULTS: Baseline volume was 116.1 mm(3) (range, 48.1 to 374.8 mm(3)) in phase A and 293.3 mm(3) (range, 109.4 to 1134.9 mm(3)) (P <.001) after 3 days of phase B; it returned to the phase A value after 4 days of phase C. The contraction index was 65.2% (range, 40.6% to 78.2%) in phase A and 1.7% (range, 0% to 8.4%) (P <.001) after 3 days of phase B. It returned to its phase A value immediately after bolus enteral feeds were resumed in phase C. CONCLUSIONS: Continuous enteral feeding leads to an enlarged, noncontractile gallbladder in infants. Emptying is observed immediately after bolus feeds are resumed, and volume returns to baseline after 4 days. The mode of feeding has important bearings on the motility of the extrahepatic biliary tree.

Cross-Over Studies↗
PubMed2001

Bone density in the Asian thalassaemic population: a cross-sectional review.

UNLABELLED: As survival improves in beta-thalassaemia, osteoporosis is emerging as a significant problem. This study examines bone mineral density (BMD) of thalassaemic patients of Asian origin (age range 9.5-24 y) to evaluate the extent of problems in this group and identify potential risk factors. Eleven patients were scanned using dual-energy X-ray absorptiometry. BMD z-scores and the bone mineral apparent density (BMAD) z-scores were calculated, to correct for short stature. All but three patients had lumbar spine BMD and BMAD z-scores below the mean. Three patients had BMAD z-scores more than 2.5 standard deviations below the mean. A negative correlation between age and BMAD was seen, as was an association between endocrine disorders and decreased bone density. CONCLUSION: The data confirm significant reductions in BMD in the Asian thalassaemic population, even after correcting for body size. Further research is needed to identify risk factors and means of prevention.

Absorptiometry, Photon↗
PubMed2001

Diabetic ketoacidosis in Asian children.

Over the 10 year period 1987-1996, 328 children with type 1 diabetes mellitus presented in the city of Birmingham, England, of whom 27% had diabetic ketoacidosis. Asian children under the age of 5 had an eightfold increased risk of presenting in diabetic ketoacidosis compared with non-Asian children of the same age.

Adolescent↗
PubMed2001

Health care utilisation of infants with chronic lung disease, related to hospitalisation for RSV infection.

AIMS: To compare the use of health care resources and associated costs between infants with chronic lung disease (CLD) who had or had not an admission with a proven respiratory syncytial virus (RSV) infection. METHODS: Review of community care, outpatient attendances, and readmissions in the first two years after birth. PATIENTS: 235 infants (median gestational age 27 weeks) evaluated in four groups: 45 infants with a proven RSV admission (RSV proven); 24 with a probable bronchiolitis admission; 60 with other respiratory admissions; and 106 with non-respiratory or no admissions. RESULTS: The RSV proven compared to the other groups required more frequent and longer admissions to general paediatric wards and intensive care units, more outpatient attendances and GP consultations for respiratory related disorders, and had a higher total cost of care. CONCLUSION: RSV hospitalisation in patients with CLD is associated with increased health service utilisation and costs in the first two years after birth.

Analysis of Variance↗
PubMed2001

Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease.

BACKGROUND: Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease. AIM: To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants. METHODS: Infants with birth weight < 1000 g were randomised at birth to receive oral vitamin A supplementation (5000 IU/day) or placebo for 28 days. The primary outcome was oxygen dependency at 28 days of age or death. RESULTS: A total of 154 infants were randomised; 77 received vitamin A (median birth weight (interquartile range) 806 (710-890) g), and 77 received placebo (median birth weight (interquartile range) 782 (662-880) g). Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth, 12 hours of age, 7 days, or 28 days of life. There were no significant differences in the proportion of infants who survived, required oxygen at 28 days, required oxygen at 36 weeks postmenstrual age, survived without chronic lung disease at 36 weeks, survived without significant retinopathy, or who survived without significant intraventricular haemorrhage. CONCLUSIONS: Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease. However, this dose may have been inadequate to achieve optimal serum retinol concentrations.

Chronic Disease↗