Prolactin receptor expression in the developing human prostate and in hyperplastic, dysplastic, and neoplastic lesions.
(1/1150)
In situ hybridization and immunohistochemistry were used to localize and compare the expression of the long form of the human prolactin receptor in fetal, prepubertal, and adult prostate. Results were then compared with hyperplastic, dysplastic, and neoplastic lesions. Both receptor message and protein were predominately localized in epithelial cells of the fetal, neonatal, prepubertal, and normal adult prostate. In hyperplastic lesions the expression of the receptor was unchanged with respect to normal epithelial cells. Irrespective of grade, markedly enhanced expression of the receptor was evident in dysplastic lesions. In lower Gleason grade carcinomas the intensity of receptor signal at the message and protein levels approximated that found in normal prostatic epithelium. However, in foci within higher grade cancers, receptor expression appeared diminished. Results from our study suggest that prolactin action plays a role in the development and maintenance of the human prostate and may also participate in early neoplastic transformation of the gland. Diminution of receptor expression in high grade neoplasms could reflect the emergence of a population of cells that are no longer responsive to the peptide hormone. (+info)
Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group.
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OBJECTIVE: The predictive value of microalbuminuria (MA) in children with type 1 diabetes has not been defined. We describe the natural history of MA in a large cohort of children recruited at diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1985 and 1996, 514 children (279 male) who developed type 1 diabetes before the age of 16 years (91% of those eligible from a region where ascertainment of new cases is 95%) were recruited for a longitudinal study with central annual assessment of HbAlc and albumin excretion (three urine samples). Dropout rates have been < 1% per year, and 287 children have been followed for > 4.5 years. RESULTS: MA (defined as albumin-to-creatinine ratio > or = 3.5 and > or = 4.0 mg/mmol in boys and girls, respectively) developed in 63 (12.8%) and was persistent in 22 (4.8%) of the subjects. The cumulative probability (based on the Kaplan-Meier method) for developing MA was 40% after 11 years. HbAlc was worse in those who developed MA than in others (mean difference +/- SEM: 1.1% +/- 0.2, P < 0.001). In subjects who had been 5-11 years of age when their diabetes was diagnosed, the appearance of MA was delayed until puberty, whereas of those whose age was < 5 years at diagnosis of diabetes, 5 of 11 (45%) developed MA before puberty. The adjusted proportional probability (Cox model) of MA was greater for female subjects (200%), after pubertal onset (310%), and with greater HbAlc (36% increase for every 1% increase in HbAlc). Despite earlier differences based on age at diagnosis of diabetes (< 5, 5-11, and > 11 years), the overall cumulative risks in these groups were similar (38 vs. 29 vs. 39%, respectively) after 10 years' duration of diabetes. CONCLUSIONS: Prepubertal duration of diabetes and prepubertal hyperglycemia contribute to the risk of postpubertal MA. The differences in rates of development of MA relating to HbAlc, sex, and age at diagnosis relative to puberty may have long-term consequences for the risk of subsequent nephropathy and for cardiovascular risk. (+info)
Pelvic ultrasonography in Turner syndrome: standards for uterine and ovarian volume.
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The purpose of this study was to investigate uterine and ovarian size according to age and pubertal stage in patients with Turner syndrome. Ultrasonographic evaluation of the uterus and the ovaries was performed in 93 patients with Turner syndrome, aged 12 days to 17.85 years. The data were compared with those of 190 healthy controls. One or both ovaries were detected in 41 of 93 patients (44%). Within the prepubertal group, mean uterine volume and mean ovarian volume of the patients with Turner syndrome were significantly (P<0.001) lower than those of controls (0.5+/-0.2 ml versus 1.0+/-0.3 ml; 0.3+/-0.3 ml versus 0.6+/-0.4 ml, respectively). In prepubertal girls, no significant relationship was found between age and uterine size or ovarian size. Both uterine volume and ovarian volume of 19 women with spontaneous puberty increased during breast development, although mean uterine volume and mean ovarian volume were significantly (P<0.01) lower than those of pubertal control patients. (+info)
Randomised controlled trial of recombinant human growth hormone in prepubertal and pubertal renal transplant recipients. British Association for Pediatric Nephrology.
(4/1150)
AIMS: To evaluate the efficacy (height velocity (HV), change in height standard deviation score (delta HSDS)), and safety (glomerular filtration rate (GFR), incidence of rejection, and calcium and glucose metabolism) of recombinant human growth hormone (rhGH) treatment after renal transplantation. DESIGN: A two year randomised controlled trial. SUBJECTS: Fifteen prepubertal and seven pubertal children: mean (SD) age, 13.0 (2.6) and 15.2 (2.4) years, respectively; mean (SD) GFR, 51 (30) and 48 (17) ml/min/1.73 m2, respectively. Six prepubertal and three pubertal children were controls during the first year; all received rhGH in the second year. RESULTS: In the first year, mean (SE) HV and delta HSDS in the prepubertal treated group increased compared with controls: 8.1 (0.9) v 3.7 (0.6) cm/year and 0.6 (0.1) v -0.3 (0.2), respectively. In the pubertal treated group, mean (SE) HV and delta HSDS were also greater: 10.1 (0.6) v 3.9 (1.3) cm/year and 0.6 (0.1) v -0.1 (0.2), respectively. Comparing all treated and control children, there was no significant change in GFR: treated group, mean (SE) 9.9 (5.4) ml/min/1.73 m2 v control group, -1.6 (7.6) ml/min/1.73 m2. There were also no differences in the incidence of rejection in the first year: eight episodes in 13 patients v five episodes in nine patients, respectively. Phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and fasting insulin concentrations rose during the first year of treatment, but not thereafter. In the second year of treatment, HV remained above baseline. CONCLUSION: Treatment with rhGH improves growth in prepubertal and pubertal children with renal transplants, with no significant change in GFR or the incidence of rejection. Phosphate, ALP, PTH, and insulin increased during the first year of treatment. (+info)
Serum galactosyl hydroxylysine as a biochemical marker of bone resorption.
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BACKGROUND: Serum-based biochemical markers of bone resorption may provide better clinical information than urinary markers because direct comparison with serum markers of bone formation is possible and because the within-subject variability of serum markers may be lower. We describe a method for the measurement of free beta-1-galactosyl-O-hydroxylysine (Gal-Hyl) in serum. METHODS: The assay used preliminary ultrafiltration of serum, dansylation, and separation by reversed-phase HPLC with fluorescence detection. Healthy subjects were recruited from population-based studies of bone turnover. RESULTS: The within-run (n = 15) and between-run (n = 15) CVs were 7% and 14%, respectively, at a mean value of 48 nmol/L. In women and pubertal girls, serum free Gal-Hyl correlated with urine free Gal-Hyl (r = 0.84; P <0.001). Serum Gal-Hyl was higher during puberty and increased after menopause. The fractional renal clearance of free Gal-Hyl relative to that of creatinine was 0.90 (95% confidence interval, 0.82-0.98). Serum free Gal-Hyl decreased by 36% (SE = 4%) in 14 patients with mild Paget disease treated with an oral bisphosphonate, and this decrease was significantly (P <0. 001) greater than that seen for either serum tartrate-resistant acid phosphatase (9%; SE = 4%) or serum C-terminal telopeptide of collagen I (19%; SE = 8%). CONCLUSION: Serum free Gal-Hyl may be useful as a serum marker of bone resorption. (+info)
Whole-body protein turnover and resting energy expenditure in obese, prepubertal children.
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BACKGROUND: Obesity is becoming more frequent in children; understanding the extent to which this condition affects not only carbohydrate and lipid metabolism but also protein metabolism is of paramount importance. OBJECTIVE: We evaluated the kinetics of protein metabolism in obese, prepubertal children in the static phase of obesity. DESIGN: In this cross-sectional study, 9 obese children (x +/- SE: 44+/-4 kg, 30.9+/-1.5% body fat) were compared with 8 lean (28+/-2 kg ,16.8+/-1.2% body fat), age-matched (8.5+/-0.2 y) control children. Whole-body nitrogen flux, protein synthesis, and protein breakdown were calculated postprandially over 9 h from 15N abundance in urinary ammonia by using a single oral dose of [15N]glycine; resting energy expenditure (REE) was assessed by indirect calorimetry (canopy) and body composition by multiple skinfold-thickness measurements. RESULTS: Absolute rates of protein synthesis and breakdown were significantly greater in obese children than in control children (x +/- SE: 208+/-24 compared with 137+/-14 g/d, P < 0.05, and 149+/-20 compared with 89+/-13 g/d, P < 0.05, respectively). When these variables were adjusted for fat-free mass by analysis of covariance, however, the differences between groups disappeared. There was a significant relation between protein synthesis and fat-free mass (r = 0.83, P < 0.001) as well as between protein synthesis and REE (r = 0.79, P < 0.005). CONCLUSIONS: Obesity in prepubertal children is associated with an absolute increase in whole-body protein turnover that is consistent with an absolute increase in fat-free mass, both of which contribute to explaining the greater absolute REE in obese children than in control children. (+info)
Plasma homocysteine concentration in a Belgian school-age population.
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BACKGROUND: Total plasma homocysteine (tHcy) is an independent risk factor for cardiovascular disease in adults. Data for children and adolescents are lacking. OBJECTIVE: The aim of this study was to provide a reference range for tHcy and to explore the relation between tHcy and nutritional indexes in a Belgian pediatric population. DESIGN: tHcy, folate, and vitamin B-12 were measured in 647 healthy children (353 girls and 294 boys) aged 5-19 y. RESULTS: The tHcy distribution was, as in adults, skewed to the right [geometric mean (-1 SD, +1 SD): 7.41 micromol/L (5.51, 9.96)]. Concentrations were lowest in younger children and increased with age. After the tHcy distribution was examined according to age, 3 age ranges were distinguished: 5-9 y [6.21 micromol/L (5.14, 7.50)], 10-14 y [7.09 micromol/L (5.69, 8.84)], and 15-19 y [8.84 micromol/L (6.36, 12.29)]. We observed no significant differences in tHcy values between girls and boys in children aged < 15 y; in postpubertal children, however, concentrations were higher in boys than in girls. In the 3 age groups, folate was inversely correlated with tHcy; the negative relation between tHcy and vitamin B-12 was less strong. Familial cardiovascular disease was more frequent in children who had hyperhomocysteinemia. CONCLUSIONS: These observations suggest that in children, as in adults, genetic, nutritional, and endocrine factors are determinants of the metabolism of homocysteine. The significance of tHcy values in childhood and young adulthood in terms of predicting cardiovascular risk in adulthood should be investigated. (+info)
Effect of low-dose testosterone treatment on craniofacial growth in boys with delayed puberty.
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Craniofacial growth was investigated in boys treated with low-dose testosterone for delayed puberty (> 14 years old; testicular volume < 4 ml; n = 7) and compared with controls (12-14 years; n = 37). Cephalometric radiographs, statural height and pubertal stage were recorded at the start of the study and after 1 year. Craniofacial growth was assessed by nine linear measurements. At the beginning of the study, statural height, mandibular ramus length, upper anterior face height, and total cranial base length were significantly shorter in the delayed puberty boys than in the controls. After 1 year, the growth rate of the statural height, total mandibular length, ramus length, and upper and total anterior face height was significantly higher in the treated boys than in the untreated height-matched controls (n = 7). The craniofacial measurements were similar in the treated boys as compared with the controls. These results show that statural height and craniofacial dimensions are low in boys with delayed puberty. Low doses of testosterone accelerate statural and craniofacial growth, particularly in the delayed components, thus leading towards a normalization of facial dimensions. (+info)