bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between serum and urinary insulin‐like growth factor‐I through childhood and adolescence: their use in the assessment of disordered growth
Authors: Hall  , Gill  , Foster  , Pennells  , Tillmann  , Jones  , Price  , Clayton  
Published: March 2003

OBJECTIVESerum insulin‐like growth factor‐I (sIGF‐I) measurement as an index of growth hormone status has become a common test in the investigation of disordered growth. IGF‐I may also be measured in the urine. The aims of this study were to investigate the correlation between serum and urinary IGF‐I in normal children and compare their use in the evaluation of growth disorders.DESIGNNormal ranges for serum and urinary IGF‐I were devised from a cross‐sectional study of normal schoolchildren. These were then used to assess the sensitivity and specificity of serum and urinary IGF‐I in the diagnosis of childhood GH deficiency.PATIENTSA cohort of 333 (M = 156, F = 177) healthy schoolchildren aged 5–19 years were recruited and data previously collected from 22 growth hormone deficient (GHD) and 47 short normal (SN) children were compared with those of the normal children.MEASUREMENTSHeight, weight and pubertal status were assessed in all children. Serum IGF‐I (sIGF‐I) (n = 305) and total amount of urinary IGF‐I excreted overnight (TuIGF‐I) (n = 205) were measured by RIA using excess IGF‐II to block the interference of IGFBPs.RESULTSSerum IGF‐I was loge transformed and overall levels (geometric mean  ± 1 tolerance factor) were higher in females than males (F: 569 (329, 985)μg/l; M: 398 (227, 696)μg/l). LogeIGF‐I correlated with age (F: r = + 0.76, P < 0.001, M: r = + 0.71, P < 0.001) and was significantly affected by both sex and Tanner stage of puberty (TS) (both P < 0.001). The distribution of TuIGF‐I was normalized by performing a square root transformation (√TuIGF‐I). √TuIGF‐I was correlated with age (F: r = + 0.36, P < 0.001; M: r = + 0.5, P < 0.001) and was significantly affected by TS (P < 0.001). In both sexes there was a highly significant correlation between logeIGF‐I and √TuIGF‐I (F: r = + 0.39, P < 0.001; M: r = + 0.41, P < 0.001). Using the third centile of our normal ranges as a cut off to identify GHD, sIGF‐I had a sensitivity of 82% and specificity of 62%, whereas TuIGF‐I had a sensitivity of 18% and specificity of 79%.CONCLUSIONSThis study demonstrates that although urinary IGF‐I has no place in the diagnosis of growth disorders, in normal children there is a highly significant relationship between serum and urinary IGF‐I with levels of each changing in a similar manner through childhood and adolescence. Thus, TuIGF‐I could be used as a valid surrogate for sIGF‐I in the physiological assessment of the relationship between IGF‐I status and the normal growth process.
Amniotic fluid levels of dimeric inhibins, pro‐αC inhibin, activin A and follistatin in Down's syndrome
Authors: Wallace Euan M. , D'Antona Donato , Shearing Catherine , Evans Lee W. , Thirunavukarasu Prema , Ashby Peter J. , Shade Mary , Groome Nigel P. 
Published: March 2003

OBJECTIVEIn the second trimester of pregnancy, inhibin A is significantly increased in maternal serum and decreased in amniotic fluid in Down's syndrome pregnancies compared to normal. We wished to further evaluate the levels of inhibin A, inhibin B, pro‐αC inhibin, activin A and the binding protein follistatin in amniotic fluid in Down's syndrome and control pregnancies.DESIGNCase‐matched control study.PATIENTS29 Down's syndrome and 290 chromosomally normal control pregnancies were identified from records and amniotic fluid, collected at second tri‐mester amniocentesis, retrieved from routine storage for analysis.MEASUREMENTSInhibin A, inhibin B, pro‐αC inhibin, total activin A and follistatin were measured using sensitive and specific enzyme linked immunosorbent assays.RESULTSThe median (10th–90th percentiles) amniotic fluid inhibin A level in the control pregnancies increased from 334 (122–553) ng/l at 14 weeks' to 695 (316–1475) ng/l at 19 weeks' gestation. The corresponding figures for inhibin B and the α‐subunit precursor inhibin pro‐αC were 632 (185–1354) and 2062 (1237–3381) ng/l, respectively at 14 weeks' and 2439 (748–5307) and 3115 (2021–6567) ng/l, respectively at 19 weeks' gestation. Total activin A increased from 3795 (1554–5296) at 14 weeks' to 5086 (3059–8224) at 18 weeks' gestation. Expressed as multiples of the median (MoM) the median (95% CI) amniotic fluid levels of inhibin A, inhibin B, pro‐αC inhibin and acitivin A in the Down's syndrome samples were 0.77 (0.59–0.85), 0.94 (0.63–1.23), 0.77 (0.49–0.84) and 0.77 (0.53–0.87), respectively. Compared to controls the levels of inhibin A, pro‐αC inhibin and activin A were significantly lower in Down's syndrome pregnancies (P < 0.01, Mann‐Whitney U test). Follistatin levels in the controls declined slightly from 2106 (1421–3538) ng/l at 14 weeks' to 1600 (1281–2543) ng/l at 18 weeks' gestation. Levels in the Downs' syndrome pregnancies were similar to controls.CONCLUSIONSThe data suggest that the production, secretion or metabolism of the inhibin α‐ and βA‐subunits is altered in Down's syndrome pregnancies in the second trimester.
Postmenopausal osteoporosis is more related to hormonal aberrations than to lifestyle factors
Authors: Landin‐Wilhelmsen Kerstin , Wilhelmsen Lars , Bengtsson Bengt‐Åke 
Published: March 2003

OBJECTIVESerum insulin‐like growth factor‐1 (IGF‐1) decreases with increasing age and this process is more pronounced in women after the menopause in parallel with the increasing prevalence of osteoporosis. This study was designed to compare IGF‐1 concentrations, vitamin D, intact parathyroid hormone (PTH) and lifestyle factors in postmenopausal, osteoporotic women with and without oestrogen replacement therapy (HRT), with an age‐matched random population sample of women.DESIGNCase control study.PATIENTSPostmenopausal, osteoporotic women, n = 128, mean age 59 ± 6 years, were compared with a female random population sample matched for age, n = 227, mean age 59 ± 5 years, from the WHO MONICA Project, Göteborg, Sweden. Osteoporotic fractures had occurred in 56% of the patients compared with 4% of the controls (P < 0.001).MEASUREMENTSAnthropometry, occupation, smoking habits, physical activity, blood pressure, IGF‐1, vitamin D, intact PTH, blood lipids.RESULTSThere were no differences in occupational class, current or previous smoking habits, degree of physical activity during occupational or leisure time between the patients and controls. Osteoporotic women had lower body weight and body mass index than the controls (P < 0.001). Height, waist/hip ratio and osteocalcin were similar. 25(OH) vitamin D and 1,25(OH)2 vitamin D were lower (P < 0.05 and P < 0.01, respectively), PTH was higher (P < 0.001) and IGF‐1 lower (P < 0.01) in osteoporotic women compared with the controls. IGF‐1 was lower (P < 0.05), in spite of similar bone mineral density, in osteoporotic women without HRT than in those with HRT, who had IGF‐1 concentrations similar to those of the population sample, of whom fewer than 10% had HRT. Among patients, IGF‐1 did not correlate with serum oestradiol or bone mineral density. PTH correlated negatively to bone mineral density at the femoral site (r = − 0.29; P = 0.003).CONCLUSIONOsteoporosis in postmenopausal women is more related to hormonal aberrations than to lifestyle factors.
Weight gain reverses bone turnover and restores circadian variation of bone resorption in anorexic patients
Authors: Caillot‐Augusseau Anne , Lafage‐Proust Marie‐Hélène , Margaillan Philippe , Vergely Nathalie , Faure Sylvie , Paillet Stephane , Lang François , Alexandre Christian , Estour Bruno 
Published: March 2003

OBJECTIVEThe present study was conducted in order to describe the variations and circadian rhythm of biochemical markers of bone remodelling at baseline and after weight gain in patients with aneroxia nervosa (AN).SUBJECTSWe studied 9 women (mean age 21 years, range: 16–30) with established AN who remained amenorrhoeic during the study and with a low body mass index (BMI) after refeeding and 6 female controls (mean age 20 years, range, 18–24 and BMI: 20.6 ± 1.1 kg/m2). Refeeding was not associated with any other intervention or treatment, especially oestrogen replacement or hormonal contraception. Serum levels of oestradiol remained below 70 pmol/l before and after refeeding.MEASUREMENTSDuring the study, PTH and 25‐hydroxyvitamin D measurements were performed. Markers of bone formation: serum intact osteocalcin (iBGP) and serum intact BGP + fragments (iBGP+F) and markers of bone resorption: urine C‐teloptide of type I collagen (uCTX) and serum C‐telopeptide ofvtype 1 collagen (s‐CTX) were measured.RESULTSAt baseline, PTH and 25 OH‐vitamin D concentrations were within the normal range in AN patients and no significant variation was observed after refeeding. Bone formation markers were found to be significantly different at baseline between AN patients and controls. After refeeding, iBGP and iBGP+F levels increased by 172% and 154%, respectively, to values no different from controls. Intact BGP and iBGP+F exhibited a significant circadian variation in controls (P < 0.05 and P < 0.002, respectively), whereas we did not find any such circadian rhythm in AN patients. After refeeding no significant circadian variation was observed; however, iGBP+F tended to peak in early morning and exhibited a nadir in the afternoon. At baseline, sCTX was 2‐fold higher in AN patients than in controls. After weight gain sCTX decreased significantly and reached control values. Refeeding induced a non‐significant 40% decrease in uCTX. We found positive correlations between uCTX and the 24‐h mean value of sCTX levels (r2 = 0.93, P < 0.0001) and between uCTX and the mean value of sCTX peak levels at 0800 h (r2 = 0.65, P < 0.0003). Serum CTX exhibited a significant circadian variation in controls (P < 0.001) with a peak at 0800 h and a nadir at 1600 h with a 60% decrease between peak and nadir values. We found that anorexia nervosa suppressed the sCTX circadian variation which was restored by refeeding. We found a significant non‐linear relationship between BMI and sCTX/iBGP ratio in AN (r2 = 0.6, P < 0.0001), thus illustrating the influence of nutritional status on bone remodelling.CONCLUSIONSIn this study we found that weight gain, related to refeeding only, reversed the anorexia nervosa‐induced uncoupling of bone remodelling and restored circadian variation of a bone resorption marker.
The prevalence of polycystic ovaries in women with type 2 diabetes mellitus
Authors: Conn Jennifer J. , Jacobs Howard S. , Conway Gerard S. 
Published: March 2003

OBJECTIVEPolycystic ovary syndrome (PCOS) and type 2 diabetes mellitus are both common conditions associated with insulin resistance and compensatory hyperinsulinaemia. Previous reports have noted that impaired glucose tolerance and diabetes are common in women with PCOS. In this report we present the results of the converse study: the prevalence of polycystic ovaries in premenopausal women presenting with type 2 diabetes mellitus.SUBJECTSSubjects were recruited from a hospital Diabetes Clinic. A search of computerized records identified 49 premenopausal women with type 2 diabetes mellitus being treated with diet alone or oral hypoglycaemic agents of whom 38 (76%) patients agreed to be studied.DESIGNA cross‐sectional study recording clinical, demographic and anthropometric data. Measurements of fasting metabolic parameters, reproductive endocrine profiles and ovarian dimensions were taken.RESULTSEighty‐two percent of women with type 2 diabetes mellitus had polycystic ovaries on ultrasound. Of these women, 52% had clinical evidence of cutaneous hyperandrogenism and/or menstrual disturbance. Correlations between metabolic and reproductive parameters were consistent with a stimulatory action of insulin on the ovary. There was no significant difference between the PCO and non‐PCO groups with respect to metabolic profiles.CONCLUSIONSWomen with type 2 diabetes mellitus have a higher prevalence of polycystic ovaries than that reported in the general population. Not all women with hyperinsulinaemia due to type 2 diabetes mellitus, however, develop PCO suggesting that hyperinsulinaemia alone is not sufficient for the expression of this ovarian morphology.
Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1,25‐dihydroxyvitamin D3
Authors: Colin Edgar M. , Weel Angelique E. A. M. , Uitterlinden André G. , Buurman Cok J. , Birkenhäger Jan C. , Pols Huibert A. P. , Van Leeuwen Johannes P. T. M. 
Published: March 2003

OBJECTIVEIn the vitamin D receptor (VDR) gene a BsmI restriction fragment length polymorphism (RFLP) in intron 8 and a translational start‐site polymorphism, identified as a FokI RFLP, have been described. Crucial for a proper interpretation of these polymorphisms in association studies is the knowledge whether they have direct consequences for 1,25‐(OH)2D3 action at cellular level. The present study was designed to assess functional significance of the FokI and BsmI VDR gene polymorphisms in peripheral blood mononuclear cells (PBMC) with a natural occurring VDR genotype for cell growth inhibition by 1,25‐(OH)2D3.DESIGNPBMC of women were isolated, VDR genotyped and in vitro inhibition by 1,25‐(OH)2D3 of Phytohemagglutinin (PHA)‐stimulated growth of PBMC was examined in relation to VDR genotype.RESULTSPHA‐stimulated growth and maximal growth inhibition were independent of VDR genotype. However, the FF genotype had a significant lower ED50 than the Ff genotype corresponding to an allele dose effect of 0.32 nm per f allele copy (P = 0.0036). For BsmI genotypes no differences in ED50 were observed.CONCLUSIONThe present study demonstrates for the first time in cells with a natural VDR genotype a direct functional consequence of the VDR gene translational start‐site polymorphism for the action of 1,25‐(OH)2D3. Especially under conditions of vitamin D insufficiency these findings might have clinical implications.
Circulating IGF‐I and its protective role in the pathogenesis of diabetic angiopathy
Authors: Janssen  , Lamberts  
Published: March 2003

Poor glycaemic control in type 1 diabetes is associated with elevated serum IGFBP‐1 levels and reduced rather than elevated serum IGF‐I levels. Increasing age is accompanied by a further decrease in serum IGF‐I levels as well as an increase in IGFBP‐l levels in adult diabetic type 1 and type 2 subjects. This is especially observed in diabetic type 1 subjects with manifest microvascular complications. IGFBP‐I has been proposed as one of the IGF‐I inhibitors in the serum of diabetics. Lowered IGF‐I and increased IGFBP‐1 levels in the blood may thus result in decreased IGF‐I bioavailability at the tissue level.We hypothesize that the premature and progressive decline in serum IGF‐I bioactivity during ageing in diabetics ultimately results in insufficient protective effects by IGF‐I in the kidneys, eyes and neurones, and thus the progression of diabetic microvascular complications. If this hypothesis is proven to be right, treatment of diabetic patients with IGF‐I (eventually complexed to IGFBPs) as an adjunct to insulin might prevent and not worsen the development of diabetic microvascular complications.
The development of a sialic acid specific lectin‐immunoassay for the measurement of human chorionic gonadotrophin glycoforms in serum and its application in normal and Down's syndrome pregnancies
Authors: Abushoufa Ramadan A. , Talbot James A. , Brownbill Kathryn , Rafferty Brian , Kane John W. , Robertson William R. 
Published: March 2003

SummaryOBJECTIVE We have developed and validated a lectin‐immunoassay for the recognition of sialic acid residues on hCG glycoforms in serum. DESIGN This assay employs a hCG specific capture antibody and a sialic acid specific lectin (Wheat Germ Agglutinin) labelled with horse radish peroxidase. RESULTS The standard curve covered hCG concentrations of 0‐4000lU/I (3rd IS for hCG, 7W537) with an analytical sensitivity of 1.0 IUA. The within and between batch coefficient of variation was<7% for all doses. Cross‐reactivity of <1% with TSH, LH, FSH, hCGa, hCGβ and desialylated hCG confirmed assay specificity. Dilutions of serum of <10% final concentration were parallel to the standard curve (within and between batch CV,<6%). The assay working range was 100 – >500000 IUh and the recovery of hCG from serum was in the range of 94.5% to 115.4%, with a mean value of 102.1%. The assay detected a time dependent change in hCG sialylation during normal pregnancy with the relative abundance of sialylated hCG declining after week 9 and increasing after week 15 of gestation. In addition preliminary studies showed that maternal serum hCG concentrations measured with the lectln‐immunoassay were elevated in high risk Down's pregnancies (as defined by conventional screening tests between weeks 16‐18 gestatlon, medlan multiple of median, 3.14; range 1‐81–19.12, P< 001) and low risk (1.57, 0.49–6.14, P=0.034) compared to normal (1.00,0–32‐3.20) pregnancies. Furthermore, the lectin immunoas‐say had greater discriminatory power compared to conventional immunoassay of hCG and hCGB between normal and both low and high risk Down's pregnancies.CONCLUSION This assay will allow analysis of serum samples for the investigation of sialylated variants of hCG glycoforms in various pathological and physiological situations.
Vasopressin and thirst in patients with posterior pituitary ectopia and hypopituitarism
Authors: Lukezic Monica , Righini Velella , Di Natale Berardo , De Angelis Riccardo , Norbiato Guido , Bevilacqua Maurizio , Chiumello Giuseppe 
Published: March 2003

OBJECTIVEPartial diabetes insipidus has been documented in patients with congenital hypopituitarism and posterior pituitary ectopia, some cases being clinically silent except for enuresis. The objective of our study was to evaluate vasopressin (AVP) secretion and thirst appreciation in hypopituitary patients with posterior pituitary ectopia.PATIENTSTwelve males and three females, aged between 13 and 38 years (median 19 years). Eleven had multiple pituitary deficiencies, adequately replaced at the time of the study, and four were only growth hormone deficient. None of the patients suffered from polyuria, polydipsia or nocturnal enuresis. We tested the patients with a 5% NaCl infusion. Five patients with abnormal vasopressin production were also tested with nitroprusside, which affects baroceptor vasopressin secretion.RESULTSWe found that only two out of 12 patients had normal AVP secretion. Thirst assessment showed severe hypodipsia in one patient, hyperdipsia in three out of 15 and more subtle abnormalities in two out of 15 patients. Concordance was found between osmotically and baroceptor‐stimulated vasopressin.CONCLUSIONSPatients with posterior pituitary ectopia showed a high prevalence of subclinical subnormal vasopressin response to the osmolar stimulus and moreover an impairment of thirst appreciation. Our data on nonosmotically stimulated AVP release suggest the existence of a damage in the hypothalamic vasopressin secreting centres.
Isocaloric carbohydrate deprivation induces protein catabolism despite a low T3‐syndrome in healthy men
Authors: Bisschop P. H. , Sauerwein H. P. , Endert E. , Romijn J. A. 
Published: March 2003

Dietary carbohydrate content is a major factor determining endocrine and metabolic regulation. The aim of this study was to evaluate the relation between thyroid hormone levels and metabolic parameters during eucaloric carbohydrate deprivation.We measured thyroid hormone levels, resting energy expenditure (by indirect calorimetry) and urinary nitrogen excretion in six healthy males after 11 days of three isocaloric diets containing 15% of energy equivalents as protein and 85%, 44% and 2% as carbohydrates.In contrast to the high and intermediate carbohydrate diets, carbohydrate deprivation decreased plasma T3 values (1·78 ± 0·09 and 1·71 ± 0·07 vs. 1·33 ± 0·05 nmol/l, respectively, P < 0·01), whereas reverse T3, T3 uptake and free T4 levels increased simultaneously compared to the other two diets. TSH values were not different among the three diets. Although dietary carbohydrate content did not influence resting energy expenditure, carbohydrate deprivation increased urinary nitrogen excretion (10·91 ± 0·67 and 12·79 ± 1·14 vs. 15·89 ± 1·10 g/24 h, respectively, P = 0·03).Eucaloric carbohydrate deprivation increases protein catabolism despite decreased plasma T3 levels. Because it has previously been shown that starvation decreases plasma T3 levels, resting energy expenditure and nitrogen excretion, these discordant endocrine and metabolic changes following carbohydrate deprivation indicate that the effects of starvation on endocrine and metabolic regulation are not merely the result of carbohydrate deprivation.
Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men
Authors: Wang Christina , Swerdloff Ronald S. , Iranmanesh Ali , Dobs Adrian , Snyder Peter J. , Cunningham Glenn , Matsumoto Alvin M. , Weber Thomas , Berman Nancy ,   the Testosterone Gel Study Group
Published: March 2003

OBJECTIVE Androgen replacement has been reported to increase bone mineral density (BMD) in hypogonadal men. We studied the effects of 6 months of treatment with a new transdermal testosterone (T) gel preparation on bone turnover markers and BMD.DESIGN This was a prospective, randomized, multicentre, parallel clinical trial where 227 hypogonadal men, mean age 51 years (range: 19–68 years) were studied in 16 academic and research institutions in the USA. Subjects were randomized to apply 1% T gel containing 50 or 100 mg T (delivering approximately 5–10 mg T/day) or two T patches (delivering 5 mg T/day) transdermally for 90 days. At day 91, depending on the serum T concentration, the T gel dose was adjusted upward or downward to 75 mg T/day until day 180. No dose adjustment occurred in the T patch group.MEASUREMENTS Serum T, free T and oestradiol, bone turnover markers and BMD were measured on days 0, 30, 90 and 180 before and after treatment.RESULTS Application of T gel 100 mg/day resulted in serum T concentrations 1·4 and 1·9‐fold higher than in the T gel 50 mg/day and the T patch groups, respectively. Proportional increases occurred in serum oestradiol. Urine N‐telopeptide/creatinine ratio, a marker for bone resorption, decreased significantly (P = 0·0019) only in the T gel 100 mg/day group. Serum bone osteoblastic activity markers (osteocalcin, procollagen and skeletal alkaline phosphatase) increased significantly during the first 90 days of treatment without intergroup differences but declined to baseline thereafter. BMD increased significantly both in the hip (+1·1 ± 0·3%) and spine (+2·2 ± 0·5%) only in the T gel 100 mg/day group (P = 0·0001).CONCLUSIONS Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long‐term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered.