bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D status in female patients with primary hyperparathyroidism: does it play a role in skeletal damage?
Authors: Carnevale Vincenzo , Manfredi Giuseppe , Romagnoli Elisabetta , De Geronimo Simona , Paglia Federica , Pepe Jessica , Scillitani Alfredo , D’Erasmo Emilio , Minisola Salvatore 
Published: December 2004

Summaryobjective  Vitamin D deficiency, even subclinical, has been considered to worsen the skeletal damage in primary hyperparathyroidism (PHPT). Our study aimed to investigate the impact of vitamin D status on skeletal involvement in PHPT.design and measurements  A cross‐sectional study was designed involving 62 female patients with PHPT. Serum total calcium (tCa), phosphate (P), creatinine (Cr) and total alkaline phosphatase activity (AP), together with 24‐h (uCa 24 h) and spot fasting (uCa/Cr) urinary calcium, were measured by autoanalyser; ionized calcium (iCa) was assessed by an ion‐specific electrode; intact parathyroid hormone (PTH) was measured by immunoradiometric assay (IRMA) and 25‐hydroxyvitamin D (25‐OHD) by radioimmunoassay (RIA). Bone mineral density (BMD) was measured by dual energy X‐ray absorptiometry (DXA) at lumbar spine in 58 patients, and at femoral neck, Ward's triangle, greater trochanter, intertrochanteric line and total hip in 56 patients. The associations of all variables with age, 25‐OHD, body mass index (BMI) and PTH were studied by linear multiple regression analysis, using progressively restricted models.results  The model including age, 25‐OHD, PTH and BMI showed significant regression with BMD values. PTH, age and BMI exerted a leading role in determining such a significance, while no significant regression was found between the parameters studied and 25‐OHD; this was confirmed by Pearson's linear correlation analysis. The progressively restricted models showed significant regression of BMD at femoral neck, femoral intertrochanteric line and total hip with age, BMI and PTH. BMD measured at the Ward's triangle and greater trochanter showed significant regression with age and BMI, and that measured at lumbar spine with age.conclusions  Our data indicate that in primary hyperparathyroidism patients the influence of 25‐hydroxyvitamin D levels on bone mineral density, if any, was overwhelmed by the effects of parathyroid hormone excess, age and body mass index. The latter unequally affected bone mineral density of various measured sites with different composition.
Serum osteoprotegerin and receptor activator of nuclear factors kB (RANKL) concentrations in normal children and in children with pubertal precocity, Turner's syndrome and rheumatoid arthritis
Authors: Buzi F. , Maccarinelli G. , Guaragni B. , Ruggeri F. , Radetti G. , Meini A. , Mazzolari E. , Cocchi D. 
Published: December 2004

Summarybackground  Osteoprotegerin (OPG) is a secreted member of the TNF receptor superfamily. OPG is made by osteoblastic cells and is expressed in a wide variety of cell and tissue types. It acts as a decoy receptor by binding the receptor activator of nuclear factors kB (RANKL) and preventing RANKL‐induced osteoclast formation and differentiation. Numerous cytokines and hormones (TGF‐β, PTH, vitamin D, glucocorticoids and oestrogens) exert their effects on osteoclastogenesis by regulating the production of OPG.patients and methods  In the present study we compared serum OPG and RANKL concentrations in a group of normal children (1–14 years old) with those of pair‐aged children affected by different diseases [Turner's syndrome (TS), early/precocious puberty (PP) and rheumatoid arthritis (RA)]. OPG and RANKL concentrations were measured by an enzyme immunoassay method using a commercial kit.results  Mean (± SD) OPG level in normal children was 4·05 ± 1·63 pmol/l with no difference between males and females. OPG values in children 1–4 years old (5·87 ± 2·22 pmol/l) were significantly higher than in children 4–14 years old (3·55 ± 0·97 pmol/l). OPG levels in children with RA were significantly higher than in controls (6·33 ± 2·57 pmol/l vs. 4·05 ± 1·63 pmol/l, P < 0·01); patients with TS or PP had OPG levels superimposable to those of controls (2·61 ± 0·67 pmol/l and 3·99 ± 0·85 pmol/l, respectively), but in TS OPG levels were significantly lower than in age‐matched females. Mean RANKL concentration in normal subjects was 0·81 ± 1·55 pmol/l; there was a slight decline in RANKL levels with age. RANKL concentrations in subjects with TS, PP, RA and controls did not differ significantly, and did not differ from those published in adult normal subjects.conclusions  It appears from our data that OPG serum levels in healthy children aged > 4 years are similar to those present in young adult men, with higher levels in the first 4 years of life. Although the meaning of the alterations of OPG levels observed in pathological conditions is still obscure, they appear potentially interesting in view of a key role played by this protein in bone homeostasis.
The effectiveness of different treatment options for non‐islet cell tumour hypoglycaemia
Authors: Teale J. D. , Wark G. 
Published: December 2004

Summaryobjective  To compare the outcome of different treatment options used in several cases of non‐islet cell tumour hypoglycaemia (NICTH).patients  Eight cases of NICTH were referred for diagnosis and monitoring following either surgical or medical treatment.methods  Serum samples collected throughout the time‐course of each case were analysed for glucose, insulin, C‐peptide, IGF‐I, total IGF‐II, total IGF‐II to IGF‐I ratio and, in most of the cases, big IGF‐II.results  Surgical excision was successful in the relief of symptoms and normalization of the biochemical parameters. Therapeutic treatment with glucocorticoids confirmed previous studies showing the suppressive effect on tumour (big) IGF‐II production. The present data show that the effect was dose‐dependent and reversible if doses were below a critical level.conclusions  Within the limits of the cases studied, and the time‐scales involved, moderate‐ to high‐dose glucocorticoid therapy had immediate beneficial influence on symptomatic hypoglycaemia and, if tolerated in the long term, was effective in correcting the underlying biochemical dysfunction, unlike other therapeutic regimens. This effectiveness was only achieved when the dose exceeded a threshold level specific to the patient. In addition, reduction of the dose or withdrawal of the drug caused a return of the abnormal biochemical profile. Surgical removal of the malignancy, where this was an option, was successful within the periods studied.
Internal jugular vein sampling in adrenocorticotropic hormone‐dependent Cushing's syndrome: a comparison with inferior petrosal sinus sampling
Authors: Erickson Dana , Huston John , Young William F. , Carpenter Paul C. , Wermers Robert A. , Bonelli Frank S. , Powell Claudia C. 
Published: December 2004

Summaryobjective  Distinguishing between pituitary‐dependent Cushing's syndrome (CS) and occult ectopic ACTH syndrome can be extremely difficult. Bilateral inferior petrosal sinus sampling has been shown to have the highest diagnostic accuracy in this subtype evaluation. Internal jugular vein sampling (IJVS) has been reported as a potentially safer invasive alternative, but data are limited. Our objective was to compare the sensitivity and specificity of bilateral IJVS and bilateral inferior petrosal sinus sampling (IPSS) in patients with ACTH‐dependent CS.design  We prospectively collected blood samples from the inferior petrosal sinus and internal jugular vein of consecutive patients with ACTH‐dependent CS.patients  The study group included 35 patients: 32 with pituitary‐dependent CS (positive immunohistochemical findings for ACTH pituitary tumour or biochemical cure after pituitary surgery) and three with histologically proven ectopic ACTH syndrome.measurements  Inferior petrosal sinus sampling and bilateral IJVS were performed simultaneously before and after administration of corticotropin‐releasing hormone (CRH), and ratios of central‐to‐peripheral ACTH concentrations were calculated.results  The basal IJVS central‐to‐peripheral ACTH ratios were diagnostic for pituitary‐dependent CS (> 2) in 15 patients (46·9%), as were basal inferior petrosal sinus sampling central‐to‐peripheral ACTH ratios in 29 patients (90·6%). The post‐CRH IJVS central‐to‐peripheral ACTH ratios were diagnostic for pituitary‐dependent disease (> 3) in 24 patients (75%), as were post‐CRH inferior petrosal sinus sampling central‐to‐peripheral ACTH ratios in 28 patients (87·5%). In the three patients with ectopic ACTH CS, the IJVS and inferior petrosal sinus sampling pre‐ and post‐CRH ACTH ratios were correctly negative. The overall sensitivity of combined pre‐ or post‐CRH was 81·3% for IJVS and 93·8% for inferior petrosal sinus sampling. Because of the difference between mean ratios in the two techniques, new criteria for IJVS were mathematically calculated: a pre‐CRH central‐to‐peripheral ACTH ratio of 1·59 and a post‐CRH central‐to‐peripheral ACTH ratio of 2·47 maximized sensitivity and specificity when both of these are equally taken into consideration.conclusion  In conclusion, IJVS is not superior to inferior petrosal sinus sampling for establishing the cause of ACTH‐dependent CS. When new criteria of basal (> 1·6) and post‐CRH (> 2·5) central‐to‐peripheral ACTH gradients were applied to ACTH ratios from IJVS, the sensitivity of this test was maximized. However, confirmatory inferior petrosal sinus sampling is recommended when there is a lack of a central‐to‐peripheral ACTH gradient and when there is only a gradient above the cut‐off on basal (pre‐CRH) sampling.
Testosterone release rate and duration of action of testosterone pellet implants
Authors: Kelleher S. , Howe C. , Conway A. J. , Handelsman D. J. 
Published: December 2004

Summaryobjective Testosterone pellets are a highly effective subdermal depot administered at regular intervals with the timing individualized depending upon return of the patient's characteristic androgen deficiency symptoms. Yet thein vivotestosterone release rate and effective duration of action of these pellets has been little studied systematically.design Analysis of prospectively collected data from three randomized controlled clinical trials. Collection of extruded pellets.patients Androgen‐deficient men (n = 136) undergoing long‐term androgen replacement therapy with a standard dose (800 mg) of testosterone pellets implanted subdermally at intervals from 5 to 7 months.measurements Testosterone release rate of pellets, consisting of pure crystalline testosterone without excipients, is estimated by measuring the dry weight lost by pellets (n = 179) over their timein situ. The effective duration of the standard regimen, and the influence of extrusion and patient or procedural characteristics on it, was estimated by timing of return for re‐implantation due to recurrence of the patient's familiar androgen deficiency symptoms.results The loss of dry weight of intact (n = 112) pellets was strongly correlated with timein situ(r2 = 0·969) providing an estimate of daily testosterone release rate per 200 mg pellet of 1·34 ± 0·02 mg/pellet/day (95% CI 1·30–1·37 mg/day) for the first 3 months. After 756 implantations of the standard dose, men return for re‐implantation at 5·8 calendar months following no or only a single pellet extrusion, but the time to return was significantly shorter after multiple extrusions. No patient or procedural features influenced the timing of return. Among men with primary hypogonadism, increases in plasma LH and FSH were more sensitive than plasma total or free testosterone to changes in testosterone delivery following an extrusion.conclusion Testosterone pellet implants release testosterone at a steady rate of 1·3 mg/200 mg implant/day (95% CI). The duration of action is about 6 months in an uncomplicated cycle with timing of return shortened by extrusions only in the 3·6% of procedures followed by multiple extrusions. No other patient or procedural features influenced duration of action. Among men with an intact hypothalamo‐pituitary unit, plasma gonadotropins are more sensitive than blood total or free testosterone to reduced testosterone delivery following an extrusion.
Dehydroepiandrosterone supplementation in women with adrenal failure: impact on twenty‐four hour GH secretion and IGF‐related parameters
Authors: Christiansen Jens Juel , Gravholt Claus Højbjerg , Fisker Sanne , Svenstrup Birgit , Bennett Paul , Veldhuis Johannes , Andersen Marianne , Christiansen Jens S. , Jørgensen Jens O. L. 
Published: December 2004

Abstractobjective  In women, GH secretion is strongly influenced by oestrogen status, whereas the role of androgens is unclear. We, therefore, examined GH secretory dynamics during low vs. normalized androgen levels in women with adrenal failure.patients  Ten females with adrenal failure (AF), mean age of 42 years (range 22–54 years).design  The effects of 8 days of oral dehydroepiandrosterone (DHEA; 50 mg/day) were studied in a double‐blind placebo‐controlled, cross‐over design. A control group of healthy women was studied once without any treatment.measurements  Before and after each treatment period, blood was sampled for measurement of androgens, IGF‐I, IGFBP‐3 and GHBP. A 24‐h GH profile with measurements every 20 min was performed at the end of each period.results  DHEA supplementation normalized the mean circulating levels of testosterone and androgen precursors. The secretory pattern of GH was unaltered during DHEA [placebo vs. DHEA; half‐life 22·83 ± 1·24 vs. 21·45 ± 1·19 (min), P = 0·429; pulse frequency 9·9 ± 0·7 vs. 10·5 ± 0·5 (/24 h), P = 0·502; total production rate 62·27 ± 13·44 vs. 52·61 ± 7·06 (µg/l/day), P = 0·317]. Subgroup analysis, however, indicated that DHEA treatment increased GH secretion in patients not receiving oestrogen (n = 5), whereas the opposite was observed among patients receiving exogenous oestrogen derivatives (n = 5). Compared to the control group (CON), GH half‐life was longer in AF (half‐life CON: 16·48 ± 0·91, P = 0·001). The additional features of GH secretion were similar. Unexpectedly, the levels of IGF‐I, IGFBP‐3 and GHBP were elevated in the patients as compared to controls, without significant effects of DHEA [AF vs. CON. IGF‐I: 186 ± 20 vs. 144 ± 7 (µg/l), P = 0·04; IGFBP‐3: 5196 ± 224 vs. 3687 ± 212 (µg/l), P = 0·001; GHBP: 2·27 ± 0·25 vs. 1·41 ± 0·13 (nmol/l), P = 0·002].conclusion  (1) Short‐term DHEA administration in women with adrenal failure normalizes the circulating levels of androgens without uniformly affecting the GH–IGF axis; (2) The observation that exogenous oestradiol may mask a stimulatory effect of DHEA on GH secretion merits future investigation.
Elevated leptin fragments in renal failure correlate with BMI and haematopoiesis and are normalized by haemodialysis
Authors: Stamatiadis Dimitrios N. , Chan Jean L. , Cogswell Rebecca , Stefanopoulou Helen C. , Bullen John , Katsilambros Nicholas , Stathakis Charalambos P. , Mantzoros Christos S. 
Published: December 2004

Summaryobjective  Leptin is an adipocyte hormone important in appetite, energy homeostasis, neuroendocrine and haematopoietic function. Patients with renal failure often have elevated total and free leptin levels. Biologically active leptin fragments (leptin22−56 and leptin57−92) have been identified, but whether these fragments are affected by renal failure and/or haemodialysis (HD) is not known.research methods  Leptin, leptin22−56 and leptin57−92 levels were measured in 28 HD patients [14 men, 14 women, age 45·5 ± 16·4 years, body mass index (BMI) 23·8 ± 3·6 kg/m2] and 25 healthy controls with similar age and BMI. In 18 HD patients, leptin and fragment levels were measured before and after 2 consecutive dialysis treatments and on the intermediate, dialysis‐free day.results  Baseline leptin levels were higher in HD patients vs. controls (69·3 ± 62·2 ng/ml vs. 30·4 ± 32·7, P < 0·02) as were leptin22−56 (7·14 ± 7·04 ng/ml vs. 1·86 ± 1·84, P < 0·02) and leptin57−92 (5·94 ± 6·08 ng/ml vs. 1·58 ± 1·98, P < 0·02). Baseline leptin and fragment levels correlated significantly and independently with BMI in HD patients (r = 0·70, r = 0·59, r = 0·72, respectively, P < 0·001). After each HD session, leptin levels were reduced to levels not different from controls, but increased on the intermediate, dialysis‐free day. Similar to and independently from total leptin, both leptin fragments were reduced after the first HD session to levels not different from controls. The reduction in leptin levels was higher with synthetic vs. cellulosic membrane types (37·7 ± 23·5%vs. 18·1 ± 21·8%, P < 0·03). Leptin correlated weakly with the erythropoietin to haematocrit ratio (T = −0·20, P = 0·14), while leptin22−56 had a significant negative correlation with this index (T = −0·42, P < 0·01), suggesting that this fragment may favour haematopoiesis.discussion  Leptin fragments are detected in human serum, and both leptin and leptin fragments correlate with BMI, are significantly elevated in HD patients compared to controls, and are significantly decreased by haemodialysis. The elevated leptin fragments may have important physiological significance for the anorexia, hypogonadism, and anaemia commonly seen in HD patients, but this remains to be conclusively shown by interventional trials.
Sources of glucose variability in insulin‐treated type 2 diabetes: the Diabetes Outcomes in Veterans Study (DOVES)
Authors: Murata Glen H. , Duckworth William C. , Shah Jayendra H. , Wendel Christopher S. , Hoffman Richard M. 
Published: December 2004

Summaryobjective  Glucose variability can be a significant barrier to glycaemic control for diabetic patients on insulin. The study identified clinical and behavioural factors associated with glucose variability in type 2 diabetes.design  Observational study.subjects  Randomly selected veterans with stable, insulin‐treated type 2 diabetes.measurements  Baseline data included demographics, clinical characteristics, diet, activity and haemoglobin A1c. Subjects self‐monitored blood glucose before all meals and at bedtime for 8 weeks. Monitoring data were used to derive an overall glucose mean and glucose coefficient of variation (100*SD/mean) for each subject. Univariate and multivariate analyses were used to evaluate the relationship between glucose coefficient of variation and clinical factors.results  Two‐hundred and four subjects completed the protocol. The 8‐week mean (± SD) glucose was 9·9 ± 2·2 mmol/l, and the average overall coefficient of variation was 35·6 ± 7·7%. Univariate analysis showed a higher variation in older subjects and in those with longer duration of insulin treatment, greater consumption of sugars and greater confidence in their self‐care abilities. Variation was lower in subjects who were obese, more compliant with medications and receiving larger insulin doses. Multivariate analysis showed that treatment duration, sugar consumption, medication compliance and insulin dose were independently associated with glucose variation. Medication compliance was more influential for fasting variation, while body mass index was more influential for before lunch variation.conclusions  Numerous behavioural, clinical and treatment factors were independently associated with glucose variability. Reducing sugar consumption and improving medication compliance might offset the greater glucose fluctuation observed in lean patients with longstanding diabetes.
Variability in anterior pituitary size within members of a family with GH deficiency due to a new splice mutation in the GHRH receptor gene
Authors: Alba Maria , Hall Catherine M. , Whatmore Andrew J. , Clayton Peter E. , Price David A. , Salvatori Roberto 
Published: December 2004

Summaryobjective  Mutations in the GHRH receptor (GHRHR) gene (GHRHR) cause autosomal recessive isolated GH deficiency (IGHD), and are usually associated with anterior pituitary hypoplasia (APH) (defined as pituitary height more than 2 SDS below normal). We searched for GHRHR mutations and studied pituitary morphology in three prepubertal sibs with severe IGHD, who were born from consanguineous parents.design  We sequenced the 13 exons and the intron–exon boundaries of the GHRHR of the index patient. After identifying a novel mutation, we sequenced the same area in the other family members. In addition, we performed magnetic resonance imaging (MRI) study of the pituitary (at age 8, 4 and 3 years) in the three affected subjects.results  The three children were homozygous for a new GHRHR mutation that alters the second base of the invariant 5′ splice site (GT) of intron 12 [IVS12 + 2T→A]. The parents and an unaffected sibling were heterozygous for the same change. MRI did not show frank APH (by height criteria) in any of the subjects: pituitary height was normal (5·6 mm, +1·8 SDS) in the oldest sibling, and it was low but not below 2 SDS by age‐adjusted criteria in the second (3 mm, −1·4 SDS), and third sibling (2·8 mm, −1·7 SDS). Calculated pituitary volume was below −2 SDS in the youngest patient.conclusions  These data demonstrate that pituitary height may fall within 2 SDS from the norm in patients with severe IGHD due to a homozygous GHRHR mutation, and that pituitary size may vary within patients with identical mutations who belong to the same family.
First trimester levels of inhibins and activin A in normal and failing pregnancies
Authors: Wallace Euan M. , Marjono Budi , Tyzack Katrina , Tong Stephen 
Published: December 2004

Summaryobjective  Miscarriage is the commonest complication of human pregnancy. We undertook this study to assess whether inhibin A, pro‐αC inhibin and/or activin A, products of the corpus luteum and placenta, might be useful in either the prediction or diagnosis of miscarriage.design  Case–control study.patients  Ninety‐eight asymptomatic women at 6–13 weeks gestation who subsequently had a miscarriage and 198 gestation‐matched women with a normal singleton pregnancy.measurements  Maternal serum levels of inhibin A, pro‐αC inhibin, activin A and human chorionic gonadotrophin (hCG) were measured.results  Inhibin A, pro‐αC and hCG, expressed as multiples of the normal median (MoM; ±95% confidence intervals) in the miscarriage cases were significantly lower than in the viable controls, 0·56 (0·48–0·69) MoM vs. 1·00 (0·98–1·13) MoM, 0·55 (0·51–0·84) MoM vs. 1·0 (0·86–1·22) MoM and 0·34 (0·23–0·36) MoM vs. 1·00 (0·94–1·08) MoM, respectively (P < 0·0001 for all). Of the three analytes, hCG was the most discriminating between cases and controls. Levels of activin A in the miscarriage cases were not significantly different from controls, 0·96 (0·86–1·07) vs. 1·0 (0·95–1·08).conclusions  These data suggest that inhibin A, pro‐αC inhibin and activin A will not be useful in either the prediction or diagnosis of early pregnancy miscarriage.