bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spectrum of parathyroid gland dysfunction associated with the microdeletion 22q11
Authors: Hiéronimus Sylvie , Bec-Roche Magali , Pedeutour Florence , Lambert Jean Claude , Wagner-Malher Kathy , Mas Jean Christophe , Sadoul Jean Louis , Fénichel Patrick 
Published: June 2006

Objective: Clinical features associated with microdeletion of chromosome 22q11 (del(22)(q11)) are highly variable. Increased awareness of this condition is needed among specialists such as endocrinologists to reduce diagnostic delay and improve clinical care. The purpose of this study was to describe the phenotype of patients with del(22)(q11), focusing on parathyroid gland dysfunction.
Design and methods: Charts of 19 patients, including one kindred of three, known to have del(22)(q11) diagnosed by fluorescence in situ hybridization (FISH) were reviewed from the register of the department of Medical Genetics. Major clinical features including hypoparathyroidism phenotype were collected.
Results: Parathyroid dysfunction was present in 8 out of 16 patients (50%). Six patients were diagnosed with overt hypoparathyroidism. Hypocalcemia manifested as laryngeal stridor within the first days of life (n=3), seizures in infancy (n=1) and adolescence (n=2). The connection between hypoparathyroidism and diagnosis of del(22)(q11) was belated at the median age of 18 years. One patient had presented with transient neonatal hypoparathyroidism, and one patient had latent hypoparathyroidism. Within the kindred family, the phenotype variability including that of parathyroid dysfunction was as marked as between unrelated individuals. Standard karyotype failed to detect the deletion in 15 out of 19 cases.
Conclusions: Abnormal parathyroid function in the del(22)(q11) ranges from severe neonatal hypocalcemia to latent hypoparathyroidism. Del(22)(q11) should be considered as a potential cause of hypocalcemia even in young adult. When suspected, the diagnosis requires investigation by FISH. Furthermore, long-term calcemia follow-up is needed in normocalcemic patients with del(22)(q11) because of the possible evolution to hypocalcemic hypoparathyroidism.
The reduction of bone mineral density in postmenopausal women with primary hyperparathyroidism is higher in the presence of concomitant GH secretion impairment
Authors: Cecconi Elisabetta , Gasperi Maurizio , Genovesi Maura , Bogazzi Fausto , Grasso Lucia , Cetani Filomena , Procopio Massimo , Marcocci Claudio , Bartalena Luigi , Martino Enio 
Published: June 2006

Objective: To investigate, in a large group of postmenopausal primary hyperparathyroidism (PHP) women, whether the concomitance of GH deficiency (GHD) may contribute to the development of changes in bone mineral density (BMD).
Design: GH secretion, bone status and metabolism were investigated in 50 postmenopausal women with PHP and in a control group of 60 women with no evidence of PHP, matched for age, age at menopause and body mass index (BMI).
Methods: GH response to growth hormone-releasing hormone (GHRH)+arginine (Arg), femoral neck BMD (g/cm2) by dual energy X-ray absorptiometry, BMI, serum-ionized calcium, parathyroid hormone (PTH) and markers of bone remodelling were evaluated in all patients and controls.
Results: Among PHP patients, GH secretion was reduced (8.8 ± 4.2 μg/l, range 1.1–16.5 μg/l) in 34 patients and normal (28.7 ± 11.8 μg/l, range 17.9–55.7 μg/l) in the remaining 16 (P < 0.05), no women in the control group had GHD (peak GH 33.8 ± 10.9 μg/l, range 21.7 ± 63.2 μg/l). Osteoporosis (T-score < − 2.5) and osteopenia (T-score > −2.5 and < −1) were found in 73.5 and 17.6% of GHD patients, in 37.5 and 43.7% of patients with normal GH secretion and 3.1 and 27% of controls. T-score and BMD were not correlated with ionized calcium, age, age at menopause, BMI, GH peak and IGF-I but were correlated with serum PTH levels in both groups. T-score was correlated with serum levels of markers of bone remodelling only in PHP patients with GHD.
Conclusions: Concomitant impairment of GH secretion may play a pathogenetic role in the occurrence of changes in bone mass observed in PHP and contribute to make them more severe.
GH secretory pattern in young adults who discontinued GH treatment for GH deficiency and decreased longitudinal growth in childhood
Authors: Svensson Johan , Johannsson Gudmundur , Iranmanesh Ali , Albertsson-Wikland Kerstin , Veldhuis Johannes D , Bengtsson Bengt-Åke 
Published: June 2006

Objective: Some adolescents who discontinue GH treatment due to GH deficiency (GHD) and short stature in childhood do not have classical GHD at retesting in adult life. It is unknown whether there is a neuroendocrine disturbance in the spontaneous pattern of GH release in these patients.
Design/patients/methods: Thirty-seven adolescents, who had received treatment with GH due to impaired longitudinal growth, were included. The adolescents were divided into two groups; one (GHD; n = 19) with classical GHD in adult life and another (GH sufficient (GHS); n = 18) without classical adult GHD. One year after GH discontinuation, 24-h GH profiles were performed with blood sampling every 30 min. Sixteen matched healthy controls were also studied. All blood samples were analysed using an ultrasensitive GH assay and then, approximate entropy (ApEn) and deconvolution analysis were performed.
Results: The GHD group had higher mean ApEn level than the healthy controls (P < 0.05). As measured by deconvolution analysis, they had lower basal GH secretion (P < 0.01), increased number of GH peaks (P < 0.001), but lower burst mass (P < 0.001), lower percentage pulsatile GH secretion (P < 0.001) and lower total GH secretion (P < 0.001), compared with control subjects. Adolescents in the GHS group had a pattern of 24-h GH release similar to that in healthy controls.
Conclusion: Young adults with childhood-onset severe GHD have a high-frequency, low-amplitude GH secretion with decreased orderliness. The adolescents without classical GHD in adult life maintain a pattern of spontaneous GH release that is not statistically different from that in the healthy controls.
Primary hypophysitis: clinical-pathological correlations
Authors: Gutenberg Angelika , Hans Volkmar , Puchner Maximilian J A , Kreutzer Jürgen , Brück Wolfgang , Caturegli Patrizio , Buchfelder Michael 
Published: June 2006

Objective: Primary hypophysitis comprises of three distinct histomorphological entities: lymphocytic, granulomatous and xanthomatous. Clinical features of the three subtypes for diagnostic and treatment strategies have yet not been well characterized.
Methods: Endocrine function, visual fields and acuity as well as magnetic resonance imaging characteristics were assessed before and after transphenoidal surgery in the largest series of 31 patients with primary hypophysitis (21 lymphocytic, 6 granulomatous, and 4 xanthomatous cases).
Results: Only lymphocytic hypophysitis occurred during pregnancy (30%) and was associated with other autoimmune diseases (24%). Visual fields and acuity abnormalities were not seen in xanthomatous hypophysitis. Lymphocytic and granulomatous hypophysitis most often resulted in severe dysfunction of the adrenal, gonadal and thyroidal axes as well as diabetes insipidus. For patients presenting with xanthomatous hypophysitis most often, mild anterior pituitary axis failure was documented and posterior pituitary involvement was hardly found. The outcome after transphenoidal biopsy was generally favorable. Pre- or postsurgical glucocorticoid treatment was very effective in 75% of the lymphocytic form in reducing the pituitary size. In contrast, glucocorticoid therapy was less effective in granulomatous or xanthomatous hypophysitis.
Conclusion: Diffuse destruction of the complete pituitary gland including the infundibulum has to be considered in lymphocytic and granulomatous hypophysitis, whereas in xanthomatous, a circumscribed anterior pituitary lesion leading to compression of the pituitary gland without alteration of the pituitary stalk and optic chiasm can be assumed.
Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms
Authors: Banerjee Indraneel , Trueman Julie A , Hall Catherine M , Price David A , Patel Leena , Whatmore Andrew J , Hirschhorn Joel N , Read Andrew P , Palmert Mark R , Clayton Peter E 
Published: June 2006

Objectives: Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress, often with dominant inheritance. It is likely that one or more genes will be associated with CDGP. Possible candidates are the leptin (L) and the leptin receptor (LR) genes, as the leptin axis links nutritional status to pubertal development. This study has assessed whether a) L or LR gene polymorphisms were associated with CDGP and b) the CDGP phenotype was influenced by these polymorphisms.
Design: Case–control and transmission disequilibrium tests were used to test genetic association of L and LR polymorphisms with CDGP.
Methods: We genotyped L (3′CTTT repeat) and LR polymorphisms (Gln>Arg substitution, exon 6) in 81 CDGP children and 94 controls in the UK and 88 CDGP children from the US and assessed the effect of genotype on their anthropometric characteristics.
Results: There was no association of these L or LR gene polymorphisms with CDGP. There was no difference in height or bone age delay within L or LR genotypes. However, UK CDGP children homozygous for the L short allele were heavier than heterozygotes and long allele homozygotes, with a similar trend in the US cohort. UK CDGP children with severe pubertal delay, who were thin, had significantly greater bone age delay and an increased frequency of parental pubertal delay than other groups and were less likely to be L short allele homozygotes.
Conclusions: There was no association of specific L or LR polymorphisms with CDGP, but L short allele carriage influenced the phenotype within CDGP.
Oxidised low-density lipoprotein concentration – early marker of an altered lipid metabolism in young women with PCOS
Authors: Macut Djuro , Damjanović Svetozar , Panidis Dimitrios , Spanos Nikolaos , Glišić Biljana , Petakov Milan , Rousso David , Kourtis Anargyros , Bjekić Jelica , Milić Nataša 
Published: June 2006

Objective: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk for cardiovascular diseases. This study examined the variations in oxidised low-density lipoprotein (OxLDL) concentration in relation to insulin levels in young women with PCOS.
Design: Cross-sectional clinical study in tertiary cares research hospitals. A total of 179 women with PCOS (79 overweight) and 56 age- and body mass index-matched controls were examined.
Methods: Blood samples were collected in follicular phase of the cycle for the basal glucose, total-, high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol, OxLDL, triglycerides, apolipoprotein–A1 (Apo-A1) and B (Apo-B), lipoprotein (a), insulin, testosterone and sex hormone-binding globulin (SHBG). Homeostatic model index (HOMA) and free androgen index (FAI) were determined.
Results: Overweight and normal weight women with PCOS had higher concentrations of OxLDL than their control counterparts (P=0.007 and 0.003 respectively). Both the basal insulin (P=0.003) and HOMA values (P<0.001) were significantly higher in overweight than normal weight patients. Testosterone and FAI were higher in patients than in the respective controls (P<0.001). The only independent predictor of increased OxLDL concentration in normal weight patients was Apo-B-to-Apo-A1 ratio (P<0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 2.3–16.4), while in obese PCOS, it was total cholesterol-to-high-density lipoprotein cholesterol ratio (P<0.001, OR 2.8; 95% CI 1.6–4.9).
Conclusion: Young normal weight and overweight PCOS women have similarly increased OxLDL levels. Our results may indicate the presence of primary alteration in lipid metabolism in patients with PCOS. To answer the question whether the alteration in LDL particle size can by itself pose a higher cardiovascular risk, a careful follow-up of these women is needed.
A gene-to-gene interaction between aromatase and estrogen receptors influences bone mineral density
Authors: Riancho José A , Zarrabeitia María T , Valero Carmen , Sañudo Carolina , Mijares Verónica , González-Macías Jesús 
Published: June 2006

Objective: The aromatization of androgenic precursors is the main source of estrogens in postmenopausal women. We tested the hypothesis that allelic variants of the genes coding for aromatase and estrogen receptors (ER) could interact to determine the estrogenic signals on the bone tissue and, consequently, bone mineral density (BMD).
Design: Cross-sectional study including 331 postmenopausal women.
Methods: BMD was measured by dual energy x-ray absorptiometry. A CG polymorphism of the aromatase gene as well as three polymorphisms of ERα (a TA repeat in the promoter region, a C T single nucleotide polymorphism (SNP) in intron 1 and an AG SNP in exon 8) and a CA repeat polymorphism of ERβ were studied.
Results: Age, body weight and the aromatase genotype were associated with BMD. Allelic variants of ERβ and the exon 8 of ERα did not show a significant association with BMD. The polymorphisms located on the promoter and intron 1 of ERα interacted strongly with aromatase. Thus, in women TT homozygous for the ERα gene, there was a marked influence of aromatase genotypes on BMD: spine BMD was 0.724±0.027 g/cm2 in women with CC aromatase alleles and 0.926±0.032 g/cm2 in those with GG alleles (P<0.001). Hip BMD in women with CC and GG aromatase genotypes was 0.722±0.020 and 0.842±0.026 g/cm2 respectively (P=0.002). On the contrary, there were no aromatase-related differences in BMD in women with CT/CC alleles of ERα. Similarly, aromatase-related differences in BMD were found in women with short alleles at the promoter region of ERα, but not in those with long alleles. Both ERα polymorphisms were in strong linkage disequilibrium (P<0.001).
Conclusion: These results suggest that the interaction between polymorphisms of genes involved in estrogen synthesis and estrogen signaling exerts an important influence on BMD in postmenopausal women, thus helping to explain, in part, its heritable component. Nevertheless, further studies are warranted to confirm this gene-to-gene interaction in other populations.
Perchlorate versus other environmental sodium/iodide symporter inhibitors: potential thyroid-related health effects
Authors: De Groef Bert , Decallonne Brigitte R , Van der Geyten Serge , Darras Veerle M , Bouillon Roger 
Published: June 2006

Objective: Perchlorate is a known competitive inhibitor of the sodium/iodide symporter (NIS). Possible thyroid-related effects of environmental perchlorate have created great health concerns, especially in the US, resulting in a debated reference dose (RfD) of 0.0007 mg/kg per day in drinking water recommended by the National Academy of Sciences (NAS). However, the impact of other environmental NIS inhibitors and the role of iodine seem to have received little attention in the whole debate.
Methods: We performed a PubMed search for articles published up to February 2006, using the key terms perchlorate, nitrate, thiocyanate, iodine, NIS, RfD, thyroid (alone or in combinations), with particular attention for human studies. In parallel, we critically analysed the January 2005 NAS’ report, entitled ‘Health implications of perchlorate ingestion’.
Results: The relative potencies of prevalent environmental NIS inhibitors (nitrate, thiocyanate and perchlorate) to inhibit iodine uptake have been estimated repeatedly with robust results. Our calculations show that nitrate and thiocyanate, acquired through drinking water or food, account for a much larger proportion of iodine uptake inhibition than perchlorate. Furthermore, the iodine uptake inhibitory effects of nitrate and thiocyanate – as defined by their legally accepted maximal contaminant levels in drinking water – exceed the potential effect of the proposed RfD for perchlorate by far.
Conclusions: Iodine uptake inhibition and any potential downstream effect by perchlorate are highly dependent on the presence of other environmental NIS inhibitors and iodine intake itself. These potential confounders should therefore be considered in future studies and calculations for risk assessment.
Incidence of GH deficiency – a nationwide study
Authors: Stochholm Kirstine , Gravholt Claus H , Laursen Torben , Jørgensen Jens O , Laurberg Peter , Andersen Marianne , Kristensen Lars Ø , Feldt-Rasmussen Ulla , Christiansen Jens S , Frydenberg Morten , Green Anders 
Published: June 2006

Objective: Data on incidence rates are scarce in GH deficiency (GHD). Here, we estimate the incidence rate in childhood onset (CO) and adult onset (AO) GHD in Denmark.
Design: We used three national registries to identify 9131 cases with an increased risk of GHD. Date of entry was defined using the date when a registration had taken place and when a date of sufficient information could be defined from a thorough examination of a record of a GHD patient, which ever came last. We considered date of entry as the incident date.
Methods: Sex-specific incidence rates of GHD in children and adults using the background population as reference.
Results: During 1980–1999, 1823 patients were incident. Three-hundred and three males and 191 females had CO, 744 males and 585 females had AO GHD. The incidence rate over time was stable for females with AO GHD and increasing for the other three subgroups. Average incidence rate for CO males, 2.58 (95% confidence interval (CI), 2.30–2.88), CO females, 1.70 (95% CI, 1.48–1.96), AO males, 1.90 (95% CI, 1.77–2.04), and AO females, 1.42 (95% CI, 1.31–1.54) all per 100 000. The incidence rate was significantly higher in males compared to females in the CO GHD group (P < 0.001) and in the AO GHD group in the age ranges of 45–64 and 65+years (P < 0.001). There was no significant difference in the 18–44 years age group.
Conclusions: In conclusion, we have identified the incidence rates of GHD in a nationwide study of Denmark. In this population-based study, we have identified in CO GHD and in the two oldest age groups of AO GHD, a statistically significant higher incidence rate in males when compared with females.
Hypothalamic–pituitary–adrenal axis activity in adults who were prenatally exposed to the Dutch famine
Authors: de Rooij Susanne R , Painter Rebecca C , Phillips David I W , Osmond Clive , Michels Robert P J , Bossuyt Patrick M M , Bleker Otto P , Roseboom Tessa J 
Published: June 2006

Objective: The hypothalamic–pituitary–adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis.
Design and methods: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1–24-stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944–1945 Dutch famine.
Results: Cortisol profiles after dexamethasone suppression and ACTH1–24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P=0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference −2% (95% confidence interval (CI) −27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI −27 to 66)), cortisol increment (−5 nmol/l (95% CI −56 to 47)) or cortisol area under the curve post-ACTH1–24 injection (4% (95% CI −4 to 12)) differed between exposed and unexposed participants.
Conclusions: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.
Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss
Authors: Kim M J , Maachi M , Debard C , Loizon E , Clément K , Bruckert E , Hainque B , Capeau J , Vidal H , Bastard J P 
Published: June 2006

Objective: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)γ2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss.
Methods: Twenty-three non-diabetic obese subjects with normal (NGT, n=11) or impaired glucose tolerance (IGT, n=12) (age, 47±3 years; body mass index, 39.3±1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue.
Results: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P=0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARγ2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARγ2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin.
Conclusion: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.
Uses and Abuses of Tumor Markers in the Diagnosis, Monitoring, and Treatment of Primary and Metastatic Breast Cancer
Authors: Henry N. Lynn , Hayes Daniel F. 
Published: June 2006

Learning Objectives
After completing this course, the reader will be able to: Identify the difference between prognostic and predictive factors.Describe the evaluation of tumor markers, including their utility, magnitude, and reliability.Discuss issues surrounding tumor markers currently in routine use in breast cancer, including estrogen receptor, Her-2/neu, and Oncotype DX™.
Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com
Aromatase Inhibitors in Breast Cancer: An Overview
Authors: Altundag Kadri , Ibrahim Nuhad K. 
Published: June 2006

Learning Objectives
After completing this course, the reader will be able to: Discuss the published data on aromatase inhibitors in breast cancer.Describe the differences in study designs, clinical outcome, and safety data on aromatase inhibitors.Select the proper aromatase inhibitor based on a thorough understanding of the data that led to the specific indication for the drug.
Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com