bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Feasibility of High Dose Iodine 131 Treatment as an Alternative to Surgery in Patients with a Very Large Goiter: Effect on Thyroid Function and Size and Pulmonary Function*
Authors: Bonnema Steen J. , Bertelsen Henrik , Mortensen Jesper , Andersen Peter B. , Knudsen Dorthe U. , Bastholt Lars , Hegedüs Laszlo 
Published: January 2014

Abstract
Some patients with very large goiters (&gt;150 mL) are not candidates for surgery. We evaluated the feasibility of high dose 131I in such patients. Twenty-three patients (2 men and 21 women; median age, 67 yr; range, 42–86 yr) with very large goiter (8 toxic) were treated with calculated high dose 131I [median, 2281 megabecquerels (61.6 mCi); range, 988-4620 megabecquerels (26.7–124.9 mCi)]. During the 12-month observation period, goiter reduction and tracheal anatomy were monitored by magnetic resonance imaging, and the respiratory capacity was monitored by pulmonary function tests.
Five patients (22%) developed hypothyroidism. Thyroid volumes were at baseline, after 1 week, and after 1 yr [mean ± sem, 311 ± 28, 314 ± 26 (P = NS), and 215 ± 26 (P &lt; 0.01) mL]. The relative changes 1 week after therapy ranged from −14.1% to 15.3%. After 1 yr the mean size was reduced by 33.9% (range, 13.5–61.4%). Only the initial goiter size showed a significant negative correlation to the percent reduction. The smallest cross-sectional area of the trachea decreased 9.2% within 1 week after treatment, but eventually emerged with a 17.9% larger area [mean ± sem, 84.3 ± 4.8, 75.5 ± 5.1 (P &lt; 0.01), and 98.2 ± 6.0 (P &lt; 0.01) mm2]. The inspiratory parameter, FIF50%, improved after an initial insignificant decline[ baseline therapy, after 1 week, after 3 months, and after 1 yr (mean ± sem), 2.37 ± 0.24, 2.20 ± 0.21 (P = NS), 2.51 ± 0.23 (P= NS), and 2.76 ± 0.25 (P = 0.01) L/s]. FIF50% correlated significantly with the smallest cross-sectional tracheal area (baseline, 1 week, and 1 yr: r = 0.74; P &lt; 0.001, r = 0.63; P &lt; 0.005, and r = 0.46; P &lt; 0.05). Changes in tracheal anatomy did not correlate with changes in either lung dynamics or goiter size. In conclusion, very large goiters can be reduced by a third, on the average, with high dose 131I therapy without any initial clinically significant tracheal compression. Tracheal cross-sectional area as well as pulmonary inspiratory capacity improve. No serious adverse effects are seen.
A Novel Mutation of the Signal Peptide of the Preproparathyroid Hormone Gene Associated with Autosomal Recessive Familial Isolated Hypoparathyroidism*
Authors: Sunthornthepvarakul Thongkum , Churesigaew Sunchai , Ngowngarmratana Supunnee 
Published: January 2014

AbstractWe report a novel mutation of the signal peptide of the prepro-PTH gene associated with autosomal recessive familial isolated hypoparathyroidism. The proposita presented with neonatal hypocalcemic seizures. Serum calcium was 1.5 mmol/L (normal, 2.0–2.5); phosphate was 3.6 mmol/L (normal, 0.9–1.5). She was born to consanguineous parents. A few years later, 2 younger sisters and her niece presented with neonatal hypocalcemic seizures. Their intact PTH levels were undetectable during severe hypocalcemia. Genomic DNA from the proposita was sequenced all exons of the prepro-PTH gene. A replacement of thymine with a cytosine was found in the first nucleotide of position 23 in the 25-amino acid signal peptide. This results in the replacement of the normal Ser (TCG) with a Pro (CCG). Genotyping of family members was carried out by identification of a new MspI site created by the mutation. Only affected family members were homozygous for the mutant allele, whereas the parents were heterozygous, supporting autosomal recessive inheritance. As this mutation is at the− 3 position in the signal peptide of the prepro-PTH gene, we hypothesized that the prepro-PTH mutant might not be cleaved by signal peptidase at the normal position, and it might be degraded in rough endoplasmic reticulum.
Skeletal Features and Growth Patterns in 14 Patients with Haploinsufficiency of SHOX: Implications for the Development of Turner Syndrome
Authors: Kosho Tomoki , Muroya Koji , Nagai Toshiro , Fujimoto Masatoshi , Yokoya Susumu , Sakamoto Hiromi , Hirano Takeki , Terasaki Hiroshi , Ohashi Hirofumi , Nishimura Gen , Sato Seiji , Matsuo Nobutake , Ogata Tsutomu 
Published: January 2014

We report on clinical features in 14 Japanese patients (4 males and 10 females) with partial monosomy of the short arm pseudoautosomal region involving SHOX (n = 11) or total monosomy of the pseudoautosomal region with no involvement of disease genes on the sex-differential regions (n = 3). Skeletal assessment showed that three patients had no discernible skeletal abnormalities, one patient exhibited short 4th metacarpals and borderline cubitus valgus, and the remaining 10 patients had Madelung deformity and/or mesomelia characteristic of Léri-Weill dyschondrosteosis (LWD), together with short 4th metacarpals and/or cubitus valgus. Skeletal lesions were more severe in females and became obvious with age. Growth evaluation revealed that patients without LWD grew along by the −2 sd growth curve before puberty and showed a normal or exaggerated pubertal growth spurt, whereas those with LWD grew along by the standard growth curves before puberty but exhibited an attenuated pubertal growth spurt and resultant short stature. Maturational assessment indicated a tendency of relatively early maturation in patients with LWD. There was no correlation between the clinical phenotype and the deletion size.
These findings suggest that haploinsufficiency of SHOX causes not only short stature but also Turner skeletal anomalies (such as short 4th metacarpals, cubitus valgus, and LWD) and that growth pattern is primarily dependent on the presence or absence of LWD. Because skeletal lesions have occurred in a female-dominant and age-influenced fashion, it is inferred that estrogens exert a maturational effect on skeletal tissues that are susceptible to premature fusion of growth plates because of haploinsufficiency of SHOX, facilitating the development of skeletal lesions.
Prevalence of Mild Apparent Mineralocorticoid Excess in Mennonites
Authors: Ugrasbul Figen , Wiens Timothy , Rubinstein Pablo , New Maria I. , Wilson Robert C. 
Published: January 2014

We have studied an unusual patient with mild low-renin hypertension due to a homozygous mutation in the HSD11B2 gene (PNAS 95:10200–10205, 1998). The patient came from an inbred Mennonite family, and though the mutation identified her as an AME patient, she had a normal birth weight and did not demonstrate the typical features of AME, such as hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. Biochemically, typical patients with AME have abnormal cortisol metabolites and an exceedingly diminished ability to convert [11-3H] cortisol to cortisone. In this patient with mild AME, the conversion of cortisol to cortisone was 58% compared to 0 to 6% in typical AME patients, while the normal conversion is 90 to 95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous mutation in codon 227 (P227L).
We studied this Mennonite population for the prevalence of the P227L mutation. Our hypothesis was that this mild form of AME would be prevalent in the somewhat inbred Mennonite population to which the patient belongs. Our proposed study was 1) to determine if there are other cases of this mild form of AME, and 2) to establish the heterozygote frequency of the mutation in the Mennonites. Results: We did not detect any additional cases of mild AME. We detected 15 carriers of the P227L mutation out of 445 Mennonites, resulting in a heterozygote frequency of 0.03. Conclusion: Since this is an inbred population, the chance of two heterozygotes marrying would be 0.001, which is 1 in 1000 people. This population is known to have large families and therefore the possibility of having an affected child is high. The population consists of 2000 members and we have discovered one affected patient. Thus, there might be one other patient in this population.
Endogenous Androgens and Carotid Intimal-Medial Thickness in Women
Authors: Bernini G.P. , Sgro’ M. , Moretti A. , Argenio G.F. , Barlascini C.O. , Cristofani R. , Salvetti A. 
Published: January 2014

The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and postmenopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P &lt; 0.03–0.0004) to several IMT measures. Higher tertiles of DHEA-S, A, and FTS corresponded to significantly lower measures of carotid thickness. DHEA-S, and all androgens were inversely related to age (P &lt; 0.03 or less), showing no unfavorable association with major cardiovascular risk factors. In contrast, serum DHEA-S was negatively associated with WHR (P &lt; 0.02), while A was negatively associated with body mass index (P &lt; 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P&lt; 0.05–0.001).
In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.
A Sexually Dimorphic Pattern of Growth Hormone Secretion in the Elderly
Authors: Hindmarsh P. C. , Dennison E. , Pincus S. M. , Cooper C. , Fall C. H. D. , Matthews D. R. , Pringle P. J. , Brook C. G. D. 
Published: January 2014

In rodents, the sexually dimorphic pattern of pulsatile GH secretion is an important determinant of growth, liver enzyme function and insulin-like growth factor I (IGF-I) expression. Whether this difference is present in humans at different ages is unclear. We studied GH secretory patterns in the elderly by constructing 24-h serum GH profiles in 45 male and 38 female (age, 59.4–73.0 yr) volunteers and related patterns to IGF-I, IGF-binding protein-3 (IGFBP-3), and GH-binding protein levels; body mass index; and waist/hip ratio.
Serum GH concentrations were measured in samples drawn at 20-min intervals and analyzed using a sensitive chemiluminescent assay (Nichols Institute Diagnostics: sensitivity, 0.036 mU/L). The 24-h serum GH profiles were analyzed using a concentration distribution method to determine GH peak and trough levels, spectral analysis, and assessment of serial irregularity by approximate entropy (ApEn).
There was a highly significant difference in mean 24-h serum GH concentrations in females compared to males (males, 0.88 mU/L; females, 1.31 mU/L; P = 0.009) as a result of significantly higher trough GH levels (males, 0.04 mU/L; females, 0.16 mU/L; P &lt; 0.001). Peak values were not significantly different. Serum IGF-I levels were significantly higher in males (males, 162.4 ng/mL; females, 87.8 ng/mL; P &lt; 0.001). Peak GH values were related to serum IGF-I levels (males: r = 0.39; P = 0.009; females: r = 0.5; P = 0.002), whereas trough GH levels were not. IGFBP-3 levels were similar and related to GH peaks only in males (r = 0.32; P = 0.03). GH was secreted with a dominant periodicity of 200 min in males and 280 min in females (P &lt; 0.025). The proportion of time taken up by regular oscillatory activity was less in females (females, 11.1%; males, 14.7%; P = 0.01). GH secretion assessed by ApEn was more disordered in females (males, 0.60; females, 0.81; P &lt; 0.001), and increasing disorder was associated with lower IGF-I levels. Body mass index was negatively related to GH in both sexes. In males, trough values were the major determinant (r = −0.31; P = 0.04), whereas in females, the peak value was the major determinant (r = −0.35; P = 0.04). Trough GH levels were inversely related in both sexes to waist/hip ratio (males: r = −0.40; P = 0.006; females: r = −0.44; P = 0.006) and to increasing secretory disorder (ApEn; r = −0.46; P &lt; 0.001). These data demonstrate a sexually dimorphic pattern of GH secretion in the elderly.
Androstenedione Does Not Stimulate Muscle Protein Anabolism in Young Healthy Men1
Authors: Rasmussen Blake B. , Volpi Elena , Gore Dennis C. , Wolfe Robert R. 
Published: January 2014

Androstenedione is the immediate precursor of testosterone. Androstenedione intake has been speculated to increase plasma testosterone levels and muscle anabolism. Thus, androstenedione supplements have become widely popular in the sport community to improve performance. This study was designed to determine whether 5 days of oral androstenedione (100 mg/day) supplementation increases skeletal muscle anabolism.
Six healthy young men were studied before the treatment period and after 5 days of oral androstenedione supplementation. Muscle protein turnover parameters were compared to those of a control group studied twice as well and receiving no treatment. We measured muscle protein kinetics using a three-compartment model involving infusion of l-[ring-2H5]phenylalanine, blood sampling from femoral artery and vein, and muscle biopsies. Plasma testosterone, androstenedione, LH, and estradiol concentrations were determined by RIA.
After ingestion of oral androstenedione, plasma testosterone and LH concentrations did not change from basal, whereas plasma androstenedione and estradiol concentrations were significantly increased (P &lt; 0.05). Compared to a control group, androstenedione did not affect muscle protein synthesis and breakdown, or phenylalanine net balance across the leg.
We conclude that oral androstenedione does not increase plasma testosterone concentrations and has no anabolic effect on muscle protein metabolism in young eugonadal men.
Preserved Forearm Endothelial Responses with Acute Exposure to Progesterone: A Randomized Cross-Over Trial of 17-β Estradiol, Progesterone, and 17-β Estradiol with Progesterone in Healthy Menopausal Women1
Authors: Mather Kieren J. , Norman Eric G. , Prior Jerilynn C. , Elliott Thomas G. 
Published: January 2014

Regularly menstruating women are relatively protected from cardiovascular disease. Epidemiological and endothelial function studies attribute this protection to estradiol (E2), but both progesterone (P) and E2 are normally present. A range of vascular effects of added progestins have been described, from neutral to detrimental, but the effects of P per se on endothelial function in humans have not been reported. We therefore investigated the acute effects of E2, P, and E2 combined with P, on endothelium-dependent and -independent forearm blood flow responses.
Using venous occlusion plethysmography, forearm blood flow (FBF) was measured during acute brachial artery infusions, achieving physiologic levels of 17-β-E2, P, and 17-β-E2 with P in healthy menopausal women with no cardiovascular disease risk factors. Vehicle or hormones were infused, in random order, on 4 days, 1 week apart. Flow responses were measured during coinfusions of hormone with the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside.
Twenty-seven healthy menopausal women were studied, and all had normal baseline endothelial responses. Small (∼15%), statistically nonsignificant increases in endothelium-dependent flow responses were seen after all acute hormone treatments. No impairment in response was seen with P alone or in combination with 17-β-E2.
In healthy menopausal women without cardiovascular disease risk factors and without baseline defects in endothelial function, acute exposure to physiologic levels of 17-β-E2, P, and 17-β-E2 with P produced equivalent endothelium-dependent responses. These data suggest that P does not have detrimental vascular effects in humans.
Binding of Human Thyrotropin Receptor Peptides to a Graves’ Disease-Predisposing Human Leukocyte Antigen Class II Molecule
Authors: Sawai Yoshikuni , DeGroot Leslie J. 
Published: January 2014

AbstractAbstractThere are many reports that Graves’ disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immuonodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds nonimmunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific HLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.
Missense Mutations in the Human Insulin Promoter Factor-1 Gene and Their Relation to Maturity-Onset Diabetes of the Young and Late-Onset Type 2 Diabetes Mellitus in Caucasians*
Authors: Hansen Lars , Urioste Sandra , Petersen Helle V. , Jensen Jan N. , Eiberg Hans , Barbetti Fabrizio , Serup Palle , Hansen Torben , Pedersen Oluf 
Published: January 2014

Abstract
Increasing evidence suggests that defects in genes encoding transcription factors that are expressed in the pancreatic β-cells may be important contributors to the genetic basis of type 2 diabetes mellitus. Maturity-onset diabetes of the young (MODY) now exists in five subtypes (MODY1–5), four of which are caused by mutations in transcription factors hepatocyte nuclear factor-4α (HNF-4α), HNF-1α, insulin promoter factor-1 (IPF-1), and HNF-1β (MODY1, -3, -4, and -5). Recent evidence from the British population even suggested that IPF-1 may be a predisposing gene for type 2 diabetes. Thus, highlighting the potential role of this transcription factor in the genetic basis of Danish and Italian MODY as well as in Danish patients with late-onset type 2 diabetes mellitus, we have examined the human IPF-1 gene for mutations by single strand conformation polymorphism and heteroduplex analysis in 200 Danish patients with late-onset type 2 diabetes and in 44 Danish and Italian MODY patients. In the patients with late-onset type 2 diabetes we identified a noncoding G insertion/deletion polymorphism at nucleotide −108, a silent G54G, and a rare missense D76N variant. Moreover, a Danish MODY patient was carrier of an A140T variant. Neither the D76N nor the A140T segregated with diabetes, and their transcriptional activation of the human insulin promoter expressed in vitro was indistinguishable from that of the wild type (115 ± 21% and 84 ± 12% vs. 100%). We conclude that variants in IPF-1 are not a common cause of MODY or late-onset type 2 diabetes in the Caucasian population, and that in terms of insulin transcription both the N76 and the T140 mutations are likely to represent functionally normal IPF-1 variants with no direct role in the pathogenesis of MODY or late-onset type 2 diabetes mellitus.
Contribution of Body Fatness and Adipose Tissue Distribution to the Age Variation in Plasma Steroid Hormone Concentrations in Men: The HERITAGE Family Study*
Authors: Couillard Charles , Gagnon Jacques , Bergeron Jean , Leon Arthur S. , Rao D. C. , Skinner James S. , Wilmore Jack H. , Després Jean-Pierre , Bouchard Claude 
Published: January 2014

Abstract
Obesity has been associated with alterations in plasma steroid hormone concentrations in men. Older men present an altered steroid hormone profile compared to younger individuals, and an increase in body fatness and changes in adipose tissue (AT) distribution are noted with advancing age. Thus, there is a need to examine the relative importance of increased body fatness and changes in AT distribution with advancing age to plasma steroid hormone and sex hormone-binding globulin levels in men. We, therefore, investigated the relationships among age, body fatness, AT distribution, and the plasma steroid hormone profile in a group of 217 Caucasian men (mean age ± sd, 36.2± 14.9 yr) who covered a wide age range (17–64 yr). Compared to young adult men, older men were characterized by increased adiposity (P &lt; 0.0001) expressed either as body mass index or total body fat mass assessed by underwater weighing. Differences in AT distribution were also noted with a preferential accumulation of abdominal fat as indicated by a larger waist girth (P &lt; 0.0001) and higher visceral AT accumulation (P &lt; 0.0001), measured by computed tomography, in older subjects. Age was associated with decreases (P &lt; 0.0001) in C19 adrenal steroid levels, namely reduced dehydroepiandrosterone (DHEA), DHEA fatty acid ester, DHEA sulfate, as well as androstenedione levels. Androgens, i.e. dihydrotestosterone and testosterone, were also affected by age, with lower levels of both steroids being found in older individuals (P &lt; 0.0005). When statistical adjustment for body fatness and AT distribution was performed, differences in C19 adrenal steroids between the age groups remained significant, whereas differences in androgens and sex hormone-binding globulin concentrations were no longer significant. The present study suggests that age-related differences in plasma steroid hormone levels, especially androgens, are partly mediated by concomitant variation in adiposity in men.