bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards Safer Treatments for Benign Anorectal Disease: The Pharmacological Manipulation of the Internal Anal Sphincter
Authors: Jones Oliver M 
Published: August 2007

INTRODUCTION The internal anal sphincter (IAS) is an important structure that is responsible for the majority of resting tone of the sphincter complex. It has a central role in continence and damage to the muscle has serious implications. Injury is most frequently from obstetric trauma though iatrogenic injury from proctological surgery is also common. This review expands on how developments in understanding of the pharmacology of IAS might identify drug treatments as alternatives for proctological conditions such as anal fissure, avoiding the risk of sphincter injury. It also examines the role of pharmacology in treatment of those patients with established incontinence. RESULTS Much of the basic physiology and pharmacology of the IAS has been established through in vitro analysis, particularly in the superfusion organ bath. Further analysis has been undertaken using animal models such the pig. Clinical trials have established the efficacy of a number of agents for reducing IAS tone including glyceryl trinitrate and botulinum toxin. These drugs are probably safer, but less effective, than surgery for sphincter spasm, as is seen in anal fissure, though surgery alone or in combination with drug treatment may be appropriate for some patients. In vitro analysis and small-scale clinical trials suggest that phenylephrine and methoxamine may have a role in treating patients with incontinence primarily attributable to inadequate IAS function. CONCLUSIONS The pharmacology of IAS has been extensively studied in the laboratory, both in vitro and in animal models. In a short time, this laboratory work has been applied to clinical problems after testing in clinical trials. It is likely, however, that the best drugs and the optimal targets for manipulation have not yet been identified.
Parenting empathy: Associations with dimensions of parent and child psychopathology
Authors: Psychogiou Lamprini , Daley Dave , Thompson Margaret J. , Sonuga‐Barke Edmund J. S. 
Published: August 2007

Background. Parenting empathy, the understanding by parents, and the sharing in their child's perspective, represents an important element of competent parenting. The present study tested the hypotheses that maternal empathy might be lower where mothers or their children display symptoms of psychopathology.Method. Mothers (N = 268) of school‐aged children completed questionnaires on child‐directed empathy and egoistic personal distress and their own and their child's symptoms of psychopathology across a number of broadly defined domains.Results. Child conduct problems were associated with decreased child‐directed empathy and increased maternal egoistic distress. Maternal aggressive characteristics and maternal ADHD symptoms were each associated with increased egoistic personal distress.Conclusion. The findings indicate that symptoms of psychopathology in children and adults are associated with deficits in empathy and increased maternal egoistic personal distress. The implications of the findings for responsive parenting and child social behaviour are discussed.
Radiation Embrittlement of Cr–Ni–Mo and Cr–Mo RPV Steels
Authors: Nikolaev Yu. A. 
Published: August 2007

Abstract
Radiation embrittlement kinetics of Cr–Mo and Cr–Ni–Mo steels, used for manufacturing VVER-440 and VVER-1000 RPV steels, respectively, are under consideration. Radiation embrittlement of VVER-440 and VVER-1000 RPV steels exposed to irradiation for 17–22 years is analyzed. Extremely high levels of thermal aging of VVER-1000 RPV steels at 320°C is pointed out. The neutron flux effect problem and the problem of accelerated radiation embrittlement of welds with high nickel contents are emphasized. The effect of phosphorus, copper, silicon, manganese, and nickel contents on radiation embrittlement of VVER-440 and VVER-1000 RPV steels is studied using the Russian surveillance database and representative results of research programs. The trend curves for VVER-440 and VVER-1000 RPV steels are proposed. The mechanisms of radiation embrittlement of Cr–Ni–Mo and Cr–Mo RPV steels are supposed.
Evaluation of a standardized short-time calcium suppression test in healthy subjects: interest for the diagnosis of primary hyperparathyroidism
Authors: Titon Isabelle , Cailleux-Bounacer Anne , Basuyau Jean Pierre , Lefebvre Hervé , Savouré Adeline , Kuhn Jean Marc 
Published: August 2007

Objective: The diagnosis of primary hyperparathyroidism (PHP) can be difficult in patients with normal plasma calcium or parathyroid hormone (PTH) levels. We perfected a standardized short-time i.v. calcium loading test in healthy controls (HC) and compared the results with those of patients with PHP.
Methods: Sixteen HC received 0.33 mmol/kg calcium gluconate intravenously for 3 h. Plasma calcium and serum PTH levels (assayed with immunoluminescent sandwich methods) were measured before, at the end of the infusion and 3 h later. Results were compared with those of 16 PHP patients.
Results: In HC, basal total plasma calcium (mean ± s.e.m.) was 2.33 ± 0.02 mmol/l. At the end of calcium loading, calcemia reached 3.21 ± 0.05 mmol/l and decreased to 2.94 ± 0.08 mmol/l 3 h later. In PHP patients, basal plasma calcium was 2.54 ± 0.03 mmol/l and reached similar values as in HC during the testing. Basal serum PTH levels were 32.5 ± 3.3 ng/l in HC and 86.9 ± 6.3 ng/l in PHP. At the end of calcium loading, they dropped to 8.8 ± 0.6 ng/l (HC) and to 31.4 ± 4.2 ng/l (PHP). Three hours later, they were 11.6 ± 0.8 and 39.8 ± 4.0 ng/l respectively. There was a cut-off in serum PTH values between the two groups at the end of calcium loading and 3 h later.
Conclusion: The standardized short-time PTH suppression test appears reliable to differentiate healthy subjects from PHP whose serum PTH levels remain >14 and >23 ng/ml respectively at the end of loading and 3 h later. This well-tolerated and easily performed test could be used for the diagnosis of PHP in patients suspected for the disease despite the normality of some basal biological markers.
Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism
Authors: Tauchmanovà Libuse , Pivonello Rosario , De Martino Maria Cristina , Rusciano Andrea , De Leo Monica , Ruosi Carlo , Mainolfi Ciro , Lombardi Gaetano , Salvatore Marco , Colao Annamaria 
Published: August 2007

Objective: Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Nevertheless, limited data are available on bone status in patients with endogenous cortisol excess. This study is aimed at investigating the role of sex steroids and severity of hypercortisolism on bone mineral density (BMD) and prevalence of vertebral fractures in female patients.
Design: Cross-sectional, case–control study.
Patients: Seventy-one consecutive women were enrolled: 36 with overt hypercortisolism (26 with ACTH-secreting pituitary adenoma and 10 with cortisol-secreting adrenal tumor) and 35 with subclinical hypercortisolism due to adrenal incidentalomas. They were compared with 71 matched controls.
Methods: At diagnosis, we measured serum cortisol, FSH, LH, estradiol, testosterone, androstenedione and DHEAS, and urinary cortisol excretion. BMD was determined by dual energy X-ray absorptiometry at the lumbar spine and femoral neck. Vertebral fractures were investigated by a semiquantitative scoring method.
Results: Between women with overt and subclinical hypercortisolism BMD values and prevalence of any vertebral (69 vs 57%, P = 0.56), clinical (28 vs 11.4%, P = 0.22), and multiple vertebral fractures (36 vs 31%, P = 0.92) did not differ. Among patients with subclinical hypercortisolism, amenorrhoic women had a lower BMD (P = 0.035) and more frequent vertebral fractures (80 vs 40%; P = 0.043) when compared with the eumenorrhoic ones. Among women with overt hypercortisolism, there was no difference in lumbar BMD (P = 0.37) and prevalence of fractures (81 vs 60%; P = 0.26) between those amenorrhoic and eumenorrhoic. By logistic regression analysis, lumbar spine BMD values and cortisol-to-DHEAS ratio were the best predictors of vertebral fractures (P < 0.01).
Conclusions: Vertebral fractures are very common in women with endogenous cortisol excess, regardless of its severity. The deleterious effects of hypercortisolism on the spine may be partly counterbalanced by DHEAS increase at any degree of cortisol excess, and by preserved menstrual cycles in women with subclinical but not in those with overt hypercortisolism.
Maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) levels in post-term pregnancy: effect of prostaglandin administration
Authors: Florio P , Lowry P J , Benedetto C , Galleri L , Torricelli M , Giovannelli A , Battista R , Reis F M , Petraglia F 
Published: August 2007

Objective: Placental corticotropin-releasing factor (CRF) affects myometrial contractility and the secretion of several uterotonins such as prostaglandins (PGs); however, the activity of CRF is counteracted by CRF-binding protein (CRF-BP). At term and pre-term labor, CRF levels in maternal plasma are highest whereas those of CRF-BP are falling, and the cause of this fall is unknown. Thus, in this study, we investigated the effect of PG administration for labor induction on maternal plasma CRF and CRF-BP concentrations.
Design: Maternal plasma CRF and CRF-BP levels were assayed before and after (2 h later) induction of labor by intracervical administration of prostaglandin E2 (PGE2), and at delivery in a group of healthy post-term pregnancies (n=18). Controls were women at term out of labor (n=22), who subsequently progressed to deliver a healthy singleton baby.
Methods: CRF was measured by two-site immunoradiometric assay, and CRF-BP was assayed by radioimmunoassay.
Results: Maternal plasma CRF levels were significantly (P<0.0001) lower and CRF-BP significantly (P<0.0005) higher in post-term than in term pregnancies. With respect to induction of labor, 2 mg PGE2 were sufficient to increase maternal plasma CRF levels at delivery (P<0.005). While 0.5 mg PGE2 significantly decreased maternal plasma CRF-BP levels at delivery (P<0.001), 2.0 mg PGE2 significantly reduced CRF-BP concentrations both after 2 h (P<0.05) and at delivery (P<0.0001).
Conclusions: In the light of the well-known stimulation of prostaglandin release by CRF, these data suggest a positive feedback effect of PGE2 on maternal CRF release during induced labor.
Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys
Authors: Wiegand Susanna , Richardt Anna , Remer Thomas , Wudy Stefan A , Tomlinson Jeremy W , Hughes Beverly , Grüters Annette , Stewart Paul M , Strasburger Christian J , Quinkler Marcus 
Published: August 2007

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing’s syndrome. The 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1) regenerates active cortisol from inactive cortisone. Altered 11β-HSD1 may cause tissue-specific Cushing’s syndrome with central obesity and impaired glucose homeostasis.
Design, patients, and methods: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12–18 years, Tanner stages 2–5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic–mass spectrometric (GC–MS) analysis.
Results: 11β-HSD1 activity (urinary tetrahydrocortisol (THF) + 5α-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11β-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11β-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11β-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index.
Conclusions: In conclusion, our findings strongly suggest that 11β-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus–pituitary–adrenal axis.
Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and genotype–phenotype correlation
Authors: Vierimaa O , Ebeling T M L , Kytölä S , Bloigu R , Eloranta E , Salmi J , Korpi-Hyövälti E , Niskanen L , Orvola A , Elovaara E , Gynther A , Sane T , Välimäki M , Ignatius J , Leisti J , Salmela P I 
Published: August 2007

Objective: The existence of genotype–phenotype correlation in multiple endocrine neoplasia type 1 (MEN1) is controversial. Two founder mutations of the MEN1 gene in Northern Finland gave us an opportunity to compare clinical features among heterozygotes of different mutations.
Design and methods: Study cohort included 82 MEN1 heterozygotes who were tested for MEN1 during the years 1982–2001. Medical records were reviewed for manifestations of MEN1, other tumours and cause of death by the end of August 2003. Logistic regression analysis was used in evaluating the impact of age, gender and mutational status of affected heterozygotes on the likelihood of developing manifestations of MEN1.
Results: Founder mutations 1466del12 and 1657insC were found in 39 and 29 individuals, and D418N, G156R and R527X mutations in 9, 3 and 2 individuals respectively. Except for pituitary adenoma and nonfunctional pancreatic tumour (NFPT), age was a risk factor for all the disease manifestations. For NFPT, frameshift/nonsense mutations (1657insC, R527X) gave an odds ratio (OR) of 3.26 (95% confidence intervals (CI), 1.27–8.33; P = 0.014) compared with in-frame/missense mutations (1466del12, D418N, G156R); including the founder mutation carriers (n = 68) only, the 1657insC mutation gave an OR of 3.56 (CI, 1.29–9.83; P = 0.015). For gastrinoma, in-frame/missense mutations predicted the risk with an OR of 6.77 (CI, 1.31–35.0; P = 0.022), and in the founder mutations group the 1466del12 mutation gave an OR of 15.09 (CI, 1.73–131.9, P = 0.014).
Conclusions: In this study population, NFPT was more common in the frameshift/nonsense or 1657insC mutation carriers, whereas gastrinoma was more common in the in-frame/missense or 1466del12 mutation carriers.
Prevalence of testicular adrenal rest tumours in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Authors: Claahsen-van der Grinten Hedi L , Sweep Fred C G J , Blickman Johan G , Hermus Ad R M M , Otten Barto J 
Published: August 2007

Objective: Testicular adrenal rest tumours (TART) are a well-known complication in adult male patients with congenital adrenal hyperplasia (CAH), with a reported prevalence of up to 94%. In adulthood, the tumours are associated with gonadal dysfunction most probably due to longstanding obstruction of the seminiferous tubules. The aim of our study was to determine the presence of TART and their influence on gonadal function in childhood.
Design: Retrospective study.
Patients and methods: Scrotal ultrasound was performed in 34 children with CAH due to 21-hydroxylase deficiency who were between 2 and 18 years old. FSH, LH, testosterone and inhibin B concentrations were measured in serum of 27 patients.
Results: TART were detected by ultrasound in 8 out of 34 (24%) children. In two of them, bilateral tumours were found. All lesions were located in the rete testis. Seven patients had the salt-wasting type of CAH; one patient had the simple virilising type of CAH. Mean tumour size was 4.1 mm (range 2–8 mm). In none of the patients were the tumours palpable. Two children with TART were between 5 and 10 years old, the other six children were above 10 years old. In all children with TART, LH, FSH, testosterone and inhibin B levels were similar to the patients without TART.
Conclusion: TART can be found in CAH children before the age of 10 years. The absence of gonadal dysfunction in our group of children suggests that gonadal dysfunction as frequently reported in adult CAH patients with TART develops after childhood.
High phenotypic intrafamilial variability in patients with Pendred syndrome and a novel duplication in the SLC26A4 gene: clinical characterization and functional studies of the mutated SLC26A4 protein
Authors: Fugazzola Laura , Cirello Valentina , Dossena Silvia , Rodighiero Simona , Muzza Marina , Castorina Pierangela , Lalatta Faustina , Ambrosetti Umberto , Beck-Peccoz Paolo , Bottà Guido , Paulmichl Markus 
Published: August 2007

Objective: Pendred syndrome (PS) is characterized by the association of sensorineural hearing loss (SNHL) and a partial iodide organification defect at the thyroid level. It is caused by mutations in the SLC26A4 gene. The encoded transmembrane protein, called pendrin, has been found to be able to transport chloride and other anions.
Design: The aim of the present study was to characterize a family with PS, which shows a strong intrafamilial phenotypic variability, including kidney atrophy in one member. The age of disease-onset was significantly different in all three affected siblings, ranging from 2 to 21 years for thyroid alterations and from 1.5 to 11 years for SNHL.
Methods: Clinical and genetic studies were carried out in affected siblings. The functional activity of the novel duplication found was studied by a fluorimetric method in a human renal cell line (HEK293 Phoenix) in which the protein was overexpressed.
Results: All three siblings were found to be compound heterozygotes for the missense mutation (1226G>A, R409H) and for a novel 11 bp duplication (1561_1571CTTGGAATGGC, S523fsX548). The latter mutation creates a frame shift leading to the loss of the entire carboxy-terminus domain. Functional studies of this mutant demonstrated impaired transport of chloride and iodide when expressed in HEK 293 Phoenix cells, when compared with wild type pendrin.
Conclusions: A novel 11 bp duplication was found in a family with Pendred syndrome, showing a high intrafamilial phenotypic variability. An impaired transmembrane anionic transport of the mutated SLC26A4 protein was demonstrated in functional studies using a heterologous cell system.
Genetic variants in the leukemia-associated Rho guanine nucleotide exchange factor (ARHGEF12) gene are not associated with T2DM and related parameters in Caucasians (KORA study)
Authors: Holzapfel C , Klopp N , Grallert H , Huth C , Gieger C , Meisinger C , Strassburger K , Giani G , Wichmann H E , Laumen H , Hauner H , Herder C , Rathmann W , Illig T 
Published: August 2007

Objective: The aim of our study was to determine the variant pattern of the leukemia-associated Rho guanine nucleotide exchange factor (LARG, or ARHGEF12) gene and investigate whether LARG variants are associated with diabetes mellitus type 2 (T2DM), the metabolic syndrome (MetS), or related parameters such as insulin sensitivity in German Caucasians.
Design: We analyzed single nucleotide polymorphisms (SNPs) in the LARG gene in the 55–74-year-old individuals of the population-based German Caucasian Cooperative Health Research in the region of Augsberg (KORA) survey 4 (S4).
Methods: Sequencing of Tyr1306Cys, which was of functional relevance in Pima Indians, in 48 randomly selected individuals and genotyping of 11 additional LARG SNPs in 1653 subjects were performed. Four linkage disequilibrium (LD) blocks (r2≥0.8) were established and each block was statistically analyzed for association with metabolic traits. The association with T2DM and the MetS was analyzed by logistic regression in 1462 subjects, and HOMA-IR (homeostasis model assessment of insulin resistance) as a measure of insulin sensitivity was analyzed by the Kruskal–Wallis test in 1346 fasting subjects.
Results: The polymorphism Tyr1306Cys, which was significantly associated with insulin sensitivity in Pima Indians, was not found in the KORA S4 population. Statistical analysis yielded no significant associations (P>0.05) between the analyzed LARG variants and T2DM, the MetS, or related parameters such as insulin sensitivity.
Conclusions: Caucasian individuals and Pima Indians differ in their genetic variance pattern in the LARG gene region. There is no evidence in the Caucasian KORA study that variants of the LARG gene confer susceptibility for T2DM, insulin sensitivity, or the MetS.
Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients
Authors: Anan Futoshi , Masaki Takayuki , Umeno Yoshikazu , Iwao Tetsu , Yonemochi Hidetoshi , Eshima Nobuoki , Saikawa Tetsunori , Yoshimatsu Hironobu 
Published: August 2007

Background: The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients.
Material and methods: The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3–1.0 mg/dl, age: 57±5 years, mean±s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57±6 years). Brachial–ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis.
Results: The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index.
Conclusions: Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.