bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of serum thyrotropin with thyroxine in patients with Graves' disease: effects on recurrence of hyperthyroidism and thyroid volume
Authors: Pfeilschifter Johannes , Ziegler Reinhard
Published: December 2008

Based on findings that thyroxine may have a beneficial effect on the recurrence of Graves' hyperthyroidism, we prospectively studied the effects of a TSH suppressive treatment with thyroxine on the course of Graves' disease in fifty patients with recent onset of hyperthyroidism. After the normalization of serum tri-iodothyronine (T3) and thyroxine (T4) concentrations, one group of patients was randomly assigned to a combined treatment with carbimazole and a TSH suppressive dose of T4 for 12 months, followed by another 12 months of TSH suppressive therapy alone. The other group of patients also received carbimazole for one year, but T4 was only added as indicated to normalize elevated TSH serum concentrations, and patients received no therapy during the second year. By the end of the second year, a relapse of hyperthyroidism had occurred in 43% of the patients with and in 45% of the patients without suppressive T4 treatment. In those patients without a relapse of hyperthyroidism, initial thyroid size significantly (P = 0·01) decreased with time in both treatment groups. However, patients on suppressive T4 treatment tended to have a greater reduction in thyroid volume than patients with normal TSH serum concentrations (P = 005). In conclusion, we were unable to detect a preventive effect of exogenous TSH suppression on the recurrence of hyperthyroidism. However, our data suggest that TSH suppressive treatment may have a beneficial effect on thyroid enlargement in Graves' disease.

European Journal of Endocrinology 136 81–86
Neuropsychological development in a child with early-treated congenital hypothyroidism as compared with her unaffected identical twin
Authors: Bargagna Stefania , Chiovato Luca , Dinetti Daniela , Montanelli Lucia , Giachetti Cristina , Romolini Elisabetta , Marcheschi Mara , Pinchera Aldo
Published: December 2008

Objective: Neonatal screening for congenital hypothyroidism (CH) prevents the serious neuropsychological features of CH, but the question remains whether intelligence and motor skills of CH children treated early are completely normal.

Design: In this report we describe the rare case of two genetically identical twins, only one of whom was affected by CH due to thyroid agenesis. L-Thyroxine (9 μg/kg body weight/day) therapy was initiated at 27 days of age and was adequate throughout the follow-up.

Methods: Neuropsychological evaluation was performed on the twins in parallel from 3 months to 8 years of age.

Results: The CH twin (NB) did not show major neuromotor impairments but, compared with the unaffected twin (EB), she had a slight delay in postural/motor achievements and in language development that completely disappeared at 8 years of age. On standardised tests of intelligence, NB was indistinguishable from control children but, compared with her twin, she had lower IQ scores in most testing occasions up to 7 years of age (NB = 108 vs EB = 115). School achievements of NB did not significantly differ from those of her classmates but, compared with her twin, she scored worse in writing, mechanical reading, verbal memory, and possibly in arithmetic.

Conclusions: Because the twins were genetically and phenotypically identical, were raised in the same environment, and received a similar education, it is concluded that hypothyroidism in utero and in the first neonatal month was responsible for the lower neuropsychological achievements of the CH twin. While foetal hypothyroidism is at present unavoidable, earlier diagnosis and initiation of treatment in neonates with CH are important and highly recommended.

European Journal of Endocrinology 136 100–104
Simultaneous xenotransplantation of human Graves' thyroid tissue and autologous bone marrow cells in severe combined immunodeficient mice: successful reconstitution of human Graves' hyperthyroidism
Authors: Yoshikawa Norio , Nishikawa Mitsushige , Mori Shigeki , Tokoro Toshiko , Yamamoto Yoshihisa , Ikehara Susumu , Kumazawa Hirofumi , Yamashita Toshio , Inada Mitsuo
Published: December 2008

Human thyroid xenografts and the autologous bone marrow (BM) cells from five patients with Graves' disease (GD) were simultaneously xenografted into severe combined immunodeficient (SCID) mice to study the role of BM cells for the perpetuation of human GD autoimmunity and hyperthyroidism. All SCID mice engrafted with thyroid tissue (TH) alone, TH+autologous peripheral blood mononuclear cells, and TH+autologous BM cells produced similar amounts of human IgG; however, the production in TH+BM-engrafted mice peaked later than that of mice without BM. Production of thyroperoxidase antibody and thyroglobulin antibody in TH+BM-bearing SCID mice peaked in later weeks after xenografting than in those without BM. Moreover, human Graves' hyperthyroidism was actually reconstituted in TH+BM-transplanted mice; this was confirmed by (A) significantly higher levels and longer periods of secreting thyroid-stimulating antibody than those in mice without BM engraftment, (B) persistent hyperthyroxinemia up to the end of the experiment, (C) extremely high radioiodine uptake of the xenografted thyroid tissue, and (D) histological findings of the maintenance of hyperplastic change of the xenografted thyroid epithelial cells. Human BM stem cells (CD34) were identified only in mice with TH+BM xenografts when analyzed by immunohistochemistry. In conclusion, (A) we have developed an animal model for human hyperthyroid GD by simultaneous xenotransplantation of GD thyroid tissue plus autologous BM cells into SCID mice, and (B) BM cells have a crucial role for perpetuating human GD autoimmunity and hyperthyroidism in this system.

European Journal of Endocrinology 136 213–222
Thyroid hormone and gene expression in the regulation of mitochondrial respiratory function
Authors: Pillar Timothy M , Seitz Hans Joachim
Published: December 2008

Thyroid hormone has a profound effect on cellular respiration. Abnormally high levels of this hormone accelerate respiration in conjunction with a general increase in metabolism while pathologically low amounts cause low levels of respiration with a general slowing of metabolic activity. The affect on respiration is primarily the result of changes in the expression of respiratory genes and modulation of inner membrane structure. This review focuses on the regulation of respiratory gene expression by thyroid hormone. Respiratory genes are encoded in both the nucleus and the mitochondrion, the products of which are required in stoichiometric amounts for proper assembly of the respiratory chain. Thyroid hormone influences the expression of a number of nuclear encoded respiratory genes at the level of mRNA and enhances expression of mitochondrially encoded respiratory genes. Therefore, thyroid hormone appears to affect gene regulation in two different cell compartments. The current evidence for a direct thyroid hormone/thyroid receptor regulation of these respiratory genes and possible indirect pathway(s) mediating the thyroid effect is discussed.

European Journal of Endocrinology 136 231–239
Regulation of the uncoupling protein gene expression
Authors: Silva J Enrique , Rabelo Rogerio
Published: December 2008

Uncoupling protein (UCP) is essential to the thermogenic function of brown adipose tissue (BAT). The thermogenic role of this protein is due to its capacity to uncouple oxidative phosphorylation in a regulated manner. The thermogenic potential of BAT is determined by its content of UCP. The gene encoding this protein is under complex regulation. Catecholamines, via cAMP, thyroid hormone and retinoic acid, directly stimulate the gene acting upon an upstream (−2·28/−2·49 kb) enhancer sequence, but cAMP may act upon other sequences of the gene as well. CCAAT enhancer binding proteins and peroxisome proliferation activator receptor (PPAR)γ2 have also been implicated in the regulation of the gene acting on discrete sequences. While the thyroid hormone response and retinoic acid response elements (TRE and RARE) have been well defined, the cAMP response elements (CRE) remain elusive. The two TREs are 27 bp apart between −2·33 kb and −2·39 kb. The synergism between cAMP and thyroid hormone seems to reside in a 39 bp sequence downstream (−2·28/−2·32 kb). The most important CRE, the RARE, a cell-specific enhancer and a putative PPAR element are all concentrated in a 90 bp regulatory element of great complexity (−2·40/−22·49 kb). Other hormones, such as insulin and glucocorticoids, and IGF-I also modulate the expression of the gene but their effects seem to be largely indirect. Understanding the regulation of the UCP gene expression may facilitate the development of interventions in obesity and related disorders.

European Journal of Endocrinology 136 251–264
Plasma dehydroepiandrosterone sulfate levels in patients with hyperfunctioning and non-hyperfunctioning adrenal tumors before and after adrenal surgery
Authors: Tóth Miklós , Rácz Károly , Varga Ibolya , Adleff Vilmos , Jakab Csilla , Fütõ László , Kiss Róbert , Gláz Edit
Published: December 2008

To investigate the clinical significance of plasma dehydroepiandrosterone sulfate (DHEAS) measurements, 175 patients with histologically confirmed adrenal tumors, 10 cortisol-producing adenomas, 59 aldosterone-producing adenomas, 56 non-hyperfunctioning adenomas, 13 adrenocortical carcinomas, 13 adrenal cysts, and 24 adrenomedullary tumors were studied. Plasma DHEAS levels were expressed as percentage of the mean of sex- and age-matched groups of healthy, normal subjects (DHEAS %). We found that before adrenal surgery, DHEAS % values were significantly reduced in patients with cortisol-producing (mean, 15·2% of control; 95% confidence interval (CI), 9·4–24·7%), non-hyperfunctioning (28·4%; 22·4–36·0% as well as aldosterone-producing adrenocortical adenomas (55·4%; 47·1–65·1%) compared with controls, while values were normal in patients with adrenal cysts and in those with adrenomedullary tumors. Plasma DHEAS % values exhibited a great variability in adrenocortical carcinomas (mean, 84·0%; 95% CI, 33·2–212·5%). Death from adrenocortical carcinoma was more frequent in patients with high plasma DHEAS % values compared with those with low DHEAS %. During long-term postoperative monitoring, we found that plasma DHEAS levels of patients with aldosterone-producing and non-hyperfunctioning adenomas returned to normal in the second and fourth postoperative year respectively. In patients with cortisol-producing adenomas, plasma DHEAS remained suppressed for as long as 8 years after the operation. These findings show that except in adrenocortical carcinomas and cysts, plasma DHEAS levels are significantly decreased in all groups of adrenocortical tumors, including non-hyperfunctioning and aldosteroneproducing tumors. The extent of this decrease and the postoperative persistence of suppressed plasma DHEAS levels may be related to the glucocorticoid production of adrenocortical tumors.

European Journal of Endocrinology 136 290–295
Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands
Authors: Weber Matthias M , Auernhammer Christoph J , Kiess Wieland , Engelhardt Dieter
Published: December 2008

We have identified and characterized insulin-like growth factor (IGF)-I and IGF-II/mannose-6phosphate (IGF-II/M6P) receptors in normal adult human adrenocortical tissue. Furthermore, we investigated the IGF-I receptor concentration and binding characteristics in benign and carcinomatous adrenocortical tumors. Membrane preparations of 14 normal adrenocortical glands showed a mean specific 125I-IGF-I binding (SB) of 5·0±0·5% and a competition by unlabeled ligands which is characteristic of the IGF-I receptor. The Scatchard analysis revealed a single class of high affinity binding sites with a dissociation constant (Kd) of 0·16±0·03 nmol/l, and a receptor concentration (RC) of 19·2±2·5 nmol/kg protein. Affinity cross-linking experiments with normal and tumorous adrenocortical tissue displayed a band at an apparent molecular mass of 135 kDa, corresponding to the size of the normal α-subunit of the IGF-I receptor. In agreement, 125I-IGF-II binding to normal adult human adrenocortical membranes was characteristic for the IGF-II/M6P receptor, and the Scatchard analysis revealed the presence of a single class of high affinity binding sites (SB 7·5±0·5, RC 1137±265 nmol/kg protein, Kd 2·20±0·46 nmol/l, n=6). The identity of the IGF-II/M6P receptor in adrenocortical tissue was further confirmed by Western blotting showing a specific band at 220 kDa. When 125I-IGF-I binding in adrenocortical hyperplasias (SB 4·1±0·4% RC 19·6± 2·0 nmol/kg protein, Kd 0·19±0·04 nmol/l, n=4) and adenomas (SB 4·0±1·1% RC 17·5± 3·1 nmol/kg protein, Kd 0·21±0·nmol/l,04 n=4) was compared with the 125I-IGF-I binding in normal adrenocortical tissue, similar IGF-I receptor concentration and binding kinetics were found. In contrast, three out of four hormonally active adrenocortical carcinomas showed a strongly elevated specific 125I-IGF-I binding with a 3- to 4-fold increase in IGF-I receptor concentration, as compared with normal adrenocortical tissue. This resulted in a significantly higher mean specific binding and receptor concentration in adrenocortical carcinomas, while the binding kinetics and the size of the α-subunit of the IGF-I receptor remained unaltered (n =4, SB 13·8±4·2%, RC 72·2 ± 21·3 nmol/kg protein, Kd 0·17±0·02 nmol/l). In summary, we show that intact IGF-I and IGF-II receptors are present in normal adult human adrenocortical tissue. While the abundance of the IGF-I receptor in adrenocortical hyperplasias and adenomas was similar to normal tissue, a strong overexpression of the intact IGF-I receptor was found in three out of four adrenocortical carcinomas.

European Journal of Endocrinology 136 296–303
Effect of ovariectomy and steroid hormone replacement on the recovery of arterial blood pressure following haemorrhage in anaesthetized Brattleboro rats
Authors: Morrissey Sinead E , Edwards Tom J , Wilson Karen J , Whitehead Saffron A , Laycock John F
Published: December 2008

There is increasing evidence that ovarian steroids inhibit vascular responsiveness to the neurohypophysial hormone vasopressin. The present study examined the recovery of the arterial blood pressure following a single (2 ml/100 g body weight) haemorrhage in ovariectomized (OVX) Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) and rats of the parent Long Evans (LE) strain. Some groups of OVX rats received subcutaneous implants of either 17β-oestradiol (E2) or progesterone 7 days prior to haemorrhage. The arterial blood pressure recovery immediately following haemorrhage was significantly impaired in both groups of steroid-treated OVX LE rats compared with the OVX controls (both comparisons P< 005). The impairment in blood pressure recovery seen in the steroidreplaced OVX LE rats was similar to that seen in pro-oestrous rats (when ovarian steroid levels are raised) compared with male rats of this strain (P<0·05). In contrast, ovariectomy with or without steroid replacement in BDI rats had no further effect on the already attenuated recovery of arterial blood pressure after haemorrhage in this strain. Heart rate responses to haemorrhage also showed strain differences, which were dependent on steroid treatment. Pro-oestrous female LE rats showed a small decrease in heart rate after haemorrhage, followed by a recovery process, and this initial bradycardia was markedly enhanced in the OVX steroid-treated animals. In contrast, untreated OVX LE rats showed an initial and sustained increase in heart rate which was significantly higher than in the steroid-treated OVX animals (P <0·05). All BDI rats, irrespective of treatment, consistently showed an increased heart rate after haemorrhage. In conclusion, ovarian steroid replacement in OVX LE, but not vasopressin-deficient BDI, rats was associated with an attenuated pressor recovery after haemorrhage. This provides further evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin. The initial decrease in heart rate observed in pro-oestrous and steroid-treated OVX LE rats after haemorrhage also appears to be related to an ovarian steroid—vasopressin interaction.

European Journal of Endocrinology 136 330–337
Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to octreotide therapy and do not correlate with tumor histology
Authors: Plöckinger Ursula , Bäder Michael , Hopfenmüller Werner , Saeger Wolfgang , Quabbe Hans-Jürgen
Published: December 2008

The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx), (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immunohistology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically nonfunctioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake; Gl, uptake comparable to normal pituitary; G2, increased uptake; G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI)) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n=10) vs G2/3 (n=8): 3·6±1·9 vs 10·±6·5 cm3 (mean±s.e.), P=0·051), but not in NF-A (g0/1 (n=12) vs G2/3 (n=12): 17·0±10·1 vs 14·3±3·6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-I in GH-A did not correlate with SRS results (G0/1 (n=17) vs G2/3 (n=8), GH: 32·3±18·2 vs 29·3±7·4 μg/l, IGF-I: 851±80 vs 1038±153 μg/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or α-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal, mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas, silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify postoperative tumor remnants not visible on MRI.

European Journal of Endocrinology 136 369–376
C-type natriuretic peptide exerts stimulatory effects on the corticotropin-releasing hormone-induced secretion of hormones in normal man
Authors: Kellner Michael , Diehl Ines , Knaudt Kristina , Schüle Cornelius , Jahn Holger , Wiedemann Klaus
Published: December 2008

C-type natriuretic peptide and atrial natriuretic peptide have been reported to bind to distinct receptors and to exert opposing effects on different systems. Although it is known that atrial natriuretic peptide inhibits the corticotropin-releasing hormone-stimulated hormone release in man, the corresponding action of C-type natriuretic peptide has so far not been characterized. We investigated the effects of 30-min infusions of 150 and 300 μg C-type natriuretic peptide on adrenocorticotropin, cortisol, and prolactin release stimulated by 100 μg corticotropin-releasing hormone and on cardiovascular parameters in 8 healthy male volunteers. Compared with placebo, 300 μg C-type natriuretic peptide significantly (P<0·05) enhanced the stimulation of cortisol (area under curve (arbitrary units): 520 ± 35 vs 651 ± 55) and prolactin (area under curve: 29 ± 3 vs 37 ± 5). Adrenocorticotropin levels were increased, but the differences did not reach statistical significance (maximum increment: 27±4 vs 36± 2 pg/ml). C-type natriuretic peptide at a dose of 150 μg had no clear effect on these hormones and C-type natriuretic peptide also produced no cardiovascular or subjective effects. Our data suggest stimulatory effects of C-type natriuretic peptide on corticotropinreleasing hormone-induced hormone release and offer further evidence for a complex role of different natriuretic peptides in endocrine regulation.

European Journal of Endocrinology 136 388–393
Anti-obesity and anti-diabetic effects of CL316,243, a highly specific β3-adrenoceptor agonist, in Otsuka Long-Evans Tokushima Fatty rats: induction of uncoupling protein and activation of glucose transporter 4 in white fat
Authors: Umekawa Tsunekazu , Yoshida Toshihide , Sakane Naoki , Saito Masayuki , Kumamoto Kenzo , Kondo Motoharu
Published: December 2008

The anti-obesity and anti-diabetic effects of a highly specific β3-adrenoceptor agonist, CL316.243 (CL; β1:β2:β3=0:1:100 000), were investigated in Otsuka Long-Evans Tokushima Fatty (fatty) and LongEvans Tokushima Otsuka (control) rats. Daily injection of CL (0·1 mg/kg, s.c.) to these rats (10 weeks old) for 14 weeks caused a significant reduction in body weight (fatty, 27% control, 15%), associated with a marked decrease in fat pad weight (inguinal: fatty, 60%; control, 36%; retroperitoneal: fatty, 75%; control, 77%) without affecting food intake. The levels of uncoupling protein mRNA and protein levels of uncoupling protein (UCP), as well as guanosine 5′-diphosphate-binding (a reliable index of thermogenesis) in brown adipose tissue, were lower in the fatty than in the control rats. However, after CL treatment, these parameters in brown adipose tissue increased significantly 2- to 3-fold in both groups. Furthermore, uncoupling protein was induced in white adipose tissue as well as in brown adipose tissue. The fatty rats showed hyperglycemia and hyperinsulinemia during the glucose tolerance test, but CL ameliorated these parameters.

These findings suggest that decreased thermogenesis in brown adipose tissue may be one of the causes of obesity in the fatty rats and that administration of CL prevents obesity by decreasing white fat mass, by activating brown adipose tissue thermogenesis, and by inducing uncoupling protein in white adipose tissue. Furthermore, CL treatment may inhibit diabetes mellitus by ameliorating obesity and by activating glucose transporter 4 in white adipose tissue and brown adipose tissue.

European Journal of Endocrinology 136 429–437
Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus
Authors: Vestergaard Henrik , Rossen Marianne , Urhammer Søren A , Müller Jørn , Pedersen Oluf
Published: December 2008

In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine the metabolic and hormonal responses to an unchanged insulin therapy with the addition of a subcutaneous administration of recombinant human IGF-I (rhIGF-I) during (a) a short-term (2 weeks) period with rhIGF-I given twice a day in a high dose (80 μg/kg body weight) in four patients with extreme insulin-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 μg/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin receptor mRNA, whereas the remaining two patients were suspected to have defects at receptor and/or post-receptor sites. In the short-term study period, plasma glucose levels decreased more than 35% in response to rhIGF-I in all but one patient which was paralleled by reduced levels of serum insulin (25–50%), proinsulin (40–50%) and C-peptide (10–65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum insulin and C-peptide levels were decreased by 40–55% after 6 weeks in the two siblings with known insulin receptor mutations. After 10 weeks of treatment fasting plasma glucose levels were still decreased whereas fasting serum insulin and C-peptide levels were increased almost to pretreatment values. In conclusion: 2 weeks of high-dose rhIGF-I therapy in insulin-treated patients with severe insulin resistance has a marked lowering effect on fasting plasma glucose and serum insulin levels whereas the metabolic and glycaemic effects of 10 weeks of treatment with low-dose rhIGF-I may be modest and transient.

European Journal of Endocrinology 136 475–482
Serum FSH levels in women with polycystic ovary syndrome during ovulation induction using down-regulation and urofollitropin
Authors: Fridström Margareta , Sjöblom Peter , Pousette Åke , Hillensjö Torbjörn
Published: December 2008

Objective: To evaluate retrospectively the use of serum FSH levels and to correlate them with follicular growth in a clinical ovulation induction program.

Methods: Twenty women with infertility due to anovulation associated with polycystic ovary syndrome (PCOS) were studied. The patients were down-regulated with a long GnRH agonist protocol and stimulated with purified urofollitropin, using a low-dose step-up regimen. Repeated serum samples were drawn and transvaginal ultrasound scans were performed. During the exogenous FSH therapy serum FSH levels resulting in continuous follicular growth were analyzed, as well as the rates of ovulation, pregnancy, cancellation and conversion to in vitro fertilization (IVF).

Results: Thirty-two out of fifty treatment cycles led to ovulation, resulting in five term pregnancies. Eight cycles were converted to IVF/embryo transfer due to multiple follicular growth. They resulted in two pregnancies. Ten cycles were cancelled because of impaired follicular growth. The serum FSH levels (median 6 IU/l) resulting in continuous growth of the follicles were relatively stable within patients (variation 15%) but varied considerably between patients (45%). The relationship between FSH dose and serum level was different for lean and obese PCOS patients after subcutaneously injected urofollitropin.

Conclusions: There seems to be a difference in resorption/metabolism between lean and obese PCOS patients with regard to s.c. injected FSH. The intra-patient coefficient of variation (C.V.) of the serum FSH response level was quite low, as was the C.V. of the FSH dose at the response level. This allowed a more rapid dose adjustment in subsequent cycles. Analysis of serum FSH during induction of ovulation with gonadotropins seems to be of limited value in clinical programs.

European Journal of Endocrinology 136 488–492
Bioelectrical impedance assessment of body composition in thyroid disease
Authors: Seppel Thomas , Kosel Andrea , Schlaghecke Reiner
Published: December 2008

To assess the metabolic effects of thyroid disease, body composition was determined by bioimpedance analysis (BIA) in 72 patients with untreated hyperthyroidism (mean age 48·7±1·9 years) and 26 patients with untreated hypothyroidism (63·8±3·4 years). Bioelectrical whole body resistance (R) and reactance (Xc) were used for computerized calculation of lean body mass (LBM), body cell mass (BCM), extracellular mass (ECM) and body fat (BF). Compared with age- and sex-matched healthy controls the most sensitive parameter indicating excess thyroid hormone was the ECM/BCM ratio which was markedly elevated in all hyperthyroid subjects. ECM/BCM alteration resulted from marked depletion of BCM with concomitant expansion of ECM. BCM change is thought to be predominantly due to a loss of muscle mass while ECM rise may reflect an increase in extracellular fluids. In contrast, hypothyroidism was characterized by an increase in BF besides a relatively unaffected LBM component. Serum parameters of thyroid function (tri-iodothyronine (T3), free thyroxine, TSH) did not correlate with the determinants of body composition except for a slight inverse relationship between the phase angle (Xc/R×180°/π) and T3 concentration in Graves' disease patients. We conclude that hyperthyroidism is primarily accompanied by quantitative as well as qualitative changes in the lean body while considerable fat increase is the most important feature of hypothyroidism. Severity of body composition derangement cannot be predicted from the degree of thyroid dysfunction. BIA could become a useful tool which allows objective determination of even subtle metabolic manifestations of thyroid disease and should, therefore, complement conventional clinical and biochemical assessment.

European Journal of Endocrinology 136 493–498
Recombinant human gonadotropins stimulate steroid and inhibin production in human granulosa cells
Authors: Bergh Christina , Selleskog Ulrika , Hillensjö Torbjörn
Published: December 2008

Objective: Recently pure gonadotropins have become available through recombinant technology. In parallel with ongoing clinical trials it is important to examine the effects of these new gonadotropin preparations in experimental studies in human granulosa cells. In the present study the effects of recombinant FSH (rFSH) and LH (rLH) on steroid and inhibin production were examined in human granulosa cells in culture.

Patients and methods: Granulosa cells were obtained during the follicular phase of the menstrual cycle in seven women undergoing gynecological laparotomy and from follicles in stimulated cycles in women undergoing oocyte retrieval in connection with in vitro fertilization/embryo transfer. The granulosa cells were cultured in modified Medium 199 containing 1% fetal bovine serum for 4–8 days with and without hormones. Media were changed on alternate days and stored at −20°C until analyzed for estradiol, progesterone and inhibin.

Results: Granulosa cells from natural cycles were highly responsive to rFSH which caused a dose-related (rFSH 0·1 to 100 ng/ml) increase in estradiol and progesterone accumulation. The maximal stimulatory effect was reached with a concentration of rFSH between 1 and 10 ng/ml. Granulosa cells from stimulated cycles responded highly to rLH in terms of increased progesterone production during the whole culture period. A maximal stimulatory effect was observed with rLH at a concentration of 0·1 ng/ml. Both types of granulosa cells responded to recombinant gonadotropins in terms of increased inhibin production.

Conclusions: The present study demonstrates that granulosa cells from human ovarian follicles are highly responsive to recombinant gonadotropins as demonstrated by increased steroid and inhibin production.

European Journal of Endocrinology 136 617–623
Role of the renin-angiotensin system in the development of thyroxine-induced hypertension
Authors: del Rio Cipriano Garcia , Moreno María Rosario R , Osuna Antonio , de Dios Luna Juan , García-Estañ Joaquín , Vargas Félix
Published: December 2008

Objective: We evaluated the influence of chronic blockade of the renin-angiotensin system on hypertension induced by long-term thyroxine (T4) administration. To this end, we determined the effects of chronic treatment with captopril on blood pressure, cardiac hypertrophy and other renal and metabolic variables of hypertensive hyperthyroid rats.

Methods: T4 was administered s.c. at 0·38 μmol/kg per day and captopril was given in the drinking water (1·38 mmol/l). Both treatments were maintained for 6 weeks. Control rats received tap water. After the treatment period, the rats were placed in metabolic cages. Later, blood pressure was measured in conscious rats by intra-arterial determination.

Results: T4-treated rats showed an increased mean arterial pressure (MAP) whereas, in rats treated with T4 plus captopril, MAP was similar to that of the control group. Captopril did not affect the increased heart rate or ventricular weight/body weight ratio of hyperthyroid rats, but it improved the reduced creatinine clearance of these animals.

Conclusions: The elevation in blood pressure produced by long-term T4 administration was prevented by chronic blockade of the renin-angiotensin system. Captopril improved the renal function of hyperthyroid rats, but did not affect the relative cardiac hypertrophy of these animals.

European Journal of Endocrinology 136 656–660
Temporal and Spatial Quantification of Fine‐Sediment Accumulation Downstream of Culverts in Brook Trout Habitat
Authors: Lachance Stephanie , Dubé Maryse , Dostie Renaud , Bérubé Pierre
Published: December 2008

We quantified fine‐sediment accumulation annually from 2000 to 2003 after culvert construction in five Laurentian Shield streams containing brook trout Salvelinus fontinalis. A significant spatial pattern (section effect) was observed in which the accumulation was lowest upstream of the culvert (section 1), peaked in the section directly below the culvert (section 2), and slightly decreased in sections further downstream (sections 3‐5) without returning to upstream levels. The accumulation was always significantly higher downstream of the culvert than in section 1. The temporal pattern (period effect) was also significant; accumulation was lowest several weeks after construction, peaked at one full year after construction, and decreased at 2‐3 years postconstruction. Fine‐sediment accumulation differed significantly among all periods. The downstream distance at which sediment accumulation returned to upstream levels varied from 358 and 1,442 m below the culvert. Owing to the accumulated sediment, which probably originates primarily from construction sand or road erosion, habitat downstream of a culvert is in many cases of lower quality for brook trout incubation and rearing. Recommendations for minimizing culvert impacts on fish habitat are discussed.
Deepwater Demersal Fish Community Collapse in Lake Huron
Authors: Riley Stephen C. , Roseman Edward F. , Nichols S. Jerrine , O'Brien Timothy P. , Kiley Courtney S. , Schaeffer Jeffrey S.
Published: December 2008

Long‐term fish community surveys were carried out in the Michigan waters of Lake Huron using bottom trawls from 1976 to 2006. Trends in abundance indices for common species (those caught in 10% or more of trawl tows) were estimated for two periods: Early (1976‐1991) and late (1994‐2006). All common species significantly decreased in abundance during the late period with the exception of the johnny darter Etheostoma nigrum and spottail shiner Notropis hudsonius, which showed no significant trends, and the round goby Neogobius melanostomus, which increased in abundance. Percentage decreases in abundance indices between 1994‐1995 and 2005‐2006 ranged from 66.4% to 99.9%, and seven species decreased in abundance by more than 90%. The mean biomass of all common species in 2006 was the lowest observed in the time series and was less than 5% of that observed in the mid‐1990s. The mean number of common species captured per trawl has also decreased since the mid‐1990s. Several factors, including recent invasion of the lake by multiple exotic species, may have contributed to these declines, but insufficient published data are currently available to determine which factors are most important. Our observations suggest that significant changes have occurred in the ecology of Lake Huron since the mid‐1990s. The extent of these changes indicates that the deepwater demersal fish community in Lake Huron is undergoing collapse.
Genetic Evaluation of Isolated Populations for Use in Reintroductions Reveals Significant Genetic Bottlenecks in Potential Stocks of Sacramento Perch
Authors: Schwartz Rachel S. , May Bernie
Published: December 2008

New populations of threatened species are often established as a conservation measure. However, if only a few individuals contribute to subsequent generations, these populations may have limited genetic diversity. Such genetic bottlenecks can result in inbreeding depression, reduced fitness, and even extirpation of populations. Eight isolated populations of Sacramento perch Archoplites interruptus established through anthropogenic translocations were examined for evidence of genetic bottlenecks. Sacramento perch are endemic to two regions of California but have been entirely extirpated from their native range; the remaining populations are essential for conservation of the species. Using 12 microsatellite DNA loci, we determined that genetic bottlenecks occurred in six of the populations. Allelic richness, richness of private alleles, and effective population size differed significantly among populations. Strong differentiation among the extant populations probably resulted from differences in the sources used to establish the populations and from genetic drift due to the small population sizes. These results indicate that genetic bottlenecks are frequent when new, isolated populations of a species are established. Although these extant populations have persisted despite bottlenecks, future Sacramento perch populations should be established by drawing from the most diverse of the current populations and should be monitored with genetic markers to evaluate diversity and the possible need for further stocking. We combine three measures of genetic diversity (allelic richness, private allelic richness, and effective population size) to recommend potential source populations.
Fonoaudiologia e educação infantil: uma parceria necessária
Authors: Maranhão Poliana Carla Santos , Pinto Sabrina Maria Pimentel da Cunha , Pedruzzi Cristiane Monteiro
Published: December 2008

OBJETIVO: investigar as informações que os professores de educação infantil possuem em relação a Fonoaudiologia na escola, bem como sobre temas ligados à área de linguagem. MÉTODOS: foi aplicado um questionário, contendo 17 questões objetivas em uma amostra com 73 professores de educação infantil da rede municipal de ensino da cidade de Maceió-AL. RESULTADOS: os participantes relacionaram a atuação fonoaudiológica na escola à presença de alterações no desenvolvimento da criança. O índice de professores da amostra que obtiveram contato com o fonoaudiólogo na escola é de 4,1%. Estes educadores relatam que apenas 57,5% receberam informações sobre a aquisição de linguagem e o desenvolvimento da escrita. CONCLUSãO: com a realização da presente pesquisa foi possível confirmar a necessidade de reforçar as ações fonoaudiológicas na escola, bem como a parceria entre fonoaudiólogos e professores.
A imunização contra a rubéola no primeiro trimestre de gestação pode levar à perda auditiva?
Authors: Dias Ana Lúcia Pereira de Andrade , Mitre Edson Ibrahim
Published: December 2008

TEMA: embora o risco da Síndrome da Rubéola Congênita após a imunização seja pequeno, é necessário assegurar a imunidade das mulheres em idade fértil, especialmente daquelas com risco mais alto de exposição, visando a prevenção. OBJETIVO: esclarecer o risco que a imunização da rubéola apresenta para a audição do recém nascido, no primeiro trimestre de gestação. CONCLUSÃO: os levantamentos realizados por este estudo permitiram concluir que ainda há um grande caminho a ser percorrido em prol da erradicação da rubéola no Brasil, bem como a diminuição dos riscos de surdez neurossensorial causados pela Síndrome da Rubéola Congênita.
Respiração oral: causa x audição
Authors: Bianchini Ana Paula , Guedes Zelita Caldeira Ferreira , Hitos Silvia
Published: December 2008

OBJETIVO: verificar a relação entre a etiologia da respiração oral e os diferentes tipos de alteração de audição. MÉTODOS: coletaram-se 97 prontuários no Centro do Respirador Bucal da UNIFESP. As etiologias foram classificadas em: Hipertrofia de Adenoamígdala, Atopia, Atopia com Hipertrofia e Funcional. Os 97 pacientes realizaram exames audiométricos e foram considerados alterados aqueles que os limiares tonais (nas freqüências de 250 a 8 kHz) e ósseos (de 500 a 4 kHz) foram superiores a 20 dBNA com Gap aéreo-ósseo maior que 10 dB e com curva timpanométrica desviada apartir de -100dapa. De acordo com o grau de comprometimento, os tipos de perda foram classificadas como leve ou moderada. Na timpanometria, a curva A representou a normalidade; a curva B, Otite média e a C, os casos de disfunção tubária. RESULTADOS: limiares compatíveis à audição normal foram encontrados em 79,5% dos pacientes atópicos; 61,8% dos atópicos com hipertrofia; 57,7% dos com hipertrofia e em 100% dos respiradores orais funcionais. Através da correlação entre as etiologias e achados imitanciométricos verificou-se que em indivíduos atópicos prevaleceu a curva tipo C (29,5 %). Em pacientes atópicos tinham hipertrofia a curva mais encontrada foi a B (32,4%) e nos indivíduos com hipertrofia, somente, observou-se tanto curva tipo B como C, com idêntica prevalência de 21,8%. Todos os respiradores orais funcionais apresentaram curva timpanométrica tipo A. CONCLUSÃO: pôde-se verificar que a freqüência de respiradores orais sem alteração de audição é expressiva, independente da etiologia, porém os pacientes com hipertrofia apresentam maior suscetibilidade á alterações timpanométricas.
Molecular genetic case-control women investigation from the first Brazilian high-risk study on functional psychosis
Authors: Krelling Renata , Cordeiro Quirino , Miracca Elisabete , Gutt Elisa Kijner , Petresco Sandra , Moreno Ricardo Alberto , Vallada Homero
Published: December 2008

OBJECTIVE: Data from epidemiological studies have demonstrated that genetics is an important risk factor for psychosis. The present study is part of a larger project, pioneer in Brazil, which has been conducted by other researchers who intend to follow a high-risk population (children) for the development of schizophrenia and bipolar disorder. In this first phase of the project, the objective was to investigate the distribution of four candidate genetic polymorphisms for functional psychosis (Ser9Gly DRD3, 5HTTLPR, the VNTR 3'-UTR SLC6A3 and Val66Met BDNF) in a case-control sample. METHOD: A total of 105 women (58 with schizophrenia and 47 with bipolar disorder) and 62 gender-matched controls were investigated. RESULTS: Allele and genotype distributions of all identified functional polymorphisms did not differ statistically between cases and controls. CONCLUSIONS: These results suggest that the investigated polymorphisms were not related to susceptibility to functional psychoses in our Brazilian sample. These findings need to be validated in larger and independent studies.
Nicotine use in patients with schizophrenia evaluated by the Fagerström Tolerance Questionnaire: a descriptive analysis from a Brazilian sample
Authors: Chaves Leonardo , Shirakawa Itiro
Published: December 2008

OBJECTIVE: This is a descriptive study to determine smoking prevalence rates in a convenience sample of patients with schizophrenia and to describe clinical/demographic variables for nicotine use in this population. METHOD: Patients with schizophrenia were consecutively invited to answer a standard clinical/demographic questionnaire and a questionnaire on smoking habits (Fagerstrom Tolerance Questionnaire). RESULTS: Eighty-three patients were interviewed. The smoking rate was 57.8% (n = 48). Male (68.8%) patients smoked more than females did (31.3%; p = 0.081). Compared to patients who smoked at the time of disease onset, those who only started smoking after disease onset had a lower mean age at the time of disease onset [24 years old (SD = ± 6.8) vs.19 years old (SD = ± 3.9; p = 0.041)]. Patients who preferred high-nicotine content cigarettes (p < 0.01) had higher frequency of smoking inhalation (p < 0.05) and had more urgency to smoke the first cigarette in the morning (p < 0.05). Twenty-seven (56.3%) of smoking patients were heavy smokers (FTQ > 8). CONCLUSIONS: Patients with schizophrenia in our convenience sample smoked in a higher rate compared to the general population in Brazil. Smoking patients were heavy smokers evaluated by the Fagerstrom Tolerance Questionnaire.
Hormonal characterization and classification of breast cyst fluid in gross cystic mastopathy
Authors: Számel I , Budai B , Daubner K , Kralovánszky J , Ottó Sz , Tóth J , Besznyák I
Published: December 2008

Gross cystic disease (GCD) of the breast may be associated with a higher risk for the development of breast cancer. High levels of sex steroids, steroid hormone precursors, prolactin and cations have been found in breast cyst fluid (BCF) by several investigators. Accordingly, endocrine parameters and the cationic composition of BCF may be considered as useful characteristics to follow patients bearing macrocysts. In this study we have investigated the concentrations of estradiol (E2), progesterone, testosterone, dehydroepiandrosterone (DHA) and DHA-3-sulfate (DHA-S), prolactin, potassium (K+) and sodium (Na+) in BCF aspirated from 99 women. The mean age of the patients was 49.8 years (range 32-58). The hormone levels were measured by RIA methods; K+ and Na+ were determined by flame photometry. Estradiol, progesterone, testosterone, DHA, DHA-S, prolactin and K+ showed significant accumulation in the BCF compared with their respective serum values. The K+/Na+ ratio proved to be useful in dividing cysts into type I (≥1), type II (<1 but ≥0.1) and type III (<0.1) subgroups. For type I BCF, higher DHA, DHA-S and prolactin concentrations were detected. Linear regression analysis established a highly significant (P<0.001) correlation between the concentrations of E2 and DHA-S (r=0.686), and also between testosterone and DHA-S (r=0.711). These findings indicate that type I BCF might be a marker for 'active' GCD of the breast, and suggest that it may be associated with an increased breast cancer risk, since this group of patients is supposed to have cysts with apocrine metaplasia. It is suggested therefore that when BCF is aspirated, sex steroids, steroid precursors and cations should be routinely measured, and women with type I cysts should be regularly examined.
Hormone replacement therapy, endocrine monitoring and cyst fluid investigations in patients who have had a breast cyst
Authors: Huber J , Gruber D
Published: December 2008

Patients with macrocysts have a two- to fourfold higher risk of developing breast cancer and should be monitored carefully while on hormone replacement therapy. Estradiol and progesterone seem to enhance the mitotic rate of breast cells and serum levels should be reduced to the lowest levels possible. Investigations are necessary to confirm the stimulatory effect of serum steroids on breast/cyst epithelial cells. The effect of norethisterone on breast tissues must also be considered. The conversion of norethisterone to ethinylestradiol may make this progestogen unsuitable for replacement therapy in breast cyst patients, but this requires conformation in clinical studies.

Recently it was demonstrated that cholic acids accumulate in breast cyst fluid and that their metabolism is influenced by sex steroids. Experimental and clinical studies are necessary to elucidate this breast-gut connection.