bluuebunny/crossref_metadata_2025 huggingface dataset:
Subfertility with Defective Folliculogenesis in Female Mice Lacking Testicular Orphan Nuclear Receptor 4
Authors: Chen Lu-Min , Wang Ruey-Sheng , Lee Yi-Fen , Liu Ning-Chun , Chang Yu-Jia , Wu Cheng-Chia , Xie Shaozhen , Hung Yao-Ching , Chang Chawnshang
Published: January 2008

Testicular orphan nuclear receptor 4 (TR4) plays essential roles for normal spermatogenesis in male mice. However, its roles in female fertility and ovarian function remain largely unknown. Here we found female mice lacking TR4 (TR4−/−) displayed subfertility and irregular estrous cycles. TR4−/− female mice ovaries were smaller with fewer or no preovulatory follicles and corpora lutea. After superovulation, TR4−/− female mice produced fewer oocytes, preovulatory follicles, and corpora lutea. In addition, more intensive granulosa apoptosis was found in TR4−/− ovaries. Functional analyses suggest that subfertility in TR4−/− female mice can be due to an ovarian defect with impaired folliculogenesis rather than a deficiency in pituitary gonadotropins. Molecular mechanism dissection of defective folliculogenesis found TR4 might induce LH receptor (LHR) gene expression via direct binding to its 5′ promoter. The consequence of reduced LHR expression in TR4−/− female mice might then result in reduced gonadal sex hormones via reduced expression of enzymes involved in steroidogenesis. Together, our results showed TR4 might play essential roles in normal folliculogenesis by influencing LHR signals. Modulation of TR4 expression and/or activation via its upstream signals or unidentified ligand(s) might allow us to develop small molecule(s) to control folliculogenesis.
The Limits of Marginal Economic Incentives in the Medicaid Program: Concerns and Cautions
Authors: Fanning Thomas , Alteriis Martin de
Published: January 2008

In January 1985, New York State implemented legislation that allowed for a 30 percent increase in Medicaid fees for physicians providing primary care services. This was intended to increase their levels of participation. Yet the outcome was not as expected. In upstate New York, the number of physicians participating in Medicaid each month actually declined; in New York City, the monthly rate of increase in participating physicians, which was part of the overall sharp rise in all licensed physicians, underwent a decline. Furthermore, utilization measures suggest that “procedural upgrading” might have become a problem in New York City. These results suggest that a marginal increase in New York State's low Medicaid fees will not have a positive effect on physician participation levels.
Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients
Authors: Kreutzer J , Buslei R , Wallaschofski H , Hofmann B , Nimsky C , Fahlbusch R , Buchfelder M
Published: January 2008

Objective

Medical therapy with dopamine agonists (DA) is the primary treatment of choice in most patients with prolactinomas. ‘Classical’ surgical indications are intolerance or lack of efficiency of DA therapy. Focusing on a possible shift of recent indications, we retrospectively analyzed our results of surgical treatment in prolactinomas.

Patients and methods

Between 1990 and 2005, we have operated on 212 consecutive patients with prolactinomas. Surgical indications were divided into ‘classical’ indications and ‘modern’ indications defined as cystic prolactinomas or patients with microprolactinomas who individually decided on a primary surgical treatment.

Results

Initial overall remission was accomplished in 53.2% including giant prolactinomas. However, in microadenomas, the remission rate was significantly higher with 91.3%. Overall remission at the latest follow-up was 42.7%, but 72.5% in intrasellar tumors, 80% in cystic prolactinomas, and 84.8% in microprolactinomas. The overall recurrence rate was 18.7%. Relapse of hyperprolactinemia in microprolactinomas was 7.1%. In our series, continually less patients were surgically treated for ‘classical’ indications. By contrast, the number of patients who individually decided on a primary surgical therapy has increased considerably.

Conclusion

Remission rates after surgical treatment of prolactinomas remain excellent, particularly in microadenoma and intrasellar macroadenomas, whereas morbidity of transsphenoidal surgery is low in the hands of experienced pituitary surgeons. Our remission rates not only confirm the already interdisciplinarily accepted surgical indications, but also emphasize the value of primary transsphenoidal surgery as a discussion-worthy alternative to dopaminergic therapy in young patients with microprolactinomas or cystic tumors.
Changes in heart rate variability and QT dispersion in patients with overt hypothyroidism
Authors: Galetta Fabio , Franzoni Ferdinando , Fallahi Poupak , Tocchini Leonardo , Braccini Lara , Santoro Gino , Antonelli Alessandro
Published: January 2008

Objective

The aim of the present study was to evaluate the effect of clinical hypothyroidism on cardiovascular autonomic function and ventricular repolarization.

Design and methods

We studied 31 patients (22 females and 9 males; mean age 53.6±11.8 years) with overt hypothyroidism (TSH=56.2±14.7 μU/ml, low free thyroxine (T4), free tri-iodothyronine (T3)) and 31 euthyroid controls, to investigate the dispersion of the QT interval in electrocardiogram (ECG) (an index of inhomogeneity of repolarization) and heart rate variability (HRV; a measure of cardiac autonomic modulation). The hypothyroid patients and controls underwent a full medical examination, standard 12-lead ECG, and 24-h ambulatory ECG monitoring. The hypothyroid patients were re-examined after 6 months of treatment with l-T4.

Results

Patients with hypothyroidism showed higher QT dispersion and lower HRV measures than controls (P<0.01 or P<0.001). In hypothyroid patients, standard deviation of all R–R intervals was inversely related (by simple regression) to serum (log)TSH levels (r=−0.47, P=0.008), while QT dispersion (r=0.50, P=0.004) and QTc dispersion (r=0.46, P=0.008) were directly related to (log)TSH. Parameters of HRV improved after 6 months of l-T4 treatment, with the correction of hypothyroidism, becoming comparable with those of the control subjects, whereas the QT and QTc dispersion results were found to be only partially restored, remaining higher than the controls.

Conclusions

The results of the study demonstrate that hypothyroidism is associated with a decreased sympatho-vagal modulation of the heart rate and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with overt hypothyroidism may represent a useful tool in monitoring the cardiovascular risks.
Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia
Authors: Vatten Lars J , Nilsen Tom I L , Juul Anders , Jeansson Stig , Jenum Pål A , Eskild Anne
Published: January 2008

Objective

To assess whether circulating IGF-I and IGF-binding protein-1 (IGFBP-1) in the first and second trimester are associated with subsequent risk of preterm and term preeclampsia.

Methods

Nested case–control study within a cohort of 29 948 pregnant women. Cases were women, who later developed preeclampsia, and controls were randomly selected women, who did not develop preeclampsia. IGF-I and IGFBP-1 were measured with ELISA in maternal blood samples that were collected in the first and second trimesters. We assessed associations of IGF-I and IGFBP-1 concentrations with later development of preterm (before the 37th week of gestation) and term preeclampsia.

Results

An increase in IGF-I from the first to second trimester was associated with higher risk of preterm preeclampsia; the odds ratio (OR) for the highest compared with lowest quartile of increase was 4.9 (95% confidence interval, 1.1–21.8). Low concentrations of IGFBP-1, both in the first and in the second trimesters, were related to higher risk of term preeclampsia (OR 4.0, 95% confidence interval, 1.9–8.4) and moderately increased risk of preterm preeclampsia (OR 2.3, 95% confidence interval, 1.2–4.4).

Conclusion

The higher risk of preterm preeclampsia related to IGF-I increase may reflect placental disease, whereas low concentrations of IGFBP-1 associated with term preeclampsia may reflect maternal metabolic aberrations, indicating different etiologies in preeclampsia.
The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation
Authors: Phan Ha T T , Jager Pieter L , van der Wal Jacqueline E , Sluiter Wim J , Plukker John T M , Dierckx Rudi A J O , Wolffenbuttel Bruce H R , Links Thera P
Published: January 2008

Objective

This retrospective study describes the role of serum thyroglobulin (Tg) in relation to tumor characteristics in the prediction of persistent/recurrent disease in patients with differentiated thyroid cancer (DTC) with negative Tg at the time of ablation.

Design

Between 1989 and 2006, 94 out of 346 (27%) patients with DTC had undetectable Tg at the time of131I ablation and were included in this evaluation. The group of 94 patients consisted of 15 males and 79 females in the age range of 16–89 years with a median follow-up of 8 years (range 1–17). All medical records and follow-up parameters of the 94 patients were evaluated for the occurrence of persistent/recurrent disease. In patients with persistent/recurrent disease hematoxylin-eosin-stained slides of the primary tumors and/or metastatic lesions were also reviewed for histological features including immunostains for Tg.

Results

During follow-up, 8 out of 94 (8.5%) patients showed persistent/recurrent disease: in the course of the disease two patients showed Tg positivity, three showed Tg antibody (TgAb) positivity, and the other three showed persistently undetectable Tg and TgAb. Patients who developed Tg and/or TgAb positivity during follow-up had a significantly shorter disease-free survival period when compared with patients with persistently undetectable Tg and TgAb (P<0.006). Histological features were not able to predict the recurrent status.

Conclusions

Follow-up of Tg and TgAb in patients with initially negative Tg and TgAb is useful since a number of patients had shown detectable Tg or TgAb during follow-up indicative for persistent/recurrent disease. Tg and TgAb negativity at the time of ablation is not a predictive determinant for future recurrent status.
Genetic investigation of four meiotic genes in women with premature ovarian failure
Authors: Mandon-Pépin Béatrice , Touraine Philippe , Kuttenn Frédérique , Derbois Céline , Rouxel Agnes , Matsuda Fumihiko , Nicolas Alain , Cotinot Corinne , Fellous Marc
Published: January 2008

Objective

The goal of this study was to determine whether mutations of meiotic genes, such as disrupted meiotic cDNA (DMC1), MutS homolog (MSH4),MSH5, andS. cerevisiaehomolog (SPO11), were associated with premature ovarian failure (POF).

Design

Case–control study.

Methods

Blood sampling, karyotype, hormonal dosage, ultrasound, and ovarian biopsy were carried out on most patients. However, the main outcome measure was the sequencing of genomic DNA from peripheral blood samples of 41 women with POF and 36 fertile women (controls).

Results

A single heterozygous missense mutation, substitution of a cytosine residue with thymidine in exon 2 ofMSH5, was found in two Caucasian women in whom POF developed at 18 and 36 years of age. This mutation resulted in replacement of a non-polar amino acid (proline) with a polar amino acid (serine) at position 29 (P29S). Neither 36 control women nor 39 other patients with POF possessed this genetic perturbation. Another POF patient of African origin showed a homozygous nucleotide change in the tenth ofDMC1gene that led to an alteration of the amino acid composition of the protein (M200V).

Conclusions

The symptoms of infertility observed in theDMC1homozygote mutation carrier and in both patients with a heterozygous substitution in exon 2 of theMSH5gene provide indirect evidence of the role of genes involved in meiotic recombination in the regulation of ovarian function.MSH5andDMC1mutations may be one explanation for POF, albeit uncommon.
A purification step prior to commercial sensitive immunoassay is necessary to achieve clinical usefulness when quantifying serum 17β-estradiol in prepubertal children
Authors: Ankarberg-Lindgren Carina , Norjavaara Ensio
Published: January 2008

Objective

To test the clinical usefulness of sensitive commercial immunoassays for determination of low 17β-estradiol concentrations in children.

Methods

The lower limit of detection and clinical usefulness (functional sensitivity) of three commercial estradiol immunoassays were validated by use of 500 sera from prepubertal and pubertal children and 55 pooled sera. The three immunoassays consisted of two modified direct immunoassays; one RIA (Spectria Estradiol RIA) and one time-resolved fluoroimmunoassay (AutoDELFIA Estradiol), both with increased serum volume in relation to antibody concentration and extended incubation time. In the third method, serum was purified and concentrated using diethyl ether extraction prior to measurement by the modified Spectria Estradiol RIA.

Results

The lower limits of detection and clinical usefulness were 9 and 30 pmol/l for the direct RIA, 11 and 50 pmol/l for the AutoDELFIA, and 4 and 6 pmol/l for serum determined by extraction RIA. When measuring the serum pool originating from girls at breast stages 1–2, the direct RIA and AutoDELFIA resulted in significantly higher 17β-estradiol concentrations when compared with the extraction RIA (+58 and +267%,P<0.001). We found a significant difference in 17β-estradiol concentrations between girls at breast stages 1 (median 6 pmol/l) and 2 (median 16 pmol/l), when quantified by the extraction RIA (P<0.0001) but no difference when quantified with the direct RIA (median values 12 and 14 pmol/l respectively).

Conclusion

For determination of low serum 17β-estradiol concentrations in children, an extraction step prior to commercial immunoassay is needed to achieve clinically useful results.
Ghrelin and acyl ghrelin in preterm infants and maternal blood: relationship with endocrine and anthropometric measures
Authors: Lányi Éva , Várnagy Ákos , Kovács Kálmán A , Csermely Tamás , Szász Mária , Szabó István
Published: January 2008

Objective

The objective of the present study was to examine the association of acylated and total ghrelin levels at birth in preterm infants with anthropometric features and with related hormones in infants and their mothers.

Design

Prospective, descriptive study.

Methods

In total 23 pregnant women and their 26 preterm infants were involved in the study (3 twin pregnancies; gestational age, 25–35 weeks). Maternal and umbilical vein blood samples were taken after the delivery. Serum acylated and total ghrelin, leptin, cortisol, insulin, GH, and glucose were determined.

Results

The mean level of acylated ghrelin concentration was higher in the maternal than in the cord blood (P<0.01) and there was a significant correlation between the fetal and maternal acylated ghrelin levels (P<0.01). The total ghrelin concentration was higher in neonates than in mothers (P<0.01), but there was no correlation between them. The multivariate regression analysis for fetal acylated and maternal total ghrelin as dependent variables shows that the fetal acylated ghrelin has two independent predictors, the maternal acylated ghrelin (P<0.01) and the fetal cortisol (P<0.05), whereas the maternal total ghrelin has only one independent predictor, the maternal glucose (P<0.05).

Conclusions

These data provide the first evidence that umbilical cord acylated ghrelin concentrations are lower than in maternal blood and support the hypothesis that the acylation process in the fetus is partly affected by cortisol and the placenta may play a role in this process.
TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study
Authors: Laurberg Peter , Wallin Göran , Tallstedt Leif , Abraham-Nordling Mirna , Lundell Göran , Tørring Ove
Published: January 2008

Introduction

Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism.

Objective

To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity.

Methods

Patients with newly diagnosed Graves' hyperthyroidism aged 20–55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients ≥35 years of age). l-thyroxine (l-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy.

Results

Medical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70–80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy.

Conclusion

The majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.
Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol
Authors: Dullaart Robin P F , Groen Albert K , Dallinga-Thie Geesje M , de Vries Rindert , Sluiter Wim J , van Tol Arie
Published: January 2008

Objective

We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol.

Design

In 76 subjects with and 94 subjects without MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined plasma (apo)lipoproteins, pre-β-HDL formation, phospholipid transfer protein (PLTP) activity, cholesterol esterification (EST), cholesteryl ester transfer (CET), adiponectin, and the ability of plasma from each subject to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single donor.

Results

Apo E, PLTP activity, EST, and CET were higher (P=0.04 to <0.001), whereas adiponectin was lower in MetS subjects (P<0.01). Pre-β-HDL and pre-β-HDL formation were not different between subjects with and without MetS. Cellular cholesterol efflux to plasma from MetS subjects was slightly higher versus plasma from subjects without MetS (8.8±1.0 vs 8.5±0.9%,P=0.05), but the difference was not significant after age, sex, and diabetes adjustment. Cellular cholesterol efflux was positively related to pre-β-HDL formation, EST, PLTP activity, and apo E (P<0.05 for all by multiple linear regression analysis), without an independent association with MetS and diabetes status.

Conclusions

The ability of plasma from MetS subjects to promote fibroblast cholesterol efflux is not defective, although HDL cholesterol is decreased. Higher cholesterol esterification, PLTP activity, and apo E levels may contribute to the maintenance of cholesterol efflux in MetS.
Relation of plasma homocysteine levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetic patients
Authors: Akalin Aysen , Alatas Ozkan , Colak Omer
Published: January 2008

Objective

Both hyperhomocysteinemia and increased inflammatory activity are shown to be associated with atherosclerosis. The relation of inflammatory activity to homocysteine (Hcy) levels is not well established. In the present study, we aimed to evaluate the relation of plasma Hcy levels to atherosclerotic vascular disease and inflammatory activity in type 2 diabetic patients.

Design and methods

In total 90 type 2 diabetic patients were included in the study. Of these patients, 41 had established atherosclerotic vascular disease and 49 had no evidence of atherosclerotic vascular disease. Hcy levels and markers of inflammation, namely C-reactive protein, fibrinogen, erythrocyte sedimentation rate, interleukin-6, and tumor necrosis factor α (TNFα), were measured. Glucose regulation, C-peptide, lipid parameters, and renal functions were also studied.

Results

Both Hcy levels and inflammation markers were all significantly elevated in patients with atherosclerotic vascular disease when compared with patients without vascular disease. Reduced renal functions were responsible for the majority of Hcy elevation in patients with vascular disease. Also, renal functions were significantly associated with both Hcy levels and inflammatory markers. There was no correlation between Hcy levels and inflammation markers except for TNFα.

Conclusions

Inflammatory activity and Hcy levels are increased in type 2 diabetic patients with atherosclerotic vascular disease. Impairment of renal functions is the key factor that affects both Hcy levels and inflammation markers. Inflammation is not involved in the process by which Hcy leads atherosclerosis in type 2 diabetes.
Restoration of ovulation after unilateral ovariectomy in a woman with McCune–Albright syndrome: a case report
Authors: Lavoué Vincent , Morcel Karine , Bouchard Philippe , Sultan Charles , Massart Catherine , Grall Jean-Yves , Lumbroso Serge , Laurent Marie-Christine
Published: January 2008

Introduction

McCune–Albright syndrome (MAS) is characterized by peripheral precocious puberty, café-au-lait spots, and polyostotic fibrous dysplasia. This syndrome is due to a post-zygotic mutation of the GNAS1 gene with mosaic distribution and unilateral predominance. Clinical manifestations depend on the tissues carrying the mutation. We describe the ovarian function before and after unilateral ovariectomy in a woman with MAS and bilateral distribution of the GNAS1 gene mutation.

Case report

A 33-year-old patient, previously diagnosed as having MAS, presented irregular menstrual cycles (30–180 days) and monophasic temperature curves. Transvaginal ultrasound and blood tests were repeated at 3-day intervals over 3 months. Findings included a persistent quiescent left ovary, a persistent polycystic right ovary, constantly high estradiol-17β (E2) levels, and very low FSH and LH levels. She also presented severe persistent pelvic pain. Because of unilateral ovarian activity, a unilateral right ovariectomy was performed as well as biopsy of the remaining left ovary. A GNAS1 gene mutation was identified in both ovaries. A regular monthly menstrual cycle was immediately restored. On day 3 of the menstrual cycle, E2 level was 30 pg/ml, FSH level was 7.5 mIU/ml, and LH level was 6.4 mIU/ml. On day 17, pelvic ultrasound showed one follicle of 25 mm in the left ovary. On day 21, the progesterone level was 13.1 ng/ml.

Discussion

This is the first report of ovulation being restored following unilateral ovariectomy in an adult patient suffering from severe MAS with GNAS1 gene mutation identified in both ovaries.
Hypothalamic–pituitary insufficiency following infectious diseases of the central nervous system
Authors: Schaefer S , Boegershausen N , Meyer S , Ivan D , Schepelmann K , Kann P H
Published: January 2008

Objective

Hypothalamic–pituitary insufficiency may have diverse causes. The aim of this study was to determine the incidence of hypothalamic–pituitary insufficiency in patients with previous infectious diseases of the central nervous system (CNS) of different etiologies and mild-to-moderate clinical course.

Design

Patient series. Basal and stimulated (insulin tolerance test) pituitary function testing was performed in 19 patients with previous neuroborreliosis, encephalitis, or meningitis following an interval of between 10 and 56 months (mean 26.1±13.1 months) after the acute event.

Results

Four patients (21%; two males, two females) showed an isolated corticotropic insufficiency (peak cortisol <181.25 μg/l during the insulin tolerance test). Two patients (11%, males) showed borderline gonadotropic insufficiency (basal testosterone between 2.4 and 3.0 μg/l). No patient had somatotropic or thyrotropic insufficiency or evidence for diabetes insipidus; all had prolactin concentrations within the reference range.

Conclusions

Hypothalamic–pituitary dysfunction and especially isolated corticotropic insufficiency may develop in a relevant proportion of patients after infectious diseases of the CNS.
Preliminary data on biochemical remission of acromegaly after somatostatin analogs withdrawal
Authors: Ronchi Cristina L , Rizzo Erica , Lania Andrea G , Pivonello Rosario , Grottoli Silvia , Colao Annamaria , Ghigo Ezio , Spada Anna , Arosio Maura , Beck-Peccoz Paolo
Published: January 2008

Objective

It is still unknown whether prolonged treatment with somatostatin analogs (SSTa) may cause a long-lasting disease remission in GH-secreting adenomas after drug discontinuation. The aim of the present study was to investigate the evolution of GH/IGF-I secretion and tumor mass after SSTa withdrawal in patients affected by acromegaly.

Patients and Design

A total of 27 patients with acromegaly (12de novoand 15 previously operated) were treated with SSTa for a median period of 48 months and considered optimally controlled in hormonal and neuroradiological terms. None of them were previously irradiated.

Methods

Basal GH, post-glucose GH nadir, IGF-I, clinical signs/symptoms, and metabolic parameters were evaluated after 12–16 weeks from drug withdrawal. Only patients who met the current criteria for disease remission remained in drug suspension being periodically re-evaluated for biochemical/clinical data and neuroradiological imaging.

Results

After 12–16 weeks withdrawal, 15 of the 27 patients had disease relapse and restarted SSTa, while 12 were considered ‘in disease remission’ (44% of total). Glucose metabolism improved in both euglycemic and diabetic patients after short-term SSTa discontinuation. Only one of the ten patients who reached 24 weeks withdrawal showed biochemical disease recurrence. On the whole, five of the patients still in remission after 6 months have already prolonged the follow-up over 12 months (median: 24 months), without clinical and biochemical/neuroradiological evidence of disease recurrence.

Conclusions

These preliminary data indicate a successful withdrawal of SSTa at least in a subset of well-responsive patients with acromegaly and challenge the previously held concept that medical therapy is always a lifelong requirement.
Effect of gender on lipid-induced insulin resistance in obese subjects
Authors: Vistisen Bodil , Hellgren Lars I , Vadset Torill , Scheede-Bergdahl Celena , Helge Jørn Wulff , Dela Flemming , Stallknecht Bente
Published: January 2008

Objective

In obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during a hyperinsulinemic–euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor the intramyocellular lipid deposition has been compared directly in obese females and males.

Design

We studied eight obese females and eight obese males (body mass index (BMI): 32.6±1.4 and 32.8±0.8 respectively, non significant (NS)) matched for cardiorespiratory fitness relative to lean body mass (43.7±1.6 and 47.6±1.3 ml/kg min respectively, NS).

Methods

Each subject underwent two hyperinsulinemic–euglycemic clamps with infusion of lipid or saline respectively. Furthermore, the subjects exercised during the last half an hour of each clamp.

Results

The lipid-induced reduction in glucose disposal during the clamp was similar in females and males (46±10 and 60±4% respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (P<0.001 andP=0.01 respectively). Muscle ceramide, triacylglycerol (TAG), diacylglycerol (DAG), and glycogen content were similar between sexes and remained unchanged during the clamp and when exercise was superimposed.

Conclusions

The lipid-induced inhibition of glucose disposal is similar in obese females and males. However, obese females are more insulin sensitive compared with obese males (both during saline and lipid infusion), which is not due to differences in the concentration of the muscle lipid intermediates such as ceramide and DAG.
Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes
Authors: Lund Søren S , Tarnow Lise , Frandsen Merete , Smidt Ulla M , Pedersen Oluf , Parving Hans-Henrik , Vaag Allan A
Published: January 2008

Objective

Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA1c). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here, we compared the effect of metformin versus repaglinide on postprandial metabolism in non-obese T2DM patients.

Design

Single-centre, double-masked, double-dummy, crossover study during 2×4 months involving 96 non-obese (body mass index≤27 kg/m2) insulin-naïve T2DM patients. At enrolment, patients stopped prior oral hypoglycaemic agents therapies and after a 1-month run-in period on diet-only treatment, patients were randomized to repaglinide (2 mg) thrice daily followed by metformin (1 g) twice daily or vice versa each during 4 months with 1-month washout between interventions.

Methods

Postprandial metabolism was evaluated by a standard test meal (3515 kJ; 54% fat, 13% protein and 33% carbohydrate) with blood sampling 0–6 h postprandially.

Results

Fasting levels and total area under the curve (AUC) for plasma glucose, triglycerides and free fatty acids (FFA) changed equally between treatments. In contrast, fasting levels and AUC of total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol and serum insulin were lower during metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: −0.17 mmol/l (−0.26; −0.08)). AUC differences remained significant after adjusting for fasting levels.

Conclusions

In non-obese T2DM patients, metformin reduced postprandial levels of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients with T2DM targeting fasting and postprandial glucose and lipid metabolism.
Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease
Authors: Castinetti F , Morange I , Jaquet P , Conte-Devolx B , Brue T
Published: January 2008

Context

Although transsphenoidal surgery remains the first-line treatment in Cushing's disease (CD), recurrence is observed in about 20% of cases. Adjunctive treatments each have specific drawbacks. Despite its inhibitory effects on steroidogenesis, the antifungal drug ketoconazole was only evaluated in series with few patients and/or short-term follow-up.

Objective

Analysis of long-term hormonal effects and tolerance of ketoconazole in CD.

Design

A total of 38 patients were retrospectively studied with a mean follow-up of 23 months (6–72).

Setting

All patients were treated at the same Department of Endocrinology in Marseille, France.

Patients

The 38 patients with CD, of whom 17 had previous transsphenoidal surgery.

Intervention

Ketoconazole was begun at 200–400 mg/day and titrated up to 1200 mg/day until biochemical remission.

Main outcome measures

Patients were considered controlled if 24-h urinary free cortisol was normalized.

Results

Five patients stopped ketoconazole during the first week because of clinical or biological intolerance. On an intention to treat basis, 45% of the patients were controlled as were 51% of those treated long term. Initial hormonal levels were not statistically different between patients controlled or uncontrolled. Ketoconazole was similarly efficacious as a primary or postoperative treatment. Among 15 patients without visible adenoma at initial evaluation, subsequent follow-up allowed identification of the lesion in five cases. No adrenal insufficiency was observed. Adverse effects were rare in patients treated long term.

Conclusions

Ketoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging.
Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men
Authors: Marsell Richard , Grundberg Elin , Krajisnik Tijana , Mallmin Hans , Karlsson Magnus , Mellström Dan , Orwoll Eric , Ohlsson Claes , Jonsson Kenneth B , Ljunggren Östen , Larsson Tobias E
Published: January 2008

Objective

Fibroblast growth factor-23 (FGF23) is a circulating factor involved in phosphate (Pi) and vitamin D metabolism. Serum FGF23 is increased at later stages of chronic kidney disease due to chronic hyperphosphatemia and decreased renal clearance. Recent studies also indicate that FGF23 may directly regulate the expression of parathyroid hormone (PTH) in vitro. Therefore, the objective of the current study was to determine the relationship between FGF23, PTH, and other biochemistries in vivo in subjects with no history of renal disease.

Design

Serum biochemistries were measured in a subsample of the population-based Swedish part of the MrOS study. In total, 1000 Caucasian men aged 70–80 years were randomly selected from the population.

Methods

Intact FGF23, Pi, calcium, albumin, estimated glomerular filtration rate (eGFR, calculated from cystatin C), PTH, and 25(OH)D3 were measured. Association studies were performed using linear univariate and multivariate regression analyses.

Results

The median FGF23 level was 36.6 pg/ml, ranging from 0.63 to 957 pg/ml. There was a significant correlation between log FGF23 and eGFR (r=−0.21; P<0.00001) and log PTH (r=0.13; P<0.001). These variables remained as independent predictors of FGF23 in multivariate analysis. In addition, log PTH (β=0.082; P<0.05) and eGFR (β=−0.090; P<0.05) were associated with log FGF23 in subjects with eGFR>60 ml/min. Only eGFR (β=−0.35; P<0.0001) remained as a predictor of log FGF23 in subjects with eGFR<60 ml/min.

Conclusions

Serum FGF23 and PTH are associated in vivo, supporting recent findings that FGF23 directly regulates PTH expression in vitro. Additionally, eGFR is associated with FGF23 in subjects with normal or mildly impaired renal function, indicating that GFR may modulate FGF23 levels independent of serum Pi.
Feed transition in larval rearing of bocudo, Steindachneridion scripta (Pisces, Pimelodidae), using Artemia spp. nauplii and artificial diet
Authors: Adamante W.B. , Weingartner M. , Nuñer A.P.O.
Published: January 2008

Feed transition of Steindachneridion scripta larvae was investigated using seven treatments in which the reference diet, Artemia spp. nauplii, was totally substituted for a 56% crude protein artificial diet in two-day intervals. Initially, all treatments were fed with Artemia spp. nauplii and, subsequently, during the transition period, feed was equally composed by Artemia sp. nauplii and artificial diet. Everyday, one of the treatments began the feed transition, which was implemented between the second and the eighth days of culturing. Two treatments were used as control: one exclusively fed Artemia spp. nauplii and another only with artificial diet. Total weight, total length, and survival rate were not influenced by the day in which feed transition was implemented (P>0.05), and their mean values (± SD) were 31.1±25.0mg, 13.3±1.5mm and 58.8±12.0%, respectively. This suggests that Steindachneridion scripta larvae adapted well the transition to artificial diet.
Photonic real-time monitoring of bacterial reduction in root canals by genetically engineered bacteria after chemomechanical endodontic therapy
Authors: Garcez Aguinaldo Silva , Nunez Silvia Cristina , Lage-Marques José Luis , Hamblin Michael R. , Ribeiro Martha Simões
Published: January 2008

Microbial infection plays an important role in the development of pulp necrosis and formation of periapical lesions. In vitro and in vivo research in this field, traditionally microbiological culture methods using paper point sampling and quantitative culture, faces difficulties in completely removing bacteria from the root canal system and analyzing sequential procedures. This study employed genetically engineered bioluminescent bacteria and a light-sensitive imaging system to allow real-time visualization of the infection. Ten extracted teeth incubated with P. aeruginosa were treated by mechanical instrumentation with K-files (#30 K-file, #35 K-file and #40 K-file) and chemical irrigation with sodium hypochlorite and hydrogen peroxide. Irrigation alone reduced the contamination in 18%; the first chemomechanical sequence (instrumentation with a #30 K-file + irrigation) provided 41% of reduction; the second sequence (#35 K-file + irrigation) achieved 62%; and the complete therapy (#30 K-file + #35 K-file + #40 K-file + irrigation) achieved 93% of bacterial reduction. These results suggest that the endodontic treatment is dependent on the association of a chemical and mechanical approaches and that root canal enlargement improves bacterial reduction probably because the irrigation has more access to the apical third.
Relationship between dental size and normal occlusion in Brazilian patients
Authors: Freire Sheila Medina , Nishio Clarice , Mendes Alvaro de Moraes , Quintão Cátia Cardoso Abdo , Almeida Marco Antonio
Published: January 2008

The present study was performed on dental casts and lateral cephalometric films of 30 Caucasian Brazilian individuals (15 males and 15 females) aged 18 to 27 years and 4 months, all presenting normal occlusion and satisfactory facial profile. The aims were to investigate the existence of dental discrepancies according to Bolton's criteria, to obtain mean values for overbite, overjet, curve of Spee and interincisal angle, and to demonstrate any correlation among these parameters. A single calibrated operator measured each variable characteristics and the process was recorded twice with an accurate modified digital caliper. It was observed that the sample of normal occlusion did not present any dental discrepancy among the 12 teeth of opposite arches. The overall ratio (91.46) and anterior ratio (77.83) were in accordance with those proposed by Bolton. The mean values for normal occlusion in this Brazilian sample were defined as: 2.45 mm for overbite; 1.92 mm for overjet; 1.01 mm for curve of Spee and 129.57° for interincisal angle. A statistically significant correlation was found between overjet and overbite.
A persistência da teoria da degeneração indígena e do colonialismo nos fundamentos da arqueologia brasileira
Authors: Noelli Francisco Silva , Ferreira Lúcio Menezes
Published: January 2008

Examina a persistência de certos fundamentos teóricos da arqueologia brasileira e do pensamento americanista. Por meio da comparação entre alguns temas da obra de personagens seminais como Karl Friedrich Philipp von Martius, Francisco Adolfo de Varnhagen e Betty Jane Meggers, analisam-se traços temáticos e políticos comuns que marcam uma secular continuidade da teoria da degeneração indígena e do argumento colonialista.
Tributo a Manoel da Gama Lobo (1835-1883), pioneiro na epidemiologia da deficiência de vitamina A no Brasil
Authors: Vasconcelos Francisco de Assis Guedes de , Santos Leonor Maria Pacheco
Published: January 2008

Analisa a contribuição do médico paraense Manoel da Gama Lobo à história da epidemiologia da deficiência de vitamina A no Brasil. Tem como foco central de investigação a obra "Da oftalmia brasiliana", publicada originalmente em 1865. A trajetória acadêmica de Gama Lobo, particularmente essa obra, nos leva a identificar estreitos laços de comunhão entre o cientista e o grupo de médicos da Escola de Medicina Tropicalista Baiana. Embora não se possa creditar a Gama Lobo uma possível filiação às idéias do movimento abolicionista, algumas das passagens de "Da oftalmia brasiliana" indicam que esse cientista foi, no mínimo, um defensor do direito humano à alimentação para os escravos brasileiros.
Un desafío a la justicia social peronista: la hidatidosis en la provincia de Buenos Aires, 1946-1952
Authors: Valobra Adriana
Published: January 2008

Analiza las políticas sanitarias del gobierno de Domingo Alfredo Mercante (1946-1952) - mano derecha de Juan Domingo Perón - en la provincia de Buenos Aires, Argentina, atendiendo a lo que fue una de sus más instigantes líneas de intervención: la erradicación de la hidatidosis. Visibilizando un problema largamente olvidado por la historiografía, especificaremos de qué modo el gobierno mercantiano colocó a la hidatidosis en la agenda estatal a través de una legitimación estadística, socioeconómica y simbólica. Luego, especificaremos las estrategias de esta gestión: sanción de leyes regulatorias contra la endemia, creación de instituciones específicas antihidatídicas estatales, generación de espacios de información y educación interdisciplinaria, interministerial y hasta supranacionales con el fin de alcanzar el mayor conocimiento sobre la enfermedad e intercambiar experiencias que enriquecieran su propia práctica y, finalmente, la definición de acciones enfocadas en el relevo, tratamiento y profilaxis de animales y personas.
Memórias de um corpo esquecido
Authors: Goia Jorge
Published: January 2008

Este artigo procura investigar os variados papéis ocupados pelo corpo humano enquanto objeto de estudo da psicologia. Utilizando recortes da história das ciências bio-médicas e da psicologia no Brasil, o autor propõe três períodos para sua análise: uma fase de determinismo biológico; depois, o abandono do corpo durante a hegemonia da psicanálise; e por fim a proliferação das terapias corporais impondo padrões de saúde. Apesar de apontarem pesos diferentes para o dualismo corpo/mente, estes modelos de psicologia continuam ativos. Uma nova abordagem para o corpo e a psicologia precisaria então discutir os aspectos políticos dentro do projeto das ciências modernas.
As tecnologias leves como geradoras de satisfação em usuários de uma unidade de saúde da família
Authors: Ferri Sonia Mara Neves , Pereira Maria José Bistafa , Mishima Silvana Martins , Caccia-Bava Maria do Carmo Guimarães , Almeida Maria Cecília Puntel de
Published: January 2008

O objetivo desta investigação foi avaliar a qualidade da assistência prestada em um núcleo de saúde da família (NSF), enfocando a satisfação dos usuários, com base nas tecnologias leves, bem como analisar aspectos dessa assistência, produtores de satisfação e de insatisfação, no que diz respeito ao vínculo, à responsabilização, à resolubilidade, às expectativas, aos relacionamentos, ao conforto e acesso, e identificar recomendações para intervenções locais. Após realizarmos uma caracterização geral da população atendida no serviço em estudo, selecionamos os sujeitos participantes da pesquisa. A coleta de dados deu-se por meio da entrevista semi-estruturada. A abordagem foi de natureza qualitativa, e os dados foram ordenados pelo método do Discurso do Sujeito Coletivo (DSC). A análise revela a importância atribuída, pelos usuários do serviço, às tecnologias leves, mas também a necessidade de diminuir o tempo de espera para as consultas e os encaminhamentos e obter o acesso a medicamentos e à atenção odontológica no próprio serviço, fatores que levam à grande insatisfação por parte dos usuários.
Considerações sobre os discursos do aconselhamento nos centros de testagem anti-HIV
Authors: Souza Vânia de , Czeresnia Dina
Published: January 2008

O objetivo do trabalho foi analisar a incorporação da prática de aconselhamento nos centros de testagem anti-HIV, como decorrência da construção discursivo-social da AIDS, no contexto da modernidade tardia e com base na proposição expressa pelo Programa Nacional de DST/AIDS do Brasil. Como principal referência analítica, foram tomadas as influências globais no processo de democratização dos discursos e das práticas modernas, contextualizadas por Fairclough. Utilizou-se também como referência teórica a evolução dos discursos preventivos veiculados desde a identificação da infecção e as tecnologias de poder disciplinar e de confissão. O aconselhamento contempla temas importantes, como tecnologização, reflexividade e diálogo. Pode-se identificar, nele, um jogo de ambigüidades entre os sistemas democrático e coercitivo, conjugando modos liberadores e disciplinares. Compreender o aconselhamento sob o ponto de vista dessa ambigüidade gera questionamentos ainda pouco investigados. É necessário entender a prática do aconselhamento do ponto de vista do usuário, a quem a proposta é dirigida.
Modelo computacional para suporte à decisão em áreas irrigadas. Parte I: Desenvolvimento e análise de sensibilidade
Authors: Borges Júnior João C. F. , Ferreira Paulo A. , Hedden-Dunkhorst Bettina , Andrade Camilo de L. T. de
Published: January 2008

Este trabalho se refere ao desenvolvimento de um modelo computacional para suporte à tomada de decisão, quanto ao planejamento e manejo de projetos de irrigação e/ou drenagem. O modelo computacional, denominado MCID, é aplicável em nível de unidade de produção, gerando informações sobre como diferentes práticas de manejo da irrigação e configurações do sistema de drenagem afetam a produtividade e o retorno financeiro. Essas informações podem ser empregadas em estudos de otimização de padrão de cultivo em nível de propriedade agrícola, em relação ao retorno financeiro e ao uso da água, associados à análise de risco com base em simulações. O balanço hídrico e de sais na zona radicular e as estimativas da profundidade do lençol freático e vazão nos drenos, são conduzidos em base diária. A análise de sensibilidade indicou que os parâmetros de entrada que mais influenciaram o requerimento de irrigação totalizado para o ciclo, foram espaçamento entre drenos, porosidade drenável, número da curva, condutividade hidráulica horizontal do solo saturado, profundidade da camada impermeável e os parâmetros n e alfa do modelo de van Genuchten-Mualem.
Cinética de produção de levedura seca em leito de jorro
Authors: Rocha Ana P. T. , Alsina Odelsia L. S. , Silva Vimário S. , Silva Flávio L. H. da
Published: January 2008

Estudou-se neste trabalho, a cinética de produção durante a secagem em um secador de leito de jorro convencional com inertes, trabalhando-se com alimentação intermitente de levedura, com umidade inicial de 70% em base úmida. Fez-se um planejamento fatorial 22 mais configuração estrela com 3 experimentos no ponto central, totalizando 11 experimentos, objetivando-se o estudo da influência da concentração de levedura e velocidade do ar na entrada sobre a cinética de produção de levedura seca. A cinética se mostrou crescente e praticamente linear em todos os experimentos. Esta análise permitiu a identificação das condições ideais de operação do secador com relação à velocidade de operação e de quantidade de levedura a ser alimentada para obtenção de um produto de qualidade para utilização como complemento protéico na alimentação de animais.