bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions and Attitudes about Corruption and Democracy in Mexico
Authors: Bailey John , Paras Pablo
Published: May 2006

Corruption is one of the most significant challenges confronting processes of democratic governability in Mexico. This article brings a methodological focus to bear on three sets of topics: (1) In what activities or instances of daily life do respondents claim to encounter corruption? (2) Who cares about corruption? That is, what is the salience of corruption to various groups? (3) What are the effects of perceptions of corruption on satisfaction with/support for democracy? Based on a secondary analysis of three data sets, our principal findings are that (1) the term, “corruption,” has several different meanings for respondents; (2) government is viewed as only slightly more corrupt than society; (3) if we include bribes as corruption, a rather small subset of the samples (about a quarter) claim to have directly experienced bribery; and (4) perceptions of corruption negatively influence satisfaction with democracy, and those who perceive corruption to be a significant problem are less likely to trust institutions or individuals. In addition to these findings, we speculate about a puzzle: If rather few respondents claim direct experience with corruption in their daily lives, why do so many express such firm and pessimistic views about corruption in so many distant spheres of political and social life?

La corrupción es uno de los retos más importantes que enfrenta el proceso de gobernabilidad democrática en México. El artículo presenta un enfoque metodológico para abordar tres preguntas: (1) según los entrevistados, ¿en qué actividades de la vida diaria se experimenta corrupción?; (2) ¿a quién le importa la corrupción?; es decir, ¿cuál es la prominencia de la corrupción para diferentes grupos?; y ¿cuáles son los efectos de las percepciones de corrupción en la apoyo y satisfacción democrática? Basados en investigación secundaria de tres bases de datos nuestros hallazgos son los siguientes: (1) la palabra, “corrupción,” tiene diferentes significados entre los entrevistados; (2) el gobierno es percibido sólo ligeramente más corrupto que la sociedad; (3) si incluimos las ‘mordidas’ como corrupción, un subgrupo de la muestra (un cuarto aproximadamente) dice haber participado directamente en los sobornos; y (4) las percepciones sobre la corrupción afectan negativamente la satisfacción con la democracia y aquellos que perciben que la corrupción es un problema grave son menos propensos a confiar en las instituciones y en los individuos. Además, especulamos sobre un enigma: si son pocos quienes afirman tener una experiencia directa con la corrupción, por qué tantos expresan un firme y marcado pesimismo sobre la corrupción en diversas esferas de la vida política y social?
Applied Anthropology in Ecuador: Development Practice and Discourse
Authors: Uquillas Jorge E. , Larreamendy Pilar
Published: May 2006

Applied anthropology in Ecuador has been influenced by both global and local contexts, particularly the development paradigms which have been in fashion in the last four or five decades and the political orientation and consequent academic curriculum of universities offering academic training in this field. Using the concept of “localized modernities,” this chapter analyzes how anthropology has contributed to the development process in Ecuador, a country characterized by a great social and cultural diversity. Responding to official efforts to build a unified nation‐state and to integrate indigenous peoples under the banner of “indigenism,” the practice of anthropology in the country initially focused on learning about the socioeconomic and cultural characteristics of indigenous communities and helping them to access some basic public goods and services. However, in more recent times, as a result of a changing international context favorable to the recognition of indigenous peoples rights and to the high degree of social organizations and mobilization of indigenous peoples, anthropologist have adapted their discourse and practice, largely becoming allies of indigenous peoples in their efforts not only to maintain their own cultures but also to participate in the political process. The case of PRODEPINE is presented as an example of how applied social scientists have contributed to strengthen indigenous peoples' social organization, as well as to improve their access to land and territories and key financial resources.
Applied Anthropology in Egypt: Practicing Anthropology within Local and Global Contexts
Authors: el‐Aswad el‐Sayed
Published: May 2006

This chapter discusses the locally and globally oriented domains of applied anthropology in Egypt. It examines the micro and macro factors that have both positive and negative impact on the progress of applied anthropology in Egypt, including extensive bureaucracy, inadequate education, insufficient funding, global violence, terrorism, security, civil society, and NGOs. Despite the challenging conditions of academic and applied research in Egypt, applied anthropology, as locally practiced but globally oriented, has developed new trends concerning the key theme of the local/global and related topics of such as development, environment, poverty, education, migration, violence, tourism, and media. A case study will examine some of these issues.
"Polemik im Concertsaal": Mahler, Beethoven, and the Viennese Critics
Authors: Knittel K.
Published: May 2006

"Polemic in the Concert Hall": the title of Richard Heuberger's article in the Neue freie Presse refers in no uncertain terms to the uproar surrounding Mahler's performances of Beethoven's Ninth Symphony in Vienna. The two performances, on 18 and 22 February 1900, used Mahler's own orchestral re-touchings of Beethoven's work, and Mahler's biographers have often identified these concerts as the first sustained attacks by the press, attacks that would, over time, only continue to increase in severity and frequency. When these concerts are placed into the context of reactions to Mahler's other Philharmonic concerts, however, this narrative of a "fall from grace" proves impossible to sustain. Not only was Mahler denounced for reorchestrating other works from his very first concert with the Vienna Philharmonic, but the language used to do so remained consistent throughout Mahler's tenure. Mahler, as a Jew, was not perceived as having the "right" to "improve" Beethoven--or any other composer for that matter. Although not overtly anti-Semitic, the language of the reviews resembles that found in Wagner's essay "Das Judentum in der Musik," where he outlines the Jewish composer's supposed handicaps: an emphasis on detail to the detriment of the whole, the prevalence of intellect over feeling, and an understanding of culture as merely "learnt" but never "mother tongue." An examination of the critical reactions points out these similarities while also suggesting that, particularly given Wagner's own suggestions (in 1873) for the reorchestration of Beethoven's symphony, the uproar had very little to do with what anyone heard.
Ultrasonographic and clinical parameters for early differentiation between precocious puberty and premature thelarche
Authors: de Vries Liat , Horev Gadi , Schwartz Michael , Phillip Moshe
Published: May 2006

Objective: To determine if uterine and ovarian measurements can significantly distinguish between precocious puberty (PP) and premature thelarche (PT) and whether ultrasound has any advantage over the gonadotropin-releasing hormone (GnRH) stimulation test.

Design: Prospective.

Methods: One hundred and three girls referred consecutively for evaluation of breast budding before age 8 years underwent physical examination, GnRH stimulation test, bone age assessment, and transabdominal pelvic ultrasound. The diagnosis of PP or PT was based on clinical judgment. The clinical, laboratory, and ultrasound data of the PP and PT groups were compared.

Results: Eighty-one girls were diagnosed with PP and 22 with PT. Significant differences in most of the uterine and ovarian measurements were found between the groups. On logistic regression analysis, bone age standard deviation score, uterine transverse diameter, and uterine volume were the most significant variables predicting PP. Comparison of 30 girls with PP and 21 with PT in whom peak luteinizing hormone was <5 mIU/ml on the GnRH stimulation test, using analysis of variance, yielded significant differences in uterine width (P<0.001), fundus diameter (P <0.04), uterine volume (P= 0.006), and ovarian circumference (P <0.02).

Conclusions: Increased uterine and ovarian measurements may be an early and sensitive sign of PP. Pelvic ultrasound, a noninvasive, inexpensive, and reliable tool, may give the clinician a complementary indication to the GnRH test in distinguishing isolated PT from early-stage PP in girls with early breast budding.
Phenotype and HFE genotype in a population with abnormal iron markers recruited from an Endocrinology Department
Authors: Vantyghem Marie-Christine , Fajardy Isabelle , Dhondt Florence , Girardot Caroline , D’Herbomez Michèle , Danze Pierre-Marie , Rousseaux Jean , Wemeau Jean-Louis
Published: May 2006

Objective: The aim of this study was to describe HFE genotype in a population of patients with altered iron markers recruited in an Endocrinology Department and to define the possible phenotype–genotype relationships.

Methods: A total of 156 patients with high serum ferritin concentrations (>300 ng/ml) or transferrin saturation (>45%) (I group), and a control group of 106 healthy subjects (C group) underwent HFE genotyping (classical C282Y and H63D mutations). We also examined the main genetic features of subgroups in I according to the presence (D) or the absence (ND) of diabetes.

Results: (1) The genotypes were significantly different in the I and C groups (P<0.001), with an increased frequency of major 282Y allele in the I group (35% vs 7.5%), but not of minor 63D allele (17 vs 18.5%). (2) The genotype of D and ND groups also differed (P<0.0001), with a lower frequency of C282 heterozygosity (P<0.0001) in the D group, and a higher prevalence of H63D heterozygosity in the D vs ND groups (P<0.01). (3) The phenotypic comparison of D and ND groups also showed a higher mean body mass index, age, and serum ferritin concentration, as well as an increased proportion of males with increased liver enzymes in the D group.

Conclusion: This population harboring abnormal iron markers had a different HFE genotype and a higher 282Y allele frequency than the control population. This suggests that blood iron markers could be checked in etiological investigations of metabolic disturbances to identify patients who should undergo genotyping, since approximately 20% were diagnosed with C282Y homozygosity.
Association of dehydroepiandrosterone-sulfate with endothelial function in young women with polycystic ovary syndrome
Authors: Dagre A , Lekakis J , Mihas C , Protogerou A , Thalassinou L , Tryfonopoulos D , Douridas G , Papamichael C , Alevizaki M
Published: May 2006

Objective: The aim of this study was to assess non-invasively endothelial function of young women with polycystic ovary syndrome (PCOS) in comparison with healthy age-matched women and a group of young women with idiopathic hirsutism (IH). The possible role of metabolic and hormonal parameters on endothelial function was also examined.

Design: Descriptive clinical trial.

Methods: Fifty-six women, 27 with PCOS, 16 with IH and 13 healthy age-matched women were studied. Endothelial function of resistance arteries was assessed by venous occlusion plethysmography. Metabolic and hormonal parameters were estimated in this study population.

Results: The duration of reactive hyperemia (durRH) was shorter in PCOS group when compared with normal controls (63.75 ± 13.33 s vs 113.18 ± 20.92 s, P = 0.036). A similar finding was observed when PCOS were compared with IH group (63.75 ± 13.33 s vs 105 ± 17.20 s, P = 0.05). The durRH did not differ between IH and control group (105 ± 17.20 s vs 113.18 ± 20.92 s, ns). A significant positive linear correlation was found between the durRH and dehydroepiandrosterone-sulfate (DHEA-S) levels (r = +0.48, P = 0.04) in the PCOS group. The basal insulin resistance index (HOMA) differed significantly between PCOS, IH and control groups. There was no significant correlation between durRH and HOMA index or testosterone levels in the PCOS group.

Conclusions: Endothelial dysfunction may be an early sign of cardiovascular system abnormalities in young PCOS women. It is possible that increased DHEA-S levels may offer a cardioprotective advantage that attenuates the effects of cardiovascular risk factors that accompany PCOS.
Thyrotropin, but not a polymorphism in type II deiodinase, predicts response to paroxetine in major depression
Authors: Brouwer Jantien P , Appelhof Bente C , Peeters Robin P , Hoogendijk Witte J G , Huyser Jochanan , Schene Aart H , Tijssen Jan G P , Van Dyck Richard , Visser Theo J , Wiersinga Wilmar M , Fliers Eric
Published: May 2006

Objective: The determinants of response to antidepressant treatment in major depression are unknown at present. The aim of the present study was to establish whether response is predicted by Hypothalamus–Pituitary–Thyroid (HPT) axis parameters or by a recently discovered polymorphism in the enzyme type II deiodinase (DII), which catalyzes the production of T3 in the brain.

Design: We analyzed prediction of response to paroxetine treatment by calculating response rates per tertile of HPT-axis parameters and per DII genotype.

Methods: Ninety-eight outpatients with major depression (DSM-IV) were included. Serum concentrations of TSH, FT4 and delta TSH in a DEX/CRH-TRH test were measured. In addition, the presence of a polymorphism in the DII sequence (Thr92Ala) was determined.

Results: The overall treatment response was 48 of 98 patients (49%). After exclusion of patients with subclinical hypothyroidism and/or TPO antibodies (n = 16), higher serum TSH significantly predicted response (response rate per tertile from low to high TSH: 36%, 42%, and 67%). Heterozygous patients for the DII polymorphism (44%) had slightly lower serum TSH (P = 0.03) as compared to patients with the wild-type DII (47%). The polymorphism was unrelated to treatment response.

Conclusion: Higher serum TSH was associated with response to paroxetine in patients with major depression.
Insulin-sensitizing agents in polycystic ovary syndrome
Authors: Pasquali Renato , Gambineri Alessandra
Published: May 2006

Insulin-sensitizing agents have been recently proposed as the therapy of choice for polycystic ovary syndrome (PCOS), since insulin resistance and associated hyperinsulinemia are recognized as important pathogenetic factors of the syndrome. Moreover, since almost all obese PCOS women and more than half of those of normal weight are insulin resistant, and therefore present some degree of hyperinsulinemia, the use of insulin sensitizers should be suggested in most patients with PCOS. Insulin sensitizer treatment has been associated with a reduction in serum androgen levels and gonadotropins, and with an improvement in serum lipids and in prothrombotic factor plasminogen-activator inhibitor type 1, whatever the insulin sensitizer used. This therapy has also been associated with a decrease in hirsutism and acne, and with a regulation of menses and an improvement of ovulation and fertility. Notable improvements in all these parameters have also been described after a change in lifestyle approach, particularly in the presence of obesity. Lifestyle interventions should therefore be combined with insulin sensitizers in PCOS when obesity is present.
Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant
Authors: Feenstra J , van Aken M O , de Herder W W , Feelders R A , van der Lely A J
Published: May 2006

We report on a patient with acromegaly who developed severe drug-induced hepatitis during combined treatment with the long-acting somatostatin-analog octreotide and the GH receptor antagonist pegvisomant. The hepatic enzyme disturbances normalized after discontinuation of pegvisomant. After rechallenge with monotherapy pegvisomant, however, the hepatic enzyme disturbances reappeared within a few weeks, indicating that most likely pegvisomant alone and not the long-acting somatostatin analog or the combination of these two drugs was responsible for this case of drug-induced hepatitis. Clinicians should be aware of this potential severe adverse drug reaction and therefore frequent control of hepatic enzymes is mandatory during treatment with pegvisomant.
Potential advantage of N363S glucocorticoid receptor polymorphism in 21-hydroxylase deficiency
Authors: Luczay A , Török D , Ferenczi A , Majnik J , Sólyom J , Fekete Gy
Published: May 2006

Objective: Congenital adrenal hyperplasia (CAH) shows a range of severity which is explained in part by the different mutations of the CYP21 gene. To better understand the incomplete concordance between genotype and phenotype in CAH the role of the sensitizing N363S polymorphism of the glucocorticoid receptor (GR) was examined in CAH patients.

Design: CAH patients were screened for N363S. Laboratory findings and clinical characteristics of carriers and non-carriers were analyzed retrospectively.

Methods: The CYP21 gene of 200 CAH patients was analyzed by allele-specific PCR. The GR gene was tested for N363S by PCR followed by restriction fragment length polymorphism. Antropometric data (height, weight), degree of intrauterine virilization, hormone concentrations (17-OH-progesterone, dehydroepiandrosterone (DHEA), aldosterone, testosterone, plasma renin activity), substitution doses and clinical course were analyzed.

Results: The carrier frequency of N363S in CAH patients was equivalent to that of the general Hungarian population (6% vs 7.8%). Interestingly, none of the non-classical CAH (NC-CAH) patients were carriers of the polymorphism. Carrier girls had milder genital virilization than mutation-matched non-carrier controls. There was no significant difference between the carriers and non-carriers in either the substitution doses, the hormonal, or the auxiological parameters.

Conclusions: The association of sensitizing the GR variant with impaired cortisol production in CAH might be compensatory in mild NC-CAH and may prevent severe intrauterine virilization in classical form. Although the exact role of N363S in extrauterine life should be further investigated, the consideration of certain genetic polymorphisms of CAH patients may lead to better, individualized therapeutic regimes.
GH deficiency in patients irradiated for acromegaly: significance of GH stimulatory tests in relation to the 24 h GH secretion
Authors: van der Klaauw A A , Pereira A M , van Thiel S W , Smit J W A , Corssmit E P M , Biermasz N R , Frolich M , Iranmanesh A , Veldhuis J D , Roelfsema F , Romijn J A
Published: May 2006

Background: Radiotherapy for pituitary adenomas frequently leads to GH deficiency (GHD). The characteristics of GH secretion in GHD induced by postoperative radiotherapy for acromegaly are not known.

Hypothesis: In the long term, stimulated and spontaneous GH release is not different between patients with GHD treated by postoperative radiotherapy for acromegaly or for other pituitary adenomas.

Design/subjects: We compared the characteristics of basal and stimulated GH secretion in patients with GHD, who had previously received adjunct radiotherapy after surgery for GH-producing adenomas (n=10) vs for other pituitary adenomas (n=10). All patients had a maximal GH concentration by insulin tolerance test (ITT) of 3 μg/l or less, compatible with severe GHD. Mean time after radiation was 17 and 18.7 years, respectively. Stimulated GH release was also evaluated by infusion of growth hormone-releasing hormone (GHRH), GHRH–arginine and arginine, and spontaneous GH by 10 min blood sampling for 24 h. Pulse analyses were performed by Cluster and approximate entropy.

Outcomes: There were no differences between both patient groups in stimulated GH concentrations in any test. Spontaneous GH secretion was not different between both patient groups, including basal GH release, pulsatility and regularity. Pulsatile secretion was lost in two acromegalic and three non-acromegalic patients. Insulin-like growth factor-I (IGF-I) was below −2 s.d. score in nine patients in each group.

Conclusion: Acromegalic patients treated by surgery and postoperative radiotherapy with an impaired response to the ITT do not differ, in the long term, in GH secretory characteristics from patients treated similarly for other pituitary tumors with an impaired response to the ITT. The ITT (or the GHRH–arginine test) is therefore reliable in establishing the diagnosis of GHD in patients treated for acromegaly by surgery and radiotherapy.
Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites
Authors: Schirpenbach Caroline , Seiler Lysann , Maser-Gluth Christiane , Rüdiger Frank , Nickel Christian , Beuschlein Felix , Reincke Martin
Published: May 2006

Objective: Primary aldosteronism has recently been recognized as the most frequent cause of secondary hypertension. Since most patients are normokalaemic, differentiation to essential hypertension is challenging. As differentiation by baseline aldosterone/renin ratio may be insufficient, diagnosis should be confirmed by additional tests. However, as most confirmatory tests have been evaluated in hypokalaemic primary aldosteronism only, we reassessed the value of the saline infusion test and 24 h urinary aldosterone metabolites as confirmatory tests for both normo- and hypokalaemic primary aldosteronism under current antihypertensive medication.

Patients and methods: 25 patients with primary aldosteronism (11 hypokalaemic, 14 normokalaemic), 29 patients with essential hypertension and 47 normotensive subjects were studied. The hypertensives received their usual medication with the exception of spironolactone. All subjects underwent a standard saline infusion test (determination of plasma aldosterone before and after 2.0 liters of isotonic saline for 4 hours i.v.) and collected a 24 h urine sample for examination of urinary tetrahydroaldosterone and aldosterone-18-glucuronide.

Results: In hypokalaemic primary aldosteronism the saline infusion test showed a reasonable sensitivity (91%) and specificity (90%). However, the test failed to differentiate sufficiently between essential hypertension and normokalaemic primary aldosteronism (sensitivity 57%, specificity 90%). Similarly, urinary tetrahydroaldosterone had higher sensitivity in hypokalaemic than in normokalaemic primary aldosteronism (sensitivity 64% vs 36%, specificity 100%), whereas for aldosterone-18-glucuronide, no differences in hypo- and normokalaemic primary aldosteronism were found (sensitivity 45% and 43%, specificity 100%).

Conclusions: These data show that the saline infusion test as an established test in classical hypokalaemic primary aldosteronism is not a reliable test in the normokalaemic variant of the disease. Due to its low accuracy, determination of urinary aldosterone metabolites did not prove useful in confirming either normo- or hypokalaemic patients. We conclude from our data that these tests should not be used as confirmatory testing in the normokalaemic variant of primary aldosteronism.
The adrenal gland may be a target of LH action in postmenopausal women
Authors: Alevizaki Maria , Saltiki Katerina , Mantzou Emily , Anastasiou Eleni , Huhtaniemi Ilpo
Published: May 2006

Objective: LH receptor expression and function have been demonstrated in the human adrenal cortex, but their involvement in normal adrenal function remains elusive. Because cortisol levels have been reported to be higher in postmenopausal women than in age-matched men, the aim of the present study was to investigate a possible association of adrenal function with the elevated LH levels in postmenopausal women.

Design and methods: A group of 112 endocrinologically normal postmenopausal women (mean age 67.6, range 50–88 years) was evaluated. A basal fasting morning sample of peripheral blood was taken for the determination of LH, cortisol, dehydroepiandrosterone-sulphate (DHEA-S), oestradiol (E2), testosterone, sex hormone-binding globulin (SHBG), insulin and glucose. Information about reproductive function, anthropometric parameters and arterial blood pressure was recorded.

Results: The correlation of LH and cortisol was bimodally distributed, with a significant linear correlation up to the LH level of 41 U/l (n = 78, P<0.01), after which the increase of cortisol levelled off. Significant associations were also found between serum DHEA-S and LH levels (P<0.05), as well as between cortisol and testosterone (P<0.0001), but not between E2 and LH. Multivariate analysis showed that the association of cortisol with LH was independent of age and testosterone; the association of DHEA-S with LH was independent of E2, cortisol and age. Significant associations were also found between E2, testosterone and DHEA-S levels (P<0.001).

Conclusions: These results indicate that adrenal cortisol and DHEA-S production may be stimulated by the highly elevated postmenopausal levels of LH; the physiological significance of this association and plausible contribution to the metabolic syndrome observed after the menopause remain to be evaluated.
Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes
Authors: Kapoor D , Goodwin E , Channer K S , Jones T H
Published: May 2006

Objective: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes.

Design: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes.

Methods: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone.

Results: Testosterone therapy reduced the HOMA index (−1.73 ± 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (−0.37 ± 0.17%, P = 0.03), as was the fasting blood glucose (−1.58 ± 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (−1.63 ± 0.71 cm, P = 0.03) and waist/hip ratio (−0.03 ± 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (−0.4 ± 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed.

Conclusions: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.
Endogenous sex hormones and risk factors for atherosclerosis in healthy Greek postmenopausal women
Authors: Lambrinoudaki Irene , Christodoulakos George , Rizos Demetrios , Economou Emmanuel , Argeitis John , Vlachou Sofia , Creatsa Maria , Kouskouni Evangelia , Botsis Dimitrios
Published: May 2006

Objective: To assess the association between endogenous sex hormones and risk factors for atherosclerosis in healthy postmenopausal women.

Design: Cross-sectional study in a university menopause clinic.

Methods: Serum sex hormones and lipid–lipoprotein profile, arterial pressure, homocysteine and insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-IR), were assessed in 598 healthy postmenopausal women not on hormone therapy.

Results: Compared with women in the lowest testosterone quartile (Q), women in the highest testosterone quartile had higher total cholesterol (Q1: 225.2 ± 41.3 vs Q4: 246.2 ± 38.4 mg/dl, P < 0.01), low-density lipoprotein (LDL)-cholesterol (Q1: 146.9 ± 37.2 vs Q4: 171.8 ± 35.3 mg/dl, P < 0.001), atherogenic index of plasma (AIP) (Q1: −0.224 ± 0.238 vs Q4: −0.087 ± 0.254, P < 0.01), apolipoprotein B (ApoB) (Q1: 100.7 ± 23.1 vs Q4: 113.9 ± 23.8 mg/dl, P < 0.001) and higher high-density lipoprotein (HDL)-cholesterol (Q1: 60.7 ± 14.5 vs Q4: 52.9 ± 13.0 mg/dl, P < 0.01). Accordingly, women in the highest free androgen index (FAI) quartile had higher AIP (Q1: −0.232 ± 0.254 vs Q4: −0.078 ± 0.243, P < 0.001) and ApoB (Q1: 102.4 ± 25.5 vs Q4: 114.2 ± 25.8 mg/dl, P < 0.01) and lower HDL-cholesterol (Q1: 62.0 ± 15.7 vs Q4: 51.9 ± 11.6 mg/dl, P < 0.001) and apolipoprotein A (Q1: 159.6 ± 25.6 vs Q4: 147.9 ± 24.1 mg/dl, P < 0.01) compared with women in the lowest FAI quartile. These differences remained significant after adjustment for age, body mass index (BMI), insulin resistance and social habits. The free estrogen index (FEI) exhibited similar associations to the FAI. HOMA-IR showed an independent positive association with total testosterone (Q1: 2.00 ± 1.36 vs Q4: 2.66 ± 1.60, P < 0.01), FAI (Q1: 1.70 ± 1.12 vs Q4: 3.04 ± 1.66, P < 0.001) and FEI (Q1: 1.70 ± 0.91 vs Q4: 3.08 ± 1.77, P < 0.001).

Conclusions: Increased androgenicity in healthy postmenopausal women is associated with an unfavorable cardiovascular risk profile. High endogenous estradiol is related to a pro-atherogenic lipid profile, an association which may, in part, be mediated by insulin resistance.
What is the evidence behind the evidence-base? The premature death of block-replace antithyroid drug regimens for Graves’ disease
Authors: Razvi Salman , Vaidya Bijay , Perros Petros , Pearce Simon H S
Published: May 2006

Block-replace and titration antithyroid drug regimens both give similar rates of medium- to long-term remission of hyperthyroid Graves’ disease. Recent meta-analysis, however, has suggested that titration regimens may be preferable owing to a higher rate of adverse events seen in the block-replace arms of published comparative studies. This article critically re-evaluates the evidence upon which these meta-analyses were based. We suggest that there is little objective evidence that is pertinent to current clinical practice to separate block-replace from titration antithyroid drug regimens and that both remain satisfactory approaches to the medical management of hyperthyroid Graves’ disease.
Tools for the Trade
Authors: Woolls David , Coulthard Malcolm
Published: May 2006

This paper describes and exemplifies the use of a series of computer programs, many of which have been specifically developed to analyse the short texts which are typical of much of the material with which forensic linguists work. The first part of the paper consists of a series of illustrations of how the programs could be used, or actually have been used, in cases of doubtful or disputed authorship, while the second half of the paper contains a more detailed description of the programs and information on how to obtain them.
Photoacclimation to Long‐Term Ultraviolet Radiation Exposure of Natural Sub‐Antarctic Phytoplankton Communities: Fixed Surface Incubations Versus Mixed Mesocosms
Authors: Hernando Marcelo , Schloss Irene , Roy Suzanne , Ferreyra Gustavo
Published: May 2006

Solar UVB radiation (280–320 nm) is known to have detrimental effects on marine phytoplankton. Associated with the seasonal ozone hole in Antarctica, stratospheric ozone depletion occasionally influences the sub‐Antarctic (Beagle Channel, Argentina) region, enhancing levels of UVB. The primary objective of this work was to study the effects of several (i.e. 6–10) days of exposure to UVB on the taxonomic composition and photosynthetic inhibition of local phytoplankton communities. For different light treatments, fixed‐depth incubations placed in an outdoors water tank were compared with incubations in 1900 L mesocosms, where vertical mixing was present. Phytoplankton growth was inhibited by UV radiation (UVR) in fixed‐depth experiments but not in the mixed mesocosms. Under fixed and mixed conditions alike, photosynthesis was significantly inhibited by UVB at the beginning of the experiment but no longer after several days of exposure, suggesting that cells had acclimated to radiation conditions. There was a change in species composition in response to UVR exposure in both experiments, which likely explained acclimation. In the community exposed to fixed conditions this change was from a phytoflagellate‐dominated assemblage to a community with high relative abundance of diatoms after 6 days of exposure. UVA was responsible for most of the observed growth inhibition; however, the reduction in photosynthesis was produced by UVB. The reasons behind this variability in responses to UVR are associated with species‐specific sensitivity and acclimation, and the previous light history of cells. In the community exposed in mesocosms, an assemblage codominated by phytoflagellates and diatoms was observed at the beginning of the experiments. After 10 days of exposure, green algae (Eutreptiella sp) had increased, and phytoflagellates were the dominant group. The synthesis of mycosporine‐like amino acids (MAAs), antioxidant enzymes and photosynthetic antenna pigments, in relation to repair and protection processes, may explain the reduced inhibition of both growth and photosynthesis that was observed in the phytoplankton community after several days of exposure. For environments such as the Beagle Channel seasonally exposed to the ozone hole, the results obtained from the fixed‐depth experiments show that species can cope with UVR by means of MAA synthesis, while mixing would primarily promote a change in species composition and defense strategies.
Ultraviolet‐B Radiation Effects on the Structure and Function of Lower Trophic Levels of the Marine Planktonic Food Web
Authors: Ferreyra Gustavo A. , Mostajir Behzad , Schloss Irene R. , Chatila Khaled , Ferrario Martha E. , Sargian Peggy , Roy Suzanne , Prod'homme Johann , Demers Serge
Published: May 2006

The impact of UV‐B radiation (UVBR; 280–320 nm) on lower levels of a natural plankton assemblage (bacteria, phytoplankton and microzooplankton) from the St. Lawrence Estuary was studied during 9 days using several immersed outdoor mesocosms. Two exposure treatments were used in triplicate mesocosms: natural UVBR (N treatment, considered as the control treatment) and lamp‐enhanced UVBR (H treatment, simulating 60% depletion of the ozone layer). A phytoplankton bloom developed after day 3, but no significant differences were found between treatments during the entire experiment for phytoplankton biomass (chlorophyllaand cell carbon) nor for phytoplankton cell abundances from flow cytometry and optical microscopy of three phytoplankton size classes (picoplankton, nanoplankton and microplankton). In contrast, bacterial abundances showed significantly higher values in the H treatment, attributed to a decrease in predation pressure due to a dramatic reduction in ciliate biomass (∼ 70–80%) in the H treatment relative to the N treatment. The most abundant ciliate species wereStrombidiniumsp.,Prorodon ovumandTintinnopsissp.; all showed significantly lower abundances under the H treatment.P. ovumwas the less‐affected species (50% reduction in the H treatment compared with that of the N control), contrasting with ∼90% for the other ones. Total specific phytoplanktonic and bacterial production were not affected by enhanced UVBR. However, both the ratio of primary to bacterial biomass and production decreased markedly under the H treatment. In contrast, the ratio of phytoplankton to bacterial plus ciliate carbon biomass showed an opposite trend than the previous results, with higher values in the H treatment at the end of the experiment. These results are explained by the changes in the ciliate biomass and suggest that UVBR can alter the structure of the lower levels of the planktonic community by selectively affecting key species. On the other hand, linearity between particulate organic carbon (POC) and estimated planktonic carbon was lost during the postbloom period in both treatments. On the basis of previous studies, our results can be attributed to the aggregation of carbon released by cells to the water column in the form of transparent exopolymer particles (TEPs) under nutrient limiting conditions. Unexpectedly, POC during such a period was higher in the H treatment than in controls. We hypothesize a decrease in the ingestion of TEPs by ciliates, in coincidence with increased DOC release by phytoplankton cells under enhanced UVBR. The consequences of such results for the carbon cycle in the ocean are discussed.
Loss of parafibromin expression in a subset of parathyroid adenomas
Authors: Juhlin C , Larsson C , Yakoleva T , Leibiger I , Leibiger B , Alimov A , Weber G , Höög A , Villablanca A
Published: May 2006

Inactivation of the hyperparathyroidism–jaw tumour syndrome (HPT– JT) gene, HRPT2, was recently established as a genetic mechanism in the development of parathyroid tumours. Its encoded protein parafibromin has tumour-suppressor properties that play an important role in tumour development in the parathyroids, jaws and kidneys. Inactivating HRPT2 mutations are common in HPT– JT and parathyroid carcinomas, and have been described in a few cases of parathyroid adenomas with cystic features. In this study, 46 cases of cystic parathyroid adenomas previously investigated for HRPT2 mutations were characterized with regard to MEN1 gene mutations, cyclin D1 expression and parafibromin expression. In normal tissues and cell lines, parafibromin was ubiquitously expressed. Furthermore, parafibromin was detected as a dominating nuclear and a weaker cytoplasmic signal in transfected cell lines. In the three parathyroid tumours with inactivating HRPT2 mutations parafibromin expression was not detectable, and in one of two cases with aberrantly sized parafibromin the protein was delocalized. Both high and low cyclin D1 levels were found among HRPT2-mutated and -unmutated tumours, suggesting that these events are not mutually exclusive in parathyroid tumour development. The presented data suggest that in the majority of benign parathyroid tumours the expression of parafibromin remains unaltered, while the loss of parafibromin expression is strongly indicative of gene inactivation through mutation of the HRPT2 gene.
Nitric oxide impairs the 17β-estradiol-induced apoptosis in human colon adenocarcinoma cells
Authors: Marino M , Galluzzo P , Leone S , Acconcia F , Ascenzi P
Published: May 2006

Nitric oxide (NO) and 17β-estradiol (E2) are both important in gastrointestinal health and disease. NO contributes to gastrointestinal motility as well as to inflammation and carcinogenic processes. By contrast, E2 reduces the incidence of colon adenoma and carcinoma by about 30%. We report the genomic and non-genomic E2–estrogen receptor (ER) β-induced effects in human colon adenocarcinoma. The effect of NO on ERβ activities was also assessed. The E2-ERβ-dependent gene transcription was inhibited by exogenous NO, whereas some non-genomic E2-dependent effects (e.g. p38/MAP kinase), important for the activation of the apoptotic cascade, were unaffected by NO. However, NO impaired the E2-induced pro-apoptotic cascade in human colon adenocarcinoma cells by inhibiting caspase-3. The effects of NO may reflect chemical modification(s) of Cys residues present in the DNA recognition domain of ERβ as well as in the caspase-3 active site. On the whole, high NO concentrations suppressed the E2 protective effects in the gastrointestinal tract, suggesting that the caspase-dependent apoptotic cascade may become critical under conditions of high redox stress such as occur under specific activation of the immune system by chronic infections or pathogen challenge.
The pleiotropic roles of transforming growth factor beta in homeostasis and carcinogenesis of endocrine organs
Authors: Fleisch Markus C , Maxwell Christopher A , Barcellos-Hoff Mary-Helen
Published: May 2006

Transforming growth factor β (TGF-β) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-β is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary glands. This review will address the role of TGF-β in regulating hormone-dependent proliferation and morphogenesis. The subversion of TGF-β regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition, will also be examined. An understanding of the multiple and complex mechanisms of TGF-β regulation of epithelial function, and the ultimate loss of TGF-β function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.
The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R
Authors: Gross David J , Munter Gabriel , Bitan Menachem , Siegal Tali , Gabizon Alberto , Weitzen Ronny , Merimsky Ofer , Ackerstein Aliza , Salmon Asher , Sella Avishai , Slavin Shimon , _ _
Published: May 2006

Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked clinical activity against the disease. Since both PDGF-R and c-kit both having a putative role in tumorigenesis, we investigated the efficacy and safety of the use of IM in patients with endocrine tumors unresponsive to conventional therapies that expressed c-kit and/or PDGF-R (within the framework of a comprehensive phase II multi-center study of IM in patients with solid tumors). IM was initiated at a dose of 400 mg/day, with possible dose escalation within 1 week to 600 mg/day and an option to raise the dose to 800 mg/day in the event of progression and in the absence of safety concerns for a period of up to 12 months. Between September 2002 and July 2003, 15 adult patients with disseminated endocrine tumors were recruited as follows: medullary thyroid carcinoma (MTC, n = 6); adrenocortical carcinoma (ACC, n = 4); malignant pheochromocytoma (pheo, n = 2); carcinoid (non-secreting, n = 2), neuroendocrine tumor (NET, n = 1). No objective responses were observed. MTC – disease progression in 4 patients, and treatment discontinuation in 2 patients due to adverse events; ACC – disease progression in 3 patients, and treatment discontinuation in 1 patient due to severe psychiatric adverse event; Pheo – disease progression in 2 patients; Carcinoid – stable disease in 1 patient (6.5 months), and disease progression in 1 patient; NET – disease progression in 1 patient. IM does not appear to be useful for treatment of malignant endocrine tumors, also causing significant toxicity in this patient population.
A new form of familial multi-nodular goitre with progression to differentiated thyroid cancer
Authors: Bakhsh A , Kirov G , Gregory J W , Williams E D , Ludgate M
Published: May 2006

We report a kindred with euthyroid multi-nodular goitre (MNG) of adolescent onset. Two of the seven subjects with MNG have progressed to papillary thyroid cancer. One affected male had nodular kidney disease, and breast cancer occurred in one affected female. Genes that were candidates on the basis of the associated kidney (PAX8) and breast diseases (sodium iodide symporter (NIS)), were sequenced. No mutations were found in the coding region, intron/exon splice sites or in the promoter sequences (from −1248 relative to the translation initiation codon) of PAX8. Similar results were obtained for NIS. Subsequently, microsatellite analyses were performed on 14 informative family members. We used 2 to 3 markers per locus for 6 loci (on chromosomes 1,2,3,14,19,X) previously reported to predispose to MNG and/or familial non-medullary thyroid cancer (FNMTC). On the basis of non-significant logarithm of the odds ratio (LOD) scores or inheritance of different alleles in affected individuals, all loci have been excluded. Thyroidectomy specimens from three members of the kindred show multiple benign lesions, with papillary cancer in two. The morphological features do not resemble those seen in familial adenomatous polyposis, Cowden syndrome, or in multiple oxyphil lesions. From these findings and from the absence of any linkage to any of the known loci associated with MNG or FNMTC, we suggest that this represents a new form of inherited MNG with a significant risk of progression to papillary carcinoma.
Folic acid and its metabolites modulate IGF-I receptor gene expression in colon cancer cells in a p53-dependent manner
Authors: Attias Z , Werner H , Vaisman N
Published: May 2006

The insulin-like growth factor-I receptor (IGF-IR) has an important role in colorectal cancer development and progression. IGF-IR displays a potent anti-apoptotic activity and is overexpressed in primary tumors and colon cancer-derived cell lines. Folic acid, a member of the vitamin B family, is a chemopreventive agent whose deficiency has been linked to an enhanced colon cancer risk. The present study was aimed at testing the hypothesis that part of the modulatory effect of folic acid on malignant transformation may be attributed to its ability to regulate IGF-IR gene expression. Regulation of IGF-IR gene expression by folic acid was assessed using western blots, RT-PCR, transient transfections and chromatin immunoprecipitation assays. Activation of the IGF-IR signaling pathway was evaluated by measuring phosphorylation of ERK, and apoptosis was assayed using poly (ADP-ribose) polymerase cleavage and annexin V-FITC staining. Results obtained showed that folic acid induced a dose-dependent decrease in IGF-IR protein and mRNA levels in the HCT116 +/+ colon cancer cell line. This effect was associated with a significant reduction in IGF-IR promoter activity. Similar effects were elicited by the folic acid metabolites dihydrofolic acid and tetrahydrofolic acid. In addition, folic acid abrogated the IGF-I-stimulated phosphorylation of the downstream signaling molecule ERK1/2 and exhibited a pro-apoptotic activity. Moreover, folic acid induced a significant decrease in Sp1 binding to the IGF-IR promoter region. Finally, folic acid had no effect in wild-type p53-depleted HCT116 −/− and Caco-2 cells. In conclusion, the mechanism of action of folic acid involves regulation of IGF-IR gene expression. The ability of folic acid to downregulate the IGF-I signal transduction pathway may allow the micronutrient to function as a chemopreventive agent. Folic acid deficiency, on the other hand, may lead to increased IGF-IR gene expression, with ensuing pathological activation by endocrine and/or autocrine/paracrine IGF-I.