bluuebunny/crossref_metadata_2025 huggingface dataset:
Empowering Automated Trading in Multi‐Agent Environments
Authors: Ash David W.
Published: October 2004

Trading in the financial markets often requires that information be available in real time to be effectively processed. Furthermore, complete information is not always available about the reliability of data, or its timeliness—nevertheless, a decision must still be made about whether to trade or not. We propose a mechanism whereby different data sources are monitored, using Semantic Web facilities, by different agents, which communicate among each other to determine the presence of good trading opportunities. When a trading opportunity presents itself, the human traders are notified to determine whether or not to execute the trade. The Semantic Web, Web Services, and URML technologies are used to enable this mechanism. The human traders are notified of the trade at the optimal time so as not to either waste their resources or lose a good trading opportunity. We also have designed a rudimentary prototype system for simulating the interaction between the intelligent agents and the human beings, and show some results through experiments on this simulation for trading of the Chicago Board Options Exchange (CBOE) options.
A Weighted‐Tree Similarity Algorithm for Multi‐Agent Systems in E‐Business Environments
Authors: Bhavsar Virendrakumar C. , Boley Harold , Yang Lu
Published: October 2004

A tree similarity algorithm for match‐making of agents in e‐Business environments is presented. Product/service descriptions of seller and buyer agents are represented asnode‐labeled, arc‐labeled, arc‐weightedtrees. A similarity algorithm for such trees is developed as the basis for semantic match‐making in a virtual marketplace. The trees are exchanged using an XML serialization in Object‐Oriented RuleML. Correspondingly, we use the declarative language Relfun to implement the similarity algorithm as a parameterized, recursive functional program. Three main recursive functions perform a top‐down traversal of trees and the bottom‐up computation of similarity. Results from our experiments aiming to match buyers and sellers are found to be effective and promising for e‐Business/e‐Learning environments. The algorithm can be applied in all environments where weighted trees are used.
A Hybrid Intelligent Multiagent System for E‐Business
Authors: Wickramasinghe L. K. , Amarasiri R. , Alahakoon L. D.
Published: October 2004

The paper describes a new multiagent system with enhanced capabilities obtained through a hybrid of intelligent techniques. The processing in the model is handled by two types of agents: distributed agents and a central administrator agent. Localized processing at the individual agents is carried out using mathematical techniques and genetic algorithms. The central administrator agent dynamically obtains information about the problem domain from the Internet and maintains a knowledge pool using a clustering technique called the growing self‐organizing map (GSOM). Distributed agents communicate with the central administrator agent if they need further knowledge about the problem domain to provide solutions to user‐defined tasks. The approach integrates traditional mathematical, data mining, and evolutionary techniques with a multiagent system. The proposed system is implemented as a travel optimizer application for the e‐tourism domain. Finally, the possibilities of integrating the proposed technique with currently available e‐tourism applications to provide the customer with enhanced solutions are identified.
Agent‐Based Web Services Framework and Development Environment
Authors: Li Yinsheng , Shen Weiming , Ghenniwa Hamada
Published: October 2004

The current Web services technologies have not exploited sufficient semantics and approaches to dynamic service‐oriented operations in open environments. This paper argues that such operations can be realized through agent‐oriented interaction approaches. The key challenge is to develop an integration framework for the two paradigms, agent‐ and service‐oriented, in a way that capitalizes on their individual strengths. This paper proposes the notion of agent‐based Web services (AWS). We address several critical issues, including the appropriate architectural framework and the structure of its main elements (agent‐based Web services), their meta‐model, supporting technologies, integration method, and implementation approach. An integrated development environment for this framework called SOAStudio has been developed and tested by implementing a case study of a reverse auction e‐marketplace.
A Conversational Approach to the Interaction With Web Services
Authors: Ardissono Liliana , Petrone Giovanna , Segnan Marino
Published: October 2004

The emerging standards for the specification of Web Services support the publication of the static interfaces of the operations they may execute. However, little attention is paid to the management of long‐lasting interactions between the service providers and their consumers. Although this is not an issue in the case of “one‐shot” services, it challenges the provision of services requiring the exchange of multiple messages between the business partners. In this article, we present a conversational model supporting the management of long‐lasting interactions where several messages have to be exchanged before the service is completed. Our model aims at facilitating the consumers during the service invocation because in this way the establishment of short‐term business relations can be simplified. To this extent, we provide a computational framework that can be exploited to manage a conversation between the consumer and the service provider. Our framework is inspired from the research developed in Computational Linguistics and in the area of Multi‐Agent Systems to manage human‐to‐computer and agent‐to‐agent dialog. However, we employ techniques suitable to comply with the emerging Web Service standards and with the scalability requirements of the Internet.
Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight
Authors: Kotani Yumiko , Yokota Ichiro , Kitamura Seiko , Matsuda Junko , Naito Etsuo , Kuroda Yasuhiro
Published: October 2004

objective  The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones.

design  Venous cord blood samples were obtained from 59 full‐term healthy newborns (36 males and 23 females, gestational age 37·0–41·4 weeks, birth weight 2,146–4,326 g, birth length 44·0–54·5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3–7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined.

measurements  The adiponectin concentration was determined by enzyme‐linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF‐1 concentrations were determined by immunoradiometric assays.

results  The plasma adiponectin concentrations in cord blood ranged from 6·0 to 55·8 µg/ml (median 22·4 µg/ml), which were much higher than those in normal‐weight adults (P < 0·0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0·43, P = 0·0005), body mass index (r = 0·44, P = 0·0005), birth weight/birth length ratio (r = 0·46, P = 0·0002) and the leptin concentrations (r = 0·39, P = 0·004). When the effects of fat mass‐related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = −0·35, P = 0·01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3–7) did not change significantly compared with those in cord blood.

conclusions  In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.
Abnormalities of proinsulin processing in functioning insulinomas: clinical implications
Authors: Wiesli Peter , Perren Aurel , Saremaslani Parvin , Pfammatter Thomas , Spinas Giatgen A. , Schmid Christoph
Published: October 2004

objective  Abnormal proinsulin processing in insulinomas may result in secretory granules containing both insulin and proinsulin, a finding not encountered in healthy β‐cells. The aim of this study was to test whether such abnormalities in the proinsulin to insulin conversion have clinical implications in patients with hypoglycaemic disorders.

design  Case‐series.

patients and methods  Fifteen patients with histologically confirmed insulinoma and two patients with islet cell hyperplasia were included. The immunohistochemical distribution pattern of proinsulin within the tumour cells was classified as Golgi pattern (predominantly perinuclear immunolabelling) or diffuse pattern (immunolabelling in the periphery of the cells, indicating the presence of proinsulin in secretory granules). Data obtained from the 72‐h fast and arterial calcium stimulation and hepatic venous sampling (ASVS) test were related to the morphological classification.

results  Six insulinomas exhibited a diffuse proinsulin distribution pattern, while nine insulinomas and two islet cell hyperplasias disclosed a Golgi pattern. Median proinsulin concentrations at the termination of the fast tended to be higher in patients with the diffuse proinsulin distribution pattern than in patients with the Golgi pattern (86·9 vs. 18·8 pmol/l, P = 0·07). Higher insulin (P < 0·005) and proinsulin (P < 0·05) concentrations were significantly correlated with earlier occurrence of hypoglycaemia during the prolonged fast. During the ASVS test, tumours with the diffuse proinsulin distribution pattern exhibited a higher increase in both insulin (median, 37·3‐ vs. 10·5‐fold, P < 0·05) and proinsulin (6·3‐ vs. 1·6 fold, P < 0·005) concentrations following calcium stimulation than the tumours with the Golgi pattern.

conclusions  Abnormalities in the proinsulin to insulin conversion in patients with insulinomas and islet cell hyperplasia correlate with impaired regulation of both insulin and proinsulin secretion during the prolonged fast as well as the ASVS test.
Inhibition of endothelial proliferation by the somatostatin analogue SOM230
Authors: Adams Robyn L. , Adams Ian P. , Lindow Stephen W. , Atkin Stephen L.
Published: October 2004

objective  Somatostatin (SST) modulates exocrine and endocrine secretion, proliferation and apoptosis via five G protein‐linked receptors (SSTRs 1–5). Long‐acting SST analogues such as Octreotide, and the new analogue SOM230, have been developed for the treatment of neuroendocrine tumours. Octreotide has previously been reported to inhibit endothelial proliferation. We wished to determine if SOM230 is a more potent inhibitor of endothelial cell proliferation than Octreotide.

design  We have determined the expression of SSTRs in proliferating human umbilical vein endothelial cells (HUVECs) in vitro, and determined their response to the somatostatin analogues SOM230 and Octreotide, following vascular endothelial growth factor (VEGF) stimulation.

measurements  Quantitative RT–PCR and western blotting were used to determine the expression of SSTRs 1–5 in proliferating HUVECs. These cells were grown in media containing 200 pg/ml VEGF and treated with 10−11 to 10−6 M Octreotide or SOM230. The WST‐1 assay was then used to determine the effects of these analogues on HUVEC proliferation.

results  Using quantitative RT–PCR and western blotting, HUVECs were found to express SSTRs 1, 2 and 5. SSTRs 3 and 4 were not detected. Using the WST‐1 assay, SOM230 was found to significantly inhibit proliferation by up to 46·0% ± 9·4% (10−6–10−7 M; P < 0·05), whereas in parallel studies Octreotide failed to inhibit HUVEC proliferation.

conclusions  The pan SST analogue SOM230 inhibits proliferation of HUVECs, which are unaffected by Octreotide. SOM230 may thus represent a suitable candidate drug for antiangiogenic therapy.
Bone mineral density in hyperthyroidism
Authors: Karga Helen , Papapetrou Peter D. , Korakovouni Areti , Papandroulaki Fotini , Polymeris Antony , Pampouras George
Published: October 2004

objective  To investigate whether previous hyperthyroidism is a cause of permanent secondary osteoporosis.

design and patients  In this cross‐sectional study, 164 women with untreated or previously treated overt and symptomatic hyperthyroidism were examined 0–31 years after the initial episode of hyperthyroidism and its treatment, and were compared with a control group of 79 age‐matched women without previous history of hyperthyroidism. Subjects with current or previous metabolic bone disease, any antiresorptive treatment for osteoporosis or treatments and habits known to affect bone metabolism were excluded.

measurements  The age of the first manifestation of the disease, the age at the measurement of bone mineral density (BMD) at the spine and femoral neck and the interval between diagnosis and treatment of hyperthyroidism and BMD measurement were recorded and the Z‐scores and T‐scores of BMD were analysed.

results  Untreated hyperthyroidism and hyperthyroidism up to 3 years after its diagnosis and treatment were associated with decreased BMD. Three or more years after the first episode of the disease the mean Z‐score at both skeletal sites was near zero and not different from the controls. The age at which hyperthyroidism was manifested for the first time had no effect on the final outcome. Women affected at a young age (13–30 years) had a more pronounced loss of BMD when examined untreated or early (< 3 years) after diagnosis, but a BMD significantly above zero if examined later (> 3 years). Older women (aged 51–70 years) showed a similar pattern, although the differences were not significant. Middle‐aged subjects (31–50 years) had the smallest loss of BMD during the first 3 years. Analysis of T‐scores of former hyperthyroid women aged ≥ 51 years showed no significantly different relative risk (RR) for osteoporosis in comparison with the controls. However, the study was not powered enough to give meaningful RR results.

conclusions  Overt symptomatic hyperthyroidism is associated with decreased BMD during the first 3 years after diagnosis and treatment of the disease. After this interval, former hyperthyroid women have a Z‐score near zero and not different from women without a history of the disease, apparently because of recovery of the bone density lost early during the course of the disease. Symptomatic hyperthyroidism does not seem to be a cause of long‐lasting osteoporosis, and the age of the patient during the first episode is irrelevant.
Insulin sensitivity in growth hormone‐deficient children: influence of replacement treatment
Authors: Radetti Giorgio , Pasquino Bruno , Gottardi Elena , Contadin Isabella Boscolo , Rigon Franco , Aimaretti Gianluca
Published: October 2004

objective  In adults, excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed children. The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of GH‐deficient children treated with GH for a period of 6 years.

patients and design  One hundred and twenty‐eight children (40 females, 88 males) were included in the study. At the beginning of treatment chronological age was 8·9 ± 3·2 years, height standard deviation score (SDS) −2·43 ± 0·90 and body mass index (BMI) SDS 0·18 ± 1·60. At the end of the study chronological age was 13·0 ± 2·9 years, height SDS −1·24 ± 1·27 and BMI SDS 0·23 ± 1·54. GH was administered at a mean weekly dosage of 0·3 mg/kg, injected subcutaneously over 6–7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICKI).

results  No cases of impaired GT or diabetes were recorded during the follow‐up period. IS, already lower than in controls before starting treatment with GH, decreased significantly during the first year of therapy (QUICKI: 0·346 ± 0·033 vs. 0·355 ± 0·044, P < 0·05), with no further decrease in the following years. No correlation was found between QUICKI, BMI, years of treatment and onset of puberty.

conclusions  GH treatment in GH‐deficient children does not lead to an impaired GT or type 2 diabetes mellitus, although it does significantly decrease IS.
Children with congenital hypothyroidism are at risk of adult obesity due to early adiposity rebound
Authors: Wong S. C. , Ng S. M. , Didi M.
Published: October 2004

objective  There is some evidence that children with congenital hypothyroidism (CH) are heavier than their reference population. There are few data on adults with CH. The timing of adiposity rebound (AR) in childhood has been shown to have strong correlations with adult obesity. Our aims were to study the timing of AR and factors affecting AR in children with CH.

patients and methods  The timing of AR was examined in a retrospective study of children with CH with growth data at least up to 5 years of age. The proportion of children with CH who reached AR by 37 months and by 49 months of age were compared with healthy children and children with acute lymphoblastic leukaemia (ALL) described in the literature. Correlation of timing of AR with body mass index (BMI) standard deviation score (SDS) at 10 years, initial severity of hypothyroidism and age at normalization of TSH were examined. Multiple logistic regression was used to identify independent factors associated with BMI ≥ 20 (overweight) at 10 years of age.

results  The study included 53 children (34 females and 19 males). AR had occurred by 37 months in 37·7% children with CH, in 42·7% children treated for ALL (CH vs. ALL, P = 0·58) and in 4·5% healthy British children (CH vs. normal, P < 0·0001). We found that 54·7% children with CH had reached AR compared with 21·4% of normal children (CH vs. normal, P < 0·0001) by the age of 49 months. Timing of AR showed significant negative correlation with BMI SDS at 10 years (r =−0·487, P = 0·01). There were no significant relationships between timing of AR and initial thyroid function or age at normalization of TSH. Multiple logistic regression analysis identified age at AR as an independent factor associated with BMI ≥ 20 at 10 years of age (P = 0·04).

conclusions  Children with CH showed significantly earlier AR compared to normal British children. This showed significant negative correlation with BMI SDS at 10 years. AR in CH does not appear to be directly related to the initial severity of hypothyroidism or to treatment factors.
Assessment of the role of 17β‐oestradiol in bone metabolism in men: does the assay technique matter? The MINOS study
Authors: Szulc Pawel , Claustrat Bruno , Munoz Françoise , Marchand François , Delmas Pierre D.
Published: October 2004

objective  17β‐Oestradiol (17β‐E2), mainly its bioavailable fraction (bio‐17β‐E2), is a determinant of bone mineral density (BMD) and bone remodelling in men. As direct measurement of bio‐17β‐E2 is time‐consuming, we compared the value of directly measured bio‐17β‐E2 and of calculated bio‐17β‐E2 and free 17β‐E2 by studying their association with BMD and markers of bone turnover in a cohort of men (MINOS).

design  A cross‐sectional study in which the association between BMD and bone markers, on the one hand, and serum levels of 17β‐E2, on the other, was analysed according to the levels of measured and calculated bio‐17β‐E2 and free 17β‐E2 in a cohort of men.

subjects  Men from the MINOS cohort including 87 men aged 19–45 to establish the reference control normal range of hormones and 637 men aged 50–85 (studied group).

measurements  Total 17β‐E2, testosterone, SHBG and albumin were measured by standard methods. bio‐17β‐E2 was directly measured after the precipitation of SHBG by ammonium sulfate. bio‐17β‐E2 and free 17β‐E2 were calculated using serum SHBG and albumin levels as described by Södegard et al. (J. Steroid Biochem., 16 (1982) 801).

results  Calculated bio‐17β‐E2 and free 17β‐E2 were correlated with measured bio‐17β‐E2 and between themselves (r = 0·90–1·00, P < 0·0001). Calculated bio‐17β‐E2 and free 17β‐E2 disclosed a similar association with BMD (difference between lowest and highest quartiles of 17β‐E2: 2·6–6·8%, P < 0·05–0·005) to that of measured bio‐17β‐E2 (3·6–6·1%, P < 0·005–0·001). The association between bone markers levels and measured vs. calculated 17β‐E2 were also similar. Predictive accuracy for lowered BMD and elevated levels of biochemical bone markers (evaluated using receiver operating characteristics) was relatively low (area under curve −0·582 to 0·709) but similar for different forms of bioavailable and free 17β‐E2.

conclusions  In elderly men, the concentrations of bioavailable and free 17β‐E2, calculated using equations including either the measured albumin concentration or the constant albumin concentration of 43 g/l, can be used, at least in clinical studies, instead of the bio‐17β‐E2 concentrations measured after ammonium sulfate precipitation.
Long‐term negative impact on quality of life in patients with successfully treated Cushing's disease
Authors: Heald Adrian H. , Ghosh Sandip , Bray Stephanie , Gibson Christine , Anderson Simon G , Buckler Helen , Fowler Helen L.
Published: October 2004

objective  A cohort of pituitary tumour patients, who had undergone definitive treatment within a 15‐year period at a single neuroscience centre, were investigated as to whether there were differences in psychological well‐being and psychosocial functioning, dependent on endocrine pathology and treatment variables.

design  A detailed assessment of 114 patients with benign pituitary tumours in relation to primary diagnosis and mode of treatment was carried out. Psychological rating scales used were: the Hospital Anxiety and Depression Scale − UK version (HADS‐UK), the World Health Organization Quality of Life Scale − abbreviated version (WHOQOL‐BREF), General Health Questionnaire 28 (GHQ‐28), the Functional Assessment of Cancer Therapy (FACT) and the Social Adjustment Scale − modified (SAS1 and SAS2; the former completed by the patient and the latter by another person who knows the patient well). All Cushing's patients were biochemically cured as defined by a normal 24‐h urine free cortisol excretion within the previous 6 months.

results  Patients with treated Cushing's disease had significantly impaired psychological well‐being and psychosocial functioning across all tested domains compared with all other pituitary tumours, where scores were similar. When participants with Cushing's disease were excluded, patients who had undergone transfrontal surgery scored significantly higher on GHQ and HADS ratings than transsphenoidally treated patients.

conclusion  Cushing's disease even when biochemically stable has long‐term adverse effects on mood and social functioning. We hypothesize that this may be related to irreversible changes in central neural function. Further studies are necessary to define the precise pathways involved.
Ghrelin secretion is inhibited by glucose load and insulin‐induced hypoglycaemia but unaffected by glucagon and arginine in humans
Authors: Broglio Fabio , Gottero Cristina , Prodam Flavia , Destefanis Silvia , Gauna Carlotta , Me Elisa , Riganti Fabrizio , Vivenza Daniela , Rapa Anna , Martina Valentino , Arvat Emanuela , Bona Gianni , Van Der Lely Aart Jan , Ghigo Ezio
Published: October 2004

objective  Circulating ghrelin levels are increased by fasting and decreased by feeding, glucose load, insulin and somatostatin. Whether hyperglycaemia and insulin directly inhibit ghrelin secretion still remains matter of debate. The aim of the present study was therefore to investigate further the regulatory effects of glucose and insulin on ghrelin secretion.

design and subjects  We studied the effects of glucose [oral glucose tolerance test (OGTT) 100 g orally], insulin‐induced hypoglycaemia [ITT, 0·1 IU/kg insulin intravenously (i.v.)], glucagon (1 mg i.v.), arginine (0·5 mg/kg i.v.) and saline on ghrelin, GH, insulin, glucose and glucagon levels in six normal subjects.

measurements  In all the sessions, blood samples were collected every 15 min from 0 up to + 120 min. Ghrelin, GH, insulin, glucagon and glucose levels were assayed at each time point.

results  OGTT increased (P < 0·01) glucose and insulin while decreasing (P < 0·01) GH and ghrelin levels. ITT increased (P < 0·01) GH but decreased (P < 0·01) ghrelin levels. Glucagon increased (P < 0·01) glucose and insulin without modifying GH and ghrelin. Arginine increased (P < 0·01) GH, insulin, glucagon and glucose (P < 0·05) but did not affect ghrelin secretion.

conclusions  Ghrelin secretion in humans is inhibited by OGTT‐induced hyperglycaemia and ITT but not by glucagon and arginine, two substances able to increase insulin and glucose levels. These findings question the assumption that glucose and insulin directly regulate ghrelin secretion. On the other hand, ghrelin secretion is not associated with the GH response to ITT or arginine, indicating that the somatotroph response to these stimuli is unlikely to be mediated by ghrelin.
K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial phaeochromocytoma and paraganglioma
Authors: McDonnell Ciara M. , Benn Diana E. , Marsh Deborah J. , Robinson Bruce G. , Zacharin Margaret R.
Published: October 2004

objective  Germline mutations in succinate dehydrogenase (SDH)B, SDHC and SDHD, encoding three of the four subunits of mitochondrial complex II, have been implicated in the tumourigenesis of familial paragangliomas and phaeochromocytomas. Twenty‐three SDHB mutations have been identified to date.

patients  We present a novel missense SDHB exon 2 mutation (c.118 A > G; K40E) identified in an Australian family. The proband was diagnosed with phaeochromocytoma at an early age following an unexpected hypertensive crisis and was found to be SDHB mutation‐positive. Subsequent genetic screening of 26 family members has identified 17 mutation‐positive relatives. In addition to the proband, four mutation positive relatives were found to have clinical symptoms or a lesion and/or catecholamine excess after the identification of the mutation led to further evaluation. Both the proband and an uncle have required surgical removal of a tumour.

conclusions  This family indicates the importance of germline screening of first‐degree relatives when a patient presents with an apparently sporadic extra adrenal phaeochromocytoma at a young age or whenever a patient with a nonsecretory paraganglioma is found.
Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH‐suppressed nodular goitre patients
Authors: Yavuz Dilek Gogas , Yüksel Meral , Deyneli Oguzhan , Ozen Yesim , Aydin Hasan , Akalin Sema
Published: October 2004

objective  Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.

patients and design  Twenty patients with hyperthyroidism, 20 patients with euthyroid multinodular goiter (MNG) and 20 age‐ and sex‐matched healthy controls were enrolled in the study. Insulin sensitivity index, PON activity and lipid peroxidation were measured at baseline and 2 months after achieving euthyroidism or subclinical hyperthyroidism. Levothyroxine was given as a part of TSH suppression therapy in multinodular goitre patients.

measurements  Insulin sensitivity was determined by an oral glucose tolerance test (OGTT) based on the insulin sensitivity index (ISI) formula, serum paraoxonase activity was determined with a spectrophotometric method. Lipid peroxidation was measured by the formation of thiobarbituric acid reactive substances (TBARs).

results  ISI was significantly lower in the hyperthyroid group than baseline levels in MNG patients and controls (P < 0·001). While ISI increased after treatment in the hyperthyroid group (P < 0·01), it significantly decreased with L‐T4 treatment in the MNG group (P < 0·01). Serum paraoxonase activity was significantly lower in the hyperthyroid group before treatment than baseline and final measurements of other groups (P < 0·05). While PON activity increased after restoration of the euthyroid state in the hyperthyroid group (P < 0·05), it decreased with L‐T4 treatment in the MNG group (P < 0·05). Lipid peroxidation was significantly higher in hyperthyroid group compared to baseline levels of other groups (P < 0·05). It decreased after treatment in the hyperthyroid group (P < 0·05) but a significant increase was observed following L‐T4 treatment in the MNG group (P < 0·05). Serum paraoxonase activity was found to be negatively correlated with serum TT4 (r =−0·32, P = 0·003), TT3 levels (r =−0·31, P = 0·004), TBARs levels (r = 0·32, P = 0·003) and positively correlated with ISI (r = 0·35, P = 0·001) and high‐density lipoprotein (HDL) cholesterol levels (r = 0·35, P = 0·0011) in the hyperthyroid and MNG groups

conclusions  Iatrogenic thyroid hormone excess seems to mimic the effects of endogenous thyroid hormone excess on paraoxonase activity, insulin sensitivity and oxidative stress. These findings suggest that TSH suppression with levothyroxine may increase oxidative stress and LDL oxidation and thereby promote atherogenesis.
Combined evaluation of resting IGF‐I, N‐terminal propeptide of type III procollagen (PIIINP) and C‐terminal cross‐linked telopeptide of type I collagen (ICTP) levels might be useful for detecting inappropriate GH administration in athletes: a preliminary report
Authors: Sartorio Alessandro , Agosti Fiorenza , Marazzi Nicoletta , Maffiuletti Nicola A. , Cella Silvano G. , Rigamonti Antonello E. , Guidetti Laura , Di Luigi Luigi , Muller Eugenio E.
Published: October 2004

objective  To verify whether combined measurements of GH‐dependent parameters might be useful in detecting exogenous recombinant GH (rGH) administration in male athletes from different disciplines.

methods  Sixty‐six athletes (control group) were sampled for the evaluation of resting IGF‐I, N‐terminal propeptide of type III procollagen (PIIINP) and telopeptide type I collagen (ICTP). Cut‐off values (mean + 2 SD) for IGF‐I, PIIINP and ICTP were calculated and arbitrary scores (1·5, 2·0) were assigned to abnormal parameters. By using the sum of individual parameter scores, positive (≥ 3) or negative (< 3) scores were obtained. In addition, a subgroup of six athletes was treated for 3 weeks with rGH (0·09 IU/kg body weight, 6 days/week) and was similarly evaluated at the end of the 1st, 2nd and 3rd week (i.e. 18 samples).

results  Abnormal IGF‐I, or PIIINP or ICTP levels were found, respectively, in one, two and four subjects (1·5–6·1%) of the control group (in the younger athletes); only one 19‐year‐old subject of this group obtained a positive score. Abnormal IGF‐I, PIIINP and ICTP levels were found in 61·1–66·7% samples of the treated group. Positive cases were 3/6 at the 1st and 2nd week and 6/6 at the 3rd week. The sensitivity of the screening approach was 50–100% (at the 1st−2nd and 3rd week, respectively) and specificity was 98·5%.

conclusion  This ‘first level’ screening test is safe, acceptable and relatively inexpensive. Further additional investigations of ‘second level’ (i.e. GH secretory profile, GH response to a GH‐releasing peptide) can be retained to validate or exclude rGH administration or for the early diagnosis of infrequent endogenous GH hypersecretion.
Novel therapeutic approach for cancer using four cardiovascular hormones
Authors: Vesely D. L. , Clark L. C. , Garces A. H. , McAfee Q. W. , Soto J. , Gower W. R.
Published: October 2004

Background  The atrial natriuretic peptide (ANP) gene synthesizes four cardiovascular hormones, i.e. vessel dilator, long‐acting natriuretic peptide, kaliuretic peptide and ANP, which decrease the number of human pancreatic adenocarcinoma cells in culture by 65%, 47%, 37%, and 34%, respectively.

Methods and materials  None of the cardiovascular hormones has been investigated to determine whether they inhibit the growth of cancers in vivo. These four hormones were evaluated for their ability to inhibit the growth of human pancreatic adenocarcinomas in athymic mice.

Results  Vessel dilator (139 ng min−1 kg−1 of body weight) infused for 14 days completely stopped the growth of human pancreatic adenocarcinomas in athymic mice (n = 14) with a decrease in their tumour volume, while the tumour volume increased 69‐fold (P < 0·001) in the placebo (n = 30)‐treated mice. When these peptide hormones (each at 1·4 µg min−1 kg−1 body weight) were infused for 4 weeks, vessel dilator, long‐acting natriuretic peptide and kaliuretic peptide decreased tumour volume after 1 week by 49%, 28%, and 11%, respectively, with a one‐ and 20‐fold increase in the tumour volume in ANP‐ and placebo‐treated mice. Cyclic GMP (2·4 µg min−1 kg−1 body weight) inhibited after 1 week the growth of this cancer 95%.

Conclusions  These results suggest that these peptide hormones have useful anticancer properties, as they each inhibited the growth of the human pancreatic adenocarcinomas in vivo and three of the four peptide hormones decreased the volume of the tumours (up to 49%, i.e. vessel dilator). Part of their mechanism of action appears to be mediated by cyclic GMP.
Granulocyte function in patients with L‐ferritin iron‐responsive element (IRE) 39C→T‐positive hereditary hyperferritinaemia–cataract syndrome
Authors: Fritsche‐Polanz R. , Wallner M. , Cohen G. , Eberle C. , Sunder‐Plassmann G. , Födinger M.
Published: October 2004

Background  Hereditary hyperferritinaemia–cataract syndrome (HHCS) is an autosomal dominant trait associated with mutations in the iron responsive element (IRE) of the ferritin light‐chain (L‐ferritin) gene. Patients typically show elevated serum ferritin concentrations without iron overload and a bilateral cataract. Hyperferritinaemia can be associated with granulocyte dysfunction in patients with thalassemia beta and in haemodialysis patients. The effect of increased L‐ferritin levels on granulocyte function in patients with HHCS is unknown.

Material and methods  We examined glucose uptake, oxidative burst, chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations in polymorphonuclear leucocytes (PMNLs) of five affected members of a family with HHCS and in five healthy individuals matched for age and gender.

Results  Mutation testing revealed a 39C→T transition in IRE in all five patients with HHCS. Serum ferritin levels of patients ranged between 907 and 2030 µg L−1, respectively. In comparison with healthy individuals, PMNLs of patients with HHCS showed a significant increase in PMA‐mediated stimulation of the oxidative burst, as well as a significantly higher stimulation of glucose uptake but no difference with respect to chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations.

Conclusion  In summary, our study suggests that hyperferritinaemia in patients with IRE 39C→T‐positive HHCS is associated with activation of PMNLs but not with disturbance of fundamental PMNL function.
Cholesterol saturation rather than phospholipid/bile salt ratio or protein content affects crystallization sequences in human gallbladder bile
Authors: Venneman N. G. , Portincasa P. , VanBerge‐Henegouwen G. P. , Van Erpecum K. J.
Published: October 2004

Background  In model biles, cholesterol crystallization (an important factor in gallstone formation) mainly depends on phospholipid/bile salt ratios with characteristic sequences of plate‐like (monohydrate) vs. non‐plate‐like (presumed anhydrous: arcs, needles, tubules, spirals) cholesterol crystals (Wang, J Lipid Res 1996; 37: 606). We now investigate whether the same phenomenon occurs in human bile.

Methods  Appearances of plate‐like and non‐plate‐like cholesterol crystals were determined in filtered bile of 80 cholesterol gallstone patients, and related to biliary lipid and pro‐nucleating protein composition.

Results  Non‐plate‐like crystals appeared before plate‐like crystals in 9 biles, on the same day in 24 biles, and after plate‐like crystals in 31 biles. In 16 biles only plate‐like crystals were observed. Crystal sequences did not depend on biliary lipid or protein composition. Cholesterol saturation indexes were higher in biles with than without non‐plate‐like crystals (150 ± 6 vs. 125 ± 12, P = 0·02). In contrast, phospholipid/(bile salt + phospholipid) ratios, bile salt species, phospholipid classes, concentrations of mucin, IgG, IgM, IgA, haptoglobin and α‐1 acid glycoprotein did not differ.

Conclusions  Cholesterol crystallization sequences in human bile depend on cholesterol saturation index rather than on phospholipid/bile salt ratio.
Lipid‐lowering and anti‐inflammatory effects of tetradecylthioacetic acid in HIV‐infected patients on highly active antiretroviral therapy
Authors: Fredriksen J. , Ueland T. , Dyrøy E. , Halvorsen B. , Melby K. , Melbye L. , Skalhegg B. S. , Bohov P. , Skorve J. , Berge R. K. , Aukrust P. , Frøland S. S.
Published: October 2004

Background  Highly active antiretroviral therapy (HAART) often leads to a dramatic improvement in clinical, viral and immunologic parameters in HIV‐infected individuals. However, the emergence of long‐term side‐effects of HAART and in particular dylipidaemia is increasingly reported. Based on the potential lipid‐lowering and immunomodulatory properties of tetradecylthioacetic acid (TTA) we examined whether TTA in combination with dietary intervention could modify lipid levels in peripheral blood in HIV‐infected patients on HAART.

Materials and methods  Ten HIV‐infected patients on protease inhibitor‐based HAART with hyperlipidaemia followed a cholesterol‐lowering diet throughout the study period (8 weeks). During the last 4 weeks of the study all patients received TTA (1 g qd) in addition to the cholesterol‐lowering diet.

Results  Our main and novel findings were: (i) TTA in combination with dietary intervention reduces total cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in these patients, and a particularly suppressing effect was observed during the TTA phase regarding total cholesterol. (ii) During the TTA phase, the cholesterol‐lowering effect was accompanied by a significant reduction in plasma levels of tumour necrosis factor α. (iii) Our studies in peripheral blood mononuclear cells from these patients and in the liver from wild‐type mice receiving TTA suggest that the hypolipidaemic effects of TTA may involve up‐regulation of scavenger and LDL‐receptor expression.

Conclusions  Although few patients were studied, the present pilot study suggests that TTA combined with dietary intervention could be an interesting therapeutic approach in HIV‐infected patients on HAART, potentially resulting in both hypolipidaemic and anti‐inflammatory effects.
N‐acetylcysteine enhances multidrug resistance‐associated protein 1 mediated doxorubicin resistance
Authors: Akan I. , Akan S. , Akca H. , Savas B. , Ozben T.
Published: October 2004

Background  Resistance of cancer cells against anticancer agents is caused partly by multidrug resistance‐associated protein 1 (MRP1). The exact mechanism of MRP1‐involved multidrug resistance has not yet been clarified, although glutathione (GSH) is likely to have a role for the resistance to occur. N‐acetylcysteine (NAC) is a pro‐glutathione drug. DL‐buthionine (S,R)‐sulfoximine (BSO) inhibits GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1‐mediated doxorubicin resistance in human embryonic kidney (HEK293) and its MRP1‐transfected 293MRP cells.

Materials and methods  Human embryonic kidney cells were transfected with a plasmid encoding the whole MRP1 gene. Both cells were incubated with doxorubicin in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. Glutathione, glutathione S‐transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs.

Results  N‐acetylcysteine increased the resistance of both cells against doxorubicin. DL‐buthionine (S,R)‐sulfoximine decreased NAC‐enhanced MRP1‐mediated doxorubicin resistance, indicating that induction of MRP1‐mediated doxorubicin resistance depends on GSH synthesis. Doxorubicin decreased the cellular GSH concentration and increased GPx activity. Glutathione S‐transferase activity was decreased by NAC.

Conclusion  Our results demonstrate that NAC enhances MRP1‐mediated doxorubicin resistance and this effect depends on GSH synthesis. DL‐buthionine (S,R)‐sulfoximine seems a promising chemotherapy improving agent in MRP1 overexpressing tumour cells.
Insulin activates vascular endothelial growth factor in vascular smooth muscle cells: influence of nitric oxide and of insulin resistance
Authors: Doronzo G. , Russo I. , Mattiello L. , Anfossi G. , Bosia A. , Trovati M.
Published: October 2004

Background  We aimed to evaluate whether insulin influences vascular endothelial growth factor (VEGF) synthesis and secretion in cultured vascular smooth muscle cells (VSMCs) via nitric oxide (NO) and whether these putative effects are lost in insulin‐resistant states.

Materials and methods  In VSMC derived from human arterioles and from aortas of insulin‐sensitive Zucker fa/+rats and insulin‐resistant Zucker fa/fa rats incubated with different concentrations of human regular insulin with or without inhibitors of phosphatidylinositol 4,5‐bisphosphate 3‐kinase (PI3‐K), mitogen‐activated protein kinase (MAPK), nitric oxide synthase (NOS) and guanosine 3′,5′cyclic monophosphate(cGMP)‐dependent protein kinase (PKG), we measured protein expression (Western blot) and secretion (ELISA) of VEGF.

Results  We found that in VSMCs from humans and from insulin‐sensitive Zucker fa/+rats, insulin increases VEGF protein expression and secretion, with mechanisms blunted by wortmannin and LY294002 (PI3‐K inhibitors), PD98059 (MAPK inhibitor), L‐NMMA (NOS inhibitor) and Rp‐8pCT‐cGMPs (PKG inhibitor). Also the NO donor sodium nitroprusside (SNP) and the cGMP analogue 8‐Bromo‐cGMP increase VEGF protein expression and secretion, with mechanisms inhibited by wortmannin and PD98059. The insulin effects on VEGF are impaired in VSMCs from Zucker fa/fa rats, which also present a reduced insulin ability to increase NO.

Conclusions  In VSMCs from humans and insulin‐sensitive Zucker fa/+rats: (i) insulin increases VEGF protein expression and secretion via both PI3‐K and MAPK; (ii) the insulin effects on VEGF are mediated by nitric oxide. The insulin action on both nitric oxide and VEGF is impaired in VSMCs from Zucker fa/fa rats, an animal model of metabolic and vascular insulin‐resistance.
Patients’ experience of the diagnosis and treatment of skin cancer
Authors: Winterbottom Anna , Harcourt Diana
Published: October 2004

Purpose.  This paper describes the experience of being diagnosed with skin cancer from the perspective of patients.

Background.  Despite the number of people with newly‐diagnosed skin cancer increasing each year, the psychological impact of receiving such a diagnosis has received little attention. Research in this area is sporadic and has predominantly focused on malignant melanoma and used a quantitative approach.

Method.  Sixteen patients were interviewed about their experiences of being diagnosed with malignant melanoma, basal cell carcinoma or squamous cell carcinoma. The interview transcripts were analysed using thematic content analysis.

Findings.  Similar themes for the two non‐melanoma forms of skin cancer patients emerged. Information and knowledge of skin cancer appeared as a key theme, and influenced experiences in a variety of different ways. Patients with malignant melanoma recounted similar experiences to those with basal cell carcinoma or squamous cell carcinoma. People with malignant melanoma, however, used a wider variety of strategies in order to cope with the diagnosis. Satisfaction with the care experienced by each of the three groups played a crucial role in minimizing the experience for the patients.

Conclusions.  Patients with skin cancer should not be conceived as a homogeneous group, but one in which there are a number of diagnoses which differ in prognosis, and so may result in a variety of different consequences and thus experiences for patients.
Nursing competencies for spiritual care
Authors: Van Leeuwen René , Cusveller Bart
Published: October 2004

Aim.  This paper aims to answer the question: What competencies do professional nurses need to provide spiritual care?

Background.  Nursing literature from The Netherlands shows little clarity on the qualities that nurses require to provide spiritual care. Although the international literature provides some practical guidance, it is far from conclusive on the required qualities of nurses.

Method.  A qualitative literature review was conducted to draw together information from the nursing literature in order to formulate nursing competencies. A format developed for higher nursing education in The Netherlands was used; this consists of description of a general domain, specific competencies, vignettes, key focus and objectives.

Results.  The resulting competency profile has three core domains (awareness and use of self, spiritual dimensions of the nursing process, and assurance and quality of expertise) and six core competencies (handling one's own beliefs, addressing the subject, collecting information, discussing and planning, providing and evaluating, and, integrating into policy).

Discussion.  Spirituality is a field in nursing that is still in its infancy.

Conclusion.  This literature review yields a competency profile that may help to structure future care, research and education in spiritual care by nurses. Implications of the work for future research and education are discussed.
Central venous catheters: a survey of ICU practices
Authors: Rickard Claire M. , Courtney Mary , Webster Joan
Published: October 2004

Aim.  This paper describes the current infection control practices for CVC care and compares these to evidence‐based practice guidelines.

Background.  Intensive care patients with central venous catheters (CVCs) are at risk of catheter‐related infection, which increases morbidity, mortality and health care costs. Infection control practices, including care of intravenous administration sets and catheter sites, are undertaken by nurses in an attempt to avoid infection. Although practice guidelines are available, infection control practices may vary between practitioners and institutions; however, current practice has not been formally surveyed.

Method.  A prospective, cross‐sectional descriptive survey was carried out. Intensive care units (n = 14) in Australia were surveyed about their infection control policies for CVC care. Results were tabulated and compared with evidence‐based practice guidelines.

Results.  A wide variety of responses was received about duration of administration set use for standard, parenteral nutrition and propofol (lipid‐based anaesthetic) infusions; ad hoc administration set connection technique; dressing frequency, materials and solutions; and barrier precautions used during procedures. There was inconsistent adherence to the guidelines.

Conclusion.  There is variation in the infection control approach to CVC care. Greater adherence to existing Centers for Disease Control Guidelines would assist in the standardization of best practice and facilitate evidence‐based care.