bluuebunny/crossref_metadata_2025 huggingface dataset:
Inactivation of Helicobacter pylori cagA Gene Affects Motility
Authors: Figura Natale , Trabalzini Lorenza , Mini Roberta , Bernardini Giulia , Scaloni Andrea , Talamo Fabio , Lusini Paola , Ferro Elisa , Martelli Paola , Santucci Annalisa
Published: May 2004

Background.  The cytotoxin‐associated protein CagA is a Helicobacter pylori immunodominant antigen whose gene resides in the cag pathogenicity island. Our purpose was to determine if the disruption or deletion of cagA gene could have an effect on the expression of other proteins at the proteome level. We analyzed two H. pylori strains, 328 and G27 wild‐type, bearing the cag pathogenicity island, and their respective isogenic cagA− mutants.

Methods.  The proteomes of two H. pylori strains (328 and its isogenic mutant SPM328_ΔcagA) were resolved by two‐dimensional electrophoresis and the digitalized images obtained were analysed both quantitatively and qualitatively. Peculiar spots of each strain were identified by mass spectrometry or by Western blotting.

Results.  The comparison between the proteome expression of an H. pylori cagA+ strain and an isogenic mutant strain where the cagA gene was disrupted showed that, as well as the lack of expression of CagA, both flagellin A and flagellin B expressions were significantly decreased. The cagA− isogenic mutant was nonmotile. G27_ΔcagA, in which CagA was inactivated by gene deletion, was nonmotile as well respecting to motile G27 wild‐type strain. Moreover, reintroduction of cagA in G27_ΔcagA restored motility.

Conclusions.  Our results suggest that CagA could quantitatively influence flaA and flaB transcription or their subsequent translation and/or correct folding.
Novel Monoclonal Antibody‐Based Helicobacter pylori Stool Antigen Test
Authors: Dore Maria Pina , Negrini Riccardo , Tadeu Vincenza , Marras Lea , Maragkoudakis Emanouel , Nieddu Salvatore , Simula Luigi , Cherchi Giovanni Battista , Massarelli Giovanni , Realdi Giuseppe
Published: May 2004

Background.  A number of noninvasive tests have been developed to establish the presence of Helicobacter pylori infection. Although polyclonal antibody‐based stool antigen testing has a good sensitivity and specificity, it is less accurate than urea breath testing. Recently, a monoclonal antibody‐based stool antigen test demonstrated an excellent performance in diagnosing H. pylori infection in adults and in pediatric populations.

Aim.  To evaluate the diagnostic accuracy of a novel stool test based on monoclonal antibodies to detect H. pylori antigens in frozen human stool in the pretreatment setting.

Patients and Methods.  Stool specimens were prospectively collected from 78 patients undergoing gastroscopy and stored at −20°C until tested. Helicobacter pylori infection was evaluated by histology, rapid urease testing and urea breath tests (13C‐UBT). Positivity of the three tests was considered the gold standard for H. pylori active infection. Patients with no positive test were considered negative. The gold standard was compare to the results of the monoclonal antibody stool antigen test. Frozen stool specimens were tested using a novel monoclonal‐antibody‐based enzyme immunoassay (HePy‐Stool, Biolife‐Italiana, Milan, Italy).

Results.  The sensitivity and specificity of the monoclonal stool antigen test were 97%[95% confidence interval, (CI) 86–100] and 94% (95% CI: 81–99), respectively. Negative and positive predictive values were 97% (95% CI: 85–99), and 95% (95% CI: 83–99), respectively. The diagnostic accuracy was 96% (95% CI: 88–99). The likelihood ratio for a positive test was 17 and for a negative test was 0.

Conclusions.  Although the 13C‐UBT is the most accurate among the available noninvasive tests, our results show that an H. pylori stool test using monoclonal antibody might be an excellent alternative.
Helicobacter pylori Infection in Children in Estonia: Decreasing Seroprevalence During the 11‐Year Period of Profound Socioeconomic Changes
Authors: Oona Marje , Utt Meeme , Nilsson Ingrid , Uibo Oivi , Vorobjova Tamara , Maaroos Heidi–Ingrid
Published: May 2004

Background.  The prevalence of Helicobacter pylori infection is inversely associated with socioeconomic conditions in childhood. In Estonia, a high prevalence of H. pylori infection has been observed among children born in 1987 and earlier. Since 1991, after the dissolution of the USSR, profound social and economic changes have taken place in the country. The aim of the study was to evaluate changes in the seroprevalence of H. pylori infection among children in the period 1991–2002.

Materials and Methods.  The hospital‐based study population consisted of two groups of children enrolled in 1991 (n = 425) and 2002 (n = 296) according to the same inclusion criteria. The immunoglobulin G antibodies to the cell surface proteins of H. pylori were determined by enzyme‐linked immunosorbent assay, and the sera with the borderline results were analyzed by immunoblot analysis. Multiple regression analysis was used to determine the associations between H. pylori seropositivity and different variables such as demographic characteristics, diagnoses and year of enrolment.

Results.  The only two variables linked independently to H. pylori serostatus were age and year of enrolment: the adjusted odds of being H. pylori seropositive were 1.92 [95% confidence interval (CI) 1.33–2.76] times higher for the children enrolled in 1991 compared with the children enrolled in 2002. The age‐standardized seroprevalence rate was 42.2% (95% CI 37.4–47.0%) for the group of 1991 and 28.1% (95% CI 23.1–33.6%) for the group of 2002.

Conclusion.  The prevalence of H. pylori infection among children has significantly decreased during the 11‐year period of profound socioeconomic changes in Estonia.
Increased Production of Matrix Metalloproteinases in Helicobacter pylori‐Associated Human Gastritis
Authors: Bergin Philip J , Anders Edebo , Sicheng Wen , Erik Johnsson , Jennie Andersson , Hans Lönroth , Pierre Michetti , Qiang Pan‐Hammarström , Marianne Quiding‐Järbrink
Published: May 2004

Background and Aims.  Helicobacter pylori infection results in an active, chronic inflammation of the gastric mucosa. Previous studies have highlighted the importance of matrix metalloproteinases (MMPs) in diseases involving mucosal inflammation, prompting us to investigate MMP activity in H. pylori‐induced gastritis.

Methods.  Gastric biopsies were obtained from H. pylori‐infected and uninfected volunteers, and MMP activity was assessed using substrate gel electrophoresis. MMP production was also evaluated by immunohistochemistry and real time‐polymerase chain reaction. In parallel, tissue inhibitors of MMPs (TIMP) levels and TIMP–MMP complexes were examined in corresponding tissues using enzyme‐linked immunosorbent assays and Western blotting. Finally, MMP production by gastric macrophages was determined after stimulation with H. pylori.

Results.  Antral mucosa of H. pylori‐infected subjects demonstrated a 19‐fold higher MMP‐9 activity than that of uninfected individuals. MMP‐2 was present at lower levels, but was also increased in H. pylori‐infected individuals, while there was no difference in the total levels of TIMP‐1 and TIMP‐2 between the groups of volunteers. Significant numbers of MMP‐9‐containing cells were only found in the H. pylori‐infected antral mucosa. Tissue‐resident macrophages were significantly increased in H. pylori‐infected individuals, and double‐staining showed MMP‐9 colocalized to macrophages. Furthermore, gastric macrophages secreted MMP‐9 in response to H. pylori bacteria. A corresponding 10‐fold increase of gene expression of MMP‐9 was seen in patients infected with H. pylori compared to uninfected individuals.

Conclusions.  Helicobacter pylori infection results in a substantial increase in MMP‐9 and MMP‐2 activity in the gastric mucosa, probably contributed to in large part by tissue‐resident macrophages, while no changes were seen in the TIMP levels. The net increase in gastric MMP activity is likely to contribute to tissue damage during H. pylori‐associated gastritis.
Contract Length as Risk Management When Labor is not Homogeneous
Authors: Maxcy Joel G.
Published: May 2004

This paper examines the choice of contract length for workers who possess unique skills. Uncertainty, facing both the worker and the firm, creates an incentive to reallocate risk. The uncertainty arises from two sources: variation in the market value of the worker's human capital and fluctuation in the worker's physical production. Long‐term contracts are typically modeled as compensating wage differentials, or as a solution to the problem of asymmetric information. This paper develops a model proposing more complex behavior in the reallocation of risk between the contracting parties. The model shows that long‐term labor contracts are most likely to be observed when price uncertainty in the labor market exceeds the worker's productive uncertainty.
Union–Firm Bargaining, Productivity Improvement and Endogenous Growth
Authors: Palokangas Tapio
Published: May 2004

This paper presents a growth model with two sectors. In the high‐tech sector, R&D increases productivity and union–firm bargaining determines wages, but in the traditional sector there are neither R&D nor labour unions. The government is able to regulate union bargaining power. The main results are as follows. Because firms try to escape wage increases through the improvement of productivity by R&D, the increase in union bargaining power boosts R&D and growth. It is welfare enhancing to strengthen (weaken) unions when the growth rate is below (above) some critical level. A specific rule is presented for when de‐unionization is socially desirable.
Do the Falling Earnings of Immigrants Apply to Self‐employed Immigrants?
Authors: Frenette Marc
Published: May 2004

It is well known that the earnings of recent cohorts of immigrant men have fallen further behind native‐born men. Using several years of Canadian Census data, this study finds that immigrants have turned to self‐employment at a much faster rate than the native born. In addition, the earnings gap between self‐employed immigrant and native‐born men has not grown with successive cohorts, but rather has followed a cyclical movement: narrowing at the peak, and widening in times of weaker economic activity. However, immigrants choosing self‐employment still face challenges, as their earnings are far below native‐born earnings, and convergence is a lengthy process.
Early Career Mobility and Earnings Profiles of German Apprentices: Theory and Empirical Evidence
Authors: Bougheas Spiros , Georgellis Yannis
Published: May 2004

We investigate how apprenticeship training affects the early career mobility and earnings profiles of young apprentices in Germany. The heterogeneous quality and nature (whether general or firm specific) of training across firms is expected to be reflected in the post‐apprenticeship mobility and earning patterns of young workers. In this paper, we argue that a simple model of training and labour turnover can explain such patterns. Specifically, assuming that job changes are associated with a loss of accumulated firm‐specific skills, the model predicts that although movers initially experience a productivity loss, their earnings grow at a faster rate than those of stayers. As job changes become more costly the longer a worker stays with the training firm, later movers experience a larger reduction in their earnings compared with direct movers. Estimated selectivity‐corrected earnings equations for movers and stayers, based on data from the German Socioeconomic Panel (GSOEP), support the predictions of the model and highlight important differences in earnings profiles and mobility patterns by apprenticeship firm size.
Urban Versus Rural Return to Human Capital in Portugal: A Cookbook Recipe for Applying Assignment Models
Authors: Teulings C. N. , Vieira J. A. C.
Published: May 2004

Abstract. The Portuguese economy has been characterized by modernization since the post‐war period, and Lisbon is a centre of this process. This paper analyses rates of return on human capital in Lisbon versus the rest of the country in the period 1982–92. An assignment model of heterogeneous workers to heterogeneous jobs is applied. We introduce the concept of the complexity dispersion parameter, which measures job heterogeneity and the ease of substitution between worker types. It is free dimension and can be compared across countries. We also develop a cookbook recipe for the estimation of this parameter. The main implication of the model — a high return to human capital is associated with similar workers being assigned to more complex jobs — is confirmed by the data. The complexity dispersion parameter suggests that paying half of the optimal wage level at least doubles the cost per efficiency unit of labour.
Propylthiouracil and carbimazole associated‐antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves’ disease
Authors: Harper L. , Chin L. , Daykin J. , Allahabadia A. , Heward J. , Gough S. C. , Savage C. O. , Franklyn J. A.
Published: May 2004

objective  Propylthiouracil treatment of Graves’ disease has been postulated to provoke antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis. We aimed to investigate whether carbimazole therapy was also associated with increased risk of ANCA.

design  The occurrence of ANCA and the relationship to thionamide treatment was investigated in a cross‐sectional study in a consecutive series of 407 patients’ with Graves’ disease, 200 with Hashimoto's thyroiditis and 649 normal euthyroid subjects.

measurements  ANCA was measured by indirect immunofluorescence (IIF) and enzyme‐linked immunosorbent assay (ELISA) for proteinase 3 and myeloperoxidase‐ANCA.

results  The prevalence of ANCA, as measured by IIF, was increased in the Graves’ disease cohort (19·9%) compared with euthyroid controls (4·6%; P < 0·001). The prevalence of MPO‐ANCA (measured by ELISA) was also increased in Graves’ disease (P = 0·019). ANCA prevalence was more strongly associated with propylthiouracil treatment than carbimazole (P = 0·0265), although risk of ANCA was also higher in Graves’ patients treated with carbimazole than controls (RR 2·2, P < 0·0001). ANCA positivity was not increased in patients with Hashimoto's thyroiditis.

conclusion  This study revealed a high prevalence of ANCA in treated patients with Graves’ disease but not in those with Hashimoto's thyroiditis. Furthermore, within the Graves’ disease population, ANCA development was associated with propylthiouracil usage to a greater extent than carbimazole. These findings suggest that the altered immune environment associated with autoimmune thyroid disease is not sufficient to develop ANCA but treatment with thionamides is important in promoting ANCA development.
Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves’ hyperthyroidism
Authors: He Chih‐Tsueng , Hsieh An‐Tsz , Pei Dee , Hung Yi‐Jen , Wu Ling‐Yi , Yang Tsao‐Chin , Lian Wei‐Cheng , Huang Wen‐Sheng , Kuo Shi‐Wen
Published: May 2004

objective  The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves’ hyperthyroidism.

background  Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels.

methods  Thirty patients with newly diagnosed Graves’ hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period.

results  There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI‐treated group were significantly lower than those of the PTU‐treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study.

conclusion  During the 12‐week treatment of Graves’ hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once‐daily regimen of antithyroid drug is considered for the treatment of Graves’ hyperthyroidism.
Vitamin A and iron supplementation is as efficient as hormonal therapy in constitutionally delayed children
Authors: Zadik Z. , Sinai T. , Zung A. , Reifen R.
Published: May 2004

objective  To assess the effect of nutritional supplementation on growth and puberty in constitutionally delayed children.

patients  One hundred and two boys, 13·6–15·5 years of age, who were referred because of short stature and delayed puberty.

methods  The boys were randomly allocated to one of the following treatment groups: oxandrolone therapy, 5 mg/day for 6 months (n = 15), testosterone depot, 100 mg monthly for 3 months (n = 15) or for 6 months (n = 20), nutritional programme (n = 17), oxandrolone and nutritional programme (n = 15) or passive observation (n = 20). Boys in the nutritional programmes received 12 mg/day iron and 6000 IU/week of vitamin A. Outcome measurements were of height, weight, pubertal signs, dietary intake, serum vitamin A, iron, GH and IGF‐1.

results  Six months of vitamin A supplementation induced growth acceleration similar to that seen in the oxandrolone‐ and testosterone‐treated children, and significantly greater than in the observation group (9·3 ± 2·9 vs. 4·0 ± 0·9 crn/yr, P < 0·001). Whereas in the vitamin A‐supplemented group, puberty (increase in testicular volume ≥ 12 ml) was induced within 12 months. In all testosterone‐treated patients, pubic hair was noted within 3 months and a testicular volume of ≥ 12 ml was observed 9–12 months after the initiation of therapy. No pubertal signs were noted in the observation group during this time.

conclusions  Subnormal vitamin A intake is one of the aetiological factors in delayed pubertal maturation. Supplementation of both vitamin A and iron to normal constitutionally delayed children with subnormal vitamin A intake is as efficacious as hormonal therapy in the induction of growth and puberty.
Extraocular muscle antibodies and the occurrence of ophthalmopathy in Graves’ disease
Authors: De Bellis A. , Perrino S. , Coronella C. , Sansone D. , Ruocco G. , Tirelli G. , Di Martino S. , Conte M. , Bellastella G. , Wall J. R. , Bellastella A. , Bizzarro A.
Published: May 2004

objective  The aim of this study was twofold: first to investigate the presence of extraocular muscle antibodies (EMAb) in sera of Graves’ patients with ophthalmopathy characterized by clinical extraocular muscle (EM) involvement; second to evaluate in Graves’ patients without ophthalmopathy whether longitudinal variations of EMAb have a predictive role for the development of eye disease.

patients  We evaluated sera of Graves’ patients previously tested for G2sAb and FpAb; in particular, sera of 32 patients with moderate or severe ophthalmopathy and EM involvement: 18 with active disease (group 1), 14 with inactive disease (group 2). Moreover, we evaluated longitudinally sera of 19 Graves’ patients without ophthalmopathy previously tested for anti‐GS2 (G2sAb) and antiflavoprotein antibodies (FpAb; group 3). During the 18‐month follow‐up, four of them did not develop ophthalmopathy (group 3a), and 15 did: seven developed eye disease (group 3b) with clinical EM involvement. In particular, moderate disease and clinical activity score (CAS) ≥ 4 in four of them, severe ophthalmopathy and CAS ≤ 1 in three were observed. The remaining eight patients showed moderate ophthalmopathy and CAS ≥ 4 without EM involvement (group 3c).

measurements  EMAb were evaluated in all samples by indirect immunofluorescence method.

results  EMAb were detected in 13 out of 18 patients (72·2%) in group 1 (titre 1/32–1/128) and in five out of 14 patients (35·7%) in group 2 (titre 1/2–1/8). As regards to group 3, at the start of the study EMAb were detected in 13 out of 19 patients (72%) at titres 1/2–1/8; during the follow‐up they became or persisted negative in all patients in group 3a, while they increased at titres ranging from 1/64 to 1/128 in all patients in group 3b before the onset of ophthalmopathy. Finally, in group 3c, four patients showed a mild increase (1/8–1/16) of EMAb before the onset of eye disease, while four patients were negative during the entire follow‐up.

conclusions  Our results indicate that EMAb are a good marker of ophthalmopathy with EM involvement and their titre is higher in patients with active than in those with inactive disease. Thus, even if our results must be confirmed on a larger cohort of patients, the increase of EMAb in patients with Graves’ disease could be considered as a risk factor for the development of ophthalmopathy with subclinical/clinical EM impairment. In this connection we propose the evaluation of EMAb, in Graves’ patients with subclinical and clinical ophthalmopathy, as a simple and sensitive marker of the EM inflammatory process.
Ghrelin does not mediate the somatotroph and corticotroph responses to the stimulatory effect of glucagon or insulin‐induced hypoglycaemia in humans
Authors: Broglio Fabio , Prodam Flavia , Gottero Cristina , Destefanis Silvia , Me Elisa , Riganti Fabrizio , Giordano Roberta , Picu Andreea , Balbo Marcella , Van der Lely Aart Jan , Ghigo Ezio , Arvat Emanuela
Published: May 2004

objective  Acylated ghrelin, a gastric peptide, possesses a potent GH‐ but also significant ACTH/cortisol‐releasing activity mediated by the activation of GH secretagogue receptors (GHS‐R) at the hypothalamus–pituitary level. The physiological role of ghrelin in the control of somatotroph and corticotroph function is, however, largely unclear. Glucagon is known to induce a clear increase of GH, ACTH and cortisol levels in humans, at least after intramuscular administration. In fact, glucagon is considered to be a classical alternative to insulin‐induced hypoglycaemia (ITT) for the combined evaluation of the function of GH and the hypothalamus–pituitary–adrenal (HPA) axis. We aimed to clarify whether ghrelin mediate the GH and corticotroph responses to intramuscular glucagon or ITT, which has recently been reported able to induce a surprising ghrelin decrease.

subjects  To this aim we enrolled six normal young male subjects [age (mean ± SD): 29·0 ± 8·0 years, body mass index (BMI) 21·9 ± 2·5 kg/m2].

design and measurements  In all the subjects we studied ghrelin, GH, ACTH, cortisol and glucose levels after glucagon (GLU; 0·017 mg/kg intramuscularly), ITT (0·1 IU/kg insulin intravenously) or saline administration.

results  Saline infusion was not followed by any significant variation in ghrelin, GH and glucose levels while ACTH and cortisol showed the expected spontaneous morning trend toward a decrease. GLU administration increased (P < 0·01) circulating GH, ACTH and cortisol as well as insulin and glucose levels. ITT induced an obvious increase (P < 0·01) of GH, ACTH and cortisol levels. The ITT‐induced increases in GH and ACTH, but not cortisol, levels were higher (P < 0·01) than those after GLU. Circulating ghrelin levels were not modified by GLU. On the other hand, ghrelin levels underwent a transient reduction (P < 0·01) after insulin‐induced hypoglycaemia.

conclusions  Ghrelin does not mediate the GH and ACTH responses to glucagon or to the ITT. In fact, ghrelin levels are not modified at all by glucagon and transiently decrease during the ITT. These findings support the assumption that ghrelin does not play a major role in the physiological control of somatotroph and corticotroph function.
Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation
Authors: Vaidya Bijay , Campbell Viv , Tripp John H. , Spyer Gill , Hattersley Andrew T. , Ellard Sian
Published: May 2004

objective  Nonautoimmune hyperthyroidism (NAH), a rare autosomal dominantly inherited condition characterized by nonremitting thyrotoxicosis and the absence of features of autoimmune thyrotoxicosis, can result from activating germline mutations in the thyrotropin receptor (TSHR) gene. We report clinical and genetic features of a new family with NAH, and highlight that premature delivery and low birth weight are important characteristics of this condition.

patients and methods  Thyrotoxicosis was diagnosed in two children at the ages 20 months and 4 years and in their father at the age of 9 years. Both children were born prematurely by Caesarian section at 33 and 30 weeks following early rupture of the membranes. Their birth weights were 1750 g (27th centile) and 790 g (< 3rd centile), respectively. Mutation analysis of the TSHR gene was performed in both children and their parents by direct DNA sequencing.

results  A heterozygous germline mutation of the TSHR gene resulting in the substitution of serine (AGC) by asparagine (AAC) at codon 505 (S505N) was found, which co‐segregated with thyrotoxicosis in the family. A review of all previously reported cases of NAH due to an activating TSHR germline mutation showed that the mean duration of gestation in these patients was significantly lower than in patients with inactivating TSHR mutations causing congenital hypothyroidism (35·8 weeks vs. 39·4 weeks, P = 0·003). In addition, the mean birth weight in patients with activating TSHR mutations was lower than in patients with inactivating TSHR mutations (2338 g vs. 3470 g, P = 0·004).

conclusions  Premature delivery and low birth weight are consistent features of NAH due to activating TSHR germline mutations. This suggests a possible role for the fetal thyroid axis in the regulation of the timing of delivery and possibly fetal growth.
Ultrasonographic screening for detection of thyroid cancer in patients with Graves’ disease
Authors: Kim Won Bae , Han Seong‐Min , Kim Tae Yong , Nam‐Goong Il Seong , Gong Gyungyub , Lee Ho Kyu , Hong Suck Joon , Shong Young Kee
Published: May 2004

objective  We prospectively screened consecutive patients with Graves’ hyperthyroidism by ultrasonography (USG), regardless of presence of palpable nodules, and evaluated patients with nodule(s) by fine‐needle aspiration (FNA) and by resulting surgery to define the prevalence of thyroid cancer in patients with Graves’ disease.

methods  Two hundred and forty‐five consecutive Graves’ disease patients without prior thyroid surgery or radio‐iodine treatment were enrolled at Asan Medical Centre endocrinology clinic. All patients with nodule(s) of 5 mm or greater were reviewed for evaluation by FNA, and of these 90·0% (n = 62) underwent FNA. All patients with suspicious/malignant cytology or those with positive immunostaining with GAL‐3 antibody underwent surgery.

results  Among 245 patients, thyroid nodule(s) were detected in 35·1% (86/245) by USG. Nodule prevalence significantly increased according to age, which was the only significant variable predicting the presence of nodule(s) in logistic regression analysis. Among patients with thyroid nodule(s), 69 patients had nodule(s) of 5 mm or greater in size, and 62 cases of them (90·0%) underwent FNA. In eight patients, thyroid cancers were histologically confirmed (all papillary thyroid cancers), so the prevalence of thyroid cancer was at least 3·3% (8/245) in Graves’ patients. Of eight patients with thyroid cancer, only one case was detected by palpation and the other seven patients were detected only by USG. In pathologic examination, mean size of tumour was 10·0 ± 6·7 mm (5–25 mm), three cases had extrathyroidal extension (37·5%), four cases had cervical node metastasis (50·0%) and one case had multifocal tumour (12·5%). Thus, five of eight patients had locally advanced cancers (pT4 or pN1 lesion), but none had distant metastasis. Prevalence of thyroid cancers in Graves’ disease tended to be higher in patients of 45 years or greater than younger patients (6·7%vs. 1·3%, P = 0·05), and that of the locally advanced cancers was significantly higher in older patients (5·6%vs. 0%, P < 0·05). Older age of the patient was the only significant factor predicting the presence of locally advanced thyroid cancers regardless of duration/severity of hyperthyroidism, goitre size, or of TBII activity.

conclusions  The prevalence of thyroid cancer in Graves’ patients was at least 3·3% in this prospective analysis; most of them were micropapillary thyroid cancers. Stimulating TSHR antibodies seems not to induce nodule/cancer formation and not to change biologic behaviour of thyroid cancers in Graves’ patients. Graves’ patients of 45 years of age or above are more likely to harbour locally advanced thyroid cancers than younger patients, regardless of duration or severity of hyperthyroidism, goitre size, or of TBII activity.
Growth hormone, IGF‐I and its binding proteins (IGFBP‐1 and ‐3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis
Authors: Iglesias Pedro , Díez Juan J. , Fernández‐Reyes María J. , Méndez Javier , Bajo María A. , Aguilera Abelardo , Selgas Rafael
Published: May 2004

objective  The GH/IGF axis is altered in chronic renal failure (CRF). CRF patients usually show normal or high serum concentrations of GH and IGF‐I, whereas all IGF binding proteins (IGFBP‐1 to ‐6), except IGFBP‐5, considerably increase with declining renal function. The aims of the present study were to quantify serum concentrations of GH, IGF‐I, IGFBP‐1 and IGFBP‐3 in a group of patients with CRF, and determine whether there were differences according to the type of dialysis, that is, peritoneal dialysis (PD) and haemodialysis (HD).

design  A cross‐sectional study in the setting of a dialysis unit of a general hospital.

patients and measurements  We studied 108 dialysis patients treated by PD (n = 54, 32 males and 22 females, mean age 61·0 ± 1·4 years) or HD (n = 54, 31 males and 23 females, age 62·6 ± 1·5 years). A group of 42 healthy subjects of similar age, sex and body mass index (BMI) served as the control group. Baseline serum concentrations of GH, insulin, IGF‐I, IGFBP‐1 and IGFBP‐3 were measured in all patients and control subjects.

results  Fasting serum concentrations of IGF‐I and its binding proteins (IGFBP‐1 and IGFBP‐3) were significantly higher in dialysis patients than in subjects with normal renal function. IGF‐I (248·9 ± 23·4 vs. 205·5 ± 15·5 µg/l, NS), IGFBP‐3 (5·6 ± 0·4 vs. 5·5 ± 0·2 mg/l, NS) and IGFBP‐1 (36·1 ± 5·9 vs. 44·1 ± 6·5 µg/l, NS) concentrations were similar in both groups of dialysis (PD vs. HD) patients. However, GH (2·3 ± 0·3 vs. 1·1 ± 0·1 µg/l, P < 0·001) and insulin (40·4 ± 4·5 vs. 30·1 ± 3·1 µU/ml, P < 0·05) levels were significantly higher in the PD group than in the HD group. Both groups of dialysis patients showed significantly higher levels of insulin than healthy subjects (14·7 ± 1·9 µU/ml, P < 0·0001 and P < 0·01 for PD and HD, respectively). In both groups of dialysis patients, IGF‐I correlated inversely with IGFBP‐1 (PD group r = −0·46, P = 0·0006; HD group r = −0·57, P = 0·0001) and directly with IGFBP‐3 (PD group r = 0·44, P = 0·001; HD group r = 0·73, P = 0·001). No correlation between insulin and IGFBP‐1 was found in any of the groups studied.

conclusions  These findings demonstrate that adult dialysis patients have elevated IGF‐I, IGFBP‐1 and IGFBP‐3 serum concentrations compared with subjects with normal renal function. Only GH and insulin show statistically significant differences in relation to type of dialysis. Finally, the negative correlation between IGF‐I and IGFBP‐1 and the positive correlation between IGF‐I and IGFBP‐3 are maintained in both groups of adult dialysis patients.
Altered serum profile of inhibin B, Pro‐αC and anti‐Müllerian hormone in prepubertal and pubertal boys with varicocele
Authors: Trigo Romina V. , Bergadá Ignacio , Rey Rodolfo , Ballerini María G. , Bedecarrás Patricia , Bergadá César , Gottlieb Silvia , Campo Stella
Published: May 2004

objective  Anti‐Müllerian hormone (AMH) and inhibin B are reliable markers of Sertoli cell function. The aim of the present study was to assess the functional state of Sertoli cells in order to detect early changes in the testicular function of prepubertal and pubertal patients with untreated grade II or III varicocele.

design and patients  Seven prepubertal and 55 pubertal boys with untreated grade II or III varicocele were studied. Seven prepubertal and 43 pubertal normal boys were considered as controls.

measurements  Serum levels of gonadotrophins, testosterone, inhibin B and Pro‐αC and AMH were determined by time‐resolved immunofluorometric assays, radioimmunoassay (RIA) and specific enzyme‐linked immunosorbent assays (ELISAs), respectively.

results  Inhibin B and Pro‐αC serum levels were higher in prepubertal patients with varicocele than in controls (P < 0·001). No further increment in inhibin B and Pro‐αC levels was observed in pubertal patients with varicocele. Higher levels of AMH were found in patients in Tanner stages I, III, IV and V when compared to normal boys by Tanner stage (P < 0·05, P < 0·01, P < 0·01, P < 0·001, respectively). The direct correlation found in normal boys between inhibin B levels and LH, testosterone and testicular volume was not observed in patients with varicocele.

conclusions  The altered serum profile of gonadal hormones observed in untreated prepubertal and pubertal patients with varicocele may indicate an early abnormal regulation of the seminiferous epithelium function.
Women's interpretation of cervical smear test results
Authors: Philips Z. , Avis M. , Whynes D. K.
Published: May 2004

Screening for cervical cancer using the Papanicolaou smear test has been available in England since the 1960s, yet very little is known about how women interpret their test results. This questionnaire study required women to explain, in their own words, the meaning of normal and abnormal test results. It was discovered that the use of the word cell as a description of findings was extremely common, and that a proportion of subjects equated abnormal results with technical inadequacy. The frequency of circularity in the interpretations, i.e. interpreting ‘normal’ as ‘not abnormal’ and vice versa, was striking. Contrary to previous research, we find that, whilst many women interpret normal results as indicating the current absence of cancer, few appear to believe that future cancer is thereby definitively ruled out. By the same token, only a very small minority interpret abnormal results as definitive of cancer.
Impacts of stocking and introductions on freshwater fisheries of Newfoundland and Labrador, Canada
Authors: Van Zyll de Jong M. C. , Gibson R. J. , Cowx I. G.
Published: May 2004

Stocking and introduction of fishes began in Newfoundland and Labrador in the early 1880s. Introduced non‐native fishes and stocking of native fishes beyond their local range have established populations in many areas. Competition, predation and the possible introduction of parasites and diseases have all resulted from such stocking and introductions. Direct genetic effects have been caused by interbreeding with native species. Indirect genetic effects may have resulted from selective forces, genetic drift and inbreeding. Aquaculture and the creation of transgenic fish also pose a new threat to native fish. The effects of introductions as mitigation or enhancement tools are discussed. Although Newfoundland and Labrador is still relatively pristine, safeguards must be introduced to reduce the potential detrimental effects of these management practices.
Fisheries for non‐native species in England and Wales: angling or the environment?
Authors: Hickley P. , Chare S.
Published: May 2004

The increase in popularity of ‘big game’ type angling in the UK has lead to a proliferation of waters stocked with non‐native species. Many introductions have been illegal and the potentially irreversible ecological consequences are yet to be realised. Some case histories are presented and show the potential impacts of these species to involve the effects of predation, competition, disease, hybridisation and habitat degradation. Responding to anglers’ demands while controlling any illegal spread of non‐native fish in the wild is a major challenge. The legislation that governs the movement of fish into and within England and Wales is shared between the Environment Agency and other Government organisations, a situation that engenders significant management difficulties and enables less scrupulous movers of fish to exploit any weaknesses in the enforcement system. The problem is being addressed in a number of ways. A fully coordinated approach to the regulation of fish movements is being facilitated by a new database and the Environment Agency has reviewed the policies through which it regulates movements of fish into the wild. The guiding principle is that fish introductions should not jeopardise the well being of naturally established ecosystems, i.e. there should be no detriment to the donor or recipient fisheries, or to the fish being introduced. This approach was endorsed by a recent Government review of fisheries legislation that recommended strengthening controls over inappropriate movements of fish.
Contribution of native and non‐native species to fish communities in French reservoirs
Authors: Irz P. , Argillier C. , Proteau J.‐P.
Published: May 2004

Previous studies showed that only 20% of the variability in fish community structure in French reservoirs could be explained by site characteristics. In addition, no relationship was found between the relative abundance of species and stocking effort. Therefore, deliberate or uncontrolled introductions are likely to be the source of a great part of the observed communities. The objective of this study was to assess the importance of species introductions in French reservoirs. Fifty‐one reservoirs were sampled to obtain species presence/absence data. Local native (LNaR) and non‐native (LNNR) species richness were negatively correlated. LNaR was strongly correlated to the lake surface area, depth and catchment area, whereas LNNR was independent of environmental variables. Furthermore, LNaR was positively correlated to regional native richness. Conversely, local total richness was independent of regional total richness, but was related to the reservoirs’ environmental characteristics. It was hypothesised that the native fish communities in French reservoirs are unsaturated and species introductions lead to saturated communities.
The effects of fisheries management practises on freshwater ecosystems
Authors: Cowx I. G. , Gerdeaux D.
Published: May 2004

The contributions presented at the European Inland Fisheries Advisory Commission Symposium on The Effects of Fisheries Management Practises on Freshwater Ecosystems in 2002 are reviewed. The principal mechanisms of inland fisheries management concentrate on four categories: fish stock enhancement (stocking and introductions); rehabilitation and habitat manipulation for fisheries purposes, including biomanipulation; fisheries regulations; and conservation and protection of fish and fisheries. The negative and beneficial impacts of these activities are summarised and options for improving the outputs of fisheries management practices to accrue wider benefits to society are discussed. Wider stakeholder participation and a shift from traditional fisheries towards ecosystem‐based management approaches are the main mechanism proposed. This calls for new management tools to cater for legitimate human demand for water abstraction, hydropower generation and effluent disposal, as well as alternative commercial use of water bodies such as bathing, boating and tourism, in addition to fisheries exploitation and conservation needs.
Assessment of the nitrogen status of grassland
Authors: Farruggia A. , Gastal F. , Scholefield D.
Published: May 2004

Two types of diagnostics are used for N management in grasslands: diagnostics based on N concentration of shoots and diagnostics based on soil mineral N. The Nitrogen Nutrition Index (NNI) is an example of the first type. However, its evaluation requires the determination of shoot dry weight per unit area and, thus, constitutes a practical limit to its utilization in the context of farm studies. In order to simplify its evaluation, a method based on the N concentration of the upper sward layer (Nup) has been proposed. The objectives of this study were to test the relationship between NNI and Nup in the context of permanent grassland and to examine the relationship between Nup and soil mineral status. The study was conducted as two experiments, one on small cut‐plots receiving contrasting rates of mineral N fertilization, and a second on plots of an existing field‐scale lysimeter experiment. In each plot and at several dates, shoot biomass within quadrats was measured, N concentration was determined on the upper leaves and on the entire shoots, and mineral nitrogen of the soil below the vegetation sampled was determined. N concentration of the upper lamina layer of the canopy was linearly related to the NNI determined on the entire shoots. Therefore, determining N concentration in leaves at the top of canopy appears to be an alternative means to evaluate NNI without having to measure shoot biomass. The absence of an overall significant correlation between soil mineral N content and sward N index, observed over the two studies, indicates that each of these two indicators has to be considered specifically in relation to the objective of the diagnostic procedure. As sward N index may vary independently of soil mineral N content, the sward N indicator does not appear to be a suitable indicator for diagnosis of environmental risks related to nitrate leaching. However, soil mineral N content does not allow the prediction of sward N status and thus is not a suitable indicator of sward growth rate. Although soil mineral N content is an important environmental indicator for nitrate‐leaching risks during potential drainage periods, it has a limited diagnosis value with respect to the herbage production function of grasslands.
Soil, site and management components of variation in species composition of agricultural grasslands in western Norway
Authors: Myklestad Å.
Published: May 2004

A partitioning of the total variance in species composition of grasslands associated with increasing fertilizer inputs (unfertilized pastures, artificially fertilized hay meadows and intensively cultivated grassland) in western Norway was undertaken. The partitioning was carried out with (partial) constrained ordinations (canonical correspondence analysis) and associated Monte Carlo permutation tests. Explained variation was high (0·651), with soil chemistry, management and site explaining 0·271, 0·228 and 0·052 of the variation, respectively, and the interaction between soil and management explaining 0·100 of the variation. However, much of the measured soil chemistry was considered to be an effect of management. The soil chemistry variable explaining most variation was extractable P content, associated with high soil extractable P contents in the intensively cultivated grassland due to high fertilizer applications. However, soil extractable P content did not explain differences in species composition when grasslands with smaller differences in fertilizer inputs (meadows vs. pastures) were compared. Total soil C and N contents and C:N ratios explained significant variation between all grassland types. Lowest levels of these variables were measured in the grassland with the highest fertilizer inputs, suggesting that total soil N content cannot be used as a predictor of fertility. Significantly higher soil N contents were measured in grasslands of low productivity, probably due to a low decomposition rate of stress‐tolerant plants and the consequent low availability of soil N and accumulation of soil organic matter. Ellenberg N values reflected soil chemical differences in this study with high Ellenberg N values reflecting high Ca, Mg and P contents and pH values and low total C and N contents and C:N ratios.
Impacts of elevated atmospheric CO2 and temperature on plant community structure of a temperate grassland are modulated by cutting frequency
Authors: Harmens H. , Williams P. D. , Peters S. L. , Bambrick M. T. , Hopkins A. , Ashenden T. W.
Published: May 2004

To determine the impacts of climate change and defoliation on the community structure and plant diversity of a semi‐natural temperate grassland, monoliths of a permanent grassland were exposed to ambient or elevated atmospheric CO2 concentrations (ambient + 235 ppmv) and temperature (ambient + 3°C) from October 1998 to December 2000. The monoliths were subjected to two different cutting frequencies, either two or six cuts per year. The grassland community structure changed during the course of the experiment and was more responsive to changes in management than to changes in climate. Increased cutting frequency stimulated plant diversity by enhancing the number of forb species, but plant diversity was not significantly affected by climate change. The contribution of individual plant species to the vegetation cover revealed species‐specific responses to climate change and cutting frequency, but for most species significant interactions between climate change and cutting frequency were present. There were no clear‐cut effects of treatments on the total annual yield and the proportion of forbs present, as significant interactions between climate change and cutting frequency occurred. It is concluded that differential grassland management will modify plant species‐specific responses to climate change and resulting changes in the botanical composition of mixed‐species, temperate grasslands.
Comparison of a pasture‐based system of milk production on a high rainfall, heavy‐clay soil with that on a lower rainfall, free‐draining soil
Authors: Shalloo L. , Dillon P. , O'Loughlin J. , Rath M. , Wallace M.
Published: May 2004

The objective of this study was to compare the biological and economic efficiency of a seasonal pasture‐based spring calving system of milk production on a high‐rainfall, heavy‐clay soil [Kilmaley (KMY)] to that on a lower‐rainfall free‐draining soil [Moorepark (MPN)] in Ireland. The physical performance data were obtained from a 3‐year study (1998–2000) carried out at both sites. Analysis of the system of milk production at the two sites was undertaken using the Moorepark Dairy System Model. Herbage dry‐matter production was greater at the MPN site with a greater proportion being produced between 1 September and 1 May. On average, over the 3 years, the system of milk production at the MPN site had a higher stocking rate (2·34 vs. 1·89 cows ha−1), higher milk production per cow (6421 vs. 5781 kg per cow), longer grazing season (250 vs. 149 d) and a higher proportion of the diet of the herd from grazed grass (0·70 vs. 0·40) than at KMY. Economic analysis showed that, in a 468 100 kg European Union milk quota scenario, the profitability at the MPN site was €28 417 greater than at the KMY site. At similar milk production per cow it was €19 138 greater. Monte Carlo simulation showed that the MPN site was stochastically dominant over the KMY site. Sensitivity analyses showed that farm profit was most sensitive to changes in milk price. The results also indicated that milk production in the future may not be sustainable economically on high‐rainfall, heavy‐clay soils in Ireland.