bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term treatment of gastro‐oesophageal reflux disease patients with frequent symptomatic relapses using rabeprazole: on‐demand treatment compared with continuous treatment
Authors: Bour B. , Staub J.‐L. , Chousterman M. , Labayle D. , Nalet B. , Nouel O. , Pariente A. , Tocque E. , Bonnot‐Marlier S. 
Published: March 2005

SummaryBackground : On‐demand treatment may be an alternative in the long‐term treatment of non‐severe gastro‐oesophageal reflux disease in patients with frequent symptomatic relapses.Aim : To compare the efficacy of on‐demand treatment with rabeprazole 10 mg versus continuous treatment in the long‐term treatment of patients with frequent symptomatic relapses of mild to moderate gastro‐oesophageal reflux disease.Methods : This randomized, open‐label study enrolled patients diagnosed with non‐erosive reflux disease or oesophagitis grade 1 or 2 (Savary–Miller classification) reporting frequent symptomatic relapses (requiring ≥2 courses of antisecretory therapy during the previous year), whose intensity is rated at least moderate (>2 on a 5‐point Likert scale). After a 4‐week selection phase with rabeprazole 10 mg once daily, patients reporting symptom relief (Likert score ≤2) were randomized to receive either rabeprazole 10 mg continuous treatment or on‐demand treatment for 6 months. The main evaluation criterion was the rate of symptom relief (scored on the Likert scale) after 6 months.Results : One hundred and seventy‐six patients were enrolled in the 4‐week selection phase (men, 53%; mean age, 49 years; non‐erosive reflux disease, 36.4%; gastro‐oesophageal reflux disease 1, 53.4%; gastro‐oesophageal reflux disease 2, 10.2%). Rabeprazole relieved symptoms in 88.6% of patients. Of this group, 152 were randomized to the comparative phase to receive rabeprazole 10 mg continuous treatment (once daily) or on‐demand treatment (continuous treatment, n = 81; on‐demand treatment, n = 71). At month 6 (end point), the symptom relief rate was slightly higher for patients in the continuous treatment group compared with those in the on‐demand treatment group: 86.4% versus 74.6%, respectively. This difference was not statistically significant (P = 0.065). For the overall quality of life score, there was no difference between the continuous treatment and on‐demand treatment groups (86.25 and 84.94). Mean daily consumption of rabeprazole was significantly lower in the on‐demand treatment group versus the continuous treatment group (0.31 tablets versus 0.96 tablets; P < 0.0001).Conclusion : On‐demand therapy with rabeprazole 10 mg provides an alternative to continuous therapy in patients with mild to moderate gastro‐oesophageal reflux disease suffering from frequent symptomatic relapses.
Systematic review and meta‐analysis: is 1‐week proton pump inhibitor‐based triple therapy sufficient to heal peptic ulcer?
Authors: Gisbert J. P. , Pajares J. M. 
Published: March 2005

SummaryAims : To systematically review the efficacy on ulcer healing of 1‐week combination of a proton pump inhibitor plus two antibiotics and to perform a meta‐analysis of randomized clinical trials to evaluate whether 7 days of proton pump inhibitor‐based triple therapy is sufficient to heal peptic ulcer.Methods : Studies where 1‐week proton pump inhibitor‐based triple therapy was administered to heal peptic ulcer were included. Randomized clinical trials comparing the efficacy on ulcer healing of 7‐day proton pump inhibitor‐based triple therapy versus this same regimen but prolonging the proton pump inhibitor for several more weeks were included in the meta‐analysis. Electronic and manual bibliographical searches were conducted. Meta‐analysis was performed combining the odds ratios of the individual studies.Results : Twenty‐four studies (2342 patients) assessed ulcer healing with 1‐week proton pump inhibitor‐based triple therapy. Mean healing rate was 86%, and 95% in Helicobacter pylori‐eradicated patients. Six studies (862 patients), were included in the meta‐analysis. Mean ulcer healing rate with a 7‐day treatment was 91% versus 92% when proton pump inhibitor was prolonged for 2–4 more weeks (odds ratio = 1.11; 95% confidence interval = 0.71–1.74).Conclusion : In patients with peptic ulcer and H. pylori infection, prolonging therapy with proton pump inhibitor after a triple therapy for 7 days with a proton pump inhibitor and two antibiotics is not necessary to induce ulcer healing.
A phase 2 clinical trial of metformin as a treatment for non‐diabetic paediatric non‐alcoholic steatohepatitis
Authors: Schwimmer J. B. , Middleton M. S. , Deutsch R. , Lavine J. E. 
Published: March 2005

SummaryBackground : Children with non‐alcoholic steatohepatitis are insulin‐resistant and metformin has been proposed as a potential therapy. However, paediatric safety and efficacy data are absent.Aim : To test the hypothesis that metformin therapy will safely improve markers of liver disease in paediatric non‐alcoholic steatohepatitis.Methods : Single‐arm open‐label pilot study of metformin 500 mg twice daily for 24 weeks in non‐diabetic children with biopsy‐proven non‐alcoholic steatohepatitis.Results : Ten obese children (mean body mass index 30.4) enrolled and completed the trial. Mean alanine aminotransferase and aspartate aminotransferase (AST) improved significantly (P < 0.01) from baseline (184, 114 U/L) to end of treatment (98, 68 U/L). Alanine aminotransferase normalized in 40% and AST normalized in 50% of subjects. Children demonstrated significant improvements in liver fat measured by magnetic resonance spectroscopy (30–23%, P < 0.01); insulin sensitivity measured by quantitative insulin sensitivity check index (0.294–0.310, P < 0.05); and quality of life measured by pediatric quality of life inventory 4.0 (69–81, P < 0.01).Conclusion : Open‐label treatment with metformin for 24 weeks was notable for improvement in liver chemistry, liver fat, insulin sensitivity and quality of life. A large randomized‐controlled trial is needed to definitively determine the efficacy of metformin for paediatric non‐alcoholic steatohepatitis.
Missing gastric cancer in dyspepsia
Authors: Schmidt N. , Peitz U. , Lippert H. , Malfertheiner P. 
Published: March 2005

SummaryBackground : Dyspepsia is common in gastric cancer, but also in many benign conditions. European Helicobacter pylori Study Group and American Gastroenterological Association guidelines recommend endoscopy in dyspepsia for patients with alarm symptoms or at age >45 years. However, recommendations are controversial.Aim : To investigate whether criteria for endoscopy in patients with dyspepsia are adequate to detect gastric cancer.Methods : In 215 patients at initial diagnosis of gastric adenocarcinoma, symptoms were classified as alarm and non‐alarm. Cases were staged according to the TNM system. Stages T1–T3NxM0 were defined as potentially curable.Results : Dyspepsia was present in 128 patients. Among patients with dyspepsia, 15 were ≤45 years and 41 denied alarm symptoms. The combination of both criteria excluded only three (2.3%) patients from endoscopy, but increasing the threshold to >50 and >55 years would have raised the rate of excluded patients to seven (5.5%) and 11 (8.6%). Only 53 potentially curable stages and 18 early gastric cancers occurred, but the tumour stage was not associated with dyspepsia duration, age threshold of 45 years, or alarm symptoms.Conclusions : Our results support current European Helicobacter Study Group and American Gastroenterological Association criteria for endoscopy in patients with dyspepsia to detect gastric cancer. Regardless, most cancers are advanced at detection.
Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study
Authors: Gaudino Rossella , Garel Catherine , Czernichow Paul , Léger Juliane 
Published: March 2005

SummaryObjective  To determine the proportion of the various types of thyroid disorders among newborns detected by the neonatal TSH screening programme, with a normally located thyroid gland.Patients and methods  Of the 882 575 infants screened in our centre between 1981 and 2002, 85 infants with a normally located gland had persistent elevation of serum TSH values (an incidence of 1/10 383). Six of these 85 patients were lost to follow‐up and were therefore excluded from the study. During follow‐up, patients were classified as having permanent or transient hypothyroidism.Results  Among the 79 patients included in the study, transient (n = 30, 38% of cases) and permanent (n = 49, 62% of cases) congenital hypothyroidism (CH) was demonstrated during the follow‐up at the age of 0·7 ± 0·6 years and 2·6 ± 1·8 years (P < 0·0001), respectively. The proportion of premature births was significantly higher in the group with transient CH (57%) than in the group with permanent CH (2%) (P < 0·0001). A history of iatrogenic iodine overload was identified during the neonatal period in 69% of transient cases. Among permanent CH cases (n = 49), patients were classified as having a goitre (n = 27, 55% of cases), a normal sized and shaped thyroid gland (n = 14, 29% of cases) or a hypoplastic gland (n = 8, 16% of cases). The latter patients demonstrated global thyroid hypoplasia (n = 3), a right hemithyroid (n = 2), hypoplasia of the left lobe (n = 2), or asymmetry in the location of the two lobes (n = 1). Patients with a normal sized and shaped thyroid gland showed a significantly less severe form of hypothyroidism than those with a goitre or a hypoplastic thyroid gland (P < 0·0002). Among permanent CH cases, those with a goitre (n = 27) had an iodine organification defect (n = 10), Pendred syndrome (n = 1), a defect of thyroglobulin synthesis (n = 8), or a defect of sodium iodine symporter (n = 1), and in seven patients no aetiology could be determined. Among permanent cases with a normal sized and shaped thyroid gland (n = 14), a specific aetiology was found in only one patient (pseudohypoparathyroidism) and two patients had Down's syndrome. Among those with a globally hypoplastic gland, a TSH receptor gene mutation was found in two patients.Conclusions  A precise description of the phenotype can enhance our understanding of various forms of neonatal hypothyroidism as well as their prevalence and management. It also helps to identify cases of congenital hypothyroidism of unknown aetiology, which will need to be investigated in collaboration with molecular biologists.
Supraphysiological growth hormone: less fat, more extracellular fluid but uncertain effects on muscles in healthy, active young adults
Authors: Ehrnborg Christer , Ellegård Lars , Bosaeus Ingvar , Bengtsson Bengt‐Åke , Rosén Thord 
Published: March 2005

SummaryObjectives  To study the effects on body composition after 1 month's administration of supraphysiological doses of growth hormone (GH) in healthy, active young adults with normal GH‐IGF‐I axis.Subjects and methods  Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25·9 years (range 18–35), participated in this study, designed as a randomized, double‐blind, placebo‐controlled, parallel study with three groups (n = 10: five men and five women in each group). The groups comprised the following: placebo (P), GH 0·1 IU/kg/day [0·033 mg/kg/day] (GH 0·1) and GH 0·2 IU/kg/day [0·067 mg/kg/day] (GH 0·2).Results  In the pooled group with active GH treatment (n = 20) the results showed significant increases: IGF‐I increased by 134% (baseline vs. after 1 month), body weight by 2·7%, fat free mass by 5·3%, total body water by 6·5% and extracellular water (ECW) by 9·6%. Body fat decreased significantly by 6·6%. No significant change in intracellular water was detected. The observed increase in fat free mass by 5·3% was explained by the ECW increase, indicating limited anabolic effects of the supraphysiological GH doses. Changes were noticeable in both genders, although more prominent in the male subjects. Fluid retention symptoms occurred in the majority of individuals.Conclusions  This is, to our knowledge, the first placebo‐controlled trial to show the effects of supraphysiological GH doses on body composition and IGF‐I levels in physically active and healthy individuals of both genders; the results indicate limited anabolic effects of GH with these supraphysiological doses. The role of GH as an effective anabolic doping agent is questioned.
Growth hormone replacement reduces C‐reactive protein and large‐artery stiffness but does not alter endothelial function in patients with adult growth hormone deficiency
Authors: McCallum Roland W. , Sainsbury Christopher A. R. , Spiers Angela , Dominiczak Anna F. , Petrie John R. , Sattar Naveed , Connell John M. C. 
Published: March 2005

SummaryHypopituitary patients have an increased risk of vascular mortality that may relate to growth hormone deficiency (GHD). We investigated the effects of 6 months of GH therapy on large‐ and small‐artery function and high‐sensitivity C‐reactive protein (hsCRP) in a cohort of GH‐deficient patients. Sixteen hypopituitary patients were randomized to 6 months of GH therapy or no treatment, then vice versa. hsCRP, 24‐h blood pressure (BP) and pulse wave velocity (PWV) were measured and resistance arteries were used to construct concentration–response curves to endothelium‐dependent and ‐independent agents. GH therapy increased IGF‐1 from 60 ± 7·2 to 167 ± 16·2 µg/l [confidence interval (CI) 94·9, 138·8, P < 0·001]. hsCRP declined after 6 months of GH from 3·8 ± 0·88 to 2·0 ± 0·49 mg/l (CI 0·73, 3·57, P = 0·006). Mean arterial BP fell from 91·7 ± 1·5 to 89·3 ± 1·2 mmHg (CI 0·81, 4·07, P = 0·005), as did PWV (8·1 ± 0·4 to 6.7 ± 0·5 m/s). The decline in PWV correlated with the decline in hsCRP (r = 0·68, P = 0·01). Resistance artery function was unchanged after GH therapy. GH replacement may lead to differentially altered production of vasorelaxant agents from the endothelium of large and small arteries. Reduction in vascular inflammation may be associated with reduced vascular risk.
Serum levels of sex hormone‐binding globulin (SHBG) are not associated with lower levels of non‐SHBG‐bound testosterone in male newborns and healthy adult men
Authors: De Ronde Willem , Van Der Schouw Yvonne T. , Pierik Frank H. , Pols Huibert A. P. , Muller Majon , Grobbee Diederick E. , Gooren Louis J. G. , Weber Rob F. A. , De Jong Frank H. 
Published: March 2005

SummaryObjective   It is generally accepted that SHBG decreases the bioavailability and activity of testosterone (T). In in vitro experiments increased levels of SHBG will be associated with decreased levels of non‐SHBG bound testosterone (non‐SHBG‐T). However, in vivo SHBG can alter both production and clearance rates and thus plasma levels of T.Design and patients   In order to study the effect of SHBG on the levels of non‐SHBG‐T in vivo in the presence of an active hypothalamo–pituitary–gonadal (HPG) axis we conducted a cross sectional study in 400 healthy adult men with an age range of 40–80 years and in 106 newborn boys.Measurements   In both groups, regression coefficients (β) and partial correlation coefficients (r) were calculated for the relationship between SHBG and T or non‐SHBG‐T. Adult men were divided into age groups per decade (40–50 years, 51–60 years, 61–70 years and 71–80 years) to study possible differences in the impact of SHBG on the level of non‐SHBG‐T throughout ageing.Results   Higher levels of SHBG were associated with higher levels of total testosterone in neonates (β = 0·02 ± 0·004, r = 0·44, P < 0·001) but not with non‐SHBG‐T (β = −0·001 ± 0·001, r = 0·05, P = 0·52). In adult men there was a significant age related increase in levels of SHBG and an age‐related decrease of both total and non‐SHBG‐T. Higher SHBG was strongly associated with higher total testosterone in all age groups (β = 0·26, 0·26, 0·26 and 0·23 for 40–50 years, 51–60 years, 61–70 years and 71–80 years, respectively, P < 0·001 for all age groups). Higher SHBG was not or only slightly associated with higher non‐SHBG‐T β = 0·02 (P = 0·32), β = 0·04 (P = 0·03), β = 0·04 (P = 0·02) and β = 0·02 (P = 0·16) for 40–50 years, 51–60 years, 61–70 years and 71–80 years, respectively.Conclusions   In contrast to general belief, SHBG levels barely influence levels of non‐SHBG‐bound testosterone both in male newborns and healthy adult men: the influence, if any, is positive. Consequently the age related increase of SHBG does not account for the age related decline in non‐SHBG‐T in healthy adult men.
The expression of messenger RNA for ADP‐ribosyl cyclase in aldosterone‐producing adenomas
Authors: Takeda Yoshiyu , Usukura Mikiya , Yoneda Takashi , Oda Nobushige , Ito Yoko , Mabuchi Hiroshi 
Published: March 2005

SummaryObjective  Cyclic ADP‐ribose (cADPR) has been reported to be as potent and powerful at releasing intracellular Ca2+ as inositol triphosphate (IP3). To determine whether the cADPR system plays a signalling role in angiotensin II (Ang II)‐induced aldosterone synthesis in the human adrenal gland, we investigated the effects of Ang II on ADP‐ribosyl cyclase activity in human adrenal cortical tissue. In addition, the expression of ADP‐ribosyl cyclase messenger RNA was evaluated in aldosterone‐producing adenomas (APAs) and compared with normal adrenal tissue and nonfunctioning adenomas.Design  ADP‐ribosyl cyclase activity was measured in crude membrane fractions of human adrenocortical tissues with Ang II or with Ang II plus the Ang II receptor (AT1R) antagonist losartan or plus the AT2R antagonist PD123319. The effect of 8‐bromo‐cADPR on Ang II‐induced aldosterone production from adrenal tissue was estimated. The expression of ADP‐ribosyl cyclase, CYP11B2 and AT1R mRNA was measured in APAs, nonfunctioning adenomas, adjacent adrenal tissue and normal adrenal tissue.Measurements  ADP‐ribosyl cyclase activity was measured by using high‐performance liquid chromatography (HPLC) and [3H] NAD+. mRNA expression was measured by competitive reverse‐transcription polymerase chain reaction (RT‐PCR).Results  Ang II (10−7 and 10−8 mol/l) significantly increased ADP‐ribosyl cyclase activity in a dose‐dependent manner. This increase was inhibited by pretreatment with losartan but not with PD123319. Treatment with 8‐bromo‐cADPR (50 µmol/l) reduced Ang II‐induced aldosterone secretion. ACTH did not significantly increase the enzyme activity. The expression of ADP‐ribosyl cyclase, CYP11B2 and AT1R mRNA was increased in APAs compared with that of nonfunctioning adenomas, adjacent adrenal tissue or normal adrenal tissue.Conclusions  These results demonstrated the existence of a signalling pathway from the Ang II receptor to ADP‐ribosyl cyclase in the human adrenal gland and suggest that the cADP‐ribose signalling system might play an important role in the pathogenesis of APAs.
Herbivory, time since introduction and the invasiveness of exotic plants
Authors: CARPENTER DAVID , CAPPUCCINO NAOMI 
Published: March 2005

Summary

We tested the enemy release hypothesis for invasiveness using field surveys of herbivory on 39 exotic and 30 native plant species growing in natural areas near Ottawa, Canada, and found that exotics suffered less herbivory than natives.
For the 39 introduced species, we also tested relationships between herbivory, invasiveness and time since introduction to North America. Highly invasive plants had significantly less herbivory than plants ranked as less invasive. Recently arrived plants also tended to be more invasive; however, there was no relationship between time since introduction and herbivory.
Release from herbivory may be key to the success of highly aggressive invaders. Low herbivory may also indicate that a plant possesses potent defensive chemicals that are novel to North America, which may confer resistance to pathogens or enable allelopathy in addition to deterring herbivorous insects.
Pre‐dispersal predation of Taraxacum officinale (dandelion) seed
Authors: HONEK ALOIS , MARTINKOVA ZDENKA 
Published: March 2005

Summary

Pre‐dispersal predation of seeds of Asteraceae has been studied in species where ripening seed is present on plants for long periods but rarely in those where seed maturation is ephemeral and density of consumers is therefore unlikely to keep pace with changes in seed availability.
We therefore followed predation of dandelion (Taraxacum officinale) seeds by the larvae of Glocianus punctiger and Olibrus bicolor and predicted that both abundance of seed consumers and seed damage will be indirectly proportional to inflorescence availability, and that overall seed damage will be less than in species with longer lived inflorescences.
We counted the number of dandelion capitula m−2, number of larvae capitulum−1 and percentage of damaged seeds at 10 sites, where the flowering time and densities of dandelions differed. The counts were made in 2002 and 2003, at half‐weekly (April–May) or weekly (June–August) intervals.
Abundance of both species of consumer varied among dandelion patches, and with change in availability of dandelion capitula. Numbers of larvae capitulum−1 were high early and late, when few capitula were available, but decreased at the time of peak flowering when there were many capitula. Production of ready‐to‐pupate larvae m−2 of a species at a site was similar in successive years, but values for O. bicolor and G. punctiger were not correlated.
Seed damage paralleled the abundance of consumer larvae, with early and late flowers suffering most. A linear relationship correcting for lost seeds, predicted 30% damage when there were five larvae capitulum−1, below levels reported for species of Asteraceae with persistent inflorescences.
The intensity of pre‐dispersal seed predation is directly proportional to the abundance of seed consumer species and indirectly proportional to the availability of maturing capitula. Consequently, in species with ephemeral, synchronized flowering, where seed is available for only a short time, the majority of plants lose only a small proportion to predators. Although those flowering earlier or later than the peak will suffer a much higher risk, the low overall level of damage is unlikely to influence population biology.
The Human MT1 Melatonin Receptor Stimulates cAMP Production in the Human Neuroblastoma Cell Line SH‐SY5Y Cells Via a Calcium‐Calmodulin Signal Transduction Pathway
Authors: Schuster C. , Williams L. M. , Morris A. , Morgan P. J. , Barrett P. 
Published: March 2005

AbstractMelatonin regulates circadian and seasonal physiology via melatonin receptors expressed in the brain. However, little is known about the signal transduction mechanisms that mediate the action of melatonin in neuronal cells. To begin to address this issue, we expressed the human MT1 receptor in the human neuroblastoma SH‐SY5Y cell line. In this cell line, melatonin acutely stimulated cAMP synthesis through a calcium‐calmodulin dependent pathway. This stimulatory effect was independent of an interaction with Gi or Gs G proteins and dependent upon internal calcium stores. Melatonin also potentiated forskolin‐activated cAMP synthesis. Differentiation of the neuroblastoma cells with retinoic acid to the neuronal phenotype did not alter the ability of melatonin to acutely stimulate cAMP. These data may be relevant to the neuronal action of melatonin and highlight the importance of the cellular context of expression of melatonin and other G protein‐coupled receptors.