bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of bowel preparation with the use of a prepackaged, low fibre diet with a low sodium, magnesium citrate cathartic vs. a clear liquid diet with a standard sodium phosphate cathartic
Authors: Delegge M. , Kaplan R.
Published: June 2005

Background: A colon free of faecal residue is required for accurate diagnostic colonoscopy. Patient tolerance of his/her colonoscopy cathartic regimen affects patient compliance and willingness to undergo repeated examinations.

Aim: To determine whether a meal could be consumed during standard bowel preparation.

Methods: This was a randomized, endoscopists’ blinded comparison of the tolerability and efficacy of a prepackaged, low‐residue diet (NutraPrep) combined with the LoSo Prep bowel cleansing system, which contains magnesium citrate, bisocodyl tablets and a bisocodyl suppository (NP‐LS regimen), compared with a clear liquid diet and a double‐dose sodium phosphate (Fleet Phospho‐soda) regimen (2F regimen). Outcome measures included efficacy of bowel preparation, patient preparation tolerability, side‐effects and patient safety.

Results: A total of 506 patients completed the study, 222 randomized to 2F and 284 to NP‐LS. The NP‐LS regimen resulted in significantly better colon cleansing in terms of the proportion with good or excellent results (P = 0.025) and in significantly better patient tolerance and willingness to repeat the cathartic preparation (P < 0.01).

Conclusion: The NP‐LS regimen proved superior to the 2F regimen.
Factors predisposing to peptic ulcer disease in asymptomatic cirrhotic patients
Authors: Kamalaporn P. , Sobhonslidsuk A. , Jatchavala J. , Atisook K. , Rattanasiri S. , Pramoolsinsap C.
Published: June 2005

Background : There is a high prevalence of peptic ulcer in cirrhotic patients, but the pathogenesis of peptic ulcer in cirrhosis remains inconclusive.

Aim : To investigate factors associated with peptic ulcer and to evaluate peptic ulcer prevalence in asymptomatic cirrhotic patients.

Methods : A total of 130 cirrhotics were recruited into the study for endoscopic screening. Data were collected and biochemical tests were done. Doppler ultrasound was used to assess the portal vein velocity and size. Patients underwent endoscopy for the presence of varices and peptic ulcer. Helicobacter pylori infection was confirmed by urease test, histology and 14C‐urea breath test. Statistical analysis was performed.

Results : Peptic ulcer was detected in 50 (39%) cases. Between peptic ulcer and non‐peptic ulcer groups, there were no significant differences in age, sex, alcoholic drinking, smoking, non‐steroidal anti‐inflammatory drug use, portal vein velocity and size, except for H. pylori infection (P = 0.006), serum albumin (P =0.02) and Child‐Pugh score (P = 0.03). By multivariate analysis, H. pylori infection (OR: 3.26; 95% CI: 1.49–7.13; P = 0.003), Child‐Pugh classes B (OR: 2.48; 95% CI: 1.04–5.91; P = 0.04) and C (OR: 3.26; 95% CI: 1.2–8.81; P = 0.02) were independently associated with peptic ulcer.

Conclusion : H. pylori infection and advanced cirrhosis are important factors associated with active peptic ulcer.
Paediatric homoeopathy in general practice: where, when and why?
Authors: Ekins‐Daukes Suzie , Helms Peter J. , Taylor Michael W. , Simpson Colin R. , McLay James S.
Published: June 2005

Aims

To investigate the extent of homoeopathic prescribing in primary care for childhood diseases and assess GP attitudes towards the use of homoeopathy in children.

Methods

Homoeopathic prescribing in primary care was assessed in 167 865 children aged 0–16 years for the year 1999–2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland. Medical attitudes towards homoeopathic prescribing to children were also assessed via a questionnaire survey.

Results

During the year 1999–2000 22% (36) of general practices prescribed homoeopathic medicines to 190 (1.1/1000 registered) children. The majority of such prescriptions were issued to children under 1 year of age (8.0/1000 registered children). The most frequently prescribed medicines were for common self‐limiting infantile conditions such as colic, cuts and bruises, and teething. A total of 259 completed questionnaires were returned by GPs, giving a response rate of 75%. GPs who frequently prescribed homoeopathic medicines to children (more than 1 per month) were more likely to claim an interest in homoeopathy, have had a formal training and keep up to date in the discipline, and refer on to a homoeopath (P < 0.001 for all variables) than those GPs who prescribed less than once a month or never. The majority of GPs who prescribed homoeopathic medicines did so when conventional treatments had apparently failed (76%), while 94% also perceived homoeopathy to be safe. Frequent prescribers reported a more positive attitude towards homoeopathic medicines than those who prescribed less frequently. Non‐prescribers reported a lack of proven efficacy and lack of training as the main reasons for not prescribing homoeopathic medicines (55% and 79%, respectively). However non‐prescribers from within homoeopathic prescribing practices reported a more favourable attitude in general towards homoeopathy and less resistance towards prescribing in the future than non‐prescribers from practices where none of the partners practiced homoeopathy.

Conclusions

In primary care paediatric prescribing of homoeopathic medicines most commonly occurs for self‐limiting conditions in infants less than 1 year of age. Although the current level of homoeopathic prescribing is low, the widespread use in the community suggests that at least some knowledge of the main indications for homoeopathy and the preparations used would be of benefit to registered medical practitioners.
Formulation of medicines for children
Authors: Nunn Tony , Williams Julie
Published: June 2005

The development of age‐adapted dosage forms and taste‐masking of bitter‐tasting drugs administered orally for children, are formidable challenges for formulation scientists. Childhood is a period of maturation requiring knowledge of developmental pharmacology to establish dose but the ability of the child to manage different dosage forms and devices also changes. Paediatric formulations must allow accurate administration of the dose to children of widely varying age and weight. Whilst the oral route will be preferred for long term use and the intravenous route for the acutely ill, many of the dosage forms designed for adults, such as oro‐dispersible tablets, buccal gels and transdermal patches, would also benefit children if they contained an appropriate paediatric dose. The age at which children can swallow conventional tablets is of great importance for their safety. Liquid medicines are usually recommended for infants and younger dhildren so the ability to mask unpleasant taste with sweeteners and flavours is crucial. More sophisticated formulations such as granules and oro‐dispersible tablets may be required but there will be limitations on choice and concentration of excipients. There are many gaps in our knowledge about paediatric formulations and many challenges for the industry if suitable preparations are to be available for all ranges. A CHMP points to consider document is soon to be released. More research and clinical feedback are important because a formulation with poor acceptability may affect compliance, prescribing practice and ultimately commercial viability.
Adverse drug reactions to nonsteroidal anti‐inflammatory drugs, COX‐2 inhibitors and paracetamol in a paediatric hospital
Authors: Titchen Thirza , Cranswick Noel , Beggs Sean
Published: June 2005

Aims  The use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in children has rapidly escalated over the last 5 years in Australia. This is primarily as a result of the availability of ibuprofen as an over‐the‐counter preparation. Several recent, significant adverse drug reactions (ADRs) to NSAIDs, at the Royal Children's Hospital (RCH) in Melbourne, Australia prompted review of all of the RCH reactions reported to these agents over 5 years.

Methods  The ADR programme documents both spontaneously reported ADRs and ADRs identified by discharge coding. For this study, reported reactions to aspirin, celecoxib, ibuprofen, indomethacin, naproxen, paracetamol and rofecoxib, for the previous 5‐year period, were retrieved from the hospital ADR database.

Results  Nineteen reports of ADRs to NSAIDs and six to paracetamol, in patients aged from 4 months to 22 years (median 10 years) were identified. Reactions were predominantly rash (n = 10), gastrointestinal (n = 5) and respiratory (n = 4) side‐effects. These included reports of haematemesis with both celecoxib and ibuprofen. One patient died of severe acute exacerbation of asthma following initiation of rofecoxib.

Conclusion  NSAID exposures are a significant cause of morbidity in children. Both nonselective NSAIDs and the newer COX‐2 inhibitors were associated with significant drug reactions. The overall severity of these ADRs highlights the need for vigilant surveillance of ADRs in paediatrics, including both established and newer agents.
Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus
Authors: Schindhelm R. K. , Diamant M. , Bakker S. J. L. , Van Dijk R. A. J. M. , Scheffer P. G. , Teerlink T. , Kostense P. J. , Heine R. J.
Published: June 2005

Background  Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer high‐risk cardiovascular disease. Alanine aminotransferase predicts the development of type 2 diabetes (DM2) in subjects with the metabolic syndrome. However, the role of elevated ALT levels in subjects with overt DM2 has yet not been explored.

Materials and methods  In a cross‐sectional study, 64 normotriglyceridaemic subjects with DM2 were studied with regard to the relation between liver transaminases with whole‐body insulin sensitivity, measured with the euglycaemic hyperinsulinaemic clamp and with brachial artery flow‐mediated dilation (FMD) as a marker of endothelial dysfunction.

Results  On average, patients were normotriglyceridaemic (plasma triglycerides 1·3 ± 0·4 mmol L−1) and had good glycaemic control (HbA1c 6·2 ± 0·8%). The mean ALT level was 15·0 ± 7·5 U L−1, and the mean aspartate aminotransferase concentration equalled 10·6 ± 2·6 U L−1. Alanine aminotransferase levels were negatively associated with whole‐body insulin sensitivity as well as with FMD (both P = 0·03, in multivariate analyses; regression coefficients beta [95%CI]: −0·76 [−1·4 to −0·08] and −0·31 [−0·58 to −0·03] respectively).

Conclusions  In metabolically well‐controlled patients with DM2, ALT levels are related to decreased insulin‐sensitivity and an impaired conduit vessel vascular function.
Left atrial systolic reserve in idiopathic vs. ischaemic‐dilated cardiomyopathy
Authors: Moyssakis I. , Papadopoulos D. P. , Kelepeshis G. , Gialafos E. , Votteas V. , Triposkiadis F.
Published: June 2005

Purpose  There are studies indicating more pronounced left atrial (LA) systolic dysfunction at rest in idiopathic (IDDC) than in ischaemic‐dilated cardiomyopathy (ISDC). It was hypothesized that the findings would be similar with regards LA systolic reserve.

Methods  Twenty‐six patients with IDDC, 28 with ISDC and 25 normal controls underwent low‐dose dobutamine stress echocardiography (5–10 µg kg−1 min−1 IV). Left atrial volumes were echocardiographically determined at rest and during stress at the mitral valve opening (maximal, Vmax), electrocardiographic P wave (onset of atrial systole, Vp) and mitral valve closure (minimal, Vmin) from the apical 4‐ and 2‐chamber views (biplane area‐length method). Left atrial systolic function was assessed with the LA‐active emptying volume (ACTEV) = Vp‐Vmin and fraction (ACTEF) = ACTEV/Vp.

Results  Vmax at rest was similar in IDDC and ISDC and greater than in the controls (54·2 ± 12 vs. 48·5 ± 18 vs. 27·1 ± 6·3 cm3 m−2, respectively, P < 0·001) and did not change with stress (53·9 ± 13·8 vs. 46·9 ± 16·2 vs. 25·8 ± 5·9 cm3 m−2, P < 0·001). The ACTEV at rest was similar in IDDC and ISDC and greater than in the controls (8·6 ± 3·5 vs. 9·7 ± 2·9 vs. 6·1 ± 2·2 cm3 m−2 P < 0·01), whereas during the dobutamine infusion it remained unaltered in IDDC (10·8 ± 4·6 cm3 m−2, P = NS vs. rest) and increased in ISDC (11·8 ± 3·3 cm3 m−2, P < 0·05) and the controls (13·1 ± 3·2 cm3 m−2, P < 0·01). The ACTEF was lower in IDDC than ISDC and the controls at rest (20 ± 10% vs. 33 ± 8% vs. 36 ± 10%, P < 0·01). Dobutamine infusion was associated with no significant increase in ACTEF in IDDC (25 ± 12%, P = NS vs. rest), and with an increase in this variable in ISDC (39 ± 10%, P < 0·05) and the controls (49 ± 12%, P < 0·01).

Conclusions  Dobutamine infusion is associated with an increase in LA ACTEV and fraction in ISDC and no significant change in these indices in IDDC. These findings indicate a reduced LA systolic reserve in IDDC.
Amino acid‐dependent modulation of glucose metabolism in humans
Authors: Krebs M.
Published: June 2005

Despite its high prevalence and severe complications, the aetiology of the primary defects leading to Type 2 diabetes mellitus remain unknown. In addition to polygenic predisposition, environmental factors including dietary behaviour are increasingly recognized as being of crucial importance for the development of this disease. This strongly supports the concept that nutrient excess leading to increased availability of substrates adversely influences whole‐body metabolic regulation and plays a major role in the development of type 2 diabetes. We have shown previously that a short‐term increase in free fatty acid availability impairs glucose metabolism in liver and skeletal muscle. Despite the widespread interest in protein‐rich diets, the effects of plasma amino acid elevation on human glucose metabolism have not yet been studied in detail. This editorial summarizes recent advances in the identification of mechanisms responsible for amino acid‐dependent modulation of glucose metabolism in liver and skeletal muscle in vivo.
l‐Arginine fails to protect against myocardial remodelling inl‐NAME‐induced hypertension
Authors: Simko F. , Luptak I. , Matuskova J. , Krajcirovicova K. , Sumbalova Z. , Kucharska J. , Gvozdjakova A. , Simko J. , Babal P. , Pechanova O. , Bernatova I.
Published: June 2005

Background We investigated whether the substrate for nitric oxide synthesisl‐arginine is able to modify hypertension and left ventricular hypertrophy development induced by chronic blockade of nitric oxide synthase activity by NG‐nitro‐l‐arginine‐methyl ester (l‐NAME).

Material and methods Four groups of rats were investigated: control,l‐arginine 1·5 g kg−1,l‐NAME 40 mg kg−1, andl‐NAME +l‐arginine in corresponding doses. Systolic blood pressure was measured by non‐invasive tail‐cuff plethysmography each week. After 4 weeks, the animals were sacrificed and hydroxyproline and coenzyme Q9and Q10concentrations in the left ventricle, and nitric oxide synthase activity in the left ventricle, kidney and brain were investigated.

Results In thel‐NAME group, nitric oxide synthase activity was decreased in the left ventricle, kidney and brain, and hypertension, left ventricular hypertrophy and fibrosis developed. Heart remodelling was associated with the decrease of coenzyme Q9and Q10concentrations in the left ventricle. Simultaneous treatment withl‐NAME andl‐arginine prevented nitric oxide synthase activity diminution in the left ventricle but not in the kidney and brain, and completely failed to prevent hypertension, left ventricular hypertrophy and fibrosis. Nevertheless,l‐arginine prevented the diminution of coenzyme Q9and Q10concentrations in the left ventricle.

Conclusions We conclude thatl‐arginine failed to prevent hypertension, left ventricular hypertrophy and fibrosis development despite restoration of nitric oxide synthase activity in the left ventricle. However,l‐arginine prevented the diminution of coenzyme Q levels in the left ventricle.
E‐cadherin expression in invasive non‐lobular carcinoma of the breast and its prognostic significance
Authors: Rakha E A , Abd El Rehim D , Pinder S E , Lewis S A , Ellis I O
Published: June 2005

Background : E‐cadherin is a cell adhesion molecule that is expressed in normal breast tissue and is often considered useful as a phenotypic marker in breast cancer diagnosis, with absence of its expression frequently observed in tumours of lobular subtype. However, the clinicopathological and prognostic value of E‐cadherin in the more frequent non‐lobular types of breast carcinoma is unclear.

Methods and results : E‐cadherin expression was assessed immunohistochemically in a large and well‐characterized series of invasive non‐lobular breast carcinoma types (n = 1665) with long‐term clinical follow‐up (median 56 months) using tissue microarray technology, to determine the relationship between its expression and primary tumour characteristics and disease outcome. Only membranous expression of E‐cadherin was considered in this study and its expression was categorized as normal (H‐score > 100) or reduced [absent or below the median (score≤100)]. Complete absence of its expression (score = 0) was detected in 7.2% of cases. On univariate analysis, reduced E‐cadherin expression was associated with a reduced disease‐free interval and overall survival and also with indicators of poor prognosis including larger tumour size, higher histological grade, development of distant metastasis and tumours negative for oestrogen receptors. No association between E‐cadherin expression and lymph node status was found. On multivariate analysis, E‐cadherin was an independent predictor of disease‐free interval [hazards ratio (HR) 1.56, 95% confidence intrerval (CI) 1.23, 1.99; P < 0.001] and overall survival (HR 1.53, 95% CI 1.09, 2.14; P = 0.013) and there was some evidence that the prognostic value was greater in those with positive lymph nodes (Pinteraction = 0.099).

Conclusions : These results suggest that E‐cadherin loss may play a role in progression, development of distant metastasis and recurrence in non‐lobular invasive carcinomas of the breast and its assessment by immunohistochemistry may help in the identification of patients with poor outcomes.
Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers
Authors: Llombart B , Monteagudo C , López‐Guerrero J A , Carda C , Jorda E , Sanmartín O , Almenar S , Molina I , Martín J M , Llombart‐Bosch A
Published: June 2005

Aims: To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers.

Methods and results: Clinical data and follow‐up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF‐1), chromogranin A, synaptophysin, p53, Ki67, Fli‐1, CD99, c‐Kit] were evaluated in 20 cases of MCC. Fli‐1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size > 30 mm, stage II, ‘absent’ lymphocytic infiltration, and the presence of > 50% of Ki67+ tumour cells, were found to be prognostic indicators of disease‐free interval (DFI), but only ‘absent’ lymphocytic infiltration constituted an independent prognostic factor of DFI after multivariate analysis. For overall survival, the same variables, together with local recurrence and lymph node involvement, had prognostic significance, with only local recurrence as an independent prognostic factor after multivariate analysis.

Conclusions: Absence of lymphocytic infiltration and Ki67 immunoreactivity in more than 50% of tumour cells should be evaluated in conjunction with other well‐known prognostic markers in MCC. Furthermore, recognizing that Fli‐1 and CD99 expression is commonly found in MCC by immunohistochemistry may avoid misinterpretation in the differential diagnosis of MCC with other small round cell tumours.
Activated CD4+ CD25+ T cells suppress antigen‐specific CD4+ and CD8+ T cells but induce a suppressive phenotype only in CD4+ T cells
Authors: Dieckmann Detlef , Plöttner Heidi , Dotterweich Stefanie , Schuler Gerold
Published: June 2005

CD4+ CD25+ regulatory T cells are increasingly recognized as central players in the regulation of immune responses. In vitro studies have mostly employed allogeneic or polyclonal responses to monitor suppression. Little is known about the ability of CD4+ CD25+ regulatory T cells to suppress antigen‐specific immune responses in humans. It has been previously shown that CD4+ CD25+ regulatory T cells anergize CD4+ T cells and turn them into suppressor T cells. In the present study we demonstrate for the first time in humans that CD4+ CD25+ T cells are able to inhibit the proliferation and cytokine production of antigen specific CD4+ and CD8+ T cells. This suppression only occurs when CD4+ CD25+ T cells are preactivated. Furthermore, we could demonstrate that CD4+ T‐cell clones stop secreting interferon‐γ (IFN‐γ), start to produce interleukin‐10 and transforming growth factor‐β after coculture with preactivated CD4+ CD25+ T cells and become suppressive themselves. Surprisingly preactivated CD4+ CD25+ T cells affect CD8+ T cells differently, leading to reduced proliferation and reduced production of IFN‐γ. This effect is sustained and cannot be reverted by exogenous interleukin‐2. Yet CD8+ T cells, unlike CD4+ T cells do not start to produce immunoregulatory cytokines and do not become suppressive after coculture with CD4+ CD25+ T cells.
Subset‐dependent modulation of dendritic cell activity by circovirus type 2
Authors: Vincent Isabelle E. , Carrasco Carlos P. , Guzylack‐Piriou Laurence , Herrmann Brigitte , McNeilly Francis , Allan Gordon M. , Summerfield Artur , McCullough Kenneth C.
Published: June 2005

Viral interactions with dendritic cells (DCs) have important consequences for immune defence function. Certain single‐stranded DNA viruses that associate with a number of species, including humans and pigs, exhibit interesting characteristics in this context. Porcine circovirus type 2 (PCV2) can persist within myeloid DCs in the absence of virus replication. Internalization was observed with both conventional blood DCs and plasmacytoid DCs [natural interferon‐producing cells (NIPCs)], as well as DC precursors. This PCV2–DC interaction neither induced nor inhibited DC differentiation. The maturation of myeloid DCs induced by a cocktail of interferon‐α/tumour necrosis factor‐α (IFN‐α/TNF‐α), and the ability to process and present antigen to T lymphocytes, remained intact in the presence of PCV2. The virus was clearly internalized by the DCs, a process noted with both mature and immature cells. This suggested a non‐macropinocytic uptake, confirmed by an insensitivity to wortmannin but sensitivity to cytochalasin D, chlorpromazine and bafilomycin. Nevertheless, PCV2 was immunomodulatory, being effected through the reaction of NIPC to danger signals. When NIPCs responded to the CpG‐oligonucleotide (CpG‐ODN), their costimulatory function which induces myeloid DC maturation was clearly impaired by the presence of PCV2. This was caused by a PCV2‐induced inhibition of the IFN‐α and TNF‐α normally produced following interaction with CpG‐ODN. Thus, the immunomodulatory activity of PCV2 is mediated through the disruption of NIPC function. This would impair the maturation of associated myeloid DC and have major implications for the efficient recognition of viral and bacterial danger signals, favouring the establishment of infections additional to that of PCV2.
Close encounters of the monoamine kind: immune cells betray their nervous disposition
Authors: Meredith Elizabeth J. , Chamba Anita , Holder Michelle J. , Barnes Nicholas M. , Gordon John
Published: June 2005

Here we review the evidence for immune cells expressing multiple components of the serotonergic and dopaminergic systems that are more commonly associated with the central nervous system (CNS). We discuss where and how peripheral encounters with these biogenic monoamines occur and posit reasons as to why the immune system would wish to deploy these pathways. A full taxonomy of serotonergic and dopaminergic constituents and their workings in component cells of the immune system should facilitate the formulation of novel therapeutic approaches in diseases characterized by immune dysfunction and potentially provide a range of surrogate peripheral markers for registering and monitoring disturbances within the CNS.
Signalling mechanisms underlying subversion of the immune response by the filarial nematode secreted product ES‐62
Authors: Goodridge Helen S. , Stepek Gillian , Harnett William , Harnett Margaret M.
Published: June 2005

Secretion of immunomodulatory molecules is a key strategy employed by pathogens to enable their survival in host organisms. For example, arthropod‐transmitted filarial nematodes, which achieve longevity within the infected host by suppressing and modulating the host immune response, produce excretory–secretory (ES) products that have been demonstrated to possess immunomodulatory properties. In this review we discuss the immunomodulatory effects of the phosphorylcholine‐containing filarial nematode‐secreted glycoprotein ES‐62 and describe the intracellular signal transduction pathways it targets to achieve these effects.
The phenotype of type 1 and type 2 CD8+ T cells activated in vitro is affected by culture conditions and correlates with effector activity
Authors: Kemp Roslyn A. , Bäckström B. Thomas , Ronchese Franca
Published: June 2005

We used various culture conditions to generate type 1 (Tc1) or type 2 (Tc2) cytotoxic T cells in vitro. T‐cell receptor (TCR) transgenic T cells were cultured with antigen and spleen cells, or antigen and dendritic cells (DC), or anti‐CD3 and anti‐CD28. Tc1 cultures contained interleukin (IL)‐2 and IL‐6, and Tc2 cultures contained IL‐2, IL‐6 and IL‐4. Tc2 cells generated in each culture condition acquired a CD62Llow CD44high phenotype, had high cytotoxic activity, and secreted IL‐4, IL‐5 and moderate amounts of interferon‐γ (IFN‐γ). In contrast, the phenotype and function of Tc1 cells varied depending on culture conditions. Tc1 cells from anti‐CD3 and anti‐CD28 cultures had high cytotoxic activity and were CD62Llow CD44high, while Tc1 cells from antigen and spleen cell cultures had low cytotoxic activity and were CD62Lhigh CD44low. Tc1 cells from antigen and DC cultures had an intermediate phenotype. All Tc1 cells secreted high amounts of IFN‐γ, but only Tc1 from anti‐CD3 and anti‐CD28 cultures had antitumour activity in vivo. Differences were not caused by suboptimal culture conditions, as Tc1 cells divided at a similar rate whether cultured with antigen and spleen cells or with anti‐CD3 and anti‐CD28. We conclude that IL‐4 not only induces ‘type 2’ cytokine secretion in CD8+ T cells, but also affects their expression of surface markers and cytotoxic activity.
Contact rates between possums revealed by proximity data loggers
Authors: JI WEIHONG , WHITE PIRAN C. L. , CLOUT MICK N.
Published: June 2005

Information on close interactions between wild animals is difficult to obtain for cryptic species, but is important for understanding their social and mating systems as well as the dynamics of directly transmitted diseases.

The persistence of bovine tuberculosis (Tb) in New Zealand is enhanced by the presence of wildlife hosts for the infection, principally the brushtail possum Trichosurus vulpecula. Quantifying the relationship between the frequency of contacts and possum population density is important for understanding the dynamics of the disease and the potential effectiveness of different methods for disease control.

We used novel proximity data loggers to record contacts (< 40 cm distance) between individual male and female wild‐living brushtail possums over 3 years at three different sites with a range of habitats and population densities.

Most contacts between male and female possums appeared to be sexual in nature, and contact rate was not related linearly to population density. Contacts occurred more frequently during the breeding season, when a female possum could interact with up to four males. However, even during this peak contact period the average contact rate was equivalent to only one contact every 2 days.

The total duration of contacts was significantly higher during the breeding season. During this time, contacts lasting for more than 1 min occurred episodically. A small proportion (2·3%) of the interactions lasted for 5–15 min, although the mean duration of contacts was only 18–26 s 24 h−1. Outside the breeding season, contacts were brief and infrequent.

The frequency of contacts showed a slight increase when the possum density increased sharply at the main study site, although the duration of contacts was unaffected. This increase in contact rate may have been the result of an influx of new animals causing perturbation to the existing population.

Previous paternity analysis using DNA profiling indicated that the possum mating system is polygynous, with males being promiscuous. Our data reveal that females are probably also promiscuous and that the mating system of possums may therefore be polygamous, including both polygyny and polyandry.

Synthesis and applications. Most contacts between possums occur in the peak mating season and appear to be related to mating and associated behaviour. There are some contacts outside the main mating season, but these are infrequent. The transmission of bovine Tb infection in possum populations may therefore occur by other routes in addition to direct contact. The non‐linear (frequency‐dependent) contact rate–density relationship recorded provides some insight as to why repeated population reduction is necessary to achieve lasting Tb control in possum populations. It also provides some support for the role that could be played by sexually transmitted, viral‐vectored immunocontraception in the control of possum populations, either alone or in conjunction with more traditional control methods.
Stubble height affects the use of stubble fields by farmland birds
Authors: BUTLER SIMON J. , BRADBURY RICHARD B. , WHITTINGHAM MARK J.
Published: June 2005

In the UK, over‐wintered stubbles are an important foraging habitat for farmland birds, many of which are of current conservation concern. Maximizing the value of stubbles for farmland birds has largely focused on increasing food abundance but has ignored other aspects of foraging behaviour, such as predator avoidance and vigilance.

In this study we investigated the effects of stubble height reduction on seed depletion and the within‐field distribution of farmland birds. Stubble on one half of each of 20 fields was topped to lower vegetation height, while the other half was left untouched to act as a control area.

The abundance of granivorous passerines and invertebrate feeders was higher on treatment plots, which had undergone stubble height reduction, while the abundance of skylark and partridges was higher on control plots. Topping had no effect on the within‐field distribution of either corvids or pigeons.

Seed densities on both plot types fell between November and March, but there was no significant difference in levels of depletion between treatment and control plots.

For many species, food accessibility and detectability are likely to have been higher, and thermo‐energetic and mobility costs lower, on treatment plots. Stubble height reduction could have led to either an increase or a decrease in associated predation risk, depending on the predator escape strategy of a species. Granivorous passerines, which flee to cover, are likely to have benefited from the reduced visual obstruction on treatment plots, while partridges, which rely on crypsis, will have benefited from the greater protection offered by the longer vegetation in control plots.

Synthesis and applications. Increasing the structural heterogeneity of over‐wintered stubble is likely to increase its value as a foraging habitat, making it better suited to the foraging requirements and predator escape strategies of a greater diversity of species. Incorporating explicit management options into agri‐environment schemes, such as the new Environmental Stewardship Scheme, may represent a cost‐effective strategy to achieve this.
The resilience of calcareous and mesotrophic grasslands following disturbance
Authors: HIRST RACHEL A. , PYWELL RICHARD F. , MARRS ROB H. , PUTWAIN PHILIP D.
Published: June 2005

Understanding habitat disturbance and recovery is vital for successful conservation management and restoration, particularly of subseral communities with high nature conservation interest and sites subject to unavoidable disturbance pressures, such as that arising from access and recreational activities.

Grassland resilience was investigated on the Salisbury Plain Training Area (SPTA) in southern England, the largest of the UK military training areas. SPTA contains the greatest expanse of unimproved chalk grassland in north‐west Europe, a habitat of particular nature conservation interest.

Historical aerial photographs were used to identify 82 calcareous and mesotrophic grassland sites disturbed over a 50‐year time period. Vegetation, soils and seed bank data were collected from each old disturbance site. Revegetation time periods following disturbance were compared, and habitat resilience following disturbance investigated using the succession of surface vegetation along the chronosequence, the combined changes of vegetation and soil chemistry, and finally vegetation and seed bank composition.

The sampled calcareous grasslands were less resilient following disturbance than the mesotrophic grasslands, with slower colonization of bare ground and target species re‐assembly. The mesotrophic grasslands typically took between 30 and 40 years to re‐establish following disturbance, whereas calcareous grasslands took at least 50 years.

Even after such long time periods, there remained subtle but significant differences between the vegetation composition of the disturbed and undisturbed swards. Perennial forb species, particularly hemicryptophytes, persisted at higher frequencies in swards disturbed 50 years ago than in undisturbed swards.

Synthesis and applications. Prediction of habitat resilience following disturbance is dependent on which components of the system are investigated. However, data such as that presented here can help land managers understand how palimpsests of current habitat characteristics may have evolved, and how disturbance regimes may be managed in the future. It is likely that the resilience of grasslands such as those on SPTA may have been overestimated, and perceptions of habitat carrying capacity for disturbance events may require re‐evaluation.
Aspect modifies the magnitude of edge effects on bryophyte growth in boreal forests
Authors: HYLANDER KRISTOFFER
Published: June 2005

The increased length of forest clear‐cut edges is considered to be one of the main ecological consequences of silviculture. The effects vary over the landscape, and studies have shown that aspect is one important factor determining the extent of microclimatic edge effects across forest clear‐cut boundaries. However, little is known about the relationship between contrasts in microclimate at edges and responses of ecological processes and biodiversity, such as growth, decomposition and species distributions.

A field experiment was conducted in the boreal forest of northern Sweden to assess the effect of aspect at north‐ and south‐facing edges using mosses as bioindicators. The growth of two species (Hylocomium splendens and Hylocomiastrum umbratum) was evaluated during one growing season. Samples of each species were planted in pots at eight north‐ and eight south‐facing forest clear‐cut edges.

Growth increased exponentially with distance from the edge to the interior, and there was a significant effect both in north‐ and south‐facing edges. The percentage decline in growth at the edge was larger in the south‐ than in the north‐facing edges.

The spatial extent of the edge effect, when measured at the point of 90% of interior growth, was similar between north‐ and south‐facing edges, although it differed between the two species evaluated.

Synthesis and applications. The difference in exposure to sunlight between north‐ and south‐facing edges was shown to modify the magnitude of the growth of a poikilohydric organism at the very edge, but not the depth of the edge influence. Aspect should be taken into account in management plans for conservation of boreal forests. In the northern hemisphere, wider buffers of uncut forest should be left at the south side than at the north side of retained forest patches. Those forest interior species that are most sensitive to alterations in microclimate will, however, need equal protection from edge effects at all aspects.
Effects of exceptional conservation measures on survival and seasonal hunting mortality in greater snow geese
Authors: CALVERT ANNA M. , GAUTHIER GILLES
Published: June 2005

Large‐scale conservation measures aimed at reducing the abundance of a wild population offer a unique opportunity to study the impacts of human exploitation on demographic parameters. We examined the effects of a spring conservation harvest and liberalized autumn/winter regulations introduced recently to control the rapid population growth of greater snow geeseAnser caerulescens atlantica.

We predicted that these changes in regulations affected survival and recovery probabilities, as well as kill rates. This was evaluated by analysing data on geese shot by hunters before and after implementation of these measures.

Annual survival and recovery probabilities were estimated using likelihood‐based ring recovery models, and we developed a new, flexible seasonal model to determine the specific effects of regulation changes made during different hunting seasons. We used harvest survey data to estimate ring‐reporting rate, and thus to convert recovery rates into kill rates.

Adult recovery and kill rates increased considerably with the implementation of the new measures in 1998–99. The addition of the spring harvest in Québec and the liberalized winter regulations in the USA had the largest impacts, whereas autumn regulation changes in Québec apparently had little effect. Juvenile recovery and kill rates also showed a moderate increase, but were highly variable.

We observed a decline in mean annual adult survival rate, from 83·0% to 72·5%, although the implementation of conservation measures did not fully explain temporal variation in adult survival; juvenile survival showed no change. Adult survival was negatively related to harvest rate in adults but not in juveniles.

Synthesis and applications. We demonstrate that the spring conservation harvest led to a decrease in adult survival and an increase in hunting mortality, and probably contributed to the decline in abundance observed since its implementation. However, regulations during the traditional autumn and winter hunting seasons could also be manipulated for future population control once the spring conservation harvest is discontinued. Our approach for evaluating hunting mortality on a seasonal basis should be useful in the management of other migratory populations that move through several jurisdictions.
Importance of drainage channels for waders foraging on tidal flats: relevasnce for the management of estuarine wetlands
Authors: LOURENÇO PEDRO M. , GRANADEIRO JOSÉ P. , PALMEIRIM JORGE M.
Published: June 2005

Despite covering a relatively small area on a global scale, estuarine tidal flats are vital to many aquatic bird species during much of the yearly cycle. Small‐scale features of tidal flats, such as water drainage channels, can influence the carrying capacity of estuarine wetlands, yet their ecological impact is poorly understood. In this study we evaluated the influence of drainage channels on the quality of feeding habitat for waders in the Tagus estuary, Portugal.

We measured the abundance of seven wader species at five distance classes from drainage channels, and analysed the variation in peck rates, step rates, turning rates and success rates. In addition we measured the density of macroinvertebrate prey and the sediment physical–chemical characteristics at different distances from the channels.

All wader species occurred at higher densities near the channels. In the study area 44% of the birds fed on just 12% of the available surface, less than 5 m away from drainage channels. Wader foraging behaviour also suggests a greater feeding effort near the channels.

While the characteristics of the sediments did not change significantly with distance from channels, prey abundance corresponded closely with wader abundance, suggesting that the small scale distribution of birds on the tidal flats may be related to the presence of their prey.

Synthesis and applications. Our study shows that the areas around drainage channels are particularly important feeding sites for waders foraging on tidal flats. Consequently, managers of estuarine wetlands should strive to preserve or improve channel networks. This can be achieved by (i) preserving saltmarshes and saltpans adjacent to tidal flats, (ii) minimizing the reclamation of upshore flats and (iii) avoiding embankments and canalizations of inland water flows that reduce the number of water entry points onto tidal flats.
Sex Differences in the Neuroendocrine Response to Short‐Term Fasting in Rhesus Macaques
Authors: Lado‐Abeal J. , Robert‐McComb J. J. , Qian X.‐P. , Leproult R. , Van Cauter E. , Norman R. L.
Published: June 2005

When energy intake is restricted in mammals, there are neuroendocrine adjustments in the secretion of reproductive and metabolic hormones to reallocate energy for vital functions. In the present study, we investigated whether there were differences in the luteinising hormone (LH), growth hormone (GH) and cortisol responses to a 48‐h fast in adult gonad‐intact male and female rhesus macaques. In both male and female macaques, blood glucose levels were significantly lower in fasted than in control studies, and levels were higher in males than in females. Male rhesus monkeys had significantly lower (P < 0.01) mean serum LH levels after a 48‐h fast than under fed conditions and this was attributable primarily to a decrease in the amount of LH released during each secretory episode. In fasted females, serum LH levels were significantly greater (P < 0.05) than during the fed conditions but no differences were found in pulse amplitude or in the number of pulses. Almost twice as many GH pulses were observed in both males and females during fasting but there was no difference in either mean serum GH levels or pulse amplitude between control and fasted studies. A typical diurnal profile in cortisol levels was observed in both sexes and both experimental conditions. Under control conditions, male macaques released less cortisol than females, and although fasting increased mean cortisol levels in both males and females, only the males shown a significant rise over levels observed in control studies. The changes in plasma LH and cortisol levels in fasted rhesus macaques are similar to those observed in humans and suggest that gonadotrophin and corticotrophin secretion are more resistant to short‐term energy deprivation in female than in male primates.
Intravenous Peptide YY3‐36 and Y2 Receptor Antagonism in the Rat: Effects on Feeding Behaviour
Authors: Scott V. , Kimura N. , Stark J. A. , Luckman S. M.
Published: June 2005

Systemic injection of peptide YY3‐36 reduces food intake in rodents and humans, although some groups have reported a lack of response. PYY3‐36 is thought to act via the Y2 receptor to presynaptically inhibit the release of neuropeptide Y and GABA from hypothalamic arcuate neurones. Due to the controversy surrounding its action in rodents, we tested the peptide intravenously on feeding behaviour in rats and attempted to block its actions with the Y2 receptor antagonist BIIE0246. PYY3‐36 significantly decreased food intake during the first hour in male Sprague‐Dawley rats fasted overnight and then re‐fed. BIIE0246 had no effect alone on re‐feeding, but completely blocked the action of PYY3‐36. In a second experiment of similar design, the behavioural satiety sequence (BSS) was studied. Normal rats eat, drink, explore and groom before entering rest. PYY3‐36 significantly reduced food eaten maintaining the normal BSS, although shifting it to the left as expected for a natural satiety factor. The latency to rest occurred earlier for animals given PYY3‐36 alone and PYY3‐36 tended to increase the total time in rest compared with controls. These behavioural effects of PYY3‐36 were blocked by BIIE0246, and BIIE0246 alone did not have an effect on the BSS. These results support the role of PYY3‐36 as a natural satiety factor acting through Y2 receptors.
Development and validation of a new model of inflammation in the cat and selection of surrogate endpoints for testing anti‐inflammatory drugs
Authors: GIRAUDEL J. M. , DIQUELOU A. , LEES P. , TOUTAIN P. L.
Published: June 2005

In laboratory animals many models of inflammation have been developed for preclinical evaluation of the pharmacological profiles of nonsteroidal anti‐inflammatory drugs (NSAIDs). In contrast, in species of veterinary interest, including the cat, NSAIDs have been studied mainly using dose‐titration or dose‐confirmation studies in clinical subjects. This is due to the scarcity of appropriate animal models and to the associated lack of quantitative validated endpoints describing the magnitude and time course of drug response. Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationships provides a powerful approach for the selection of effective and safe dosage regimens. In this study, a paw inflammation model in the cat was developed for the preclinical evaluation of NSAIDs using PK/PD modelling. Subcutaneous injection of 500 mg kaolin in the paw produced a well‐defined and reproducible inflammatory response that lasted 4–5 days. Several endpoints were assessed for their clinical relevance and for their metrological performance (accuracy and reproducibility). Body temperature, lameness scoring, locomotion tests and possibly skin temperature were the most appropriate endpoints for testing the antipyretic, analgesic and anti‐inflammatory effects of NSAIDs in the cat.
Effect of dietary fat on oral bioavailability of tepoxalin in dogs
Authors: HOMER L. M. , CLARKE C. R. , WEINGARTEN A. J.
Published: June 2005

A pharmacokinetic study was conducted to compare the oral bioavailability of tepoxalin and its pharmacologically active acid metabolite in fasted dogs and dogs fed either a low‐fat or high‐fat commercial diet. Using a cross‐over design, six beagles were administered tepoxalin (10 mg/kg) intravenously (i.v.) and orally (p.o.) after being fed one of three diets (fasted, low‐fat, or high‐fat). Thereafter, blood samples were collected at frequent intervals, concentrations of tepoxalin and acid metabolite in plasma were determined by high performance liquid chromatography, and pharmacokinetic parameters were estimated. After i.v. dosing, the mean (±SD) half‐life of elimination (t1/2(β)) was 2.45 ± 1.47 h. After p.o. administration, plasma concentrations of acid metabolite were consistently higher than corresponding concentrations of the parent tepoxalin, indicating that tepoxalin is subject to a substantial first‐pass effect. Mean (±SD) peak concentrations of tepoxalin were significantly higher after feeding of low‐fat (1.08 ± 0.37 μg/mL) and high‐fat (1.19 ± 0.29 μg/mL) diets than in fasted dogs (0.53 ± 0.20 μg/mL), suggesting that feeding improves oral bioavailability.