bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of obstructive sleep apnoea on left ventricular mass and global function
Authors: Dursunoglu D. , Dursunoglu N. , Evrengül H. , Özkurt S. , Kuru Ö. , Kiliç M. , Fisekci F.
Published: July 2005

Obstructive sleep apnoea syndrome (OSAS) might be a cause of heart failure. The present study aimed to assess left ventricular mass and myocardial performance index (MPI) in OSAS patients.

A total of 67 subjects without any cardiac or pulmonary disease, referred for evaluation of OSAS, had overnight polysomnography and echocardiography. According to apnoea-hypopnoea index (AHI), subjects were classified into three groups: mild OSAS (AHI: 5–14; n = 16), moderate OSAS (AHI: 15-29; n = 18), and severe OSAS (AHI: ≥30; n = 33). Thickness of interventricular septum (IVS) and posterior wall (LVPW) were measured by M-mode, along with left ventricular mass (LVM) and LVM index (LVMI). Left ventricular MPI was calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic ejection time by Döppler echocardiography.

There were no differences in age or body mass index among the groups, but blood pressures were higher in severe OSAS compared with moderate and mild OSAS. In severe OSAS, thickness of IVS (11.2±1.1 mm), LVPW (11.4±0.9 mm), LVM (298.8±83.1 g) and LVMI (144.7±39.8 g·m−2) were higher than in moderate OSAS (10.9±1.3 mm; 10.8±0.9 mm; 287.3±74.6 g; 126.5±41.2 g·m−2, respectively) and mild OSAS (9.9±0.9 mm; 9.8±0.8 mm; 225.6±84.3 g; 100.5±42.3 g·m−2, respectively). In severe OSAS, MPI (0.64±0.14) was significantly higher than in mild OSAS (0.50±0.09), but not significantly higher than moderate OSAS (0.60±0.10).

In conclusion, severe and moderate obstructive sleep apnoea syndrome patients had higher left ventricular mass and left ventricular mass index, and also left ventricular global dysfunction.
Time course of cigarette smoke-induced pulmonary inflammation in mice
Authors: D'hulst A. I. , Vermaelen K. Y. , Brusselle G. G. , Joos G. F. , Pauwels R. A.
Published: July 2005

Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease. In the present study a murine model of tobacco smoke-induced emphysema was used to investigate the time course of airway and pulmonary inflammatory response, with a special emphasis on pulmonary dendritic cell (DC) populations.

Groups of mice were exposed to either cigarette smoke or to control air for up to 24 weeks. In response to cigarette smoke, inflammatory cells (i.e.neutrophils, macrophages and lymphocytes) progressively accumulated both in the airways and lung parenchyma of mice. Furthermore, a clear infiltration of DCs was observed in airways (10-fold increase) and lung parenchyma (1.5-fold increase) of cigarette-exposed mice at 24 weeks.

Flow cytometric analysis of bronchoalveolar lavage (BAL) DCs of smoke-exposed mice showed upregulation of major histocompatability complex II molecules and costimulatory molecules CD40 and CD86, compared with BAL DCs of air-exposed mice. Morphometric analysis of lung histology demonstrated a significant increase in mean linear intercept and alveolar wall destruction after 24 weeks of smoke exposure.

In conclusion, the time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.
Breath condensate ammonium is lower in children with chronic asthma
Authors: MacGregor G. , Ellis S. , Andrews J. , Imrie M. , Innes A. , Greening A. P. , Cunningham S.
Published: July 2005

Exhaled breath condensate pH and ammonium reflect asthmatic status and acute exacerbations in adults. The aim of this study was to assess whether pH and ammonium could reflect asthma and its severity in children.

The current study comprised two parts: 1) a cross-section of 74 children with asthma (median age 10.5 yrs) compared with 47 healthy controls (median age 10 yrs); and 2) longitudinal assessment of eight children (mean age 8.5 yrs) admitted with asthma exacerbation. Condensate pH and ammonium were compared with clinical observations.

In the cross-sectional part of the study, lower per cent forced expiratory volume in one second was associated with more symptoms and treatment. There was no significant difference between median pH in children with stable asthma (6.05) compared with controls (5.90). Ammonium was significantly lower in children with asthma (median 258 µM) compared with controls (median 428 µM). No association was found between ammonium or pH and lung function or symptom-free days. In the longitudinal study, significant improvements in oxygen saturation and respiratory rate with treatment of an acute exacerbation were not reflected by changes in pH or ammonium.

In conclusion, pH does not appear to reflect disease or severity in children with asthma. Ammonium was significantly lower in children with asthma when compared with controls.
Dependency on mask ventilation after acute respiratory failure in the intermediate care unit
Authors: Cuvelier A. , Viacroze C. , Bénichou J. , Molano L. C. , Hellot M-F. , Benhamou D. , Muir J-F.
Published: July 2005

The predictive factors for long-term dependency (LTD) on noninvasive ventilation (NIV) immediately after acute hypercapnic respiratory failure (AHRF) have not been identified.

The present authors studied 42 patients with chronic obstructive pulmonary disease (COPD) and 58 non-COPD patients successfully treated by NIV for an AHRF episode. Parameters at stable state, at admission for AHRF and during a 1-yr follow-up were compared in patients with or without LTD-NIV at discharge.

The incidence of LTD-NIV was 39% in non-COPD patients and 19% in COPD patients. Based on multivariate analysis with stepwise logistic regression, lower baseline pH values and noninfectious causes of AHRF were independently associated with LTD-NIV. Mutually adjusted odds ratios were found to be 1.316 (95% confidence interval (CI) = 1.127–1.536) for a 0.01 decrease of baseline pH value and 5.1 (95% CI = 1.8–14.0) for a noninfectious cause of AHRF. Outcome after 1 yr was poor in COPD patients.

Long-term dependency on noninvasive ventilation is not an uncommon situation after resolution of an acute hypercapnic respiratory failure episode, especially in patients with non-chronic obstructive pulmonary disease causes of respiratory failure. The present study raises the need for prospective validation of a weaning protocol in patients managed by noninvasive ventilation for an acute hypercapnic respiratory failure episode.
Morbidity and mortality in the surgery arm of EORTC 08941 trial
Authors: Van Schil P. , Van Meerbeeck J. , Kramer G. , Splinter T. , Legrand C. , Giaccone G. , Manegold C. , van Zandwijk N.
Published: July 2005

Controversial results of surgical treatment after induction chemotherapy, especially in relation to the extent of resection, have previously been reported. Mortality and morbidity were studied in the surgical arm of the European Organisation for Research and Treatment of Cancer (EORTC) 08941 trial.

EORTC 08941 is a multicentre, prospective, randomised, phase-III trial of surgical resectionversusradiotherapy in patients with proven stage IIIA-N2nonsmall cell lung cancer after an objective response to platinum-based induction chemotherapy. Operative results in the 167 patients randomised in the surgical arm are presented within this study. Among these patients, one switched to the radiotherapy arm and 17 patients did not get any protocol treatment or information is not yet available.

Radical resection with negative surgical margins was obtained in 74 patients (49.7%). In 61 patients (40.9%), a pathological down-staging to N0or N1was present. Operative 30-day mortality was 4.0%. Post-operative complications were mainly pneumonia, respiratory insufficiency, arrhythmias, air leak, cardiac decompensation, empyema and bronchopleural fistula. In total, 12 (8.1%) patients underwent re-operation due to positive margins, haemothorax, empyema and bronchopleural fistula.

In conclusion, surgical resection after induction chemotherapy in the multicentre European Organisation for Research and Treatment of Cancer trial has yielded acceptable rates of morbidity and mortality.
Microscopic pulmonary embolisation of an indwelling central venous catheter with granulomatous inflammatory response
Authors: Baydur A. , Koss M. N. , Sharma O. P. , Dalgleish G. E. , Nguyen D. V. , Mullick F. G. , Murakata L. A. , Centeno J. A.
Published: July 2005

Indwelling catheters can disintegrate into tiny fragments and embolise. Once the fragments are detected radiographically, they can be removed using vascular intervention techniques. Rarely, indwelling catheters dwindle into inextricable pieces that embolise into minute pulmonary vessels and lymphatics, causing granulomatous changes microscopically.

The present study reports a 54-yr-old female who had received several indwelling central lines during several abdominal surgeries over a 5-yr period. The patient developed a noncaseating granulomatous skin lesion followed by exertional dyspnoea a few months later. Chest radiographs and computed tomography showed diffuse interstitial infiltrates. Open lung biopsy showed two types of granulomas: 1) peri-lymphangitic and peri-bronchiolar non-necrotising granulomas consistent with sarcoidosis; and 2) distinct foreign body granulomas.

In some of the foreign body granulomas, confocal Raman spectroscopy identified the presence of bisphenol-A-polycarbonate, a polymer commonly used in biomedical devices. The patient improved following treatment with prednisone followed by methotrexate.

The present case illustrates an interesting combination of two causes of granulomatous disease, the importance of examining all biopsy specimens from sarcoidosis patients for foreign particles and the rare occurrence of microscopic embolisation of catheter fragments to the lung with foreign-body giant cell reaction to them.
P53 and Beta-Catenin Activity during Estrogen treatment of Osteoblasts
Authors: Chandar Nalini , Saluja Rasleen , Lamar Peter C , Kolman Kevin , Prozialeck Walter C
Published: July 2005

Background

This study was undertaken to examine the relationship between the tumor suppressor gene p53 and the nuclear signaling protein beta-catenin during bone differentiation. Cross talk between p53 and beta-catenin pathways has been demonstrated and is important during tumorigenesis and DNA damage, where deregulation of beta catenin activates p53. In this study, we used estrogen treatment of osteoblasts as a paradigm to study the relationship between the two proteins during osteoblast differentiation.

Results

We exposed osteoblast-like ROS17/2.8 cells to 17-beta estradiol (E2), in a short term assay, and studied the cellular distribution and expression of beta-catenin. We found beta-catenin to be up regulated several fold following E2 treatment. Levels of p53 and its functional activity mirrored the quantitative changes seen in beta-catenin. Alkaline phosphatase, an early marker of osteoblast differentiation, was increased in a manner similar to beta-catenin and p53. In order to determine if there was a direct relationship between alkaline phosphatase expression and beta-catenin, we used two different approaches. In the first approach, treatment with LiCl, which is known to activate beta-catenin, caused a several fold increase in alkaline phosphatase activity. In the second approach, transient transfection of wild type beta-catenin into osteoblasts increased alkaline phosphatase activity two fold over basal levels, showing that beta catenin expression can directly affect alkaline phosphatase expression. However increase in beta catenin activity was not associated with an increase in its signaling activity through TCF/LEF mediated transcription. Immunofluorescence analyses of p53 and beta-catenin localization showed that E2 first caused an increase in cytosolic beta-catenin followed by the accumulation of beta-catenin in the nucleus. Nuclear p53 localization was detected in several cells.

Expression of p53 was accompanied by distribution of beta-catenin to the cytoplasm and cell borders. A sub population of cells staining strongly for both proteins appeared to be apoptotic.

Conclusion

These results suggest that interactions between p53 and beta-catenin signaling pathways may play a key role in osteoblast differentiation and maintenance of tissue homeostasis.
Causal thinking and causal language in epidemiology: it's in the details
Authors: Lipton Robert , Ødegaard Terje
Published: July 2005

Although epidemiology is necessarily involved with elucidating causal processes, we argue that there is little practical need, having described an epidemiological result, to then explicitly label it as causal (or not). Doing so is a convention which obscures the valuable core work of epidemiology as an important constituent of public health practice. We discuss another approach which emphasizes the public health "use value" of research findings in regard to prediction and intervention independent from explicit metaphysical causal claims. Examples are drawn from smoking and lung cancer, with particular focus on the original 1964 Surgeon General's report on smoking and the new version released in 2004. The intent is to help the epidemiologist focus on the pertinent implications of research, which, from a public health point of view, in large part entails the ability to predict and to intervene. Further discussion will center on the importance of differentiating between technical/practical uses of causal language, as might be used in structural equations or marginal structural modeling, and more foundational notions of cause. We show that statistical/epidemiological results, such as "smoking two packs a day increases risk of lung cancer by 10 times" are in themselves a kind of causal argument that are not in need of additional support from relatively ambiguous language such as "smoking causes lung cancer." We will show that the confusion stemming from the use of this latter statement is more than mere semantics. Our goal is to allow researchers to feel more confident in the power of their research to tell a convincing story without resorting to metaphysical/unsupportable notions of cause.
High expression of Lewisy/bantigens is associated with decreased survival in lymph node negative breast carcinomas
Authors: Madjd Zahra , Parsons Tina , Watson Nicholas FS , Spendlove Ian , Ellis Ian , Durrant Lindy G
Published: July 2005

Introduction

There is sufficient evidence that blood group related Lewis antigens are tumour-associated molecules. The Lewisy and Lewisb antigens are complex carbohydrates that are over-expressed by breast, lung, colon and ovarian cancers. The SC101 mAb is a unique Lewisy/b binding antibody that binds to native and extended Lewisy and Lewisb haptens, displaying no cross reactivity with H type 1, H type 2, Lewisx or normal blood group antigens.

Methods

Immunohistochemical detection of Lewisy/b was performed on 660 formalin-fixed, paraffin embedded breast tumour specimens using a streptavidin-biotin peroxidase technique. Tissue from these patients had previously been included in tissue microarrays. This cohort comprises a well characterized series of patients with primary operable breast cancer diagnosed between 1987 and 1992, obtained from the Nottingham Tenovus Primary Breast Carcinoma Series. This includes patients 70 years of age or less, with a mean follow up of 7 years.

Results

Of the breast carcinomas, 370 of 660 (56%) were negative for Lewisy/b expression, 110 (17%) cases showed a low level of expression (<25% of positive cells) and only 54 cases (8%) showed extensive expression of Lewisy/b (>75% of positive cells). We found significant positive associations between histological grade (p < 0.001), Nottingham Prognostic Index (p = 0.016), tumour type (p = 0.007) and the level of Lewis y/b expression. There was a significant correlation between the proportion of Lewisy/b positive tumour cells and survival in lymph-node negative patients (p = 0.006).

Conclusion

The unique epitope recognised by SC101 mAb on Lewisy/b hapten is over-expressed on breast tumour tissue compared with normal breast. In this large series of invasive breast cancers, higher expression of Lewisy/b was more often found in high grade and poor prognosis tumours compared to good prognosis cancers. Moreover, in lymph node negative breast carcinomas, over-expression of Lewisy/b hapten was associated with significantly decreased patient survival.
Tandem repeat copy-number variation in protein-coding regions of human genes
Authors: O'Dushlaine Colm T , Edwards Richard J , Park Stephen D , Shields Denis C
Published: July 2005

Background

Tandem repeat variation in protein-coding regions will alter protein length and may introduce frameshifts. Tandem repeat variants are associated with variation in pathogenicity in bacteria and with human disease. We characterized tandem repeat polymorphism in human proteins, using the UniGene database, and tested whether these were associated with host defense roles.

Results

Protein-coding tandem repeat copy-number polymorphisms were detected in 249 tandem repeats found in 218 UniGene clusters; observed length differences ranged from 2 to 144 nucleotides, with unit copy lengths ranging from 2 to 57. This corresponded to 1.59% (218/13,749) of proteins investigated carrying detectable polymorphisms in the copy-number of protein-coding tandem repeats. We found no evidence that tandem repeat copy-number polymorphism was significantly elevated in defense-response proteins (p = 0.882). An association with the Gene Ontology term 'protein-binding' remained significant after covariate adjustment and correction for multiple testing. Combining this analysis with previous experimental evaluations of tandem repeat polymorphism, we estimate the approximate mean frequency of tandem repeat polymorphisms in human proteins to be 6%. Because 13.9% of the polymorphisms were not a multiple of three nucleotides, up to 1% of proteins may contain frameshifting tandem repeat polymorphisms.

Conclusion

Around 1 in 20 human proteins are likely to contain tandem repeat copy-number polymorphisms within coding regions. Such polymorphisms are not more frequent among defense-response proteins; their prevalence among protein-binding proteins may reflect lower selective constraints on their structural modification. The impact of frameshifting and longer copy-number variants on protein function and disease merits further investigation.
Brief psychotherapy in Alzheimer's disease
Authors: Burns Alistair , Guthrie Else , Marino-Francis Federica , Busby Charlotte , Morris Julie , Russell Eve , Margison Frank , Lennon Sean , Byrne Jane
Published: July 2005

Background

Although there is good evidence that interventions for carers of people with Alzheimer's disease can reduce stress, no systematic studies have investigated psychotherapeutic intervention for patients themselves. This may be important in the earlier stages of Alzheimer's disease, where insight is often preserved.

Aims

The aim was to assess, in a randomised controlled trial, whether psychotherapeutic intervention could benefit cognitive function, affective symptoms and global well-being.

Method

Individuals were randomised to receive six sessions of psychodynamic interpersonal therapy or treatment as usual; cognitive function, activities of daily living, a global measure of change, and carer stress and coping were assessed prior to and after the intervention.

Results

No improvement was found on the majority of outcome measures. There was a suggestion that therapy had improved the carers' reactions to some of the symptoms.

Conclusions

There is no evidence to support the widespread introduction of brief psychotherapeutic approaches for those with Alzheimer's disease. However, the technique was acceptable and helpful individually.
Crisis card following self-harm: 12-month follow-up of a randomised controlled trial
Authors: Evans Jonathan , Evans Mark , Morgan H. Gethin , Hayward Alan , Gunnell David
Published: July 2005

No intervention has been shown to be effective in preventing repetition of self-harm. In the 6-month follow-up of a large randomised controlled trial, we previously reported no effectiveness of the provision of a card offering 24-h crisis telephone consultation on repetition of self-harm. However, there was a possible benefit among those presenting following a first episode (OR=0.64, 95% CI 0.34–1.22). Here we report the 12-month follow-up of the trial. The results confirm no overall benefit of the intervention (OR=1.19, 95% CI 0.85–1.67). Among those with a first episode of self-harm, the possible benefit of the intervention had diminished (OR=0.89, 95% CI 0.52–1.52), although a modest effect cannot be excluded.
Problems with early and very early intervention in psychosis
Authors: Warner Richard
Published: July 2005

‘Early intervention’ can refer to two different approaches-intervention when the psychosis is already evident and intervention before a psychosis is fully apparent. Each carries a distinctly different set of risks. The hoped-for benefits of early intervention in a fully evident psychosis are based on research that reveals an association between intervention early in the illness and good outcome. Those suffering from a psychosis of recent onset, however, are more likely to experience a spontaneous remission of illness, and this may readily explain the observed association. Early intervention in such cases of good-prognosis psychosis may lead to unnecessary and, sometimes, protracted treatment for those who would do well with no treatment. Intervention in the supposed prodromal phase of psychosis presents more serious hazards. The screening instruments currently available are inadequate for the accurate prediction of psychosis, and the risks of negative effects for the large numbers of people who screen false-positive are considerable. These risks include unnecessary fear of illness, restriction of life goals, use of medication and their side-effects.
Early intervention in psychotic disorders: beyond debate to solving problems
Authors: Mcgorry Patrick D.
Published: July 2005

The challenges of early diagnosis are similar in psychiatry to the rest of medicine. For potentially severe and persistent disorders there is great value in early diagnosis, however, only under certain conditions. Early diagnosis would not be justified if there were no efficacious treatments or if such treatments provided earlier would do more harm than good for those exposed. There is growing evidence that earlier and sustained intervention improves at least short-term outcomes. However, early intervention may be iatrogenic where systems of care are poor in quality. One thing is clear, the general pattern of care is still ‘too little, too late’ even in the most affluent countries. Consistent and extensive reform of health systems, with recognition of early intervention as an increasingly evidence-based ‘best buy’, represents one of the key priorities in international mental health.
Early intervention and recovery for young people with early psychosis: consensus statement
Authors: Bertolote J. , Mcgorry P.
Published: July 2005

International declarations that articulate core values, goals and standards have played an important role in enhancing the quality of care in a number of areas of medicine. This document attempts this task for early intervention in psychotic disorders. It was originally inspired by the St Vincents declaration on the care of diabetes and carefully developed by David Shiers and Jo Smith with support from the Initiative to Reduce the Impact of Schizophrenia, National Institute for Mental Health in England and Rethink, resulting in the UK-focused Newcastle Declaration. The World Health Organization and the International Early Psychosis Association then collaborated to produce an international version of the declaration, which articulates the universal principles of early intervention and tries to blend these with local capacities and cultural diversity.
Pathways to care for first-episode psychosis in an early detection healthcare sector
Authors: Johannessen Jan Olav , Larsen Tor K. , Joa Inge , Melle Ingrid , Friis Svein , Opjordsmoen Stein , Rund Bjørn Rishovd , Simonsen Erik , Vaglum Per , Mcglashan Thomas H.
Published: July 2005

Background

Early detection programmes aim to reduce the duration of untreated psychosis (DUP) by public education and by prompt access to treatment via active outreach detection teams.

Aims

To determine whether those with first-episode psychosis in an early detection healthcare area with existing referral channels differ from those who access care via detection teams.

Method

Those with first-episode psychosis recruited via detection teams were compared with those accessing treatment via conventional channels, at baseline and after 3 months of acute treatment.

Results

Patients recruited via detection teams are younger males with a longer DUP a less dramatic symptom picture and better functioning; however they recover more slowly, and have more symptoms at 3-month follow-up.

Conclusions

After establishing low threshold active case-seeking detection teams, we found clear differences between those patients entering treatment via detection teams v. those obtaining treatment via the usual channels. Such profiling may be informative for early detection service development.
Prepsychotic phase of schizophrenia and related disorders: recent progress and future opportunities
Authors: Phillips Lisa J. , Mcgorry Patrick D. , Yung Alison R. , Mcglashan Thomas H. , Cornblatt Barbara , Klosterkötter Joachim
Published: July 2005

Background

Clinical and research focus has recently shifted from established psychotic disorders to first-episode psychosis and the prepsychotic phase of illness.

Aims

To describe the principles, progress and dilemmas associated with the prospective detection, engagement and treatment of young people at risk of developing a psychotic disorder.

Method

Strategies to identify young people at heightened risk of a psychotic disorder are described. Preventive interventions and results of their evaluation are provided.

Results

Well-validated criteria for identifying young people at heightened risk of psychosis have been developed, evidence of the efficacy of various psychological and pharmacological interventions in preventing progression has accumulated and progress towards the identification of clinical and neurobiological predictors of transition to acute psychosis has been made.

Conclusions

The detection, monitoring and treatment of young people in the prepsychotic phase is a growth area in psychiatry. The ethical considerations about treatment options, treatment of minors and provision of information about risk status must be treated with sensitivity if the potential benefit to many young people and their families is to be realised.
Role of distress in delusion formation
Authors: Hanssen Manon , Krabbendam Lydia , De Graaf Ron , Vollebergh Wilma , Van Os Jim
Published: July 2005

Background

Contemporary cognitive psychological theories suggest that distress plays a mediating role in delusion formation.

Aims

To study the amplifying role of distress from early perceptual intrusions to delusion formation.

Method

A general population sample of 7076 individuals was interviewed with the Composite International Diagnostic Interview (CIDI) in 1996 (baseline), 1997 (T1) and 1999 (T2). At T2, clinicians also scored the Brief Psychiatric Rating Scale (BPRS) item ‘unusual thought content’. Analyses compared hallucinatory experiences with and without subjective distress at baseline for risk of delusion formation at follow-up.

Results

Individuals experiencing hallucinations with distress, compared with those without distress had a fourfold increased risk of subsequent delusion formation.

Conclusions

This finding corroborates the hypothesis that distress associated with early perceptual intrusions serves as a catalyst in the development of delusions.
Implementing cognitive-behavioural therapy for first-episode psychosis
Authors: Addington Jean , Gleeson John
Published: July 2005

Significant symptomatic improvement after a first episode of psychosis is not matched by a similar improvement in functional outcome. Thus, increased attention has been given to psychological intervention, in particular cognitive-behavioural therapy (CBT), with the hope of enhancing functional recovery. Outcome trials of CBT for schizophrenia are few, in particular for the first episode, and have been occasionally criticised for their lack of significance compared with supportive therapies. We describe a modular CBT approach for those with a first episode of psychosis that addresses adaptation as well as both functional and symptomatic outcome and one that parallels the theoretical shift in CBT that has occurred in the last decade. Guidelines for integrating CBT into an early psychosis service are presented.
Rational pharmacotherapy in early psychosis
Authors: Remington Gary
Published: July 2005

Background

An increased focus in research specific to first-episode schizophrenia has provided a rapidly growing body of evidence that can be directly translated to clinical practice.

Aims

To provide clinical recommendations specific to effective pharmacotherapy of first-episode schizophrenia.

Method

Evidence from clinical trials focused on the first-episode population is combined with data from other areas of investigation.

Results

In first-episode psychosis, when to initiate treatment is not always clear, being intimately linked to challenges regarding early detection and diagnosis. There may be differences in antipsychotic dosing, patterns of response and sensitivity to side-effects. Adherence appears to be even more problematic at this stage.

Conclusions

Clinicians currently treating early psychosis have considerably more information to guide their decision-making. However, the speed at which the field is growing is a reminder totreatthis knowledge as a work in progress.
Integrated treatment of first-episode psychosis: effect of treatment on family burden
Authors: Jeppesen Pia , Petersen Lone , Thorup Anne , Abel Maj-Britt , ⊘ehlenschlæger Johan , Christensen Torben Ø. , Krarup Gertrud , Hemmingsen Ralf , J⊘rgensen Per , Nordentoft Merete
Published: July 2005

Background

The families of patients with first-episode psychosis often play a major role in care and often experience lack of support.

Aims

To determine the effect of integrated treatment v. standard treatment on subjective burden of illness, expressed emotion (EE), knowledge of illness and satisfaction with treatment in key relatives of patients with a first episode of schizophrenia-spectrum disorder.

Method

Patients with ICD-10 schizophrenia-spectrum disorders (first episode) were randomly assigned to integrated treatment or to standard treatment. Integrated treatment consisted of assertive community treatment, psychoeducational multi-family groups and social skills training. Key relatives were assessed with the Social Behaviour Assessment Schedule (SBAS, burden of illness), the 5-min speech sample (EE), and a multiple choice questionnaire at entry and after 1 year.

Results

Relatives in integrated treatment felt less burdened and were significantly more satisfied with treatment than relatives in standard treatment. There were no significant effects of intervention groups on knowledge of illness and EE.

Conclusions

The integrated treatment reduced family burden of illness and improved satisfaction with treatment.
Improving 1-year outcome in first-episode psychosis
Authors: Petersen Lone , Nordentoft Merete , Jeppesen Pia , ⊘hlenschlæger Johan , Thorup Anne , Christensen Torben Østergaard , Krarup Gertrud , Dahlstr⊘m Jytte , Haastrup Bodil , J⊘rgensen Per
Published: July 2005

Background

Because early illness course and outcome may affect the long-term outcome of schizophrenia-spectrum disorders, it is especially important to address poor outcome in this early critical period.

Aims

To evaluate whether integrated treatment compared with standard treatment reduced the proportion of patients with poor clinical and social outcome after 1 year.

Method

A total of 547 patients with first-episode psychosis were included in the study, 275 randomly assigned to integrated treatment and 272 to standard treatment. Measures assessed psychotic symptoms and social functioning.

Results

There was a significant beneficial effect of integrated treatment v. standard treatment on ‘any poor outcome’. Integrated treatment had a significantly better effect on ‘any poor outcome’ in patients with schizophrenia compared with patients in standard treatment.

Conclusions

The integrated treatment significantly reduced the proportion of patients with poor clinical and social outcome compared with standard treatment.
Conflict of interest in psychiatry
Authors: Ahmer Syed , Arya Pradeep , Anderson Duncan , Faruqui Rafey
Published: July 2005

Aims and Method

To study the association between study support and outcome in randomised controlled trials (RCTs) of psychotropic drugs, we reviewed all RCTs published in four psychiatry journals over a 5-year period. Chi-squared tests were used to analyse the association between RCT support and outcome, and logistic regression to determine which variable best predicted outcome.

Results

A significantly higher proportion of manufacturer-supported RCTs (125/138, 91%, 95% CI 88–93) had a positive outcome than non-manufacturer-supported RCTs (39/50, 78%, 95% CI 72–84; P=0.02). Having an employee author almost guaranteed a positive outcome (56/58, 97%, 95% CI 94–99).

Clinical Implications

Outcomes of drug RCTs have a significant association with support by the manufacturer of the experimental drug. Systematic reviews and meta-analyses based on these RCTs may be biased in favour of newer drugs.
Potential Impact of Nutritional Strategy on Noninvasive Measurements of Hormones in Birds
Authors: KLASING KIRK C.
Published: July 2005

Abstract: The dietary preferences, gastrointestinal anatomy, digestive physiology, biochemical capabilities, and commensal microflora of a bird are collectively known as its nutritional strategy. Measurement of hormones in droppings requires an appreciation of an animal's nutritional strategy in order to optimize collection protocols, validate techniques, interpret results, and minimize variability and artifacts. Foods of animal origin, nectar, and seeds are highly digestible by relatively simple digestive tracts and result in low rates of feces production. Most frugivorous species also have simple digestive tracts, and they digest the fruit's simple sugars and proteins, but not the fiber in its pulp. Consequently, retention time of food in the digestive tract is short, and their droppings are voluminous. Herbivorous species possess enlarged ceca that house microorganisms that aid in the digestion of fibrous components of their food. Part of the digesta enters the ceca and is subjected to lengthy microbial fermentation. The rest is excluded and quickly passes through the rectum, and is quickly defecated. For measurement of hormones in droppings it appears prudent to collect only rectal feces and to avoid cecal feces. One‐third of the avian families are omnivorous and consume a wide variety of foods. Their digestive strategies are highly variable and change with diet, as does the amount and composition of feces and the rate of passage.
Noninvasive Monitoring of Hormones in Bird Droppings: Physiological Validation, Sampling, Extraction, Sex Differences, and the Influence of Diet on Hormone Metabolite Levels
Authors: GOYMANN WOLFGANG
Published: July 2005

Abstract: During the past several years, the noninvasive measurement of steroid metabolites from mammalian feces and bird droppings has become more and more popular. With an increasing acceptance of the method, investigators may become less aware of the need to validate their assays. It is shown why such validations are essential for each new species investigated and various ways to physiologically validate such noninvasive methods are described. Using the European stonechat (Saxicola torquata rubicola) as a model, it is explained why a validated method to measure androgen metabolites in males does not necessarily work in females. In addition the difficulties that may be neglected owing to the superficial ease of sampling and processing of excreta are investigated. Various issues that may arise during sampling, storage, and extraction of excreta are addressed. Finally, results suggesting that experimental manipulations of the diet may affect hormone metabolite levels in European stonechats are presented. So far, only a few studies have investigated the impact of diet on hormone metabolite levels, and these are the first data to report such an impact in birds. More studies are urgently needed to learn more about differences between the sexes, individuals, and populations and the impact of diet and energy metabolism on hormone metabolites.
Measuring Fecal Glucocorticoid Metabolites in Mammals and Birds: The Importance of Validation
Authors: TOUMA CHADI , PALME RUPERT
Published: July 2005

Abstract: In recent years, the noninvasive monitoring of steroid hormone metabolites in feces of mammals and droppings of birds has become an increasingly popular technique. It offers several advantages and has been applied to a variety of species under various settings. However, using this technique to reliably assess an animal's adrenocortical activity is not that simple and straightforward to apply. Because clear differences regarding the metabolism and excretion of glucocorticoid metabolites (GCMs) exist, a careful validation for each species and sex investigated is obligatory. In this review, general analytical issues regarding sample storage, extraction procedures, and immunoassays are briefly discussed, but the main focus lies on experiments and recommendations addressing the validation of fecal GCM measurements in mammals and birds. The crucial importance of scrutinizing the physiological and biological validity of fecal GCM analyses in a given species is stressed. In particular, the relevance of the technique to detect biologically meaningful alterations in adrenocortical activity must be shown. Furthermore, significant effects of the animals' sex, the time of day, season, and different life history stages are discussed, bringing about the necessity to seriously consider possible sex differences as well as diurnal and seasonal variations. Thus, comprehensive information on the animals' biology and stress physiology should be carefully taken into account. Together with an extensive physiological and biological validation, this will ensure that the measurement of fecal GCMs can be used as a powerful tool to assess adrenocortical activity in diverse investigations on laboratory, companion, farm, zoo, and wild animals.
Measuring Fecal Steroids: Guidelines for Practical Application
Authors: PALME RUPERT
Published: July 2005

Abstract: During the past 20 years, measuring steroid hormone metabolites in fecal samples has become a widely appreciated technique, because it has proved to be a powerful, noninvasive tool that provides important information about an animal's endocrine status (adrenocortical activity and reproductive status). However, although sampling is relatively easy to perform and free of feedback, a careful consideration of various factors is necessary to achieve proper results that lead to sound conclusions. This article aims to provide guidelines for an adequate application of these techniques. It is meant as a checklist that addresses the main topics of concern, such as sample collection and storage, time delay extraction procedures, assay selection and validation, biological relevance, and some confounding factors. These issues are discussed briefly here and in more detail in other recent articles.
A Noninvasive Technique to Evaluate Human‐Generated Stress in the Black Grouse
Authors: BALTIC MARJANA , JENNI‐EIERMANN SUSANNE , ARLETTAZ RAPHAËL , PALME RUPERT
Published: July 2005

Abstract: The continuous development of tourism and related leisure activities is exerting an increasingly intense pressure on wildlife. In this study, a novel noninvasive method for measuring stress in the black grouse, an endangered, emblematic species of European ecosystems that is currently declining in several parts of its European range, is tested and physiologically validated. A radiometabolism study and an ACTH challenge test were performed on four captive black grouse (two of each sex) in order to get basic information about the metabolism and excretion of corticosterone and to find an appropriate enzyme‐immunoassay (EIA) to measure its metabolites in the feces. Peak radioactivity in the droppings was detected within 1 to 2 hours. Injected 3H‐corticosterone was excreted as polar metabolites and by itself was almost absent. A cortisone‐EIA was chosen from among seven tested EIAs for different groups of glucocorticoid metabolites, because it cross‐reacted with some of the formed metabolites and best reflected the increase of excreted corticosterone metabolites, after the ACTH challenge test. Concentrations of the metabolites from fecal samples collected from snow burrows of free‐ranging black grouse were within the same range as in captive birds. The noninvasive method described may be appropriate for evaluating the stress faced by free‐living black grouse populations in the wild, particularly in mountain ecosystems where human disturbance, especially by winter sports, is of increasing conservation concern.
Sampling Effort/Frequency Necessary to Infer Individual Acute Stress Responses from Fecal Analysis in Greylag Geese (Anser anser)
Authors: SCHEIBER ISABELLA B. R. , KRALJ SIMONA , KOTRSCHAL KURT
Published: July 2005

Abstract: Measuring hormone metabolites from excreta is a powerful method to study hormone‐behavior relationships. Currently, fecal corticosterone metabolite concentrations are used to estimate individual short‐term stress responses. From the free‐roaming, semitame flock of greylag geese (Anser anser), as many fecal samples as possible were collected over 3 h following a challenge (social density stress) or in a control situation. This time span corresponds to the gut passage time of geese. It was asked how many samples were necessary to determine differences in excreted corticosterone immunoreactive metabolites (CORTs) between control and social density stress and which parameters (means, maxima, range) reliably showed this difference. A large variation of CORT was found between consecutive samples. Still, means, maxima, and ranges of the samples in a fecal series consistently showed the response to a stressor both within and between individuals. Three samples sufficed if the maximum value of CORT was used, whereas four or more samples were necessary to work with the mean. It was concluded that by increasing the number of fecal samples collected, the course of CORT could be measured more precisely and an individual's acute stress response inferred more reliably.
Investigating Maternal Hormones in Avian Eggs: Measurement, Manipulation, and Interpretation
Authors: GROOTHUIS TON G. G. , Von ENGELHARDT NIKOLAUS
Published: July 2005

Abstract: The last decade has witnessed a surge in studies on steroid hormones of maternal origin present in avian eggs and affecting offspring development. The value of such studies for the understanding of maternal effects and individual differentiation is endorsed and a series of methodological and conceptual issues in the current approaches is discussed. First to be addressed is the topic of correct sampling of eggs or yolk for hormone analyses. Changes in yolk hormone levels during the incubation period and the uneven distribution of hormones within the egg are discussed. Different ways of calculating hormone levels and the importance of collecting data for specific a priori hypotheses are explained. Next to be discussed are the pros and cons of different techniques for manipulating yolk hormone levels and their proper scaling to naturally occurring levels. Third, several issues hampering the interpretation of results from descriptive and experimental studies are addressed. These concern biased embryonic mortality, clutch size, and egg quality that may confound the interpretation of the effect of egg position in the laying order, and the possibility of sex‐specific effects and long‐term effects. Also discussed are the probability of context‐dependent results (due to, e.g., other egg components affecting egg quality, parental quality, and environmental factors), the difficulty in demonstrating adaptive effects due to individual optimization, and the lack of insight in the underlying physiological processes. Finally, it is concluded that this field has shown much progress but that it would profit from a more careful consideration of methodology and from a better integration of behavioral ecology and endocrinology.
Measuring Steroid Hormones in Avian Eggs
Authors: Von ENGELHARDT N.KOLAUS , GROOTHUIS TON G. G.
Published: July 2005

Abstract: Avian eggs contain substantial levels of various hormones of maternal origin and have recently received a lot of interest, mainly from behavioral ecologists. These studies strongly depend on the measurement of egg hormone levels, but the method of measuring these levels has received little attention. This paper describes the sampling, extraction, and assay of hormones in avian eggs and related methodological problems. The method of sampling is important because hormones are not homogeneously distributed within the egg, and after onset of embryonic development their levels may decrease and increase due to changes in egg structure and secretion or uptake of hormones by the embryo. The extraction of hormones from the yolk and chromatographic separation of different hormones for immunoassays can strongly influence the results because such procedures remove interfering substances such as proteins, lipids, and other hormones and their metabolites, which can cross‐react with the antiserum used. Finally, the assay itself needs more validation than many studies report, especially with respect to the accuracy and specificity of the hormone measurements. We conclude that the addressed issues need more attention for the correct interpretation of differences in hormone levels within and between studies.
Steroids in Allantoic Waste: An Integrated Measure of Steroid Exposure in Ovo
Authors: BENOWITZ‐FREDERICKS Z.MORGAN , KITAYSKY ALEXANDER S. , WINGFIELD JOHN C.
Published: July 2005

Abstract: Recent studies examining patterns and consequences of variation in maternally deposited steroids in avian egg yolk have demonstrated that these maternal hormones can have dramatic effects on chick phenotypes. However, maternal steroids are not the only source for avian embryos, which activate endocrine axes relatively early in development and are capable of producing substantial amounts of endogenous steroids. Although organizational effects of steroids have been demonstrated, the interactions between steroids from yolk and endogenous production have not been addressed. Steroids in the yolk are likely to alter development of the embryo's endocrine axes. The ability to assess total steroid exposure in ovo in a nonlethal fashion would improve our understanding of these interactions and help elucidate the mechanisms by which maternal steroids alter chick phenotype. Steroid levels in allantoic waste provide a cumulative measure of steroids excreted in ovo and may prove to be a useful tool. We present data from semiprecocial seabirds, common murres, demonstrating the presence of detectable steroids in allantoic waste and suggesting that some reflect differences in timing of hatching and may provide information about aspects of chick phenotype.