bluuebunny/crossref_metadata_2025 huggingface dataset:
Recommendations on the use of exercise testing in clinical practice
Authors: Palange P. , Ward S. A. , Carlsen K-H. , Casaburi R. , Gallagher C. G. , Gosselink R. , O'Donnell D. E. , Puente-Maestu L. , Schols A. M. , Singh S. , Whipp B. J.
Published: December 2006

Evidence-based recommendations on the clinical use of cardiopulmonary exercise testing (CPET) in lung and heart disease are presented, with reference to the assessment of exercise intolerance, prognostic assessment and the evaluation of therapeutic interventions (e.g.drugs, supplemental oxygen, exercise training). A commonly used grading system for recommendations in evidence-based guidelines was applied, with the grade of recommendation ranging from A, the highest, to D, the lowest.

For symptom-limited incremental exercise, CPET indices, such as peak O2uptake (V′O2),V′O2at lactate threshold, the slope of the ventilation–CO2output relationship and the presence of arterial O2desaturation, have all been shown to have power in prognostic evaluation. In addition, for assessment of interventions, the tolerable duration of symptom-limited high-intensity constant-load exercise often provides greater sensitivity to discriminate change than the classical incremental test. Field-testing paradigms (e.g.timed and shuttle walking tests) also prove valuable.

In turn, these considerations allow the resolution of practical questions that often confront the clinician, such as: 1) “When should an evaluation of exercise intolerance be sought?”; 2) “Which particular form of test should be asked for?”; and 3) “What cluster of variables should be selected when evaluating prognosis for a particular disease or the effect of a particular intervention?”
Genes, environments, development and asthma: a reappraisal
Authors: Martinez F. D.
Published: December 2006

Significant advances have been made in our understanding of the role of genetic variation in determining complex human phenotypes such as asthma. It is now well established that there is no single “gene for asthma”, in the way that the cystic fibrosis transmembrane receptor is the “gene for cystic fibrosis”. It is also clear that among all genetic variants eventually found to be associated with asthma, only a few will be replicated, and in the same direction, in the majority of well-performed studies. Current evidence suggests that most asthma-related polymorphisms determine risk for the disease in a context-dependent manner,i.e. they interact with environmental factors, with polymorphisms in other genes and with the specific developmental phase of the disease in which the association is tested. Elucidating these complex interactions will allow us to understand better the heterogeneity of the disease and thus to develop therapeutic tools tailored to the specific form of the disease in each patient.
The human lung: did evolution get it wrong?
Authors: West J. B. , Watson R. R. , Fu Z.
Published: December 2006

Some 300 million yrs ago, the ancestors of modern reptiles emerged from water and were committed to air breathing. They were exothermic and incapable of sustained levels of high physical activity. But from them evolved the two great classes of vertebrates with high levels of maximal oxygen consumption: the mammals and birds. A remarkable feature of these two divergent evolutionary lines is that, although the physiology of many organ systems shows many similarities, the lungs are radically different. A major difference is that the ventilation of the gas-exchanging tissue has a flow-through pattern in the bird but is reciprocating in the mammal. The result is that mammals have a reduced alveolar and arterial oxygen tension, a potential for uneven ventilation, and relatively large terminal air spaces. This in turn means that the pulmonary capillaries are poorly supported compared with the bird. The result is that the pulmonary capillaries in the bird have much thinner and more uniform walls, with more efficient gas exchange. Other advantages of the bird lung are that it utilises a more efficient cross-current pattern of gas-exchange, and the bird has separated the ventilatory and gas exchange functions. From a structure–function standpoint, the bird lung is superior.
A novel statistical method to estimate the effective SNP size in vertebrate genomes and categorized genomic regions
Authors: Seo Daekwan , Jiang Cizhong , Zhao Zhongming
Published: December 2006

Background

The local environment of single nucleotide polymorphisms (SNPs) contains abundant genetic information for the study of mechanisms of mutation, genome evolution, and causes of diseases. Recent studies revealed that neighboring-nucleotide biases on SNPs were strong and the genome-wide bias patterns could be represented by a small subset of the total SNPs. It remains unsolved for the estimation of the effective SNP size, the number of SNPs that are sufficient to represent the bias patterns observed from the whole SNP data.

Results

To estimate the effective SNP size, we developed a novel statistical method, SNPKS, which considers both the statistical and biological significances. SNPKS consists of two major steps: to obtain an initial effective size by the Kolmogorov-Smirnov test (KS test) and to find an intermediate effective size by interval evaluation. The SNPKS algorithm was implemented in computer programs and applied to the real SNP data. The effective SNP size was estimated to be 38,200, 39,300, 38,000, and 38,700 in the human, chimpanzee, dog, and mouse genomes, respectively, and 39,100, 39,600, 39,200, and 42,200 in human intergenic, genic, intronic, and CpG island regions, respectively.

Conclusion

SNPKS is the first statistical method to estimate the effective SNP size. It runs efficiently and greatly outperforms the algorithm implemented in SNPNB. The application of SNPKS to the real SNP data revealed the similar small effective SNP size (38,000 – 42,200) in the human, chimpanzee, dog, and mouse genomes as well as in human genomic regions. The findings suggest strong influence of genetic factors across vertebrate genomes.
Uptake of 3H-cAMP by retinal pigment epithelium isolated from bluegill sunfish (Lepomis macrochirus)
Authors: Keith Thomas A , Radhakrishnan Varsha , Moredock Steve , García Dana M
Published: December 2006

Background

In bluegill sunfish, the melanin-containing pigment granules of the retinal pigment epithelium undergo cyclic movements in response both to ambient lighting and circadian cues. Pigment granules aggregate into the cell body at night (in the dark), and disperse into apical processes during the day (in the light). Regulation of pigment granule aggregation in a number of fishes depends on modulating the intracellular levels of cyclic adenosine monophosphate.

Results

Here we show isolated RPE takes up cyclic adenosine monophosphate (cAMP) in a saturable manner, exogenously applied cAMP induces pigment granule aggregation in retinal pigment epithelium isolated from bluegill, and aggregation induced in this manner is inhibited by treatment with probenecid, an organic anion transport inhibitor.

Conclusion

Our results raise the possibility that cAMP functions as a messenger secreted from the neural retina to signal darkness to the RPE, which takes it up. It further suggests that organic anion transport systems are the route by which cAMP crosses RPE cell membranes since probenecid inhibits extracellular cAMP from causing pigment granule aggregation.
Lutein is needed for efficient chlorophyll triplet quenching in the major LHCII antenna complex of higher plants and effective photoprotection in vivounder strong light
Authors: Dall'Osto Luca , Lico Chiara , Alric Jean , Giuliano Giovanni , Havaux Michel , Bassi Roberto
Published: December 2006

Background

Lutein is the most abundant xanthophyll in the photosynthetic apparatus of higher plants. It binds to site L1 of all Lhc proteins, whose occupancy is indispensable for protein folding and quenching chlorophyll triplets. Thus, the lack of a visible phenotype in mutants lacking lutein has been surprising.

Results

We have re-assessed the lut2.1 phenotypes through biochemical and spectroscopic methods. Lhc proteins from the lut2.1 mutant compensate the lack of lutein by binding violaxanthin in sites L1 and L2. This substitution reduces the capacity for regulatory mechanisms such as NPQ, reduces antenna size, induces the compensatory synthesis of Antheraxanthin + Zeaxanthin, and prevents the trimerization of LHCII complexes. In vitro reconstitution shows that the lack of lutein per se is sufficient to prevent trimerization. lut2.1 showed a reduced capacity for state I – state II transitions, a selective degradation of Lhcb1 and 2, and a higher level of photodamage in high light and/or low temperature, suggesting that violaxanthin cannot fully restore chlorophyll triplet quenching. In vitro photobleaching experiments and time-resolved spectroscopy of carotenoid triplet formation confirmed this hypothesis. The npq1lut2.1 double mutant, lacking both zeaxanthin and lutein, is highly susceptible to light stress.

Conclusion

Lutein has the specific property of quenching harmful 3Chl* by binding at site L1 of the major LHCII complex and of other Lhc proteins of plants, thus preventing ROS formation. Substitution of lutein by violaxanthin decreases the efficiency of 3Chl* quenching and causes higher ROS yield. The phenotype of lut2.1 mutant in low light is weak only because rescuing mechanisms of photoprotection, namely zeaxanthin synthesis, compensate for the ROS production. We conclude that zeaxanthin is effective in photoprotection of plants lacking lutein due to the multiple effects of zeaxanthin in photoprotection, including ROS scavenging and direct quenching of Chl fluorescence by binding to the L2 allosteric site of Lhc proteins.
Analysis of rice glycosyl hydrolase family 1 and expression of Os4bglu12 β-glucosidase
Authors: Opassiri Rodjana , Pomthong Busarakum , Onkoksoong Tassanee , Akiyama Takashi , Esen Asim , Ketudat Cairns James R
Published: December 2006

Background

Glycosyl hydrolase family 1 (GH1) β-glucosidases have been implicated in physiologically important processes in plants, such as response to biotic and abiotic stresses, defense against herbivores, activation of phytohormones, lignification, and cell wall remodeling. Plant GH1 β-glucosidases are encoded by a multigene family, so we predicted the structures of the genes and the properties of their protein products, and characterized their phylogenetic relationship to other plant GH1 members, their expression and the activity of one of them, to begin to decipher their roles in rice.

Results

Forty GH1 genes could be identified in rice databases, including 2 possible endophyte genes, 2 likely pseudogenes, 2 gene fragments, and 34 apparently competent rice glycosidase genes. Phylogenetic analysis revealed that GH1 members with closely related sequences have similar gene structures and are often clustered together on the same chromosome. Most of the genes appear to have been derived from duplications that occurred after the divergence of rice and Arabidopsis thaliana lineages from their common ancestor, and the two plants share only 8 common gene lineages. At least 31 GH1 genes are expressed in a range of organs and stages of rice, based on the cDNA and EST sequences in public databases. The cDNA of the Os4bglu12 gene, which encodes a protein identical at 40 of 44 amino acid residues with the N-terminal sequence of a cell wall-bound enzyme previously purified from germinating rice, was isolated by RT-PCR from rice seedlings. A thioredoxin-Os4bglu12 fusion protein expressed in Escherichia coli efficiently hydrolyzed β-(1,4)-linked oligosaccharides of 3–6 glucose residues and laminaribiose.

Conclusion

Careful analysis of the database sequences produced more reliable rice GH1 gene structure and protein product predictions. Since most of these genes diverged after the divergence of the ancestors of rice and Arabidopsis thaliana, only a few of their functions could be implied from those of GH1 enzymes from Arabidopsis and other dicots. This implies that analysis of GH1 enzymes in monocots is necessary to understand their function in the major grain crops. To begin this analysis, Os4bglu12 β-glucosidase was characterized and found to have high exoglucanase activity, consistent with a role in cell wall metabolism.
Case report: Infective endocarditis caused by Brevundimonas vesicularis
Authors: Yang Mei-Li , Chen Yen-Hsu , Chen Tun-Chieh , Lin Wei-Ru , Lin Chun-Yu , Lu Po-Liang
Published: December 2006

Background

There are few reports in the literature of invasive infection caused by Brevundimonas vesicularis in patients without immunosuppression or other predisposing factors. The choice of antimicrobial therapy for bacteremia caused by the pathogen requires more case experience to be determined.

Case presentation

The case of a 40-year-old previously healthy man with subacute endocarditis proposed to be contributed from an occult dental abscess is described. The infection was found to be caused by B. vesicularis on blood culture results. The patient recovered without sequelae after treatment with ceftriaxone followed by subsequent ciprofloxacin therapy owing to an allergic reaction to ceftriaxone and treatment failure with ampicillin/sulbactam.

Conclusion

To our knowledge, this is the first report of B. vesicularis as a cause of infective endocarditis. According to an overview of the literature and our experience, we suggest that third-generation cephalosporins, piperacillin/tazobactam, and ciprofloxacin are effective in treating invasive B. vesicularis infections, while the efficacy of ampicillin-sulbactam needs further evaluation.
Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders
Authors: Mukerji Gaurav , Waters Janet , Chessell Iain P , Bountra Chas , Agarwal Sanjiv K , Anand Praveen
Published: December 2006

Background

The Bladder cooling reflex (BCR) i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO) and painful bladder syndrome (PBS), but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders.

Methods

The BCR, elicited by ice water test (IWT) was performed in patients with painful bladder syndrome (PBS, n = 17), idiopathic detrusor overactivity (IDO, n = 22), neurogenic detrusor overactivity (NDO, n = 4) and stress urinary incontinence (as controls, n = 21). The IWT was performed by intravesical instillation of cold saline (0 – 4°C). A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test.

Results

A positive IWT was observed in IDO (6/22, 27.3%) and NDO (4/4, 100%) patients, but was negative in all control and PBS patients. Thirteen (76.5%) PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002), or equivalent amount of bladder filling (100 mls) with saline at room temperature (P = 0.015). None of the control or overactive (NDO/IDO) patients reported any pain during the IWT.

Conclusion

The BCR in DO may reflect loss of central inhibition, which appears necessary to elicit this reflex; the pain elicited in PBS suggests afferent sensitisation, hence sensory symptoms are evoked but not reflex detrusor contractions. The ice water test may be a useful and simple marker for clinical trials in PBS, particularly for novel selective TRPM8 antagonists.
Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest
Authors: Ujiki Michael B , Ding Xian-Zhong , Salabat M Reza , Bentrem David J , Golkar Laleh , Milam Ben , Talamonti Mark S , Bell Richard H , Iwamura Takeshi , Adrian Thomas E
Published: December 2006

Background

Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro.

Results

Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition.

Conclusion

Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer.
Nectin-2-mediated entry of a syncytial strain of herpes simplex virus via pH-independent fusion with the plasma membrane of Chinese hamster ovary cells
Authors: Delboy Mark G , Patterson Jennifer L , Hollander Aimee M , Nicola Anthony V
Published: December 2006

Background

Herpes simplex virus (HSV) can utilize multiple pathways to enter host cells. The factors that determine which route is taken are not clear. Chinese hamster ovary (CHO) cells that express glycoprotein D (gD)-binding receptors are model cells that support a pH-dependent, endocytic entry pathway for all HSV strains tested to date. Fusion-from-without (FFWO) is the induction of target cell fusion by addition of intact virions to cell monolayers in the absence of viral protein expression. The receptor requirements for HSV-induced FFWO are not known. We used the syncytial HSV-1 strain ANG path as a tool to evaluate the complex interplay between receptor usage, membrane fusion, and selection of entry pathway.

Results

Inhibitors of endocytosis and endosome acidification blocked ANG path entry into CHO cells expressing nectin-1 receptors, but not CHO-nectin-2 cells. Thus, under these conditions, nectin-2 mediates pH-independent entry at the plasma membrane. In addition, CHO-nectin-2 cells supported pH-dependent, endocytic entry of different strains of HSV-1, including rid1 and HFEM. The kinetics of ANG path entry was rapid (t1/2 of 5–10 min) regardless of entry route. However, HSV-1 ANG path entry by fusion with the CHO-nectin-2 cell plasma membrane was more efficient and resulted in larger syncytia. ANG path virions added to the surface of CHO-nectin-2 cells, but not receptor-negative CHO cells or CHO-nectin-1 cells, induced rapid FFWO.

Conclusion

HSV-1 ANG path can enter CHO cells by either endocytic or non-endocytic pathways depending on whether nectin-1 or nectin-2 is present. In addition to these cellular receptors, one or more viral determinants is important for the selection of entry pathway. HSV-induced FFWO depends on the presence of an appropriate gD-receptor in the target membrane. Nectin-1 and nectin-2 target ANG path to divergent cellular pathways, and these receptors may have different roles in triggering viral membrane fusion.
Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes
Authors: Dijkman Ronald , Jebbink Maarten F , Wilbrink Berry , Pyrc Krzysztof , Zaaijer Hans L , Minor Philip D , Franklin Sally , Berkhout Ben , Thiel Volker , van der Hoek Lia
Published: December 2006

Background

The genome of coronaviruses contains structural and non-structural genes, including several so-called accessory genes. All group 1b coronaviruses encode a single accessory protein between the spike and envelope genes, except for human coronavirus (HCoV) 229E. The prototype virus has a split gene, encoding the putative ORF4a and ORF4b proteins. To determine whether primary HCoV-229E isolates exhibit this unusual genome organization, we analyzed the ORF4a/b region of five current clinical isolates from The Netherlands and three early isolates collected at the Common Cold Unit (CCU) in Salisbury, UK.

Results

All Dutch isolates were identical in the ORF4a/b region at amino acid level. All CCU isolates are only 98% identical to the Dutch isolates at the nucleotide level, but more closely related to the prototype HCoV-229E (>98%). Remarkably, our analyses revealed that the laboratory adapted, prototype HCoV-229E has a 2-nucleotide deletion in the ORF4a/b region, whereas all clinical isolates carry a single ORF, 660 nt in size, encoding a single protein of 219 amino acids, which is a homologue of the ORF3 proteins encoded by HCoV-NL63 and PEDV.

Conclusion

Thus, the genome organization of the group 1b coronaviruses HCoV-NL63, PEDV and HCoV-229E is identical. It is possible that extensive culturing of the HCoV-229E laboratory strain resulted in truncation of ORF4. This may indicate that the protein is not essential in cell culture, but the highly conserved amino acid sequence of the ORF4 protein among clinical isolates suggests that the protein plays an important role in vivo.
Hindcasting of nutrient loadings from its catchment on a highly valuable coastal lagoon: the example of the Fleet, Dorset, UK, 1866–2004
Authors: Weber Geraint J , O'Sullivan Patrick E , Brassley Paul
Published: December 2006

Background

Nutrient loadings from its catchment upon The Fleet, a highly valuable coastal lagoon in Southern England, were hindcast for the period AD 1866–2004, using a catchment model, export coefficients, and historical data on land use changes, livestock numbers, and human population. Agriculture was the main nutrient source throughout, other inputs representing minor contributions. Permanent pasture was historically the main land use, with temporary grassland and cereals increasing during the mid-20th century. Sheep, the main 19th century livestock, were replaced by cattle during the 1930s.

Results

Total nitrogen loadings rose from ca 41 t yr-1 during the late 19th century to 49–54 t yr-1 for the mid-20th, increasing to 98 t yr-1 by 1986. Current values are ca 77 t yr-1. Total phosphorus loads increased from ca 0.75 t yr-1 for the late 19th century to ca 1.6 t yr-1 for the mid-20th, reached ca 2.2 t yr-1 in 1986, and are now ca 1.5 t yr-1. Loadings rose most rapidly between 1946 and 1988, owing to increased use of inorganic fertilisers, and rising sheep and cattle numbers. Livestock were the main nutrient source throughout, but inputs from inorganic fertilisers increased after 1946, peaking in 1986. Sewage treatment works and other sources contribute little nitrogen, but ca 35% of total phosphorus. Abbotsbury Swannery, an ancient Mute Swan community, provides ca 0.5% of total nitrogen, and ca 5% of total phosphorus inputs.

Conclusion

The Fleet has been grossly overloaded with nitrogen since 1866, climaxing during the 1980s. Total phosphorus inputs lay below 'permissible' limits until the 1980s, exceeding them in inner, less tidal parts of the lagoon, during the 1940s. Loadings on Abbotsbury Bay exceeded 'permissible' limits by the 1860s, becoming 'dangerous' during the mid-20th century. Phosphorus stripping at point sources will not significantly reduce loadings to all parts of the lagoon. Installation of 5 m buffer strips throughout the catchment and shoreline will marginally affect nitrogen loadings, but will reduce phosphorus inputs to the West Fleet below 'permissible' limits. Only a combination of measures will significantly affect Abbotsbury Bay, where, without effluent diversion, loadings will remain beyond 'permissible'.
A proteomics study of the response of North Ronaldsay sheep to copper challenge
Authors: Simpson Deborah M , Mobasheri Ali , Haywood Susan , Beynon Robert J
Published: December 2006

Background

The objective of this proteomics study was to identify proteins that changed expression as a result of copper challenge in the uniquely copper sensitive North Ronaldsay sheep and further, to compare those changes in expression with the more copper tolerant Cambridge breed. Such data gives us a proteome-centered perspective of the pathogenesis of copper-induced oxidative stress in this breed.

Results

Many proteins respond to copper challenge, but this study focuses on those exhibiting a differential response between the two breeds, related to liver copper content. As copper accumulated in the tissue, the pattern of expression of several proteins was markedly different, in North Ronaldsay sheep as compared to the Cambridge breed.

Conclusion

The pattern of changes was consistent with the greatly enhanced susceptibility of North Ronaldsay sheep to copper-induced oxidative stress, focused on mitochondrial disturbance with consequent activation of hepatic stellate cells. The expression profiles were sufficiently complex that the response could not simply be explained as a hypersensitivity to copper in North Ronaldsay sheep.
p66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify patients likely to relapse despite tamoxifen therapy
Authors: Frackelton A Raymond , Lu Li , Davol Pamela A , Bagdasaryan Robert , Hafer Laurie J , Sgroi Dennis C
Published: December 2006

Introduction

Shc adapter proteins are secondary messenger proteins involved in various cellular pathways, including those mediating receptor tyrosine kinase signaling and apoptosis in response to stress. We have previously reported that high levels of tyrosine-phosphorylated Shc (PY-Shc) and low levels of its inhibitory p66 Shc isoform are strongly prognostic for identifying both early node-negative and more advanced, node-positive, primary breast cancers with high risk for recurrence. Because aberrant activation of tyrosine kinases upstream of Shc signaling proteins has been implicated in resistance to tamoxifen – the most widely prescribed drug for treatment of estrogen receptor-positive breast cancer – we hypothesized that Shc isoforms may identify patients at increased risk of relapsing despite tamoxifen treatment.

Methods

Immunohistochemical analyses of PY-Shc and p66 Shc were performed on archival primary breast cancer tumors from a population-based cohort (60 patients, 9 relapses) and, for validation, an independent external cohort (31 patients, 13 relapses) in which all patients received tamoxifen as a sole systemic adjuvant prior to relapse.

Results

By univariate and multivariate analyses, the Shc proteins were very strong and independent predictors of treatment failure in both the population-based cohort (interquartile hazard ratio = 8.3, 95% confidence interval [CI] 1.8 to 38, P = 0.007) and the validating cohort (interquartile relative risk = 12.1, 95% CI 1.7 to 86, P = 0.013).

Conclusion

These results suggest that the levels of PY-Shc and p66 Shc proteins in primary tumors identify patients at high risk for relapsing despite treatment with tamoxifen and therefore with further validation may be useful in guiding clinicians to select alternative adjuvant treatment strategies.
A modified McCabe score for stratification of patients after intensive care unit discharge: the Sabadell score
Authors: Fernandez Rafael , Baigorri Francisco , Navarro Gema , Artigas Antonio
Published: December 2006

Introduction

Mortality in the ward after an intensive care unit (ICU) stay is considered a quality parameter, and is described as a source of avoidable mortality. Additionally, the attending intensivist frequently anticipates fatal outcome after ICU discharge. Our objective was to test the ability of a new score to stratify patients according to ward mortality after ICU discharge.

Methods

A prospective cohort study was performed in the general ICU of a university-affiliated hospital. In 2003 and 2004 we prospectively recorded the attending intensivist's subjective prognosis at ICU discharge about the hospital outcome for each patient admitted to the ICU (the Sabadell score), which was later compared with the real hospital outcome.

Results

We studied 1,521 patients with a mean age of 60.2 ± 17.8 years. The median (25–75% percentile) ICU stay was five (three to nine) days. The ICU mortality was 23.8%, with 1,156 patients being discharged to the ward. Post-ICU ward mortality was 9.6%, mainly observed in patients with a Sabadell score of 3 (81.3%) or a score of 2 (41.1%), whereas lower mortality was observed in patients scoring 1 (17.2%) and scoring 0 (1.7%). Multivariate analysis selected age and the Sabadell score as the only variables associated with ward mortality, with an area under the receiver operating curve of 0.88 (95% CI 0.84–0.93) for the Sabadell score.

Conclusion

The Sabadell score at ICU discharge works effectively to stratify patients according to hospital outcome.
An eye’s view of T regulatory cells
Authors: Stein-Streilein Joan , Taylor Andrew W
Published: December 2006

T regulatory (Treg) cells have been studied for more than 30 years. Recently, changing technology and attitudes have led to new interest in T cell regulation of the immune responses. The eye is an immune-privileged site with unique mechanisms for the prevention of damaging immune inflammation. The eye fashions its Treg cells in novel ways to prevent immune inflammation locally and systemically. The purpose of this mini-review is to condense and summarize reports of Treg cells dependent on the eye in the context of the Treg literature in general.
Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice
Authors: Mishra Anil , Schlotman James , Wang Meiqin , Rothenberg Marc E
Published: December 2006

We have previously developed a murine model of allergen-induced eosinophilic esophagitis (EE), characterized by intraepithelial eosinophils, extracellular granule deposition, and epithelial cell hyperplasia, features that mimic the pathophysiological changes observed in individuals with various forms of EE. We now test the hypothesis that adaptive T cell immunity is critical in initiating experimental EE. We first demonstrate that EE induction is associated with an increase in lymphocyte subpopulations (B+, CD4+, and CD8+ cells) in the esophagus. We induced experimental EE in wild-type and various lymphocyte subpopulation-deficient mice by intranasal allergen sensitization. Eosinophil levels and epithelial cell proliferation were determined by performing antimajor basic protein and antiproliferation cell nuclear antigen immunohistochemical analysis. Eosinophil accumulation in the esophagus was ablated completely in RAG1 gene-deficient mice, but no role for B cells or antigen-specific antibodies was found, as B cell-deficient (IgH6) mice developed unabated, experimental EE. In addition, T cell-deficient (forkhead box N1−/−) mice were protected from the induction of experimental EE. CD8α-deficient mice developed unaltered, experimental EE, and CD4-deficient mice were only protected moderately from disease induction. Taken together, these studies indicate a role for CD4+ and CD4− cell populations in EE pathogenesis and demonstrate that experimental allergen-induced EE is dependent on adaptive T cell immunity.
Uncertainty and risk assessment
Authors: Dixon Mandy , Oyebode Femi
Published: December 2006

Risk assessment forms an integral part of clinical practice. Traditionally, risk has been portrayed as a binary concept, and its assessment regarded as a test that can be correctly or incorrectly classified. However, this article discusses how risk assessments are less straightforward than is commonly perceived and are often complicated by multiple forms of uncertainty. These uncertainties arise where psychiatrists are unsure about their interpretation of information, where information is missing, or where interpretation of the risk situation is open to challenge. They centre on doubts about the accuracy and the defensibility of assessment of patients' risk status and the need for risk containment. Like other professionals, psychiatrists adopt a range of strategies to resolve uncertainties. These strategies, which often involve some ‘risk-taking’, enable the practising clinician to make a more confident decision. There is an argument for including ‘certainty’ as a theoretical feature of risk assessment in psychiatry and for recognising it as a multifaceted phenomenon. There is also an argument for considering with greater precision the manner in which uncertainty is managed within psychiatric risk assessments.
Supportive psychotherapy in dementia
Authors: Junaid Ola , Hegde Soumya
Published: December 2006

The role of psychotherapy for elderly people is the subject of much debate. Yet this has not resulted in a shift of resources towards increasing its availability within the UK's National Health Service. Over the past decade the pessimistic view of psychotherapy for elderly people has diminished owing to the growing evidence base and the commitment of champions in old age psychiatry and psychotherapy. However, there is still very little structured research into psychotherapy in dementia. Supportive psychotherapy is a poorly understood but very practical means of helping people with dementia to adjust to the effects of their illness. Its inherent flexibility enables individual sessions to be tailored to the patient's needs and deficits. An understanding of supportive psychotherapy and its benefits could enable clinicians to improve the quality of life of people with dementia and their carers within the ever-present constraints of limited time and resources. This article explores the use of supportive psychotherapy as a treatment option in dementia.
Choice in mental health: myths and possibilities
Authors: Valsraj Koravangattu Menon , Gardner Nichola
Published: December 2006

The government in England and Wales is promoting policies and initiatives to offer patients choice across all healthcare specialties. This has raised concerns in mental healthcare, particularly if the physical healthcare model of implementation is imposed. However, the ‘choice agenda’ is an opportunity for mental health services to be innovative and act as beacons to other disciplines in healthcare. The south-east London programme introducing choice in mental health services is offered as an example here. There already exists an ‘ethos of choice’ within mental health services, but current practices may require a focused approach and structuring to fit in with national policy. This also might be necessary to influence policy makers to take a different perspective on choice in mental health. The principle of choice goes hand in hand with the drive towards greater social inclusion for people with mental health problems.
Catatonia
Authors: Rajagopal Sundararajan
Published: December 2006

Catatonia is an important phenomenon in both psychiatry and general medicine. This article provides an overview of the key aspects of catatonia, including clinical features, differential diagnoses, management and prognosis. The different types of catatonia, the position of catatonia in the psychiatric classificatory systems, use of catatonia rating scales and the association between catatonia and neuroleptic malignant syndrome are also covered. Abnormalities that have been hypothesised as being possible underlying mechanisms in catatonia are highlighted. The article aims to provide clinicians with a comprehensive update on the subject, with information derived from an extensive range of relevant references.
Choice: wake up and smell the coffee!
Authors: Holloway Frank
Published: December 2006

The ‘choice agenda’ reflects a key element of the modernisation of public services. There are many conceptual and practical difficulties with the implementation of choice within mental health services, but these are not in any way unique to this client group. Professionals will have to adapt to the new world that will encompass a plurality of paradigms of care and service providers.
Negotiating styles adopted by consultant psychiatrists when prescribing antipsychotics
Authors: Chaplin Robert , Lelliott Paul , Quirk Alan , Seale Clive
Published: December 2006

A good therapeutic alliance between mental health professionals and patients with psychosis can enhance adherence to medication regimens and improve clinical outcome. This article explores how the therapeutic alliance might be developed with respect to decisions to prescribe antipsychotic medication. It does this by presenting the implications for practice that arise from a recent qualitative interview study with consultant psychiatrists. We consider strategies for strengthening the therapeutic alliance, occasions when it might be appropriate to suspend shared decision-making temporarily, techniques used to enable discussion of symptoms and side-effects, and how issues of adherence are uncovered and addressed. Psychiatrists already possess considerable skills in these areas. The dissemination of these to colleagues forms an important opportunity for CPD.
Payment by results in mental health: the current state of play in England
Authors: Fairbairn Andrew
Published: December 2006

The Department of Health is introducing a ‘payment by results’ system for mental health services in the UK. The system is already being used in the acute healthcare sector, but is still under development for application in mental healthcare. This article outlines the concept of payment by results, briefly reports on its use in other countries and describes the pilot study underway in England to define currencies to be used in a payment by results system planned for NHS mental healthcare throughout England and Wales.
Lost online: an overview of internet addiction
Authors: Murali Vijaya , George Sanju
Published: December 2006

A significant minority of people who use the internet develop ‘internet addiction’ – a relatively new concept in psychiatry not yet recognised by ICD–10 or DSM–IV. Preliminary research offers interesting insight into predisposing factors and psychosocial treatment options. Mental health professionals need a basic understanding of internet addiction so that they can recognise it early and intervene appropriately. In this article, we present an overview of the aetiological frameworks, assessment and treatments of internet addiction.
Computer addiction – a sceptical view
Authors: Lenihan Fionnbar
Published: December 2006

The concept of computer addiction is examined and the importance of conceptual and nosological clarity emphasised. The risk of tautology in the construction of such conditions is raised, as is the issue of whether it would be better to classify many affected individuals in terms of the end behaviour rather than the mediating mechanism. Definitional difficulties and sociocultural contexts are explored.
Payment by volume (not results)
Authors: Oyebode Femi
Published: December 2006

Payment by results, a system for paying healthcare trusts, is intended as a fair and consistent basis for hospital funding. It relies on a national tariff structured around a case-mix measure known as healthcare resource groups. It is often argued that if payment by results works as planned, the National Health Service will become more efficient and productive. However, the use of a case-mix measure, the healthcare resource group, which derives from the diagnostic related (or diagnosis-related) group, has attendant problems. These include the risk that the payment structure will be inaccurate, unfair and liable to cause the financial destabilisation of trusts. There is also the risk that healthcare institutions will falsify patient classifications (‘up-coding’) to ensure higher remuneration. It has been argued that payment by results may be particularly unsuited to psychiatry. The ability of healthcare resource groups to accurately predict resource use in psychiatry is doubtful. In conclusion, mental health trusts will need to adapt to payment by results but there will inevitably be losers.
Adolescent-onset psychosis: prevalence, needs and service
provision
Authors: Boeing Leonie , Murray Val , Pelosi Anthony , McCabe Robert , Blackwood Douglas , Wrate Robert
Published: December 2006

Background

Little is known of the epidemiology and care needs of people with
adolescent-onset psychosis.

Aims

To examine prevalence and the cross-sectional disability, needs and
service provision for adolescent-onset psychosis in areas of central
Scotland with a total population of 1.75 million.

Method

We identified and contacted 103 young people using an opt-out research
design. Fifty-three participants and their carers and keyworkers were
interviewed using a modified version of the Cardinal Needs Schedule.

Results

The 3-year prevalence was 5.9 per 100 000 general population. Twenty-one
(20%) adolescents were not in contact with mental health services; 80% of
first admissions were to adult acute psychiatric wards. Those interviewed
had high levels of morbidity: 29 (55%) had serious to pervasive
impairment of functioning; there were relatively high levels of
side-effects, negative symptoms, anxiety, occupational, friendship and
family difficulties. Care provision was better for ‘clinical' than for
‘social' domains; 20% had five or more unmet needs; 17% had at least one
intractable problem.

Conclusions

This low-prevalence disorder requires an assertive multi-agency approach
in the context of a national planning framework.
Mood disorders and migration
Authors: Swinnen Sanne G. H. A. , Selten Jean-Paul
Published: December 2006

Background

Migration is a risk factor for the development of schizophrenia.

Aims

To examine whether migration is also a risk factor for bipolar affective
disorder, unipolar depressive disorder and mood disorders in general.

Method

Medline was searched for population-based incidence studies concerning
mood disorders among migrants and mean relative risks were computed using
a mixed-effects statistical model.

Results

Only a few studies of unipolar depressive disorder were retrieved. The
mean relative risk of developing bipolar affective disorder among
migrants was 2.47 (95% C11.33–4.59). However, after excluding people of
African-Caribbean origin in the UK this risk was no longer significantly
increased. The mean relative risk of mood disorders of unspecified
polarity was 1.25 (95% CI 1.04–1.49) and that of any mood disorder was
1.38 (95% CI 1.17–1.62).

Conclusions

There is no conclusive evidence for a large increase in the risk of mood
disorders associated with migration.
Perceived discrimination and psychological distress in
Sweden
Authors: Wamala Sarah , Boström Gunnel , Nyqvist Karin
Published: December 2006

There is lack of evidence on the health effects of perceived discrimination.
We analysed the association between perceived discrimination and
psychological distress, and whether socio-economic disadvantage explains
this association in 15 406 men and 17 922 women in Sweden during 2004. After
adjustment for age and long-term illness, frequent experiences of
discrimination were associated with increased likelihood of psychological
distress. Socio-economic disadvantage explained about 25% of this
association.
Psychiatric and psychosocial predictors of substance use
disorders among adolescents
Authors: Gau Susan S. F. , Chong Mian-Yoon , Yang Pincheng , Yen Cheng-Fang , Liang Kung-Yee , Cheng Andrew T. A.
Published: December 2006

Background

Few studies have prospectively examined psychosocial and psychiatric
predictors of adolescent substance use disorders simultaneously.

Aims

To identify psychosocial and psychiatric predictors of substance use
disorders in adolescence.

Method

School children aged 12 years (s. d. =0. 3) free from any substance use
disorder at grade7(n=428) were assessed in three
consecutive years, using a standardised psychiatric interview. Their
baseline psychosocial information was also collected. The outcome was the
onset age of a substance use disorder. The Cox regression model was used
for data analysis.

Results

The most significant predictive factors for adolescent substance use
disorder included male gender, attention-deficit hyperactivity disorder,
conduct disorder and sibling use of tobacco. Three protective factors
against such morbidity included living in a household with two parents, a
good academic grade at grade 7 and objection to the use of
substances.

Conclusions

Early intervention for disruptive behaviour disorders and specific
psychosocial risk factors might prevent substance use disorders in early
adolescence.
Life stress and depression in a tribal area of
Pakistan
Authors: Husain N. , Chaudhry I. B. , Afridi M. A. , Tomenson B. , Creed F.
Published: December 2006

Background

Depression is common in Pakistan but no research on this subject has been
reported from the North West Frontier Province (NWFP), host to numerous
Afghan refugees.

Aims

To measure depressive symptoms and associated features in a
population-based sample.

Method

A Pushto translation of the Self Reporting Questionnaire (SRQ) was
administered to 471 adults living in a village in one of the federally
administered tribal areas. Respondents were also assessed with a life
events checklist for social problems, a social support questionnaire and
the Brief Disability Questionnaire.

Results

Sixty per cent (95/158) of women and 45% (140/313) of men scored 9 or
more on the SRQ. High SRQ score was associated with few years of
education, higher social problem score, less social support and greater
disability. High social problem score was the strongest correlate.

Conclusions

This population reports more depressive symptoms than other communities
in Pakistan and this probably reflects the very high degree of social
stress experienced in the NWFP, which has been affected by years of
turmoil in neighbouring Afghanistan.
Changes in regional cerebral blood flow during acute electroconvulsive therapy in patients with depression
Authors: Takano Harumasa , Motohashi Nobutaka , Uema Takeshi , Ogawa Kenichi , Ohnishi Takashi , Nishikawa Masami , Kashima Haruo , Matsuda Hiroshi
Published: December 2006

Background

Although electroconvulsive therapy (ECT) is widely used to treat psychiatric disorders such as depression, its precise neural mechanisms remain unknown.

Aims

To investigate the time course of changes in cerebral blood flow during acute ECT.

Method

Cerebral blood flow was quantified serially prior to, during and after acute ECT in six patients with depression under anaesthesia using [15O]H2O positron emission tomography (PET).

Results

Cerebral blood flow during ECT increased particularly in the basal ganglia, brain-stem, diencephalon, amygdala, vermis and the frontal, temporal and parietal cortices compared with that before ECT. The flow increased in the thalamus and decreased in the anterior cingulate and medial frontal cortex soon after ECT compared with that before ECT.

Conclusions

These results suggest a relationship between the centrencephalic system and seizure generalisation. Further, they suggest that some neural mechanisms of action of ECT are mediated via brain regions including the anterior cingulate and medial frontal cortex and thalamus.