bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Transient Outward Currents Coupled With Ca2+-Induced Ca2+Release Mediates Oscillatory Membrane Potential in Ascidian Muscle Cells
Authors: Nakajo Koichi , Okamura Yasushi
Published: April 2004

Isolated ascidian Halocynthia roretzi blastomeres of the muscle lineage exhibit muscle cell-like excitability on differentiation despite the arrest of cell cleavage early in development. This characteristic provides a unique opportunity to track changes in ion channel expression during muscle cell differentiation. Here, we show that the intrinsic membrane property of ascidian cleavage-arrested muscle-type cells becomes oscillatory by expressing transient outward currents ( Ito) activated by Ca2+-induced Ca2+release (CICR) in a maturation-dependent manner. In current-clamp mode, most day 4 (72 h after fertilization) cleavage-arrested muscle cells exhibited an oscillatory membrane potential of –20 mV at 15 Hz, whereas most day 3 (48 h after fertilization) cells exhibited a spiking pattern. In voltage-clamp mode, the day 4 cells exhibited prominent transient outward currents that were not present in day 3 cells. Itowas abolished by the application of 10 mM caffeine, implying that CICR was involved in Itoactivation. Itowas based on K+efflux and sensitive to tetraethylammonium and some Ca2+-activated K+channel inhibitors. We found a 60-pS single channel conductance that was activated by local Ca2+release in ascidian muscle cell. Voltage-clamp recording with an oscillatory waveform as a command pulse showed that CICR-activated K+currents were activated during the falling phase of the membrane potential oscillation. These results suggest that developmental expression of CICR-activated K+current plays a role in the maturation of larval locomotion by modifying the intrinsic membrane excitability of muscle cells.
Potassium Model for Slow (2-3 Hz) In Vivo Neocortical Paroxysmal Oscillations
Authors: Bazhenov M. , Timofeev I. , Steriade M. , Sejnowski T. J.
Published: April 2004

In slow neocortical paroxysmal oscillations, the de- and hyperpolarizing envelopes in neocortical neurons are large compared with slow sleep oscillations. Increased local synchrony of membrane potential oscillations during seizure is reflected in larger electroencephalographic oscillations and the appearance of spike- or polyspike-wave complex recruitment at 2- to 3-Hz frequencies. The oscillatory mechanisms underlying this paroxysmal activity were investigated in computational models of cortical networks. The extracellular K+ concentration ([K+]o) was continuously computed based on neuronal K+ currents and K+ pumps as well as glial buffering. An increase of [K+]o triggered a transition from normal awake-like oscillations to 2- to 3-Hz seizure-like activity. In this mode, the cells fired periodic bursts and nearby neurons oscillated highly synchronously; in some cells depolarization led to spike inactivation lasting 50–100 ms. A [K+]o increase, sufficient to produce oscillations could result from excessive firing (e.g., induced by external stimulation) or inability of K+ regulatory system (e.g., when glial buffering was blocked). A combination of currents including high-threshold Ca2+, persistent Na+ and hyperpolarization-activated depolarizing ( Ih) currents was sufficient to maintain 2- to 3-Hz activity. In a network model that included lateral K+ diffusion between cells, increase of [K+]o in a small region was generally sufficient to maintain paroxysmal oscillations in the whole network. Slow changes of [K+]o modulated the frequency of bursting and, in some case, led to fast oscillations in the 10- to 15-Hz frequency range, similar to the fast runs observed during seizures in vivo. These results suggest that modifications of the intrinsic currents mediated by increase of [K+]o can explain the range of neocortical paroxysmal oscillations in vivo.
Novel slc22 transporter homologs in fly, worm, and human clarify the phylogeny of organic anion and cation transporters
Authors: Eraly Satish A. , Monte Julio C. , Nigam Sanjay K.
Published: April 2004

Slc22 family organic anion and cation transporters (OATs, OCTs, and OCTNs) are transmembrane proteins expressed predominantly in kidney and liver. These proteins mediate the uptake or excretion of numerous physiologically (and pharmacologically) important compounds, and accordingly have been the focus of intensive study. Here we investigate the molecular phylogeny of the slc22 transporters, identifying homologs in Drosophila and C. elegans, several of which are developmentally regulated, as well as reporting the cloning of a novel human family member, UST6, expressed exclusively in liver in both embryo and adult. The latter helps define a subfamily within the OATs, which appears to have human- and rodent-specific members, raising potential issues with respect to the use of rodents as models for the transport of organic anions (which include many pharmaceuticals) in humans. Although this phylogenetic inference could not be made on the basis of sequence alignment, analysis of intron phasing suggests that the OAT, OCT, and OCTN lineages of the slc22 family formed after the divergence of vertebrates and invertebrates. Subsequently, these lineages expanded through independent tandem duplications to produce multiple gene pairs. After analyzing over 200 other transporter genes, we find such pairing to be relatively specific to vertebrate organic anion and cation transporters, suggesting selection for gene pairing operating within this family in particular. This might reflect a requirement for redundancy or broader substrate specificity in vertebrates (compared to invertebrates), due to their greater physiological complexity and thus potentially broader exposure to organic ions.
Lack of Interleukin-1 Receptor Antagonist Modulates Plaque Composition in Apolipoprotein E–Deficient Mice
Authors: Isoda Kikuo , Sawada Shojiro , Ishigami Norio , Matsuki Taizo , Miyazaki Koji , Kusuhara Masatoshi , Iwakura Yoichiro , Ohsuzu Fumitaka
Published: April 2004

Objective—Interleukin (IL)-1 plays an important role in atherosclerosis. IL-1 receptor antagonist (IL-1Ra) is an endogenous inhibitor of IL-1. However, the role of IL-1Ra in the development of atherosclerosis is poorly understood.

Methods and Results—Mice that lacked IL-1Ra (IL-1Ra−/−) were crossed with apolipoprotein E-deficient (E−/−) mice and formation of atherosclerotic lesions was analyzed after 16 weeks or 32 weeks consumption of a normal chow diet. This study focused on the comparison of atherosclerotic lesion between IL-1Ra+/+/apoE−/− (n=12) and IL-1Ra+/−/apoE−/− mice (n=12), because of the significantly leaner phenotype in IL-1Ra−/−/apoE−/− mice compared with the others. Interestingly, atherosclerotic lesion size in IL-1Ra+/−/apoE−/− mice at age 16 weeks was significantly increased (30%) compared with IL-1Ra+/+/apoE−/− mice (P<0.05). At 32 weeks, the differences of lesion size between these mice failed to achieve statistical significance. However, immunostaining demonstrated an 86% (P<0.0001) increase in the MOMA-2–stained lesion area of IL-1Ra+/−/apoE−/− mice. In addition, α-actin staining in these lesions was significantly decreased (−15%) compared with those in IL-1Ra+/+/apoE−/− mice (P<0.05).

Conclusions—These results suggest an important role of IL-1Ra in the suppression of lesion development during early atherogenesis and furthermore indicate its role in the modulation of plaque composition.
In Vivo Molecular Imaging of Acute and Subacute Thrombosis Using a Fibrin-Binding Magnetic Resonance Imaging Contrast Agent
Authors: Botnar René M. , Perez Alexandra S. , Witte Sonia , Wiethoff Andrea J. , Laredo James , Hamilton James , Quist William , Parsons Edward C. , Vaidya Anand , Kolodziej Andrew , Barrett John A. , Graham Philip B. , Weisskoff Robert M. , Manning Warren J. , Johnstone Michael T.
Published: April 2004

Background—

Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis.

Methods and Results—

Fifteen male New Zealand White rabbits (weight, ≈3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell’s viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as “hot spots” after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology.

Conclusions—

We demonstrate the feasibility of in vivo “molecular” MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.
Transforming Growth Factor-β-Induced Differentiation of Smooth Muscle From a Neural Crest Stem Cell Line
Authors: Chen Shiyou , Lechleider Robert J.
Published: April 2004

During vascular development, nascent endothelial networks are invested with a layer of supporting cells called pericytes in capillaries or smooth muscle in larger vessels. The cellular lineage of smooth muscle precursors and factors responsible for regulating their differentiation remain uncertain. In vivo, cells derived from the multipotent neural crest can give rise to vascular smooth muscle in parts of the head and also the cardiac outflow tract. Although transforming growth factor-β (TGF-β) has previously been shown to induce some smooth muscle markers from primary cultures of neural crest stem cells, the extent of the differentiation induced was not clear. In this study, we demonstrate that TGF-β can induce many of the markers and characteristics of vascular smooth muscle from a neural crest stem cell line, Monc-1. Within 3 days of in vitro treatment, TGF-β induces multiple smooth muscle-specific markers, while downregulating epithelial markers present on the parent cells. Treatment with TGF-β also induces a contractile phenotype that responds to the muscarinic agonist carbachol and is not immediately reversed on TGF-β withdrawal. Examination of the signaling pathways involved revealed that TGF-β activation of Smad2 and Smad3 appear to be essential for the observed differentiation. Taken together, this system provides a novel model of smooth muscle differentiation that reliably recapitulates the process observed in vivo and allows for dissection of the pathways and processes involved in this process.
Essential Role of PDGFRα-p70S6K Signaling in Mesenchymal Cells During Therapeutic and Tumor Angiogenesis In Vivo
Authors: Tsutsumi Norifumi , Yonemitsu Yoshikazu , Shikada Yasunori , Onimaru Mitsuho , Tanii Mitsugu , Okano Shinji , Kaneko Kazuhiro , Hasegawa Mamoru , Hashizume Makoto , Maehara Yoshihiko , Sueishi Katsuo
Published: April 2004

Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-α (PDGFRα)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor-free assay system, we demonstrated that p70S6K inhibitor rapamycin (RAPA) targets mesenchymal cells to shut down the sustained expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via silencing of the PDGFRα-p70S6K pathway. Irrespective of the varied expression profiles of angiogenic factors in each tumor tested, RAPA constantly led the tumors to dormancy and severe ischemia in the time course, even associated with upregulated expression of VEGF from tumors. Because RAPA showed only a minimal effect to hypoxia-related expression of VEGF in culture, these results suggest that RAPA targets the host-vasculature rather than tumor itself in vivo. Thus, our current study indicates that the PDGFRα-p70S6K pathway is an essential regulator for FGF-2–mediated therapeutic neovascularization, as well as for the host-derived vasculature but not tumors during tumor angiogenesis, via controlling continuity of expression of multiple angiogenic growth factors.
Using Avida to Test the Effects of Natural Selection on Phylogenetic Reconstruction Methods
Authors: Hagstrom George I. , Hang Dehua H. , Ofria Charles , Torng Eric
Published: April 2004

Phylogenetic trees group organisms by their ancestral relationships. There are a number of distinct algorithms used to reconstruct these trees from molecular sequence data, but different methods sometimes give conflicting results. Since there are few precisely known phylogenies, simulations are typically used to test the quality of reconstruction algorithms. These simulations randomly evolve strings of symbols to produce a tree, and then the algorithms are run with the tree leaves as inputs. Here we use Avida to test two widely used reconstruction methods, which gives us the chance to observe the effect of natural selection on tree reconstruction. We find that if the organisms undergo natural selection between branch points, the methods will be successful even on very large time scales. However, these algorithms often falter when selection is absent.
WHEN NATURAL PHENOMENA ENTER THE SYMBOLIC SPHERE: AN ECOLOGICAL PERSPECTIVE ON RITUAL TEXTS WITHIN THE EGYPTIAN FUNERARY CULT
Authors: Meyer-Dietrich Erika
Published: April 2004

This article presents a new approach in the study of the ecology of religion. Single ecological factors that appear as subject matter in religious sources are analyzed as factors in the religious world. The symbolic value is applied to environmental factors through ritualization. The natural phenomenon of the inundation of the river Nile was a regular event in ancient Egypt. To investigate the reproduction and use of this ecological factor in religious ritual a model has been developed called "The Dynamic Ecology of Religion." This model and its theoretical and hermeneutical basis are outlined, some methodological considerations are made, and the explanatory value of the model discussed.
Does the urban environment cause psychosis?
Authors: Van Os Jim
Published: March 2004

The paper by Sundquist et al is a welcome addition to a growing body of evidence linking exposures in the urban environment to the onset of schizophrenia (Sundquist et al, 2004, this issue). They also report, in agreement with the literature, that a similar association exists for depression of severity requiring hospital admission, albeit of a much lower effect size than that for schizophrenia and with the caveat that only in a small and biased proportion of cases is the person with clinical depression ever admitted to hospital. The paper represents a truly prospective analysis, and also considers confounding by other important demographic variables and changing exposure status over the period of observation.
International and regional variation in the prevalence of common mental disorders: do we need more surveys?
Authors: Weich Scott , Araya Ricardo
Published: March 2004

Vicente and his colleagues present admirably concise findings from a large epidemiological survey of non-psychotic psychiatric morbidity in four different geographical locations in Chile (Vicente et al, 2004, this issue). Without gainsaying the importance of psychiatric morbidity in that country, many readers, including local decision-makers, may find it difficult to assimilate these results.
Mental health services for adults with learning disabilities
Authors: Bouras Nick , Holt Geraldine
Published: March 2004

Services for people with learning disabilities have been transformed since the late 1960s by the move from institutional to community care. (Learning disabilities is the term currently used in the UK in preference to mental retardation, developmental disabilities and mental handicap.) Important changes include the progress towards integration, participation, inclusion and choice for people with learning disabilities, which have occurred in the context of the broader civil and human rights movements. It is time to examine the services delivered to people with learning disabilities and comorbid psychiatric disorders (mental illness, personality disorders, behavioural problems with aggression) and the evidence for their effectiveness.
Urbanisation and incidence of psychosis and depression
Authors: Sundquist Kristina , Frank Gölin , Sundquist Jan
Published: March 2004

Background

Previous studies of differences in mental health between urban and rural populations are inconsistent.

Aims

To examine whether a high level of urbanisation is associated with increased incidence rates of psychosis and depression, after adjustment for age, marital status, education and immigrant status.

Method

Follow-up study of the total Swedish population aged 25–64 years with respect to first hospital admission for psychosis or depression. Level of urbanisation was defined by population density and divided into quintiles.

Results

With increasing levels of urbanisation the incidence rates of psychosis and depression rose. In the full models, those living in the most densely populated areas (quintile 5) had 68–77% more risk of developing psychosis and 12–20% more risk of developing depression than the reference group (quintile 1).

Conclusions

A high level of urbanisation is associated with increased risk of psychosis and depression for both women and men.
Cognitive therapy for command hallucinations: randomised controlled trial
Authors: Trower Peter , Birchwood Max , Meaden Alan , Byrne Sarah , Nelson Angela , Ross Kerry
Published: March 2004

Background

Command hallucinations are a distressing and high-risk group of symptoms that have long been recognised but little understood, with few effective treatments. In line with our recent research, we propose that the development of an effective cognitive therapy for command hallucinations (CTCH) would be enhanced by applying insights from social rank theory.

Aims

We tested the efficacy of CTCH in reducing beliefs about the power of voices and thereby compliance, in a single-blind, randomised controlled trial.

Method

A total of 38 patients with command hallucinations, with which they had recently complied with serious consequences, were allocated randomly to CTCH or treatment as usual and followed up at 6 months and 12 months.

Results

Large and significant reductions in compliance behaviour were obtained favouring the cognitive therapy group (effect size=1.1). Improvements were also observed in the CTCH but not the control group in degree of conviction in the power and superiority of the voices and the need to comply, and in levels of distress and depression. No change in voice topography (frequency, loudness, content) was observed. The differences were maintained at 12 months' follow-up.

Conclusions

The results support the efficacy of cognitive therapy for CTCH.
Expressed emotion at first-episode psychosis: investigating a carer appraisal model
Authors: Raune D. , Kuipers E. , Bebbington P. E.
Published: March 2004

Background

Even at the first episode of psychosis, high expressed emotion (EE) characterises over half of patient–carer relationships. This study compared a carer appraisal model of EE with the ability of illness factors to predict EE at the first episode.

Aims

To investigate the utility of a carer appraisal model of EE in first-episode psychosis.

Method

We compared high- and low-EE carers of people who had first-episode psychosis (n=46).

Results

High EE in carers was associated with higher avoidant coping, higher subjective burden and lower perceived patient interpersonal functioning. Patient illness factors and carers ‘distress levels were not associated with EE.

Conclusions

Even at the first episode, carers' psychological appraisal, not patient illness factors, is influential in determining high EE. Carers ‘appraisal of their situation should be a primary target to lower or prevent high EE in early intervention for psychosis.
Psychosis and academic performance
Authors: Karlsson Jon L.
Published: March 2004

Background

It has been suggested that psychosis genes might be associated with beneficial effects, explaining their high frequency in all human populations.

Aims

To test the relationship between academic success and the incidence of psychotic disorders.

Method

The unusually complete demographic and scholastic records available in Iceland were used to locate academically accomplished individuals and assess the probability of previously identified patients with mental disorders and their relatives being among such groups.

Results

Close relatives of successful students showed increased risks of psychosis. Individuals who subsequently developed psychosis and relatives of people with psychosis excelled in school performance, particularly in mathematics.

Conclusions

The study supports the hypothesis that stimulation associated with psychotic tendencies enhances performance in academic settings.
Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone
Authors: Tohen Mauricio , Chengappa K. N. Roy , Suppes Trisha , Baker Robert W. , Zarate Carlos A. , Bowden Charles L. , Sachs Gary S. , Kupfer David J. , Ghaemi S. Nassir , Feldman Peter D. , Risser Richard C. , Evans Angela R. , Calabrese Joseph R.
Published: March 2004

Background

Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder.

Aims

To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.

Method

Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6–1.2 mmol/l) or valproate (50–125 μg/ml) received lithium or valproate plus either olanzapine 5–20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.

Results

The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy42 days; P=0.023).

Conclusions

Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.
Relapse in schizophrenia: costs, clinical outcomes and quality of life
Authors: Almond Stephen , Knapp Martin , Francois Clement , Toumi Mondher , Brugha Traolach
Published: March 2004

Background

Relapse is one of the most costly aspects of schizophrenia.

Aims

To compare costs, clinical outcomes and quality of life for patients who experienced relapse in schizophrenia with a control group who did not relapse.

Method

Patients were randomly selected from current psychiatric case-loads drawn from urban and suburban areas of Leicester. Differences in costs and outcomes by relapse status in the previous 6 months were examined using parametric and non-parametric tests, and multivariate analysis was used to examine factors associated with relapse and costs.

Results

Costs for the patients who relapsed were over four times higher than those for the non-relapse group. There were few statistically significant differences in clinical and quality of life measures by relapse status. Multivariate analyses suggested some significant correlates of relapse and costs.

Conclusions

The higher costs associated with relapse will be of interest to policy-makers who face difficult choices concerning new but more expensive treatments for patients with schizophrenia.
Unusually persistent complainants
Authors: Lester Grant , Wilson Franzcp Beth , Griffin Lynn , Mullen Paul E.
Published: March 2004

Background

Querulous paranoia may have disappeared from the psychiatric literature, but is it flourishing in modern complaints organisations and the courts? Aims To investigate the unusually persistent complainants who lay waste to their own lives and place inordinate demands and stress on complaints organisations.

Method

Complaints officers completed questionnaires on both unusually persistent complainants and matched controls.

Results

Persistent complainants (distinguished by their pursuit of vindication and retribution) consumed time and resources and resorted to both direct and veiled threats. Attempts to distinguish these people from a control group on the basis of the manner in which their claims were initially managed failed.

Conclusions

Persistent complainants' pursuit of vindication and retribution fits badly with complaints systems established to deliver reparation and compensation. These complainants damaged the financial and social fabric of their own lives and frightened those dealing with their claims. The study suggests methods of early detection and alternative management strategies.
Spontaneous improvement in severe, chronic schizophrenia and its neuropsychological correlates
Authors: Murray G. K. , Leeson V. , McKenna P. J.
Published: March 2004

Cognitive impairment is well established in schizophrenia but its relationship to the course of the illness remains incompletely understood. Here we document two patients with schizophrenia who underwent neuropsychological testing while chronically unwell, and this was repeated after improvement took place. Both patients showed significant recovery of general intellectual function, accompanied by improvements in some but not all areas of neuropsychological function: executive function remained particularly impaired.
Psychiatric complications in patients with severe acute respiratory syndrome (SARS) during the acute treatment phase: a series of 10 cases
Authors: Cheng Sammy Kin-Wing , Tsang Jenny Suk-Kwan , Ku Kwok-Hung , Wong Chee-Wing , Ng Yin-Kwok
Published: March 2004

In February 2003, Hong Kong was hit by a community-wide outbreak of severe acute respiratory syndrome (SARS). During the period of the outbreak, 10 patients with SARS with psychiatric complications were referred to our Consultation and Liaison Psychiatry Team for assessment and management. We found that both the direct and indirect effects of SARS such as symptom severity total isolation during treatment and administration of steroid were probable causes of psychiatric complications. In this paper, we report on the nature of their psychiatric problems, challenges to management and psychiatric treatment strategies used during the acute phase.
Focus on psychiatry in India
Authors: Thara R. , Padmavati R. , Srinivasan T. N.
Published: March 2004

India is a country with a population of over 1 billion, and immense diversity in the languages spoken, levels of literacy, and social and cultural practices. Organising mental health services for this predominantly rural population is indeed a daunting task. Compounding this problem are low budgetary resources, the presence of competing and conflicting healing systems, scarcity of mental health personnel, ‘brain drain’, and the stigma of seeking help for problems related to the mind. This paper looks at the mental health scene in India with respect to services and research. It deals with conditions such as schizophrenia, acute psychoses, minor mental morbidity and drug misuse, highlighting aspects unique to the Indian scene. Indian families exhibit great tenacity in caring for relatives who are ill, and are a great resource in treatment and rehabilitation.
Diet, diabetes and schizophrenia: Review and hypothesis
Authors: Peet Malcolm
Published: March 2004

Background

Diabetes is more common in people with schizophrenia than in the general population.

Aims

To explore the possible reasons for the association between diabetes and schizophrenia.

Method

Diet and other lifestyle factors in patients with schizophrenia were reviewed as risk factors for diabetes.

Results

People with schizophrenia show features of the metabolic syndrome at the onset of illness, before treatment. They also eat a poor diet, take little exercise and have high rates of smoking. Food intake may be increased further by antipsychotic medication. Nutritional factors appear to have a key role in the development of diabetes in patients with schizophrenia and may also affect the outcome and severity of schizophrenia. A common pathway through which diet might contribute to the development of both diabetes and schizophrenia is proposed.

Conclusions

Lifestyle factors may influence outcomes in both diabetes and schizophrenia. Lifestyle interventions are the key to improving the long-term health of people with schizophrenia.
Introduction
Authors: Dinan Timothy G.
Published: March 2004

It has been known for over a century that abnormalities of glucose metabolism are more common in those suffering from certain forms of mental illness (Kasanin, 1926), but only in the past few years has there been any serious attempt to establish the exact nature of the association. We are now in a situation where a great deal of data and opinions have surfaced in a short space of time. In order to bring this body of data into a single forum to debate its significance and – more importantly – to examine how it should influence practice, it was felt appropriate to convene a consensus meeting on diabetes and schizophrenia. The aims of the meeting were to bring a group of interested and informed clinicians and pharmacologists together to present and debate all the currently available data, opinions and practices from around the world that relate to the association between schizophrenia and glucose abnormalities. In order to do this we felt it crucial to involve experts not only in psychiatry but also in diabetology. One of the major roles of the convened group was to give some sort of hierarchical basis to the many types of data that have been published. The prime focus of the group was to agree a consensus statement that would give practising psychiatrists and diabetologists a clear message as to the current state of knowledge, beliefs and potential best practices.
Prevalence of diabetes and impaired glucose tolerance in patients with schizophrenia
Authors: Bushe Chris , Holt Richard
Published: March 2004

Background

A number of studies have examined the prevalence of diabetes mellitus and impaired glucose tolerance in general populations and in those with schizophrenia and other forms of serious mental illness.

Aims

To establish whether it is possible to describe accurately comparative rates of diabetes mellitus and impaired glucose tolerance in populations of people with schizophrenia and those without mental illness.

Method

Review of current literature.

Results

Research published in the pre-neuroleptic era suggested that people with severe mental illness were at increased risk of developing glycaemic abnormalities. Recent studies appear to confirm that the prevalence of diabetes and impaired glucose tolerance may be higher in people with schizophrenia than in the general population, and suggest that patients with schizophrenia have impaired glucose tolerance even before they begin treatment.

Conclusions

Schizophrenia may be a significant and independent risk factor for both diabetes and impaired glucose tolerance. Current data preclude precise estimates of the prevalence of these conditions among people with schizophrenia.
Stress and the genesis of diabetes mellitus in schizophrenia
Authors: Dinan Timothy G.
Published: March 2004

Background

The incidence of diabetes mellitus is higher in patients with schizophrenia than in the general population. Antipsychotic drugs have been implicated in the development of diabetes, but as non-medicated patients with schizophrenia have high rates of diabetes it is likely that factors other than medication are involved.

Aim

To examine the role of stress in the emergence of diabetes mellitus in patients with schizophrenia.

Method

Selective literature review.

Results

A model is developed suggesting that patients with schizophrenia show overactivation of both the hypothalamic–pituitary–adrenal and sympathoadrenal medullary axes, manifested by increased production of cortisol and adrenaline. Both of these hormones are known to be diabetogenic and are proposed as playing a part in the onset of diabetes mellitus in schizophrenia.

Conclusions

Stress has an important role in the onset of schizophrenia and may also play a part in relapse. Further research is needed to clarify the extent to which stress accounts for the genesis of diabetes in such patients.
Metabolic disturbance in first-episode schizophrenia
Authors: Thakore Jogin H.
Published: March 2004

Background

Schizophrenia shortens life, e.g. through suicide and obesity-related diseases such as type 2 diabetes mellitus. It is assumed that medications play a major role, but most of the evidence for this comes from studies poorly controlled for variables such as lifestyle and medication status.

Aims

To determine whether schizophrenia is associated (independently of medication) with the development of certain metabolic disturbances and whether these might be explained by stress axis dysfunction.

Method

Literature review.

Results

Most studies did not control for confounding factors such as previous usage of medication, lifestyle, age and ethnicity. A few conducted in drug-naive patients with first-episode schizophrenia appear to indicate that these patients have higher than expected rates of visceral obesity and impaired fasting glucose concentrations, which may be related to a subtle disturbance of the hypothalamic–pituitary–adrenal axis.

Conclusions

Schizophrenia is independently associated with physical illnesses that have a metabolic signature. Therefore, patients need to have a thorough physical assessment at diagnosis and at regular intervals thereafter. Metabolic disturbances have been found in drug-naïve patients with first-episode illness and may be an inherent part of the illness.
Antipsychotics and diabetes: Review of non-prospective data
Authors: Haddad Peter M.
Published: March 2004

Background

Much of the existing data regarding the relationship between antipsychotic medications and diabetes mellitus are non-prospective.

Aims

To review critically non-prospective studies examining antipsychotic medications as risk factors for diabetes mellitus.

Method

Database and manual searches.

Results

Anecdotal reports indicate that conventional and atypical antipsychotics can cause diabetes mellitus. However, retrospective studies cannot reliably quantify this association, as they do not adequately control for confounding risk factors for diabetes, or for variation in detection and diagnosis of this illness. Most studies report a higher rate of diabetes in patients who use antipsychotic medication than in non-users, and in patients taking atypical v. conventional antipsychotics. Studies assessing the relative risks of diabetes between individual atypical antipsychotics are contradictory.

Conclusions

Retrospective data are of limited value. Well-designed prospective studies, which account for potential confounders, are needed to investigate the true association between antipsychotic medications and diabetes.
Association between atypical antipsychotic agents and type 2 diabetes: Review of prospective clinical data
Authors: Bushe Chris , Leonard Brian
Published: March 2004

Background

Most evidence suggesting an association between schizophrenia, antipsychotic medications and diabetes has been based on retrospective studies not controlled for important confounders.

Aims

To compare diabetogenic risk between antipsychotic medications; and to describe the limitations of current prospective data-sets.

Method

Systematic review of prospective clinical data.

Results

No difference in the incidence of glycaemic abnormalities between placebo cohorts and antipsychotic medication cohorts was identified. No significant difference between any of the antipsychotic medications studied in terms of their association with glycaemic abnormalities was identified. Treatment-related weight gain did not appear to increase the risk of developing diabetes.

Conclusions

Diabetogenic potential ascribed to atypical antipsychotic drugs, resulting from retrospective studies, may be incorrect. Cohort sizes and incomplete sampling must preclude any definitive conclusions. Long-term, large, comparative prospective trials are needed, along with agreement upon glucose measurement of choice.
Retrospective analysis of risk factors in patients with treatment-emergent diabetes during clinical trials of antipsychotic medications
Authors: Cavazzoni Patrizia , Mukhopadhyay Nitai , Carlson Christopher , Breier Alan , Buse John
Published: March 2004

Aims

In this retrospective analysis, we assessed the short-term risk of treatment-emergent diabetes (TED) among patients with schizophrenia during clinical trials of antipsychotic medications.

Method

From a non-diabetic cohort of patients with schizophrenia (n=5013), the relationship between baseline non-fasting glucose measurement, presence at baseline of risk factors for diabetes, weight gain and therapy assignment on the risk of treatment-emergent diabetes were assessed.

Results

At the baseline assessment, about a third of patients identified with TED during treatment had non-fasting glucose levels over 7.8 mmol/l and two-thirds had multiple diabetes risk factors. Both baseline non-fasting glucose level and the presence of multiple pre-existing diabetes risk factors appeared to have a major impact on the risk of developing diabetes.

Conclusions

Overall, risk factors for diabetes in patients with schizophrenia overlap those in the general population. The results also suggest that many patients identified with TED might have had pre-existing glycaemic abnormalities or a high baseline burden of diabetes risk factors.
Universal rights and mental illness in Ireland
Authors: Rush Gavin , Lyons Declan
Published: March 2004

The human rights group Amnesty International has recently expanded the range of rights it promotes to include the right of persons with mental illness to enjoy the best available mental health care. The Irish section of Amnesty has launched a report and promotional campaign on the rights of persons with mental illness, using internationally recognised norms of best practice reflected in international conventions that generate binding legal obligations of the Irish state. The report is critical of piecemeal reforms and inadequate resourcing of mental health services, and calls for a more comprehensive implementation of the recommendations of domestic and international reports.
Cognitive therapy training for psychiatrists: impact on individual clinical practice
Authors: Swift G. , Durkin I. , Beuster C.
Published: March 2004

Aims and Method

We aimed to survey how psychiatrists with in-depth training in cognitive therapy use these skills. A postal questionnaire based on a previous survey was sent to all psychiatrists who are accredited members of the British Association for Behavioural and Cognitive Psychotherapies.

Results

There was a 94% response rate. Psychiatrists in non-psychotherapy posts used formal cognitive therapy, with an average of 20% of new patients compared with 65% for those in psychotherapy posts, and were less satisfied with the extent to which they were able to use their skills (20%v. 80%). A total of 85% of respondents described themselves as being involved in teaching, training and supervision of cognitive therapy.

Clinical Implications

Unless psychiatrists are planning on working in specialised psychotherapy posts, they are unlikely to use cognitive therapy training in formal therapy sessions. Further research is needed to determine whether cognitive therapy training for psychiatrists translates into improved outcomes for patients.
Domiciliary phlebotomy for elderly people with mental illness
Authors: Darley Malcolm , Siller Catherine , Anderson David
Published: March 2004

Aims and Method

This paper reports the evaluation of a pilot domiciliary phlebotomy service provided by an old age psychiatry service to enhance the management of patients in their own homes. Clinical and demographic data were collected and the costs of phlebotomy home visits compared with those of ambulance transport.

Results

Of 511 phlebotomy visits made to 307 patients, only 8% were unsuccessful. A subgroup analysis indicated that 70% of patients would have been unable to leave home unaccompanied to attend for venepuncture. The cost of the phlebotomist's travel was comparable with the estimated cost of providing ambulance transport for patients who would have required it.

Clinical Implications

Domiciliary phlebotomy can be a viable method of performing blood investigations in an old age psychiatry service to support home assessment.
Trainee psychiatrists' assessment outcomes
Authors: Tunbridge Michael , Dickinson David , Swan Pauline
Published: March 2004

Aims and Method

The Record of In-Training Assessment grades of all registrars in the psychiatric specialties in the UK were analysed for each of three successive years, specialty by specialty, and compared with the average outcome for registrars in all disciplines over the same period.

Results

Over 98% of psychiatry registrars were assessed as satisfactory, 1.2% needed targeted training and 0.7% were graded as unsatisfactory, requiring repeat training. Targeted training and repeat training led to a satisfactory outcome in the majority of cases.

Clinical Implications

The process of assessment needs to become more objective, and should do so as the Royal Colleges develop better measures of clinical competence.
The Disability Discrimination Act 1995 and psychiatry: lessons from the first seven years
Authors: Glozier Nick
Published: March 2004

Aims and Method

To extract relevant information for clinicians from reported and/or accessible cases involving psychiatric illness brought under the Disability Discrimination Act 1995 (DDA). Institutional databases were searched for DDA cases and relevant guidance from case law extracted.

Results

Over half the cases reaching higher courts involve psychiatric illness. A number of decisions provide guidance for clinicians wishing to aid their own patients, and those involved as expert witnesses. These cover which conditions are included as impairments (almost everything in ICD–10), what associated effects are to be considered, and the relevance of comorbidity and treatment. Cases often involve recovery of clinical documents that reveal interesting variation in professional standards.

Clinical Implications

Virtually all patients of psychiatrists in secondary care would be covered by the DDA. Knowledge of this Act could be used to enhance a patient's access to employment and services, and potentially overcome some of the effects of stigmatisation.
Retirement intentions of older consultant psychiatrists
Authors: Mears Alex , Kendall Tim , Katona Cornelius , Pashley Carole , Pajak Sarah
Published: March 2004

Aims and Method

This survey gathered data on the retirement intentions of consultant psychiatrists over the age of 50 years, in order to address retention issues. A questionnaire was sent to all 1438 consultants over this age in the UK.

Results

A total of 848 questionnaires were returned, an adjusted response rate of 59%. The mean age at which consultants intended to retire in this sample was 60 years (s.d. 4.16), suggesting a potential loss of 5725 consultant years. Reasons for early retirement are complex: factors encouraging retirement include too much bureaucracy, lack of free time and heavy case-loads; those discouraging retirement include enjoyment of work, having a good team and money. Mental Health Officer status is an important determinant in the decision to retire early.

Clinical Implications

With numerous vacancies in consultant psychiatrist posts throughout the UK, premature retirement is a cause for concern, possibly contributing to an overall reduction in consultant numbers of 5%. Addressing factors that influence consultants' decisions to leave the health service early should form an important part of an overall strategy to increase consultant numbers.
The College's Anti-Stigma Campaign, 1998–2003
Authors: Crisp Arthur , Cowan Liz , Hart Deborah
Published: March 2004

In autumn 1996, under the Presidency of Dr Robert Kendell, the College decided to mount a campaign to tackle the stigmatisation of people with mental illnesses. In 1997, a working party proposed goals, content, process and a 5-year governance. Other campaigns, both here and abroad, have either generically addressed ‘mental health problems' (e.g. Mind's ‘Respect’ Campaign) or targeted a specific mental illness, e.g. the World Psychiatric Association's anti-stigma campaign in respect of people with schizophrenia. Our working party decided that it might be timely to recognise the differences in public attitudes to the variety of mental illnesses. The campaign thus addressed six categories of mental illness: anxiety disorders, depressive disorders, schizophrenia, the dementias, eating disorders, and drug and alcohol misuse/addiction. Target populations were identified as doctors, children and adolescents, the workplace, the media and the general public. The working party had also secured funding and arranged for a survey, in July 1998, by the Office for National Statistics of opinions of the British public concerning people with these mental illnesses (Crisp et al, 2000). The Campaign started on 7 October 1998. Since that time, and drawing upon our survey findings within its initial literature review (Kelly, 1999) the Department of Health mounted its own anti-stigma campaign, ‘Mind Out for Mental Health’, which addressed a similar range of mental illnesses.
Establishing a clinical database for hospital attendances because of self-harm
Authors: Horrocks Judith , House Allan , Owens David
Published: March 2004

Self-harm is a major risk factor for suicide (Gunnell & Frankel, 1994) with around a quarter of suicides preceded by non-fatal self-harm in the previous year (Owens & House, 1994). Strategies for suicide prevention should include accurate monitoring of health service contacts due to self-harm. Unfortunately, the published literature points to few practical steps for ensuring this accuracy. We offer an account of running a database, to assist others who might be setting out on this monitoring process.
Castles in the air: civilian trainee experiences with the RAF
Authors: Murray Brian
Published: March 2004

It is a little-known fact that specialist registrar training allows an elective period of up to 3 months without affecting a trainee's Certificate of Completion of Specialist Training (CCST). The Postgraduate Dean for Oxford had discussed the idea of such an elective scheme with the military and I therefore saw in the elective an opportunity to do something different before becoming a consultant. As an ex-member of the Territorial Army, my wife was very supportive and encouraged me by telling me that I would never withstand the rigours of a military lifestyle.