bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased Levels of Cytochrome P450 2E1–Derived Eicosanoids Sensitize Renal Arteries to Constrictor Agonists in Spontaneously Hypertensive Rats
Authors: Zhang Fan , Deng Huan , Kemp Rowena , Singh Harpreet , Gopal Venkat Raj , Falck John R. , Laniado-Schwartzman Michal , Nasjletti Alberto
Published: November 2004

We compared renal interlobar arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in terms of cytochrome P450 (CYP) 4A and CYP2E1 protein expression; levels of 20-HETE, 19-HETE, and 18-HETE; and responsiveness to phenylephrine in the absence and presence of
N-
methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; 30 μmol/L), a CYP4A inhibitor. Relative to data in WKY, arteries of SHR exhibited diminished (
P
<0.05) CYP2E1 and levels of 19-HETE (66.7±6.0 versus 44.9±2.8 pmol/mg) and 18-HETE (13.8±1.6 versus 7.9±0.5 pmol/mg), whereas CYP4A and 20-HETE levels (99.3±9.1 versus 98.9±12.8 pmol/mg) were unchanged. Phenylephrine contracted vascular rings of SHR and WKY; the R
max
was similar in both strains, but SHR vessels were more sensitive as denoted by the lower (
P
<0.05) EC
50
(0.28±0.07 versus 0.71±0.12 μmol/L). DDMS decreased 20-HETE and, to a lesser extent, 19-HETE, while increasing (
P
<0.05) the EC
50
for phenylephrine by 475% and 54% in vessels of SHR and WKY, respectively. The desensitizing effect of DDMS was reversed by 20-HETE. Notably, the minimal concentration of 20-HETE that decreased the EC
50
for phenylephrine in DDMS-treated vessels was smaller in SHR (0.1 μmol/L) than WKY (10 μmol/L), and the sensitizing effect of 20-HETE was blunted (
P
<0.05) by the (R) stereoisomers of 19-HETE and 18-HETE. We conclude that the increased sensitivity to phenylephrine in arteries of SHR is attributable to a vasoregulatory imbalance produced by a deficit in vascular CYP2E1-derived products, most likely 19(R)-HETE and 18(R)-HETE, which condition amplification of the sensitizing action of 20-HETE.
Relations of Serum Uric Acid to Longitudinal Blood Pressure Tracking and Hypertension Incidence
Authors: Sundström Johan , Sullivan Lisa , D’Agostino Ralph B. , Levy Daniel , Kannel William B. , Vasan Ramachandran S.
Published: November 2004

Serum uric acid (UA) has been implicated in the pathogenesis of hypertension. We investigated the relationship of serum UA to hypertension incidence and blood pressure (BP) progression in 3329 Framingham Study participants (mean age 48.7 years; 55.6% women) free of hypertension, myocardial infarction, heart failure, renal failure, or gout. At follow-up 4 years from baseline, 458 persons (13.8%) had developed hypertension, and 1201 persons (36.1%) had experienced progression to a higher BP stage. Age- and sex-adjusted rates of hypertension incidence increased progressively from 9.8% for the lowest quartile to 15.6% for the top quartile of serum UA; BP progression rates increased from 32.8% (lowest quartile) to 39.6% (top quartile). In multivariable analyses adjusting for age, sex, body mass index, diabetes, smoking, alcohol intake, serum creatinine, proteinuria, glomerular filtration rate, baseline BP, and interim weight change, a 1 SD higher serum UA was associated with an odds ratio (OR) of 1.17 (95% confidence interval [CI], 1.02 to 1.33) for developing hypertension, and an OR of 1.11 (95% CI, 1.01 to 1.23) for BP progression. In analyses of a subsample of 3157 individuals not on antihypertensive treatment at the follow-up examination, serum UA was positively associated with changes in systolic (
P
=0.02) and diastolic pressure 4 years later (
P
=0.04). In summary, serum UA level was an independent predictor of hypertension incidence and longitudinal BP progression at short-term follow-up in our community-based sample.
Stroke Unit Care and Outcome
Authors: Rudd A.G. , Hoffman A. , Irwin P. , Lowe D. , Pearson M.G.
Published: November 2004

Background and Purpose—

Stroke unit care is one of the most powerful interventions available to help stroke patients. There are limited data available to assess the impact of stroke units in routine clinical practice outside randomized clinical trials. This article uses data from the 2001 to 2002 National Stroke Audit to assess the effectiveness of stroke unit care in England, Wales, and Northern Ireland in delivering effective processes of care and in reducing case fatality and disability.

Methods—

An observational study of the organization, structure, process of care, and outcomes for stroke in 2001. Case fatality after stroke in England was compared using data from the audit and routinely collected data from the Department of Health. 240 hospitals (196 Trusts) from England, Wales, and Northern Ireland took part in the 2001 to 2002 National Stroke Audit, a response rate of >95%. These sites assessed a total of 8200 patients using the Royal College of Physicians Intercollegiate Working Party Stroke Audit Tool.

Results—

The availability of stroke unit care varies hugely across the country. Case fatality after stroke was higher in Trusts with least availability of stroke unit care. These differences persisted after control for case mix. The process of care was better for patients managed on stroke units compared with other settings. Overall, the risk of death for patients who received stroke unit care was estimated to be ≈75% that of the risk for those having no stroke unit care (95% CI, 60 to 90).

Conclusions—

Stroke unit care as provided in routine clinical practice in England, Wales, and Northern Ireland reduces case fatality by ≈25%, which is in line with the figures obtained from systematic analysis of stroke unit trial data.
Representation of Number in Animals and Humans: A Neural Model
Authors: Verguts Tom , Fias Wim
Published: November 2004

This article addresses the representation of numerical information conveyed by nonsymbolic and symbolic stimuli. In a first simulation study, we show how number-selective neurons develop when an initially uncommitted neural network is given nonsymbolic stimuli as input (e.g., collections of dots) under unsupervised learning. The resultant network is able to account for the distance and size effects, two ubiquitous effects in numerical cognition. Furthermore, the properties of the network units conform in detail to the characteristics of recently discovered number-selective neurons. In a second study, we simulate symbol learning by presenting symbolic and nonsymbolic input simultaneously. The same number-selective neurons learn to represent the numerical meaning of symbols. In doing so, they show properties reminiscent of the originally available number-selective neurons, but at the same time, the representational efficiency of the neurons is increased when presented with symbolic input. This finding presents a concrete proposal on the linkage between higher order numerical cognition and more primitive numerical abilities and generates specific predictions on the neural substrate of number processing.
Neural Bases of Cognitive ERPs: More than Phase Reset
Authors: Fell Juergen , Dietl Thomas , Grunwald Thomas , Kurthen Martin , Klaver Peter , Trautner Peter , Schaller Carlo , Elger Christian E. , Fernández Guillén
Published: November 2004

Up to now, two conflicting theories have tried to explain the genesis of averaged event-related potentials (ERPs): Whereas one hypothesis claims that ERPs originate from an event-related activation of neural assemblies distinct from background dynamics, the other hypothesis states that ERPs are produced by phase resetting of ongoing oscillatory activity. So far, this question has only been addressed for early ERP components. Late ERP components, however, are generally thought to represent superimposed activities of several anatomically distinct brain areas. Thus, the question of which mechanism underlies the genesis of late ERP components cannot be easily answered based on scalp recordings. In contrast, two well-investigated late ERP components recorded invasively from within the human medial temporal lobe (MTL) in epilepsy patients, the so-called MTL-P300 and the anterior MTL-N400 (AMTL-N400), are based on single source activity. Hence, we investigated whether the MTL-P300 and the AMTL-N400 are based on an event-related activity increase, a phase reset of ongoing oscillatory activity or both. ERPs were recorded from the hippocampus and rhinal cortex in subjects performing a visual oddball paradigm and a visual word recognition paradigm. With wavelet techniques, stimulus-related phase-locking and power changes were analyzed in a frequency range covering 2 to 48 Hz. We found that the MTLP300 is accompanied by both phase reset and power increase and that both effects overlap partly in time. In contrast, the AMTL-N400 is initially associated with phase locking without power increase and only later during the course of the AMTL-N400 we observed an additional power increase. In conclusion, both aspects, event-related activation of neural assemblies and phase resetting of ongoing activity seem to be involved in the generation of late ERP components as recorded in cognitive tasks. Therefore, separate analysis of event-related power and phase-locking changes might reveal specific insights into the mechanisms underlying different cognitive functions.
Default-Mode Activity during a Passive Sensory Task: Uncoupled from Deactivation but Impacting Activation
Authors: Greicius Michael D. , Menon Vinod
Published: November 2004

Deactivation refers to increased neural activity during low-demand tasks or rest compared with high-demand tasks. Several groups have reported that a particular set of brain regions, including the posterior cingulate cortex and the medial prefrontal cortex, among others, is consistently deactivated. Taken together, these typically deactivated brain regions appear to constitute a default-mode network of brain activity that predominates in the absence of a demanding external task. Examining a passive, block-design sensory task with a standard deactivation analysis (rest epochs vs. stimulus epochs), we demonstrate that the default-mode network is undetectable in one run and only partially detectable in a second run. Using independent component analysis, however, we were able to detect the full default-mode network in both runs and to demonstrate that, in the majority of subjects, it persisted across both rest and stimulus epochs, uncoupled from the task waveform, and so mostly undetectable as deactivation. We also replicate an earlier finding that the default-mode network includes the hippocampus suggesting that episodic memory is incorporated in default-mode cognitive processing. Furthermore, we show that the more a subject's default-mode activity was correlated with the rest epochs (and “deactivated” during stimulus epochs), the greater that subject's activation to the visual and auditory stimuli. We conclude that activity in the default-mode network may persist through both experimental and rest epochs if the experiment is not sufficiently challenging. Time-series analysis of default-mode activity provides a measure of the degree to which a task engages a subject and whether it is sufficient to interrupt the processes—presumably cognitive, internally generated, and involving episodic memory—mediated by the default-mode network.
Reference Frames for Spatial Cognition: Different Brain Areas are Involved in Viewer-, Object-, and Landmark-Centered Judgments About Object Location
Authors: Committeri Giorgia , Galati Gaspare , Paradis Anne-Lise , Pizzamiglio Luigi , Berthoz Alain , LeBihan Denis
Published: November 2004

Functional magnetic resonance imaging was used to compare the neural correlates of three different types of spatial coding, which are implicated in crucial cognitive functions of our everyday life, such as visuomotor coordination and orientation in topographical space. By manipulating the requested spatial reference during a task of relative distance estimation, we directly compared viewer-centered, object-centered, and landmark-centered spatial coding of the same realistic 3-D information. Common activation was found in bilateral parietal, occipital, and right frontal premotor regions.

The retrosplenial and ventromedial occipital–temporal cortex (and parts of the parietal and occipital cortex) were significantly more activated during the landmark-centered condition. The ventrolateral occipital–temporal cortex was particularly involved in object-centered coding. Results strongly demonstrate that viewer-centered (egocentric) coding is restricted to the dorsal stream and connected frontal regions, whereas a coding centered on external references requires both dorsal and ventral regions, depending on the reference being a movable object or a landmark.
Aristotle on the Firmness of the Principle of Non-Contradiction
Authors: Wedin Michael
Published: November 2004

In Metaphysics Gamma 3 Aristotle declares that the philosopher investigates things that are qua things that are and that he therefore should be able to state the firmest principles of everything. The firmest principle of all is identified as the principle of non-contradiction (PNC). The main focus of Gamma 3 is Aristotle's proof for this identification. This paper begins with remarks about Aristotle's notion of the firmness of a principle and then offers an analysis of the firmness proof for PNC. It focuses on some key assumptions of the proof and on the range and force of the proof. Aristotle closes Gamma 3 with the claim that PNC is ultimate in the sense that all other principles somehow rest on it. This, rather controversial, claim is given a defensible reading and shown to be central to the chapter's effort to establish PNC as the firmest principle of all. As such it completes the firmness proof and is not simply an appended remark.
A Chiastic Contradiction at Euthyphro 9e1-11b5
Authors:   Kim
Published: November 2004

One of Euthyphro's proposed de finitions of to hosion says: '[T]he pious is what all the gods love . . .'. Scholarly analyses of Socrates' refutation of this de finition have focused on its validity or even its 'truth'. By contrast, this paper restricts itself to the refutation's logical structure, particularly the way Socrates juxtaposes the agreed-upon premises to derive a double or 'chiastic' contradiction. In this article, I lay out the details of Socrates' ingenious logical construction, without regard to its validity or fallaciousness, and argue that the chiastic contradiction alone makes possible Socrates' refutation of Euthyphro's claim to expertise in the realm of to hosion.
Complex Variable Solutions for an Inhomogeneous Thick Plate Containing a Hole or a Crack
Authors: England A. H.
Published: November 2004

Exact solutions have been found to the equations of elasticity in a thick plate of inhomogeneous isotropic linearly elastic material in which the elastic moduli are known functions of the coordinate normal to the plane of the plate. The upper and lower surfaces of the plate are assumed to be traction free. In a previous paper these solutions were expressed in terms of four complex potentials that are analytic functions of ζ = x + iy, the coordinates in the mid-plane of the plate. Whilst the solutions obtained do not contain enough generality to satisfy the boundary conditions pointwise around the edge of the plate, resultant force and moment conditions or averaged displacements may be specified over the edge of the plate. The intention in this paper is to examine the elastic field in a plate containing a cylindrical hole or a through-thickness line crack under the action of a uniform force field at infinity.
The Derivative of Isotropic Tensor Functions, Elastic Moduli and Stress Rate: I. Eigenvalue Formulation
Authors: Chen Yi-Chao , Dui Guansuo
Published: November 2004

We derive basis-free formulae for the derivative of general isotropic tensor functions of symmetric tensors, and the formulae for elastic moduli and stress rate for compressible isotropic elastic materials. Part I of this paper concerns the tensor functions with the representation of spectral decomposition. The solution is obtained through the directional derivatives on certain subspaces that span the set of symmetric tensors.
Derivatives of the Rotation and Stretch Tensors
Authors: Carroll M. M.
Published: November 2004

Previous work on representing the rotation and stretch tensors, their time derivatives and their gradients with respect to the deformation gradient tensor is reviewed and some new results are presented. The correspondence between rates and gradients leads to a unification and clarification of previous results and to new representations of the gradients.
Ecological associations between asthma prevalence and potential exposure to farming
Authors: Elliott L. , Yeatts K. , Loomis D.
Published: November 2004

Farming and exposure to livestock have been proposed as protective against the development of asthma in children. An ecological study was conducted to examine the support for these relationships in the USA.

County-specific aggregate measures were used to examine the relationship between the prevalence of asthma and wheeze in 7th and 8th grade school children (aged 12–14 yrs) and selected measures of potential exposure to farming in the state of North Carolina. Binomial regression models were fitted to quantify these relationships, with adjustments for parental smoking, socioeconomic status, sex and race. Regression coefficients were reported for an increment of one interquartile range (IQR) in each indicator of exposure.

The prevalence of asthma showed decreasing trends for most indicators of farm exposure. Regression results suggested that the largest decreases in asthma prevalence were associated with the number of farms (−5.0% per IQR increment), acreage of hay (−7.2% per IQR increment) and beef cattle (−7.8% per IQR increment). The pattern of results was similar for wheezing.

In conclusion, the findings of this study are consistent with the hypothesis that certain farm exposures are protective against childhood asthma. Further research with individual-level data is needed to identify the specific protective exposures.
Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension
Authors: Hoeper M.M. , Faulenbach C. , Golpon H. , Winkler J. , Welte T. , Niedermeyer J.
Published: November 2004

It has been proposed that targeted treatments should be combined for patients with idiopathic pulmonary arterial hypertension (IPAH) responding insufficiently to monotherapy.

This study followed the clinical course of nine patients with severe IPAH, in whom the endothelin receptor antagonist bosentan caused transient clinical improvement, eventually followed by a decline in exercise tolerance, who received adjunct treatment with the phospodiesterase-5-inhibitor sildenafil. Measurements included the 6-min walk distance (6MWD) and cardiopulmonary exercise testing (CPET).

The 6MWD at baseline was 346±66 m and improved to 403±80 m 3 months after introduction of bosentan treatment. However, this effect was not sustained and, after an interval of 11±5 months, the walk distance had declined to 277±80 m. At this point, sildenafil was added to bosentan. Three months later, the 6MWD had increased to 392±61 m and the patients remained stable throughout the median follow-up of 9 months (range 6–12). Measurement of the maximum oxygen uptake during CPET confirmed these results. The combination of bosentan and sildenafil was well tolerated by all patients.

These preliminary data suggest that combining bosentan and sildenafil may be safe and effective in patients with idiopathic pulmonary arterial hypertension.
The immune response to resistive breathing
Authors: Vassilakopoulos T. , Roussos C. , Zakynthinos S.
Published: November 2004

Resistive breathing is an “immune challenge” for the body, initiating an inflammatory response consisting of an elevation of plasma cytokines, and the recruitment and activation of lymphocyte subpopulations. These cytokines do not originate from monocytes, but are, instead, produced within the diaphragm, secondary to the increased muscle activation.

Oxidative stress is a major stimulus for the cytokine induction, secondary to resistive breathing. The production of cytokines within the diaphragm may be mediating the diaphragm muscle fibre injury that occurs with strenuous contractions, or contributing towards the expected repair process. These cytokines may also compromise diaphragmatic contractility or contribute towards the development of muscle cachexia. They may also have systemic effects, mobilising glucose from the liver and free fatty acid from the adipose tissue to the strenuously working respiratory muscles. At the same time, they stimulate the hypothalamic-pituitary-adrenal axis, leading to production of adrenocorticotropin and β-endorphins.

The adrenocorticotropin response may represent an attempt of the organism to reduce the injury occurring in the respiratory musclesviathe production of glucocorticoids and the induction of the acute phase-response proteins. The β-endorphin response would decrease the activation of the respiratory muscles and change the pattern of breathing, which becomes more rapid and shallow, possibly in an attempt to reduce and/or prevent further injury to the respiratory muscles.
Assessments for oxygen therapy in COPD: are we under correcting arterial oxygen tensions?
Authors: Dheda K. , Lim K. , Ollivere B. , Leftley J. , Lampe F.C. , Salisbury A. , Dilworth J.P. , Rajakulasingum R.K.
Published: November 2004

There is little data about the use of different oxygen sources during assessment for long-term oxygen therapy (LTOT) and how this impacts upon blood oxygen tensions and prescribed flow rates.

Patients with chronic obstructive pulmonary disease (COPD), n=30, had assessments for LTOT using both an oxygen-concentrator and piped hospital oxygen (wall-oxygen) as supply sources. In addition, a random survey of 64 hospitals was conducted to determine what source of oxygen supply was used during assessments.

Wall-oxygen was used by 89% of hospitals to perform assessments. During assessments, the median oxygen flow required to achieve an arterial oxygen tension (Pa,O2) >8 kPa was significantly greater for an oxygen-concentrator than for wall-oxygen, with a median difference (range) in flow of 1 (0–3) L. This difference was most likely in those with an forced expiratory volume <30% of predicted. At an oxygen flow of 1 L·min−1, the meanPa,O2using an oxygen-concentrator was significantly lower than that of the wall-oxygen value, with a difference of 1.32±1.19 kPa (mean±sd).

The common practice of using wall-oxygen to perform assessments significantly underestimates the required oxygen-concentrator flow rate. This may have implications for the long-term effect of domiciliary oxygen therapy.
Night-to-night variation of the oxygen desaturation index in sleep apnoea syndrome
Authors: Fietze I. , Dingli K. , Diefenbach K. , Douglas N.J. , Glos M. , Tallafuss M. , Terhalle W. , Witt C.
Published: November 2004

The current study investigated the night-to-night variability and diagnostic accuracy of the oxygen desaturation index (ODI), as measured by ambulatory monitoring, in the diagnosis of mild and moderate obstructive sleep apnoea–hypopnoea syndrome.

To assess the variability of the ODI, 35 patients were monitored at home during 7 consecutive nights by means of a portable recording device, the MESAM-IV®. The ODI variability factor and the influence of age, body mass index (BMI), alcohol, and body position were assessed. Furthermore, the diagnostic accuracy of the MESAM-IV was measured by comparison with polysomnographical outcomes in 18 patients.

During home recording, the median ODI was 10.9 (interquartile range: 5.8–16.1) across the patients. Although the reliability of the ODI was adequate, the probability of placing the patient in the wrong severity category (ODI ≤15 or ODI >15) when only one single recording was taken is 14.4%. ODI variability was not significantly influenced by age, BMI, time spent in a supine position, or mild dosages of alcohol. A good correlation was found between the apnoea–hypopnoea index and the ODI.

In conclusion, the findings suggest that the diagnostic accuracy of the MESAM-IV is strong, since the oxygen desaturation index is correlated with the apnoea–hypopnoea index. In most obstructive sleep apnoea–hypopnoea syndrome patients, oxygen desaturation index variability is rather small, and screening could be reliably based on single 1-night recordings.
Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases
Authors: Welker L. , Jörres R.A. , Costabel U. , Magnussen H.
Published: November 2004

The current authors aimed to quantify how the likelihood for a given diagnosis changes with the knowledge of bronchoalveolar lavage (BAL) cell differentials.

As an initial estimate (a prioriprobability), frequencies of final diagnoses were taken. Using categorisations for cell differentials,a posterioriprobabilities were then derived for each disease, according to Bayes. The analysis was performed in three of five groups of diagnoses suspected prior to BAL: interstitial lung disease (ILD; n=710), inflammatory disease (n=583), or lung tumour mimicking ILD (n=455).

Overall, out of 1,971 patients, 18.3% had sarcoidosis, 7.7% usual interstitial pneumonia (UIP), 4.4% extrinsic allergic alveolitis (EAA), and 19.0% tumours. In the group with suspected ILD, the likelihood for sarcoidosis increased from 33.7 to 68.1% when lymphocyte numbers were 30–50% and granulocyte numbers were low; the likelihood for UIP increased from 15.8 to 33.3% when lymphocyte numbers were <30% with granulocytes elevated. CD4/CD8 was informative, especially in sarcoidosis and EAA. Despite considerable increases, the likelihood of rare diseases rarely reached appreciable values. Similar results were obtained in the other two groups of suspected diagnoses.

In conclusion, these data suggest that bronchoalveolar lavage cell countsper seprovide substantial diagnostic information only in relatively frequent diseases, such as sarcoidosis and usual interstitial pneumonia, and are less helpful in infrequent diseases.
The CMRF58 antibody recognizes a subset of CD123hi dendritic cells in allergen-challenged mucosa
Authors: Vuckovic Slavica , Khalil Dalia , Angel Nicola , Jahnsen Frode , Hamilton Iona , Boyce Amanda , Hock Barry , Hart Derek N J
Published: November 2004

CD123hi CD11c− dendritic cells (CD123hi DC) are a distinct subset of human DC present in bone marrow, blood, lymphoid organs, and peripheral tissues. Pathogen stimulation, cytokine, or CD40 ligation induces CD123hi DC maturation, involving a shift from their innate immune to cognate antigen-presenting functions. In this study, we revealed that blood CD123hi DC in the presence of cytokine (granulocyte macrophage-colony stimulating factor and interleukin-3) undergo progressive, step-wise maturation through an “early” stage, delineated by expression of the antigen detected by the new monoclonal antibody CMRF58 (CD123hiCMRF58+CD40−CD86−CD83−) to the “late” stage with costimulatory antigen expression (CD123hiCMRF58+CD40+CD86+CD83+/−). In this early stage, cytokine-maintained CD123hi DC do not display changes in their morphology, no longer produce interferon-α (IFN-α) in response to bacteria, and develop the capacity to induce proliferation and polarization of allogeneic T cells. CD123hiCMRF58+ DC, phenotypically similar to in vitro cytokine-maintained CD123hi DC, were not detected in tonsil but are present in allergen-challenged nasal mucosa of allergic individuals. Thus, CD123hi DC in certain tissue environments such as allergen-challenged nasal mucosa share a common CD123hiCMRF58+ phenotype with in vitro cytokine-maintained blood CD123hi DC characterized by lack of IFN-α production.
Acute and transient psychotic disorders: precursors, epidemiology, course and outcome
Authors: Singh Swaran P. , Burns Tom , Amin Shazad , Jones Peter B. , Harrison Glynn
Published: November 2004

Background

ICD–10 has introduced the diagnostic group acute and transient psychotic disorders (ATPDs; F23). Aims To validate the nosological distinctiveness of ICD–10 ATPDs by following up an inception cohort with first-episode psychosis. Method All patients with first-episode psychosis identified in Nottingham between 1992 and 1994 and diagnosed using ICD–10 criteria were reassessed 3 years later. ATPD outcomes were compared with schizophrenia and affective psychosis. Multivariate analyses were conducted to determine whether acute onset and early remission predicted favourable 3-year outcome in first-episode psychosis. Results Of 168 cases of first-episode psychosis, 32 (19%) received an intake diagnosis of ATPD. The diagnosis of ATPD was stable in women over 3 years, but not in men. Outcomes in ATPD were better than in schizophrenia and similar to affective psychosis. In non-affective psychoses, favourable outcomes were a function of gender and premorbid functioning rather than acute onset and early remission. Conclusions The ICD–10 criteria for ATPDs identify a diagnostically unstable group of disorders. Acute onset and early remission do not independently predict favourable outcome over 3 years in first-episode psychosis.
Rates and predictors of mental illness in gay men, lesbians and bisexual men and women
Authors: Warner James , Mckeown Éamonn , Griffin Mark , Johnson Katherine , Ramsay Angus , Cort Clive , King Michael
Published: November 2004

Background

There is a dearth of research into the mental health of gay men, lesbians and bisexual men and women in the UK.

Aims

To assess rates and possible predictors of mental illness in these groups.

Method

A comprehensive assessment was made of the psychological and social well-being of a sample of gay men, lesbians and bisexual men and women, identified using ‘snowball’ sampling.

Results

Of the 1285 gay, lesbian and bisexual respondents who took part, 556 (43%) had mental disorder as defined by the revised Clinical Interview Schedule (CIS – R). Out of the whole sample, 361 (31%) had attempted suicide. This was associated with markers of discrimination such as recent physical attack (OR=l.7, 95% CI 1.3–2.3) and school bullying (OR=l.4, 95% CI 1.1–2.0), but not with higher scores on the CIS-R.

Conclusions

Gay, lesbian and bisexual men and women have high levels of mental disorder, possibly linked with discrimination.
Factor structure in the Camberwell Assessment of Need
Authors: Wennström Erik , Sörbom Dag , Wiesel Frits-Axel
Published: November 2004

Background

In order to define needs for care of people with severe mental illness, the Camberwell Assessment of Need (CAN) is focused on measuring personal and social functioning. However, previous studies of the CAN have given inconsistent results in terms of what variables are actually being measured.

Aims

To investigate the factor structure of the CAN.

Method

Assessments of 741 out-patients (mean age 45.5 years, 50% females) with severe mental illness (68% schizophrenia or other psychotic disorder) were used in an exploratory maximum likelihood factor analysis.

Results

Support was found for a three-factor model, comprising 13 of the 22 variables in the CAN, with the factors corresponding to functional disability (7 variables), social loneliness (3 variables) and emotional loneliness (3 variables). The remaining variables did not load on any factor.

Conclusions

Exploratory factor analysis revealed three homogeneous dimensions in the CAN that may represent functional disability and two aspects of social health.
Meeting the unmet need for depression services with psycho-educational self-confidence workshops: preliminary report
Authors: Brown June S. L. , Elliott Sandra A. , Boardman Jed , Ferns Joe , Morrison Joanna
Published: November 2004

Background

The prevalence of depression has not fallen despite effective treatments being available.

Aims

To examine the effectiveness of a psycho-educational intervention designed to be easily accessible.

Method

Large-scale, self-referral ‘How to improve your self-confidence’ workshops were run in a leisure centre at weekends. The day-long programme used a cognitive–behavioural approach. A randomised controlled trial design using waiting-list controls was employed. Three months after the workshop, results of workshop participants were compared with those of the waiting list control group.

Results

Among 120 people who self-referred, 75% of participants had General Health Questionnaire scores of 3 and above. Over 39% had never previously consulted their general practitioners about their depression. At 3-month follow-up, members of the experimental group were significantly less depressed, less distressed and reported higher self-esteem.

Conclusions

Workshops were shown to be accessible and effective; a larger, more rigorous trial is now needed.
Temporal course of auditory hallucinations
Authors: Shergill Sukhwinder S. , Brammer Mick J. , Amaro Edson , Williams Steve C. R. , Murray Robin M. , Mcguire Phillip K.
Published: November 2004

We used functional magnetic resonance imaging to examine how brain activity associated with auditory verbal hallucinations in schizophrenia changed during hallucinatory events. Activation in the left inferior frontal and right middle temporal gyri was evident 6–9s before the person signalled the onset of the hallucination, whereas activation in the bilateral temporal gyri and the left insula coincided with the perception of the hallucination. This supports the hypothesis that during hallucinations activation in cortical regions mediating the generation of inner speech may precede the engagement of areas implicated in the perception of auditory verbal material.
Prevalence of personality disorder in the case-load of an inner-city assertive outreach team
Authors: Ranger Maja , Methuen Caroline , Rutter Deborah , Rao Bharti , Tyrer Peter
Published: November 2004

Aims and Method

The aim was to record the prevalence, type and severity of personality disorder dealt with by an inner-city outreach team. Patients on the register of an assertive outreach team were approached and asked to give informed consent for an informant interview with their principal worker to determine their personality status, using the informant-based ICD–10 version of the Personality Assessment Schedule.

Results

Of the 73 patients, 62 (85%) of whom had a psychotic diagnosis, 67 (92%) had at least one personality disorder, with 37 (51%) having complex or severe personality disorders.

Clinical Implications

The findings suggest that the National Service Framework requirements for assertive outreach teams tend to select many patients with comorbid personality disorder in addition to other severe psychiatric disorders.
Systematic Review Evaluating the Timing of Thoracic Radiation Therapy in Combined Modality Therapy for Limited-Stage Small-Cell Lung Cancer
Authors: Fried Daniel B. , Morris David E. , Poole Charles , Rosenman Julian G. , Halle Jan S. , Detterbeck Frank C. , Hensing Thomas A. , Socinski Mark A.
Published: November 2004

Purpose

We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing.

Methods

Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods.

Results

Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS.

Conclusion

A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.
Allele 2 of the Interleukin-1 Receptor Antagonist Gene Is Associated With Early Gastric Cancer
Authors: Glas Jürgen , Török Helga-Paula , Schneider Agnes , Brünnler Günter , Kopp Reinhard , Albert Ekkehard D. , Stolte Manfred , Folwaczny Christian
Published: November 2004

Purpose

In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined.

Patients and Methods

Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene. Statistical analysis was performed using the χ2 test and the Fisher's exact test, respectively.

Results

The homozygous genotype IL-1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer (P < .0001), whereas further associations with the IL-1 gene cluster were not observed. A weak association of the TNF-A−308A allele with the diffuse type of early-stage gastric cancer, and an association with a composite of two or three proinflammatory polymorphisms, which predispose to increased production of the proinflammatory cytokines IL-1β and TNF-α, could also be demonstrated.

Conclusion

The genotype IL-1RN*2/2 seems to be associated with early-stage gastric cancer. As opposed to advanced-stage gastric cancer, further proinflammatory cytokine polymorphisms were not associated independently, but might act in combination and mirror early steps of gastric carcinogenesis in hosts colonized by Helicobacter pylori. However, these findings await confirmation in future trials and should be underscored by gene expression studies.
Randomized Multicenter Phase II Trial of Bolus Plus Infusional Fluorouracil/Leucovorin Compared With Fluorouracil/Leucovorin Plus Oxaliplatin As Third-Line Treatment of Patients With Advanced Colorectal Cancer
Authors: Kemeny Nancy , Garay Carlos A. , Gurtler Jayne , Hochster Howard , Kennedy Peter , Benson Al , Schwab Brandt Debra , Polikoff Jonathan , Wertheim Michael , Shumaker Grace , Hallman Doreen , Burger Brent , Gupta Sunil
Published: November 2004

Purpose

The addition of oxaliplatin to fluorouracil (FU) and leucovorin (LV) improves the outcome of patients with colorectal cancer (CRC). This multicenter study evaluated FU/LV with or without oxaliplatin in patients with metastatic CRC after disease progression on sequential fluoropyrimidine and irinotecan.

Patients and Methods

Two hundred fourteen patients were randomly assigned to receive LV 200 mg/m2 intravenously (IV) and FU 400 mg/m2 IV bolus, followed by FU 600 mg/m2 IV over 22 hours on days 1 and 2, every 2 weeks (LV5FU2); or LV and FU as described, plus oxaliplatin 85 mg/m2 IV over 2 hours on day 1 of the schedule (FOLFOX4). The primary end point was overall response.

Results

Baseline characteristics were similar in the two treatment arms. Objective response (complete + partial) rates for LV5FU2 versus FOLFOX4 were 2% v 13% (P = .0027), respectively. Median time to disease progression was 2.4 v 4.8 months (P < .0001), and median survival was 11.4 v 9.9 months (P = .20) for LV5FU2 and FOLFOX4, respectively. Among the 72 patients who crossed over from LV5FU2 to FOLFOX4, 6% responded. Symptomatic improvement was significantly better for patients in the FOLFOX4 arm (32% v 18% for LV5FU2, P = .05). Grade 3/4 toxicities for LV5FU2 and FOLFOX4 were neutropenia (13% and 42%, respectively), diarrhea (6% and 16%, respectively), and overall neuropathy (0% and 6%, respectively).

Conclusion

In patients with metastatic CRC, the FOLFOX4 regimen was superior to LV5FU2 with a higher response rate and time to disease progression. FOLFOX4 is an effective regimen even after disease progression on two previous chemotherapy regimens with fluoropyrimidines and irinotecan.
Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas
Authors: Kouvaraki Maria A. , Ajani Jaffer A. , Hoff Paulo , Wolff Robert , Evans Douglas B. , Lozano Richard , Yao James C.
Published: November 2004

Purpose

The role of systemic chemotherapy in the management of pancreatic endocrine carcinoma (islet cell carcinoma; PEC) is an area of considerable controversy. Response rates ranging from 6% to 69% have been reported for streptozocin-based chemotherapy. We retrospectively studied 84 patients with locally advanced or metastatic PEC who had been treated with fluorouracil, doxorubicin, and streptozocin (FAS) to determine the objective response rate, duration of progression-free survival (PFS), and duration of overall survival (OS).

Patients and Methods

Eligible patients had histologic or cytologic confirmation of their tumor and measurable disease on computed tomography or magnetic resonance imaging scans. Response to treatment was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee.

Results

Sixty-one of the patients were male and 23 were female, with a median age of 54 years (range, 24 to 78 years). The response rate (RR) to FAS was 39%, with a median response duration of 9.3 months. The 2-year PFS rate was 41%, and the 2-year OS rate was 74%. The extent of liver metastatic disease correlated with a worse PFS (P = .01 by log-rank test) and a worse OS (P < .0001 by log-rank test). Analyses showed that metastatic replacement of more than 75% of the liver and prior chemotherapy were independently associated with inferior PFS.

Conclusion

Patients with locally advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and responders may experience longer PFS and OS. The volume of metastases in the liver is the most important predictor of outcome.
Second-Line Chemotherapy With Irinotecan Plus Carmustine in Glioblastoma Recurrent or Progressive After First-Line Temozolomide Chemotherapy: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)
Authors: Brandes Alba A. , Tosoni Alicia , Basso Umberto , Reni Michele , Valduga Francesco , Monfardini Silvio , Amistà Pietro , Nicolardi Linda , Sotti Guido , Ermani Mario
Published: November 2004

Purpose

Glioblastoma multiforme (GBM), the most frequent brain tumor in adults, is not considered chemosensitive. Nevertheless, there is widespread use of first-line chemotherapy, often with temozolomide, as a therapeutic option in patients with progressive disease after surgery and radiotherapy. However, at the time of second recurrence and/or progression, active and noncross-resistant chemotherapy regimens are required. The aim of the present multicenter phase II trial, therefore, was to ascertain the efficacy of second-line carmustine (BCNU) and irinotecan chemotherapy.

Patients and Methods

Patients with histologically confirmed GBM, recurring or progressing after surgery, standard radiotherapy and a first-line temozolomide-based chemotherapy, were considered eligible. The primary end-point was progression-free survival at 6 months (PFS-6), and secondary end-points included response rate, toxicity, and survival. All patients were on enzyme-inducing antiepileptic prophylaxis. Chemotherapy consisted of BCNU (100 mg/m2 on day 1) plus irinotecan (175 mg/m2/weekly for 4 weeks), every 6 weeks, for a maximum of eight cycles. In the absence of grade 2 toxicity, the irinotecan dose was increased to 200 mg/m2.

Results

A total of 42 patients (median age, 53.4 years; median Karnofsky performance status, 80; range, 60 to 90) were included in the study. PFS-6 was 30.3% (95% CI, 18.5% to 49.7%). Median time to progression was 17 weeks (95% CI, 11.9 to 23.9). Nine partial responses (21.4%; 95% CI, 9% to 34%) were obtained. Toxicity was manageable.

Conclusion

The BCNU plus irinotecan regimen seems active and non–cross-resistant in patients with GBM with recurrence after temozolomide-based chemotherapy.
Recruitment of Patients Into an Internet-Based Clinical Trials Database: The Experience of OncoLink and the National Colorectal Cancer Research Alliance
Authors: Wei S.J. , Metz J.M. , Coyle C. , Hampshire M. , Jones H.A. , Markowitz S. , Rustgi A.K.
Published: November 2004

Purpose

In March 2001, the National Colorectal Cancer Research Alliance (NCCRA) and OncoLink ( http://www.oncolink.org ) established a database to facilitate patient enrollment onto clinical trials. This study describes the population registering with the database and identifies discrepancies between individuals registering through the Internet and those registering through a telephone call center.

Methods

Participants registered with the NCCRA/OncoLink database through the Internet or a telephone call center. All participants entering the database completed a questionnaire regarding basic demographics, colon cancer risk factors, and indicated how they became aware of the database. Comparisons were made between individuals registering through the Internet and those registering through the telephone call center.

Results

A total of 2,162 participants registered during the first 16 months of the database. Most patients registered through the Internet rather than the telephone call center (88% v 12%; P < .001). More females than males registered (73% v 27%; P < .001). The majority (89%) were white. Participants registering through the Internet were younger than those registering through the call center (mean, 48.8 v 55.0 years; P < .001). There was no difference between the two groups with regard to sex or ethnicity.

Conclusion

The Internet has the potential to increase the likelihood that interested individuals find appropriate clinical trials. Some of the discrepancies that are known to exist for access to the Internet were also seen for those registering with the database through the Internet. Despite these differences, the potential to increase clinical trial enrollment with this type of Internet-based database is high.
Exponential ergodicity for single-birth processes
Authors: Mao Yong-Hua , Zhang Yu-Hui
Published: November 2004

An explicit, computable, and sufficient condition for exponential ergodicity of single-birth processes is presented. The corresponding criterion for birth–death processes is proved using a new method. As an application, some sufficient conditions are obtained for exponential ergodicity of an extended class of continuous-time branching processes and of multidimensional Q-processes, by comparison methods.
The collision branching process
Authors: Chen Anyue , Pollett Phil , Zhang Hanjun , Li Junping
Published: November 2004

We consider a branching model, which we call the collision branching process (CBP), that accounts for the effect of collisions, or interactions, between particles or individuals. We establish that there is a unique CBP, and derive necessary and sufficient conditions for it to be nonexplosive. We review results on extinction probabilities, and obtain explicit expressions for the probability of explosion and the expected hitting times. The upwardly skip-free case is studied in some detail.
The eigentime identity for continuous-time ergodic Markov chains
Authors: Mao Yong-Hua
Published: November 2004

The eigentime identity is proved for continuous-time reversible Markov chains with Markov generator L. When the essential spectrum is empty, let {0 = λ0 < λ1 ≤ λ2 ≤ ···} be the whole spectrum of L in L2. Then ∑n≥1 λn-1 < ∞ implies the existence of the spectral gap α of L in L∞. Explicit formulae are presented in the case of birth–death processes and from these formulae it is proved that ∑n≥1 λn-1 < ∞ if and only if α > 0.