bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection of pulmonary epithelial cells from oxidative stress by hMYH adenine glycosylase
Authors: Kremer Ted M , Rinne Mikael L , Xu Yi , Chen Xian Ming , Kelley Mark R
Published: September 2004

Background

Oxygen toxicity is a major cause of lung injury. The base excision repair pathway is one of the most important cellular protection mechanisms that responds to oxidative DNA damage. Lesion-specific DNA repair enzymes include hOgg1, hMYH, hNTH and hMTH.

Methods

The above lesion-specific DNA repair enzymes were expressed in human alveolar epithelial cells (A549) using the pSF91.1 retroviral vector. Cells were exposed to a 95% oxygen environment, ionizing radiation (IR), or H2O2. Cell growth analysis was performed under non-toxic conditions. Western blot analysis was performed to verify over-expression and assess endogenous expression under toxic and non-toxic conditions. Statistical analysis was performed using the paired Student's t test with significance being accepted for p < 0.05.

Results

Cell killing assays demonstrated cells over-expressing hMYH had improved survival to both increased oxygen and IR. Cell growth analysis of A549 cells under non-toxic conditions revealed cells over-expressing hMYH also grow at a slower rate. Western blot analysis demonstrated over-expression of each individual gene and did not result in altered endogenous expression of the others. However, it was observed that O2 toxicity did lead to a reduced endogenous expression of hNTH in A549 cells.

Conclusion

Increased expression of the DNA glycosylase repair enzyme hMYH in A549 cells exposed to O2 and IR leads to improvements in cell survival. DNA repair through the base excision repair pathway may provide an alternative way to offset the damaging effects of O2 and its metabolites.
cuticleDB: a relational database of Arthropod cuticular proteins
Authors: Magkrioti Christiana K , Spyropoulos Ioannis C , Iconomidou Vassiliki A , Willis Judith H , Hamodrakas Stavros J
Published: September 2004

Background

The insect exoskeleton or cuticle is a bi-partite composite of proteins and chitin that provides protective, skeletal and structural functions. Little information is available about the molecular structure of this important complex that exhibits a helicoidal architecture. Scores of sequences of cuticular proteins have been obtained from direct protein sequencing, from cDNAs, and from genomic analyses.

Most of these cuticular protein sequences contain motifs found only in arthropod proteins.

Description

cuticleDB is a relational database containing all structural proteins of Arthropod cuticle identified to date. Many come from direct sequencing of proteins isolated from cuticle and from sequences from cDNAs that share common features with these authentic cuticular proteins. It also includes proteins from the Drosophila melanogaster and the Anopheles gambiae genomes, that have been predicted to be cuticular proteins, based on a Pfam motif (PF00379) responsible for chitin binding in Arthropod cuticle. The total number of the database entries is 445: 370 derive from insects, 60 from Crustacea and 15 from Chelicerata. The database can be accessed from our web server at http://bioinformatics.biol.uoa.gr/cuticleDB.

Conclusions

CuticleDB was primarily designed to contain correct and full annotation of cuticular protein data. The database will be of help to future genome annotators. Users will be able to test hypotheses for the existence of known and also of yet unknown motifs in cuticular proteins. An analysis of motifs may contribute to understanding how proteins contribute to the physical properties of cuticle as well as to the precise nature of their interaction with chitin.
Prediction of DtxR regulon: Identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae
Authors: Yellaboina Sailu , Ranjan Sarita , Chakhaiyar Prachee , Hasnain Seyed Ehtesham , Ranjan Akash
Published: September 2004

Background

The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae.

Result

Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG), an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps) which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin.

Conclusions

We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a molecular link between Fe+2-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2 and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase, a potential vaccine candidate and proteins of secretory system.
Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment
Authors: Liljedahl Ulrika , Lind Lars , Kurland Lisa , Berglund Lars , Kahan Thomas , Syvänen Ann-Christine
Published: September 2004

Background

Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment.

Methods

Ten single nucleotide polymorphisms (SNP) in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the β1-adrenergic receptor blocker atenolol for twelve weeks.

Results

The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele.

Conclusions

Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.
Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC) patients
Authors: Fliss-Jaber Lilia , Houissa-Kastally Radhia , Bouzouita Kamel , Khediri Naceur , Khelifa Ridha
Published: September 2004

Background

Undifferentiated Nasopharyngeal Carcinoma (NPC) patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV) which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL) and tumor- infiltrating (TIL) lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10) and three immunoglobulin isotypes (IgM, IgG, IgA).

Methods

Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM) for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA). Data were analysed using Student's t-test and probability values below 5% were considered significant.

Results

The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002), IL-10 (p = 0,020), IgM (p= 0,0003) and IgG (p < 0,0001) than their PBL. On the other hand, patients PBL produced significantly higher levels of IL-2 (p = 0,022), IL-10 (p = 0,016) and IgM (p = 0,004) than those of controls. No significant differences for IL-6 and IgA were observed.

Conclusion

Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.
Magnesium administration provokes motor unit survival, after sciatic nerve injury in neonatal rats
Authors: Gougoulias N , Hatzisotiriou A , Kapoukranidou D , Albani M
Published: September 2004

Background

We examined the time course of the functional alterations in two types of muscles following sciatic nerve crush in neonatal rats and the neuroprotective effect of Mg2+.

Methods

The nerve crush was performed on the 2nd postnatal day. MgSO4*7H2O was administered daily for two weeks. Animals were examined for the contractile properties and for the number of motor units of extensor digitorum longus and soleus muscles at three postnatal stages and adulthood. Four experimental groups were included in this study: i) controls, ii) axotomized rats, iii) magnesium treated controls and iv) axotomized and Mg2+-treated rats.

Results

Axotomy resulted in 20% MU survival in EDL and 50% in soleus. In contrast, magnesium treatment resulted in a significant motor unit survival (40% survival in EDL and 80% in soleus). The neuroprotective effects of Mg2+ were evident immediately after the Mg2+-treatment. Immature EDL and soleus muscles were slow and fatigueable. Soleus gradually became fatigue resistant, whereas, after axotomy, soleus remained fatigueable up to adulthood. EDL gradually became fastcontracting. Tetanic contraction in axotomized EDL was just 3,3% of the control side, compared to 15,2% in Mg2+-treated adult rats. The same parameter for axotomized soleus was 12% compared to 97% in Mg2+-treated adult rats.

Conclusions

These results demonstrate that motoneuron death occurs mostly within two weeks of axotomy. Magnesium administration rescues motoneurons and increases the number of motor units surviving into adulthood. Fast and slow muscles respond differently to axotomy and to subsequent Mg2+ treatment in vivo.
The PedsQL™ Family Impact Module: Preliminary reliability and validity
Authors: Varni James W , Sherman Sandra A , Burwinkle Tasha M , Dickinson Paige E , Dixon Pamela
Published: September 2004

Background

The PedsQL™ Measurement Model was designed to measure health-related quality of life (HRQOL) in children and adolescents. The PedsQL™ 4.0 Generic Core Scales were developed to be integrated with the PedsQL™ Disease-Specific Modules. The newly developed PedsQL™ Family Impact Module was designed to measure the impact of pediatric chronic health conditions on parents and the family. The PedsQL™ Family Impact Module measures parent self-reported physical, emotional, social, and cognitive functioning, communication, and worry. The Module also measures parent-reported family daily activities and family relationships.

Methods

The 36-item PedsQL™ Family Impact Module was administered to 23 families of medically fragile children with complex chronic health conditions who either resided in a long-term care convalescent hospital or resided at home with their families.

Results

Internal consistency reliability was demonstrated for the PedsQL™ Family Impact Module Total Scale Score (α = 0.97), Parent HRQOL Summary Score (α = 0.96), Family Functioning Summary Score (α = 0.90), and Module Scales (average α = 0.90, range = 0.82 – 0.97). The PedsQL™ Family Impact Module distinguished between families with children in a long-term care facility and families whose children resided at home.

Conclusions

The results demonstrate the preliminary reliability and validity of the PedsQL™ Family Impact Module in families with children with complex chronic health conditions. The PedsQL™ Family Impact Module will be further field tested to determine the measurement properties of this new instrument with other pediatric chronic health conditions.
Exposure to malaria affects the regression of hepatosplenomegaly after treatment for Schistosoma mansoniinfection in Kenyan children
Authors: Booth Mark , Vennervald Birgitte J , Butterworth Anthony E , Kariuki Henry C , Amaganga Clifford , Kimani Gachuhi , Mwatha Joseph K , Otedo Amos , Ouma John H , Dunne David W
Published: September 2004

Background

Schistosoma mansoni and malaria infections are often endemic in the same communities in sub-Saharan Africa, and both have pathological effects on the liver and the spleen. Hepatosplenomegaly associated with S. mansoni is exacerbated in children with relatively high exposure to malaria. Treatment with praziquantel reduces the degree of hepatosplenomegaly, but the condition does not completely resolve in some cases. The present analysis focused on the possibility that exposure to malaria infection may have limited the resolution of hepatosplenomegaly in a cohort of Kenyan schoolchildren.

Methods

Ninety-six children aged 6–16, from one community in Makueni district, Kenya, were treated with praziquantel. At baseline, all children had hepatomegaly and most had splenomegaly. The source of S. mansoni infection, a river, was molluscicided regularly over the following three years to limit S. mansoni re-infection, whereas malaria exposure was uninterrupted. Hepatic and splenic enlargement was assessed annually outside the malaria transmission season.

Results

Children living in an area of relatively high exposure to both infections presented with the largest spleens before treatment and at each follow-up. Spleens of firm consistency were associated with proximity to the river. The regression of hepatomegaly was also affected by location, being minimal in an area with relatively low S. mansoni exposure but high exposure to malaria, and maximal in an area with relatively low exposure to both infections.

Conclusions

The outcome of treating cases of hepatosplenomegaly with praziquantel in this cohort of Kenyan children depended strongly on their level of exposure to malaria infection. Furthermore, a residual burden of hepatosplenic morbidity was observed, which was possibly attributable to the level of exposure to malaria. The results suggest that exposure to malaria infection may be a significant factor affecting the outcome of praziquantel treatment to reduce the level of hepatosplenic morbidity.
A mathematical model for LH release in response to continuous and pulsatile exposure of gonadotrophs to GnRH
Authors: Washington Talitha M , Blum J Joseph , Reed Michael C , Conn P Michael
Published: September 2004

In a previous study, a model was developed to investigate the release of luteinizing hormone (LH) from pituitary cells in response to a short pulse of gonadotropin-releasing hormone (GnRH). The model included: binding of GnRH to its receptor (R), dimerization and internalization of the hormone receptor complex, interaction with a G protein, production of inositol 1,4,5-trisphosphate (IP3), release of calcium from the endoplasmic reticulum (ER), entrance of calcium into the cytosol via voltage gated membrane channels, pumping of calcium out of the cytosol via membrane and ER pumps, and release of LH. The extended model, presented in this paper, also includes the following physiologically important phenomena: desensitization of calcium channels; internalization of the dimerized receptors and recycling of some of the internalized receptors; an increase in G
q
concentration near the plasma membrane in response to receptor dimerization; and basal rates of synthesis and degradation of the receptors. With suitable choices of the parameters, good agreement with a variety of experimental data of the LH release pattern in response to pulses of various durations, repetition rates, and concentrations of GnRH were obtained. The mathematical model allows us to assess the effects of internalization and desensitization on the shapes and time courses of LH response curves.
Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
Authors: Gay Wilfried , Lauret Evelyne , Boson Bertrand , Larghero Jérome , Matheux Franck , Peyramaure Sophie , Rousseau Véronique , Dormont Dominique , De Maeyer Edward , Le Grand Roger
Published: September 2004

Background

The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251.

Results

Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 106 peripheral mononuclear cells.

Conclusion

Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4+ cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection.
Genomic neighborhoods for Arabidopsisretrotransposons: a role for targeted integration in the distribution of the Metaviridae
Authors: Peterson-Burch Brooke D , Nettleton Dan , Voytas Daniel F
Published: September 2004

Background

Retrotransposons are an abundant component of eukaryotic genomes. The high quality of the Arabidopsis thaliana genome sequence makes it possible to comprehensively characterize retroelement populations and explore factors that contribute to their genomic distribution.

Results

We identified the full complement of A. thaliana long terminal repeat (LTR) retroelements using RetroMap, a software tool that iteratively searches genome sequences for reverse transcriptases and then defines retroelement insertions. Relative ages of full-length elements were estimated by assessing sequence divergence between LTRs: the Pseudoviridae were significantly younger than the Metaviridae. All retroelement insertions were mapped onto the genome sequence and their distribution was distinctly non-uniform. Although both Pseudoviridae and Metaviridae tend to cluster within pericentromeric heterochromatin, this association is significantly more pronounced for all three Metaviridae sublineages (Metavirus, Tat and Athila). Among these, Tat and Athila are strictly associated with pericentromeric heterochromatin.

Conclusions

The non-uniform genomic distribution of the Pseudoviridae and the Metaviridae can be explained by a variety of factors including target-site bias, selection against integration into euchromatin and pericentromeric accumulation of elements as a result of suppression of recombination. However, comparisons based on the age of elements and their chromosomal location indicate that integration-site specificity is likely to be the primary factor determining distribution of the Athila and Tat sublineages of the Metaviridae. We predict that, like retroelements in yeast, the Athila and Tat elements target integration to pericentromeric regions by recognizing a specific feature of pericentromeric heterochromatin.
Insertion bias and purifying selection of retrotransposons in the Arabidopsis thalianagenome
Authors: Pereira Vini
Published: September 2004

Background

Genome evolution and size variation in multicellular organisms are profoundly influenced by the activity of retrotransposons. In higher eukaryotes with compact genomes retrotransposons are found in lower copy numbers than in larger genomes, which could be due to either suppression of transposition or to elimination of insertions, and are non-randomly distributed along the chromosomes. The evolutionary mechanisms constraining retrotransposon copy number and chromosomal distribution are still poorly understood.

Results

I investigated the evolutionary dynamics of long terminal repeat (LTR)-retrotransposons in the compact Arabidopsis thaliana genome, using an automated method for obtaining genome-wide, age and physical distribution profiles for different groups of elements, and then comparing the distributions of young and old insertions. Elements of the Pseudoviridae family insert randomly along the chromosomes and have been recently active, but insertions tend to be lost from euchromatic regions where they are less likely to fix, with a half-life estimated at approximately 470,000 years. In contrast, members of the Metaviridae (particularly Athila) preferentially target heterochromatin, and were more active in the past.

Conclusion

Diverse evolutionary mechanisms have constrained both the copy number and chromosomal distribution of retrotransposons within a single genome. In A. thaliana, their non-random genomic distribution is due to both selection against insertions in euchromatin and preferential targeting of heterochromatin. Constant turnover of euchromatic insertions and a decline in activity for the elements that target heterochromatin have both limited the contribution of retrotransposon DNA to genome size expansion in A. thaliana.
Anorexia nervosa among female secondary school students in Ghana
Authors: Bennett Dinah , Sharpe Michael , Freeman Chris , Carson Alan
Published: September 2004

Background

We set out to determine whether anorexia nervosa exists in a culture where the pressure to be thin is less pervasive.

Aims

To determine whether there were any cases of anorexia nervosa in female students attending two secondary schools in the north-east region of Ghana.

Method

The body mass index (BMI) of consenting students was calculated after measuring their height and weight. Those with a BMI ⩽19 kg/m2underwent a structured clinical assessment including mental state, physical examination and completion of the Eating Attitudes Test and the Bulimic Investigatory Test, Edinburgh. Participants nominated a best friend to serve as a comparison group, and these young women underwent the same assessments.

Results

Of the 668 students who were screened for BMI, 10 with a BMI <175 kg/m2appeared to have self-starvation as the only cause of their low weight. All 10 viewed their food restriction positively and in religious terms. The beliefs of these individuals included ideas of self-control and denial of hunger, without the typical anorexic concerns about weight or shape.

Conclusions

Morbid self-starvation may be the core feature of anorexia nervosa, with the attribution for the self-starvation behaviour varying between cultures.
Needs for mental health treatment among general practice attenders
Authors: Boardman Jed , Henshaw Carol , Willmott Sasi
Published: September 2004

Background

No study has directly assessed the need for mental health care among those consulting in general practice.

Aims

To make a direct assessment of the needs for mental health care in people with non-psychotic disorders consulting their general practitioner.

Method

In a two-phase study design, consecutive general practice attenders aged 17–65 years were interviewed using the Structured Clinical Interview for DSM–IV Axis I Disorders. Needs for care were assessed using the community version of the Medical Research Council Needs for Care Assessment Schedule.

Results

Three hundred and thirty-six people were interviewed. The overall prevalence of need was 27.3%. More than half of the consulters (59.6%) had unmet needs and a further 6.2% had partially met needs. Needs were met in 28.1% and unmeetable in 6.2%. The prevalence of unmet need in those with anxiety disorders was 13.9% and depressive disorders 9.5%.

Conclusions

The unmet need for mental health treatment in primary care attenders is high.
Post-traumatic stress after terrorist attack: psychological reactions following the US embassy bombing in Nairobi
Authors: Njenga Frank G. , Nicholls P. J. , Nyamai Caroline , Kigamwa Pius , Davidson Jonathan R. T.
Published: September 2004

Background

Most studies of post-traumatic stress disorder following terrorist attacks are of small samples in industrialised nations and take place months or years after the incident.

Aims

To describe reactions following the US embassy bombing in Nairobi and the characteristic features of and risk factors for post-traumatic stress symptoms in a large, non-Western sample soon after the attack.

Method

A self-report questionnaire which assessed potential risk factors and identified symptoms matching DSM–IV criteria for post-traumatic stress disorder was answered by 2883 Kenyans, 1–3 months after the bombing.

Results

Symptoms approximating to the criteria for post-traumatic stress disorder occurred in 35%. Factors associated with post-traumatic stress included female gender, unmarried status, lack of college education, seeing the blast, injury, not recovering from injury, not confiding in a friend, bereavement and financial difficulty since the blast. Many other factors were not significant.

Conclusions

Specific factors often cited to predict marked short-term post-traumatic stress were confirmed in this large, non-Western sample.
Patterns of hospital admission for adult psychiatric illness in England: analysis of Hospital Episode Statistics data
Authors: Thompson Andrew , Shaw Mary , Harrison Glynn , Ho Davidson , Gunnell David , Verne Julia
Published: September 2004

Background

The assessment and reporting of national patterns of psychiatric hospital admissions is important for strategic service development and planning.

Aims

To investigate patterns of psychiatric hospital admissions of patients aged 16–64 years in England.

Method

We used the Department of Health's national Hospital Episode Statistics data on admissions to National Health Service hospitals in England between April 1999 and March 2000, to investigate patterns by region, gender, age and diagnosis.

Results

The annual admission rate for England was 3.2 per 1000 population. There were marked regional variations and rates were higher in males than in females. Depression and anxiety together were the most common (29.6%) reason for admission. Length of stay exceeded 90 days in 9.2% of admissions and 1 year in 0.9% (highest in London and for psychoses).

Conclusions

Depression and anxiety together were the most frequent diagnoses leading to hospitalisation. There has been a reversal of the previously reported predominance of female admissions. Regional variations in activity and the significant numbers of patients remaining for long periods in acute’ in-patient care have important policy implications.
Effect of web-based depression literacy and cognitive–behavioural therapy interventions on stigmatising attitudes to depression
Authors: Griffiths Kathleen M. , Christensen Helen , Jorm Anthony F. , Evans Kimberley , Groves Chloe
Published: September 2004

Background

Little is known about the efficacy of educational interventions for reducing the stigma associated with depression.

Aims

To investigate the effects on stigma of two internet depression sites.

Method

A sample of 525 individuals with elevated scores on a depression assessment scale were randomly allocated to a depression information website (BluePages), a cognitive–behavioural skills training website (MoodGYM) or an attention control condition. Personal stigma (personal stigmatising attitudes to depression) and perceived stigma (perception of what most other people believe) were assessed before and after the intervention.

Results

Relative to the control, the internet sites significantly reduced personal stigma, although the effects were small. BluePages had no effect on perceived stigma and MoodGYM was associated with an increase in perceived stigma relative to the control. Changes in stigma were not mediated by changes in depression, depression literacy or cognitive–behavioural therapy literacy.

Conclusions

The internet warrants further investigation as a means of delivering stigma reduction programmes for depression.
Affective problems in adults with mild learning disability: the roles of social disadvantage and ill health
Authors: Collishaw Stephan , Maughan Barbara , Pickles Andrew
Published: September 2004

Mild learning disability is associated with an increased risk of affective disorder. This study examines the extent to which adult socio-economic disadvantage and ill health contribute to this risk. Samples were drawn from the 1958 National Child Development Study. Relative to a comparison group, mild learning disability at age 11 was associated with elevated rates of depressive symptoms throughout adult life, and carried a six-fold risk of chronic depressed mood. The group difference in depressed mood at age 43 years was in large part mediated by variations in adult socio-economic disadvantage and ill health.
Psychiatry in the future
Authors: Turner Trevor , Turner Trevor
Published: September 2004

As a general adult consultant psychiatrist who has worked full-time in the National Health Service (NHS) for 15 years, I have seen that things do change, but rarely in the ways expected or planned for. Having done the same job for six different reconfigurations of local services, I can confirm that reorganisation is largely irrelevant. However, new treatments (such as selective serotonin reuptake inhibitors and atypical antipsychotics) and new buildings, along with enthusiastic staff, can be seen as genuine advances. Changing social attitudes, in particular the rise of morbid individualism and an increasingly virulent, reactionary anti-science lobby, alongside sheer social overcrowding and pollution, do bring fears for the future. Community care has become a joke term rather than a watchword for acceptance of the stigmatised among ‘normal’ society. Three visions are possible: the dystopian, the normotopian and the utopian, looked at along the biopsychosocial spectrum.
Psychotherapy meets neuroscience
Authors: Fonagy Peter
Published: September 2004

The ‘evidence base’ for my contribution to futurology is a set of integrative reviews of outcome studies of psychotherapy on which I have collaborated with a number of colleagues (Roth & Fonagy 1996; Fonagy et al, 2002a,b). This work is a pleasure, not so much because of the enlightenment that reading hundreds of papers provides, but rather because of the technical challenges that compiling material across broad fields invariably presents.
Irish Psychiatric Association survey of psychiatric services in Ireland
Authors: O'Keane V. , Jeffers A. , Moloney E. , Barry S.
Published: September 2004

Aims and Method

The Irish Psychiatric Association conducted a national survey of psychiatric services in Ireland to examine clinical resources in relation to the relative affluence of catchment areas. A consultant psychiatrist from each catchment area was sent a postal survey form (August 2002) and the data received were cross-referenced with measures of relative affluence.

Results

There was a 72% response rate. A negative relationship emerged between indices of need and both the number of acute beds and the number of consultant psychiatrists per head of the population.

Clinical Implications

The results of this survey indicate that clinical resources in mental health in Ireland are not concentrated in areas of greatest need, but paradoxically have been best developed in areas of greatest affluence.
Does a limited nurse triage service reduce junior doctor psychiatric on-call workload?
Authors: Moore A. P. , Willmott S.
Published: September 2004

Aims and Method

To investigate whether nurse triage might reduce junior doctors' on-call workloads in a general adult psychiatry in-patient unit, we measured changes in workload after the introduction of a limited (overnight and weekend mornings) nurse triage service on the unit, comparing pre-triage work levels with levels 1 year later. This time frame allowed the new service to settle in, and controlled for seasonal variations in workload.

Results

The number of ‘work episodes' went up, especially during the night shifts, but the average length of each episode went down (both statistically significant, P < 0.001). The net result was a slight increase in workload in terms of total time spent dealing with episodes, most notably at night.

Clinical Implications

A limited overnight nurse triage service was ineffective on its own as a means of reducing the out-of-hours workload of junior doctors, and even slightly increased it. A more comprehensive triage service, with a greater range of alternatives to admission, might have had a different result.
‘You don't bring me flowers any more’: an investigation into the experience of stigma by psychiatric in-patients
Authors: Bromley Joanna S. , Cunningham Sara J.
Published: September 2004

Aims and Method

A structured interview-based questionnaire was used to measure the number of cards and gifts received by 40 people undergoing psychiatric in-patient treatment, compared with an age- and gender-matched group of medical in-patients. The study also assessed the amount of disclosure of admission and diagnosis to family and friends in the two groups.

Results

The psychiatric patients received about half as many cards as the medical patients (60 v. 112). Gifts to the psychiatric patients were often practical in nature and seldom included luxury items such as flowers. Disclosure of admission for mental illness (compared with the physical illness group) was significantly lower, both to family members (139 v. 193, P=0.041) and friends (74 v. 332, P=0.0001).

Clinical Implications

The stigma of mental illness is reflected in the secrecy surrounding disclosure of hospital admission and the lack of tokens of support. Clinicians should be aware of the resulting sense of isolation and shame, and the consequences for mental health in view of reduced social networks increasing the risk of future relapse rates. Reduced contact with mentally ill patients has implications for society as a whole in maintaining the status quo of stigma.
The future of memory clinics
Authors: Passmore A. P. , Craig D. A.
Published: September 2004

Memory clinics have been in existence in the UK for over 15 years. Initially set up for research purposes, these clinics have been transformed by the advent of treatments for Alzheimer's disease. Clinics increasingly provide for early diagnosis, information dissemination, initiation and monitoring of treatment, and education and training. There are variations in clinic design, and availability nationally. There continue to be significant demands on existing services, which have traditionally offered domiciliary care. The valuable contribution of these traditional services deserves greater recognition, as do the benefits provided by memory clinics, which are often not fully appreciated by health care professionals or the public.
Time for change to a developmental perspective in the education and training of psychiatrists
Authors: Eminson D. Mary , Goodyer Ian M.
Published: September 2004

The practice of psychiatry in the UK has for most of its existence been focused on the needs of adults, and it has been with this age group in mind that educational programmes and training needs have been formulated. It is not surprising, then, that the content and shape of psychiatric training programmes have followed this clinically-driven pattern. Trainees entering psychiatry begin their clinical careers working with adults or older people and are expected to obtain a grasp of the fundamental clinical tools of the trade working with these populations. Experience with younger people's mental health is explicitly excluded in the first year of training, emphasising the primacy of adulthood in the approach to learning clinical mental health skills.
Clinical Nature and Prognosis of Locally Recurrent Rectal Cancer After Total Mesorectal Excision With or Without Preoperative Radiotherapy
Authors: van den Brink Mandy , Stiggelbout Anne M. , van den Hout Wilbert B. , Kievit Job , Klein Kranenbarg Elma , Marijnen Corrie A.M. , Nagtegaal Iris D. , Rutten Harm J.T. , Wiggers Theo , van de Velde Cornelis J.H.
Published: September 2004

Purpose

To document the clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision (TME) with or without 5 × 5 Gy preoperative radiotherapy (PRT) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after local recurrence.

Patients and Methods

For 96 Dutch patients with a local recurrence who participated in a multicenter randomized clinical trial, data on treatments and follow-up were gathered from surgeons and radiation and medical oncologists. Twenty-three patients (24%) had previously been treated with PRT plus TME, and 73 patients (76%) had been treated with TME alone. Eighty-one patients (84%) were followed until death; median follow-up time of the alive patients after local recurrence was 21 months (range, 5 to 48 months).

Results

Survival after local recurrence in the PRT + TME group was significantly shorter than in the TME group (median survival, 6.1 v 15.9 months; hazard ratio for death, 2.1; P = .008). Patients with a local recurrence in the PRT + TME group had distant metastases more often (74% v 40%; P = .004), underwent surgical resection of local recurrence less often (17% v 35%; P = .11), and received radiotherapy for local recurrence at a total dose ≥ 45 Gy less often (4% v 42%; P = .001) than patients without PRT. In a multivariate analysis, the difference in survival after local recurrence between randomization groups was no longer statistically significant (hazard ratio for death of PRT, 1.53; P = .16).

Conclusion

The clinical nature and prognosis of patients with locally recurrent rectal cancer has changed since the introduction of PRT. The majority of patients who present with a local recurrence after previous PRT have simultaneous distant metastases, and median survival has decreased to 6 months.
Identification of Novel Prognosticators of Outcome in Squamous Cell Carcinoma of the Head and Neck
Authors: Wreesmann Volkert B. , Shi Weiji , Thaler Howard T. , Poluri Ashok , Kraus Dennis H. , Pfister David , Shaha Ashok R. , Shah Jatin P. , Rao Pulivarthi H. , Singh Bhuvanesh
Published: September 2004

Purpose

The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC).

Patients and Methods

We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate χ2statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than .15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the χ2approximation of the final model by MCS.

Results

CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P = .0009 to P = .01).

Conclusion

HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.
Positron Emission Tomography in Combination With Sentinel Node Biopsy Reduces the Rate of Elective Neck Dissections in the Treatment of Oral and Oropharyngeal Cancer
Authors: Kovács Adorján F. , Döbert Natascha , Gaa Jochen , Menzel Christian , Bitter Klaus
Published: September 2004

Purpose

To assess the impact of a diagnostic ladder including [18F]fluorodeoxyglucose positron emission tomography (PET) and lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC).

Patients and Methods

Prospectively, 62 patients with resectable T1-3 OOSCC underwent computed tomography (CT) and PET. Patients without neck uptake in PET were defined as cN0 and were accrued for LS/SNB. Results were correlated with histopathology. The traditional guidelines according to CT findings were compared to the actual regimen and the outcome.

Results

Sensitivity, specificity, validity, and positive and negative predictive value of PET versus CT were 72% v 89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant). Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were found in all 38 patients. Five patients had positive nodes (PET false-negatives) and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were CT-negative would have been treated with selective ND according to the guidelines, and at least 45 neck sides would have had to undergo extensive ND because of positive CT findings (96 of 124 neck sides). In contrast, PET in combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually underwent ND as a result of PET staging, LS/SNB, and intraoperative decision. After a median follow-up of 35 months, two patients (both cN+ve and pN+ve) suffered from neck relapses.

Conclusion

Diagnostics using PET in combination with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared to CT without locoregional hazard.
Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study
Authors: Thigpen J. Tate , Brady Mark F. , Homesley Howard D. , Malfetano John , DuBeshter Brent , Burger Robert A. , Liao Shu
Published: September 2004

Purpose

Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone.

Patients and Methods

Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m2 intravenously or doxorubicin 60 mg/m2 plus cisplatin 50 mg/m2 every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m2 doxorubicin.

Results

There were 12 (8%) complete (CR) and 26 (17%) partial responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and 30 (23%) PRs among patients receiving the combination. The overall response rate was higher among patients receiving the combination (42%) compared with patients receiving doxorubicin (25%; P = .004). Median PFS was 5.7 and 3.8 months, respectively, for the combination and single agent. The PFS hazard ratio was 0.736 (95% CI, 0.577 to 0.939; P = .014). Median OS was 9.0 and 9.2 months, respectively, for the combination and single agent. Overall death rates were similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea, vomiting, and hematologic toxicities were common. The combination produced more grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v 4%), and nausea/vomiting (13% v 3%).

Conclusion

Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity. These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma.
Matched-Pair Analysis of Survival of Never Smokers and Ever Smokers With Squamous Cell Carcinoma of the Head and Neck
Authors: Pytynia Kristen B. , Grant Jonathan R. , Etzel Carol J. , Roberts Dianna B. , Wei Qingyi , Sturgis Erich M.
Published: September 2004

Purpose

To compare survival rates between patients with squamous cell carcinoma of the head and neck (SCCHN) without a history of smoking (never smokers) and those with a current or previous history of smoking (ever smokers).

Patients and Methods

Fifty never smokers with newly diagnosed SCCHN were matched to 50 ever smokers according to sex, age, tumor site, overall stage, nodal stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model.

Results

The never smokers had a greater overall survival (P = .020), disease-specific survival (P = .022), and recurrence-free survival (P = .016). Furthermore, matched-pair analysis demonstrated smoking was associated with a significant increase in risk of overall death (relative risk [RR] = 3.50; 95% CI, 1.14 to 10.77; P = .029), risk of death owing to disease (RR = 3.98; 95% CI, 1.11 to 14.33; P = .034), and risk of disease recurrence (RR = 3.29; 95% CI, 1.18 to 9.14; P = .023). Smoking was associated with three-fold increases in risk for overall death, death owing to disease, and recurrence after adjustment for cancer-associated symptom severity and alcohol use, but the 95% CI for these adjusted risk estimates each included the null.

Conclusion

Survival differed significantly between never smokers and ever smokers with SCCHN. These results are not substantively explained by differences in cancer-associated symptoms or alcohol use, but the CIs are wide and some imprecision remains. Regardless, possible fundamental differences in SCCHN between ever smokers and never smokers may exist, and further molecular characterization of these tumors is needed to determine whether biologic differences needing targeted therapies exist.