bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins
Authors: Macaulay Iain C. , Tijssen Marloes R. , Thijssen-Timmer Daphne C. , Gusnanto Arief , Steward Michael , Burns Philippa , Langford Cordelia F. , Ellis Peter D. , Dudbridge Frank , Zwaginga Jaap-Jan , Watkins Nicholas A. , van der Schoot C. Ellen , Ouwehand Willem H.
Published: December 2006

To identify previously unknown platelet receptors we compared the transcriptomes of in vitro differentiated megakaryocytes (MKs) and erythroblasts (EBs). RNA was obtained from purified, biologically paired MK and EB cultures and compared using cDNA microarrays. Bioinformatical analysis of MK–up-regulated genes identified 151 transcripts encoding transmembrane domain-containing proteins. Although many of these were known platelet genes, a number of previously unidentified or poorly characterized transcripts were also detected. Many of these transcripts, including G6b, G6f, LRRC32, LAT2, and the G protein–coupled receptor SUCNR1, encode proteins with structural features or functions that suggest they may be involved in the modulation of platelet function. Immunoblotting on platelets confirmed the presence of the encoded proteins, and flow cytometric analysis confirmed the expression of G6b, G6f, and LRRC32 on the surface of platelets. Through comparative analysis of expression in platelets and other blood cells we demonstrated that G6b, G6f, and LRRC32 are restricted to the platelet lineage, whereas LAT2 and SUCNR1 were also detected in other blood cells. The identification of the succinate receptor SUCNR1 in platelets is of particular interest, because physiologically relevant concentrations of succinate were shown to potentiate the effect of low doses of a variety of platelet agonists.
Pathogenic proline mutation in the linker between spectrin repeats: disease caused by spectrin unfolding
Authors: Johnson Colin P. , Gaetani Massimiliano , Ortiz Vanessa , Bhasin Nishant , Harper Sandy , Gallagher Patrick G. , Speicher David W. , Discher Dennis E.
Published: December 2006

Pathogenic mutations in α and β spectrin result in a variety of syndromes, including hereditary elliptocytosis (HE), hereditary pyropoikilocytosis (HPP), and hereditary spherocytosis (HS). Although some mutations clearly lie at sites of interaction, such as the sites of spectrin α-βtetramer formation, a surprising number of HE-causing mutations have been identified within linker regions between distal spectrin repeats. Here we apply solution structural and single molecule methods to the folding and stability of recombinant proteins consisting of the first 5 spectrin repeats of α-spectrin, comparing normal spectrin with a pathogenic linker mutation, Q471P, between repeats R4 and R5. Results show that the linker mutation destabilizes a significant fraction of the 5-repeat construct at 37°C, whereas the WT remains fully folded well above body temperature. In WT protein, helical linkers propagate stability from one repeat to the next, but the mutation disrupts the stabilizing influence of adjacent repeats. The results suggest a molecular mechanism for the high frequency of disease caused by proline mutations in spectrin linkers.
Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation, and proliferation in CD8 T cells of patients with human immunodeficiency virus-1 (HIV)
Authors: White Lesley , Krishnan Subramaniam , Strbo Natasa , Liu Huanliang , Kolber Michael A. , Lichtenheld Mathias G. , Pahwa Rajendra N. , Pahwa Savita
Published: December 2006

An urgent need exists to devise strategies to augment antiviral immune responses in patients with HIV who are virologically well controlled and immunologically stable on highly active antiretroviral therapy (HAART). The objective of this study was to compare the immunomodulatory effects of the cytokines interleukin (IL)–21 with IL-15 on CD8 T cells in patients with HIV RNA of less than 50 copies/mL and CD4 counts greater than 200 cells/mm.3 Patient CD8 T cells displayed skewed maturation and decreased perforin expression compared with healthy controls. Culture of freshly isolated patient peripheral-blood mononuclear cells (PBMCs) for 5 hours to 5 days with IL-21 resulted in up-regulation of perforin in CD8 T cells, including memory and effector subsets and virus-specific T cells. IL-21 did not induce T-cell activation or proliferation, nor did it augment T-cell receptor (TCR)–induced degranulation. Treatment of patient PBMCs with IL-15 resulted in induction of perforin in association with lymphocyte proliferation and augmentation of TCR-induced degranulation. Patient CD8 T cells were more responsive to cytokine effects than the cells of healthy volunteers. We conclude that CD8 T cells of patients with HIV can be modulated by IL-21 to increase perforin expression without undergoing overt cellular activation. IL-21 could potentially be useful for its perforin-enhancing properties in anti-HIV immunotherapy.
K-RasG12D expression induces hyperproliferation and aberrant signaling in primary hematopoietic stem/progenitor cells
Authors: Van Meter Margaret E. M. , Díaz-Flores Ernesto , Archard Joehleen A. , Passegué Emmanuelle , Irish Jonathan M. , Kotecha Nikesh , Nolan Garry P. , Shannon Kevin , Braun Benjamin S.
Published: December 2006

Defining how cancer-associated mutations perturb signaling networks in stem/progenitor populations that are integral to tumor formation and maintenance is a fundamental problem with biologic and clinical implications. Point mutations in RAS genes contribute to many cancers, including myeloid malignancies. We investigated the effects of an oncogenic KrasG12D allele on phosphorylated signaling molecules in primary c-kit+ lin−/low hematopoietic stem/progenitor cells. Comparison of wild-type and KrasG12D c-kit+ lin−/low cells shows that K-RasG12D expression causes hyperproliferation in vivo and results in abnormal levels of phosphorylated STAT5, ERK, and S6 under basal and stimulated conditions. Whereas KrasG12D cells demonstrate hyperactive signaling after exposure to granulocyte-macrophage colony-stimulating factor, we unexpectedly observe a paradoxical attenuation of ERK and S6 phosphorylation in response to stem cell factor. These studies provide direct biochemical evidence that cancer stem/progenitor cells remodel signaling networks in response to oncogenic stress and demonstrate that multi-parameter flow cytometry can be used to monitor the effects of targeted therapeutics in vivo. This strategy has broad implications for defining the architecture of signaling networks in primary cancer cells and for implementing stem cell–targeted interventions.
Linkage disequilibrium of evolutionarily conserved regions in the human genome
Authors: Kato Mamoru , Sekine Akihiro , Ohnishi Yozo , Johnson Todd A , Tanaka Toshihiro , Nakamura Yusuke , Tsunoda Tatsuhiko
Published: December 2006

Background

The strong linkage disequilibrium (LD) recently found in genic or exonic regions of the human genome demonstrated that LD can be increased by evolutionary mechanisms that select for functionally important loci. This suggests that LD might be stronger in regions conserved among species than in non-conserved regions, since regions exposed to natural selection tend to be conserved. To assess this hypothesis, we used genome-wide polymorphism data from the HapMap project and investigated LD within DNA sequences conserved between the human and mouse genomes.

Results

Unexpectedly, we observed that LD was significantly weaker in conserved regions than in non-conserved regions. To investigate why, we examined sequence features that may distort the relationship between LD and conserved regions. We found that interspersed repeats, and not other sequence features, were associated with the weak LD tendency in conserved regions. To appropriately understand the relationship between LD and conserved regions, we removed the effect of repetitive elements and found that the high degree of sequence conservation was strongly associated with strong LD in coding regions but not with that in non-coding regions.

Conclusion

Our work demonstrates that the degree of sequence conservation does not simply increase LD as predicted by the hypothesis. Rather, it implies that purifying selection changes the polymorphic patterns of coding sequences but has little influence on the patterns of functional units such as regulatory elements present in non-coding regions, since the former are generally restricted by the constraint of maintaining a functional protein product across multiple exons while the latter may exist more as individually isolated units.
Comprehensive analysis of alternative splicing in rice and comparative analyses with Arabidopsis
Authors: Campbell Matthew A , Haas Brian J , Hamilton John P , Mount Stephen M , Buell C Robin
Published: December 2006

Background

Recently, genomic sequencing efforts were finished for Oryza sativa (cultivated rice) and Arabidopsis thaliana (Arabidopsis). Additionally, these two plant species have extensive cDNA and expressed sequence tag (EST) libraries. We employed the Program to Assemble Spliced Alignments (PASA) to identify and analyze alternatively spliced isoforms in both species.

Results

A comprehensive analysis of alternative splicing was performed in rice that started with >1.1 million publicly available spliced ESTs and over 30,000 full length cDNAs in conjunction with the newly enhanced PASA software. A parallel analysis was performed with Arabidopsis to compare and ascertain potential differences between monocots and dicots. Alternative splicing is a widespread phenomenon (observed in greater than 30% of the loci with transcript support) and we have described nine alternative splicing variations. While alternative splicing has the potential to create many RNA isoforms from a single locus, the majority of loci generate only two or three isoforms and transcript support indicates that these isoforms are generally not rare events. For the alternate donor (AD) and acceptor (AA) classes, the distance between the splice sites for the majority of events was found to be less than 50 basepairs (bp). In both species, the most frequent distance between AA is 3 bp, consistent with reports in mammalian systems. Conversely, the most frequent distance between AD is 4 bp in both plant species, as previously observed in mouse. Most alternative splicing variations are localized to the protein coding sequence and are predicted to significantly alter the coding sequence.

Conclusion

Alternative splicing is widespread in both rice and Arabidopsis and these species share many common features. Interestingly, alternative splicing may play a role beyond creating novel combinations of transcripts that expand the proteome. Many isoforms will presumably have negative consequences for protein structure and function, suggesting that their biological role involves post-transcriptional regulation of gene expression.
Detection of transcriptional difference of porcine imprinted genes using different microarray platforms
Authors: Tsai Shengdar , Mir Bashir , Martin Amy C , Estrada Jose L , Bischoff Steve R , Hsieh Wen-ping , Cassady Joseph P , Freking Bradley A , Nonneman Dan J , Rohrer Gary A , Piedrahita Jorge A
Published: December 2006

Background

Presently, multiple options exist for conducting gene expression profiling studies in swine. In order to determine the performance of some of the existing microarrays, Affymetrix Porcine, Affymetrix Human U133+2.0, and the U.S. Pig Genome Coordination Program spotted glass oligonucleotide microarrays were compared for their reproducibility, coverage, platform independent and dependent sensitivity using fibroblast cell lines derived from control and parthenogenic porcine embryos.

Results

Array group correlations between technical replicates demonstrated comparable reproducibility in both Affymetrix arrays. Glass oligonucleotide arrays showed greater variability and, in addition, approximately 10% of probes had to be discarded due to slide printing defects. Probe level analysis of Affymetrix Human arrays revealed significant variability within probe sets due to the effects of cross-species hybridization. Affymetrix Porcine arrays identified the greatest number of differentially expressed genes amongst probes common to all arrays, a measure of platform sensitivity. Affymetrix Porcine arrays also identified the greatest number of differentially expressed known imprinted genes using all probes on each array, an ad hoc measure of realistic performance for this particular experiment.

Conclusion

We conclude that of the platforms currently available and tested, the Affymetrix Porcine array is the most sensitive and reproducible microarray for swine genomic studies.
Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937
Authors: Nyaga Simon G , Lohani Althaf , Jaruga Pawel , Trzeciak Andrzej R , Dizdaroglu Miral , Evans Michele K
Published: December 2006

Background

Breast cancer is the second leading cause of cancer deaths in women in the United States. Although the causes of this disease are incompletely understood, oxidative DNA damage is presumed to play a critical role in breast carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH-Gua), which has been implicated in carcinogenesis. The aim of this study was to investigate the ability of HCC1937 and MCF-7 breast cancer cell lines to repair 8-OH-Gua relative to a nonmalignant human mammary epithelial cell line, AG11134.

Methods

We used oligonucleotide incision assay to analyze the ability of the two breast cancer cell lines to incise 8-OH-Gua relative to the control cell line. Liquid chromatography/mass spectrometry (LC/MS) was used to measure the levels of 8-OH-Gua as its nucleoside, 8-OH-dG in the cell lines after exposure to H2O2 followed by 30 min repair period. Protein expression levels were determined by Western blot analysis, while the hOGG1 mRNA levels were analyzed by RT-PCR. Complementation of hOGG1 activity in HCC1937 cells was assessed by addition of the purified protein in the incision assay, and in vivo by transfection of pFlagCMV-4-hOGG1. Clonogenic survival assay was used to determine sensitivity after H2O2-mediated oxidative stress.

Results

We show that the HCC1937 breast cancer cells have diminished ability to incise 8-OH-Gua and they accumulate higher levels of 8-OH-dG in the nuclear genome after H2O2 treatment despite a 30 min repair period when compared to the nonmalignant mammary cells. The defective incision of 8-OH-Gua was consistent with expression of undetectable amounts of hOGG1 in HCC1937 cells. The reduced incision activity was significantly stimulated by addition of purified hOGG1. Furthermore, transfection of pFlagCMV-4-hOGG1 in HCC1937 cells resulted in enhanced incision of 8-OH-Gua. HCC1937 cells are more sensitive to high levels of H2O2 and have up-regulated SOD1 and SOD2.

Conclusion

This study provides evidence for inefficient repair of 8-OH-Gua in HCC1937 breast cancer cell line and directly implicates hOGG1 in this defect.
An association of a simultaneous nuclear and cytoplasmic localization of Fra-1 with breast malignancy
Authors: Song Yuhua , Song Santai , Zhang Dong , Zhang Yan , Chen Liyong , Qian Lu , Shi Ming , Zhao Huibin , Jiang Zefei , Guo Ning
Published: December 2006

Background

Overexpression of Fra-1 in fibroblasts causes anchorage-independent cell growth and oncogenic transformation. A high level of Fra-1 expression is found in various tumors and tumorigenic cell lines, suggesting that Fra-1 may be involved in malignant progression. This study aimed to investigate the significance of Fra-1 expression in breast carcinogenesis.

Methods

The expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast diseases ranging from benign fibroadenoma to very aggressive undifferentiated carcinoma. The correlations of Fra-1 expression with other indicators of breast carcinoma prognosis (ER, PR and ErbB2 receptors) were analyzed.

Results

All neoplastic breast tissues, either benign or malignant breast tissues, were nuclear immunoreactive for Fra-1-recognizing antibody. The pattern of Fra-1 expression by benign neoplastic cells was predominantly nuclear. However, the nuclear/cytoplasmic concomitant immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in ~90% of breast carcinomas.

Conclusion

The overall expression, pattern and intensity of Fra-1 proteins were correlated with breast oncogenesis. Overexpression of Fra-1, leading to a persistent high cytoplasmic accumulation, may play a role in the process of breast carcinogenesis.
The effect of the holiday season on body weight and composition in college students
Authors: Hull Holly R , Hester Casey N , Fields David A
Published: December 2006

Background

With the rapid increase in obesity rates, determining critical periods for weight gain and the effects of changes in fat mass is imperative. The purpose of this study was to examine changes in body weight and composition over the holiday season (Thanksgiving through New Year's) in male and female college students.

Methods

Subjects completed three visits: the first occurred within 2 weeks prior to Thanksgiving, the second occurred within 5 to 7 days following Thanksgiving, and the third occurred within 10 days following New Year's Day. A total of 82 healthy male and female college age subjects participated. Body composition by dual energy x-ray absorptiometry (DXA) was assessed at visits 1 and 3 while body weight was assessed at all three visits.

Results

Average body weight remained relatively unchanged from pre-Thanksgiving to post-New Year's (71.3 ± 14 kg vs. 71.2 ± 15 kg; P = 0.71) and, in fact, a subset of normal weight subjects lost a significant amount of body weight. However, percent body fat (25.9 ± 9 %fat vs. 27.0 ± 9 %fat; P < 0.01) and fat mass (18.3 ± 8 kg and 19.1 ± 8 kg; P < 0.01) significantly increased from pre-Thanksgiving to post-New Year's while fat-free mass (48.7 ± 12 kg and 48.3 ± 11 kg; P = 0.08) was not significantly different than the post-New Year's. A significant positive relationship (P < 0.001) between the change in BMI and percent fat, total fat mass, total fat free mass, and trunk fat mass for the pre-Thanksgiving and post-New Year's visits were found. The same significant positive relationships (P < 0.001) were also observed between the change in body weight and percent fat, total fat mass, total fat free mass, and trunk fat mass.

Conclusion

Despite the fact that body weight remained unchanged over the course of the holiday season, a significant increase in %body fat and fat mass was observed. With recent evidence showing marked morbidity and mortality to be associated with increased body fat (particularly abdominal adiposity), results from this study suggest body weight alone may underestimate the potentially deleterious effects of the holiday season.
Compressive loading at the end plate directly regulates flow and deformation of the basivertebral vein: an analytical study
Authors: Yeh Ming-Long , Heggeness Michael H. , Chen Hsiang-Ho , Jassawalla Jennifer , Luo Zong-Ping
Published: December 2006

Background

Metastatic diseases and infections frequently involve the spine. This is the result of seeding of the vertebral body by tumor cells or bacteria delivered by venous blood from Batson's plexus, which is hypothesized to enter the vertebral body via the epidural veins. Isolated spinal segments deform significantly at the bony end plate when under compression. This deformation could cause a volume change of the vertebral body and may be accompanied by retrograde flow of venous blood. To date, this process has not been investigated quantitatively. The purpose of this study was to determine the volume changes of the vertebral body and basivertebral vein for a vertebral body under compression.

Methods

A three-dimensional finite element mesh model of the L4 segment with both adjacent discs was modified from a 3-D computed tomography scan image. An octagon representing the basivertebral vein was introduced into the center of the vertebral body in the model. Four compressive orientations (1500 N) were applied on the top disc. The volume change of the vertebral body model and the basivertebral vein were then computed.

Results

The volume change of the vertebral body was about 0.1 cm3 (16.3% of the basivertebral vein) for the four loading conditions. The maximum cross-sectional area reductions of the basivertebral vein and volume reduction were 1.54% and 1.02%, for uniform compression.

Conclusion

Our study quantified the small but significant volume change of a modeled vertebral body and cross-sectional areas and that of the basivertebral vein, due to the inward bulging of the end plate under compression. This volume change could initiate the reverse flow of blood from the epidural venous system and cause seeding of tumors or bacterial cells.
Psychodynamic contributions to early intervention in psychosis
Authors: Martindale Brian V.
Published: December 2006

This article considers the contribution that psychodynamics can make to the work of teams providing early intervention in psychosis. Psychodynamic understanding enriches the stress and vulnerability psychosis model; can contribute to resolving the issues involved in relapse prevention; informs individualised formulations; and can make sense of patients' reactions to prescribing in psychosis. A rationale is given for longer-term individual, group and family dynamic psychotherapies within early intervention teams.
Postgraduate psychiatric training and education in the UK: a search for evidence
Authors: Chaturvedi Santosh K. , Goel Ritu , Bhugra Dinesh
Published: December 2006

We discuss the implications of our systematic review of the evidence regarding current postgraduate psychiatric training methods in the UK. The review found only 24 papers on the topic, 10 of which were research based. None of the papers addressed the reliability and validity of the teaching methods studied. These papers suggest that issues regarding psychiatric training and education in the UK have been addressed only to a limited extent. There is thus an urgent need for more rigorous and scientific evaluation of training methods, especially now that training and assessment are changing in the UK.
Attachment theory in adult psychiatry. Part 2: Importance to the therapeutic relationship
Authors: Ma Kenneth
Published: December 2006

This article focuses on how the general adult psychiatrist, in thinking about everyday clinical problems, may usefully apply attachment theory to gain insight. Fictional case vignettes are used to illustrate the importance of attachment in shaping and understanding the clinician–patient relationship. Ways in which service configurations may be informed by attachment theory are also examined.
Distribution of CORE–OM scores in a general population, clinical
cut-off points and comparison with the CIS–R
Authors: Connell Janice , Barkham Michael , Stiles William B. , Twigg Elspeth , Singleton Nicola , Evans Olga , Miles Jeremy N. V.
Published: December 2006

Background

Although measures of psychopathology are designed for use in clinical
populations, their meaning derives from comparison with normal
populations.

Aims

To compare the distribution of scores on the Clinical Outcomes in Routine
Evaluation — Outcome Measure (CORE-OM) from a general population sample
with the distribution in an aggregated clinical sample to derive
recommended cut-off points for determining clinical significance.

Method

The CORE-OM general population sample was based on a weighted subsample
of participants in the psychiatric morbidity follow-up survey who
completed valid CORE-OM forms following their interview (effective
n=535).

Results

Comparison of the CORE-OM general population sample with a clinical
sample aggregated from previous studies (n=10761)
yielded a cut-off score of 9.9 on the 0–40 scale of the CORE-OM. The
CORE-OM was highly correlated (r=0.77) with the Clinical
Interview Schedule — Revised, supporting convergent validity.

Conclusions

We recommend rounding the CORE-OM cut-off score to 10. However, cut-off
scores must be used thoughtfully and adjusted to fit context and
purpose.
Mental ill-health in adults with intellectual disabilities:
prevalence and associated factors
Authors: Cooper Sally-Ann , Smiley Elita , Morrison Jillian , Williamson Andrew , Allan Linda
Published: December 2006

Background

Reported prevalence of mental ill-health among adults with intellectual
disabilities ranges from 7 to 97%, owing to methodological limitations.
Little is known about associations.

Aims

To determine the prevalence of mental ill-health in adults with
intellectual disabilities and to investigate factors independently
associated with it.

Method

Population-based study (n=1023) with comprehensive
individual assessments modelled using regression analyses.

Results

Point prevalence of mental ill-health was 40.9% (clinical diagnoses),
35.2%(DC–LD), 16.6% (ICD–10–DCR) and 15.7% (DSM–IV–TR). The most
prevalent type was problem behaviours. Mental ill-health was associated
with more life events, female gender, type of support, lower ability,
more consultations, smoking, incontinence, not having severe physical
disabilities and not having immobility; it was not associated with
deprived areas, no occupation, communication impairment, epilepsy,
hearing impairment or previous institutional residence.

Conclusions

This investigation informs further longitudinal study, and development of
appropriate interventions, public health strategy and policy. ICD–10–DCR
and DSM–IV–TR undercount mental ill-health in this population compared
with DC–LD.
Competition for neuronal resources: how hallucinations make themselves heard
Authors: Hubl Daniela , Koenig Thomas , Strik Werner K. , Garcia Lester Melie , Dierks Thomas
Published: December 2006

Background

Hallucinations are perceptions in the absence of a corresponding external sensory stimulus. However, during auditory verbal hallucinations, activation of the primary auditory cortex has been described.

Aims

The objective of this study was to investigate whether this activation of the auditory cortex contributes essentially to the character of hallucinations and attributes them to alien sources, or whether the auditory activation is a sign of increased general auditory attention to external sounds.

Method

The responsiveness of the auditory cortex was investigated by auditory evoked potentials (N100) during the simultaneous occurrence of hallucinations and external stimuli. Evoked potentials were computed separately for periods with and without hallucinations; N100 power, topography and brain electrical sources were analysed.

Results

Hallucinations lowered the N100 amplitudes and changed the topography, presumably due to a reduced left temporal responsivity.

Conclusions

This finding indicates competition between auditory stimuli and hallucinations for physiological resources in the primary auditory cortex. The abnormal activation of the primary auditory cortex may thus be a constituent of auditory hallucinations.
Efficacy of the Community Re-Entry Module for patients with
schizophrenia in Beijing, China: outcome at 2-year follow-up
Authors: Xiang Yu-Tao , Weng Yong-Zhen , Li Wen-Yong , Gao Liang , Chen Guo-Lan , Xie Ling , Chang Yan-Li , Tang Wai-Kwong , Ungvari Gabor Sandor
Published: December 2006

Background

Few psychosocial interventions have been developed in China that are
suitable for use in the community.

Aims

To evaluate the effectiveness of the Chinese version of the Community
Re-Entry Module (CRM; a module of a standardised, structured social
skills training programme devised at the University of California, Los
Angeles) for patients with schizophrenia compared with standard group
psychoeducation.

Method

Patients with schizophrenia (n=103) were randomly
allocated to CRM or psychoeducation groups and followed up for 24 months.
Outcome measures included social functioning, psychiatric symptoms,
insight, re-employment, relapse and re-hospitalisation rates.

Results

The CRM group significantly improved in terms of social functioning,
insight and psychiatric symptoms compared with the psychoeducation group;
the re-employment rate was significantly higher and relapse and
rehospitalisation rates were significantly lower in the CRM group.

Conclusions

The findings support the feasibility and effectiveness of CRM as a
psychosocial intervention for Chinese patients with schizophrenia in the
community.
Contribution of low- and middle-income countries to research
published in leading general psychiatry journals, 2002–2004
Authors: Patel Vikram , Kim Youl-Ri
Published: December 2006

We aimed to describe the contribution of low- and middle-income (LAMI)
countries to leading general psychiatric journals. We reviewed original
research published over a 3-year period (2002–2004) in the six
highest-impact general psychiatry journals and contacted editorial offices
to gather data on country of origin of submitted and accepted articles. Only
3.7% of published research emerges from these less affluent countries, which
account for over 80% of the global population. Compared with the findings of
a similar review of the period 1996–1998, there has been little change. The
three European journals had a higher representation than the three American
Journals. The proportion of psychiatrists in a country was associated with
that country's research output. As much as 50% of the research from LAMI
countries is led by authors from high-income countries. The proportion of
submissions from LAMI countries was very low, and articles from them were
more frequently rejected. Strengthening the research capacity of these
countries and reviewing the editorial policies of leading journals can help
increase the international representation of LAMI countries in psychiatric
research.
The simulated mental health review tribunal – a valuable training tool for senior house officers?
Authors: Naeem Asim , Gupta Bhanu , Rutherford Joan , Gachen Audrey , Roberts Sarah
Published: December 2006

Aims and Method

Psychiatric senior house officers currently receive little formal training in how to give testimony at mental health review tribunals. The development of a simulated tribunal workshop for trainees, which is group-based, interactive and experiential in nature, with meaningful user and carer input is described.

Results

We have incorporated simulated mental health review tribunal workshops into our academic programme and these have been successfully evaluated. Feedback has shown a marked increase in the confidence levels of trainees regarding tribunals.

Clinical Implications

The new Mental Health Act (England and Wales) is likely to place increasing demands on psychiatrists, in terms of giving testimony at mental health review tribunals. Simulated training for senior house officers, incorporating user and carer perspectives, can improve their skills and confidence in presenting at actual tribunals.
The National Trend in Quality of Emergency Department Pain Management for Long Bone Fractures
Authors: Ritsema Tamara S. , Kelen Gabor D. , Pronovost Peter J. , Pham Julius Cuong
Published: December 2006

Background

Despite national attention, there is little evidence that the quality of emergency department (ED) pain management is improving.

Objectives

To compare the quality of ED pain management before and after implementation of the Joint Commission on the Accreditation of Healthcare Organizations' standards in 2001.

Methods

The authors performed a retrospective cohort study by using the National Hospital Ambulatory Medical Care Survey from 1998–2003. Patients who presented to the ED with a long bone fracture (femur, humerus, tibia, fibula, radius, or ulna) were compared. The authors extracted data on patient, visit, and hospital characteristics. The primary outcomes were the proportion of patients who received assessment of pain severity and who received analgesic treatment.

Results

There were 2,064 patients with a qualifying fracture in the study period, 834 from 1998–2000 and 1,230 from 2001–2003. Compared with the early period, a higher proportion of patients in the late period had their pain assessed (74% vs. 57%), received opiates (56% vs. 50%), and received any analgesic (76% vs. 56%). Patients in the late period had higher odds of receiving any analgesia (adjusted odds ratio [OR], 1.43) and opioid analgesia (adjusted OR, 1.27) compared with the early period. Patients in the middle age group (adjusted OR, 2.28) or those seen by physician assistants (adjusted OR, 2.05) were more likely, whereas those with Medicaid (adjusted OR, 0.58) and those in the Northeast were less likely, to receive opiates.

Conclusions

Although the quality of ED pain management for acute fractures appears to be improving, there is still room for further improvement.
Anticipating Demand for Emergency Health Services due to Medication‐related Adverse Events after Rapid Mass Prophylaxis Campaigns
Authors: Hupert Nathaniel , Wattson Daniel , Cuomo Jason , Benson Samuel
Published: December 2006

Objectives: Mass prophylaxis against infectious disease outbreaks carries the risk of medication‐related adverse events (MRAEs). The authors sought to define the relationship between the rapidity of mass prophylaxis dispensing and the subsequent demand for emergency health services due to predictable MRAEs.

Methods: The authors created a spreadsheet‐based computer model that calculates scenario‐specific predicted daily MRAE rates from user inputs by applying a probability distribution to the reported timing of MRAEs. A hypothetical two‐ to ten‐day prophylaxis campaign for one million people using recent data from both smallpox vaccination and anthrax chemoprophylaxis campaigns was modeled.

Results: The length of a mass prophylaxis campaign plays an important role in determining the subsequent intensity in emergency services utilization due to real or suspected adverse events. A two‐day smallpox vaccination scenario would produce an estimated 32,000 medical encounters and 1,960 hospitalizations, peaking at 5,246 health care encounters six days after the start of the campaign; in contrast, a ten‐day campaign would lead to 41% lower peak surge, with a maximum of 3,106 encounters on the busiest day, ten days after initiation of the campaign. MRAEs with longer lead times, such as those associated with anthrax chemoprophylaxis, exhibit less variability based on campaign length (e.g., 124 out of an estimated 1,400 hospitalizations on day 20 after a two‐day campaign versus 103 on day 24 after a ten‐day campaign).

Conclusions: The duration of a mass prophylaxis campaign may have a substantial impact on the timing and peak number of clinically significant MRAEs, with very short campaigns overwhelming existing emergency department (ED) capacity to treat real or suspected medication‐related injuries. While better reporting of both incidence and timing of MRAEs in future prophylaxis campaigns should improve the application of this model to community‐based emergency preparedness planning, these results highlight the need for coordination between public health and emergency medicine planning for infectious disease outbreaks to avoid preventable surges in ED utilization.
International Emergency Medicine: A Review of the Literature
Authors: Levine Adam C. , Gadiraju Silpa , Goel Ashish , Johar Sandeep , King Renee , Arnold Kris
Published: December 2006

The field of international emergency medicine has grown rapidly over the past several decades, with an increase in the number of interested individuals and in the range of topics included under its rubric. One of the greatest obstacles, however, faced by international emergency medicine researchers and practitioners alike remains the lack of a high‐quality, consolidated, and easily accessible evidence base of literature. In response to this perceived need, members of the Emergency Medicine Residents' Association International Emergency Medicine Committee, in conjunction with members of the Society for Academic Emergency Medicine International Interest Group, embarked on the task of creating a recurring review of international emergency medicine literature. Articles for this first annual review, covering research published in 2005, were selected according to explicit, predetermined criteria that included both methodological quality and perceived impact of the research. It is our hope that this annual review will act as a forum for disseminating best practices, while also stimulating further research in the field of international emergency medicine.
Need for Standardized Sign‐out in the Emergency Department: A Survey of Emergency Medicine Residency and Pediatric Emergency Medicine Fellowship Program Directors
Authors: Sinha Madhumita , Shriki Jesse , Salness Rebecca , Blackburn Paul A.
Published: December 2006

Objectives

To determine the existing patterns of sign‐out processes prevalent in emergency departments (EDs) nationwide. In addition, to assess whether training programs provide specific guidance to their trainees regarding sign‐outs and attitudes of emergency medicine (EM) residency and pediatric EM fellowship program directors toward the need for the development of standardized guidelines relating to sign‐outs.

Methods

A Web‐based survey of training program directors of each Accreditation Council for Graduate Medical Education (ACGME)–accredited EM residency and pediatric EM fellowship program was conducted in March 2006.

Results

Overall, 185 (61.1%) program directors responded to the survey. One hundred thirty‐six (73.5%) program directors reported that sign‐outs at change of shift occurred in a common area within the ED, and 79 (42.7%) respondents indicated combined sign‐outs in the presence of both attending and resident physicians. A majority of the programs, 119 (89.5%), stated that there was no uniform written policy regarding patient sign‐out in their ED. Half (50.3%) of all those surveyed reported that physicians sign out patient details “verbally only,” and 79 (42.9%) noted that transfer of attending responsibility was “rarely documented.” Only 34 (25.6%) programs affirmed that they had formal didactic sessions focused on sign‐outs. A majority (71.6%) of program directors surveyed agreed that specific practice parameters regarding transfer of care in the ED would improve patient care; 80 (72.3%) agreed that a standardized sign‐out system in the ED would improve communication and reduce medical error.

Conclusions

There is wide variation in the sign‐out processes followed by different EDs. A majority of those surveyed expressed the need for standardized sign‐out systems.
Phase II Study of Neoadjuvant Androgen Deprivation Followed by External-Beam Radiotherapy With 9 Months of Androgen Deprivation for Intermediate- to High-Risk Localized Prostate Cancer
Authors: Heymann Jonas J. , Benson Mitchell C. , O'Toole Kathleen M. , Malyszko Bozena , Brody Rachel , Vecchio Darleen , Schiff Peter B. , Mansukhani Mahesh M. , Ennis Ronald D.
Published: December 2006

Purpose

To evaluate the toxicity and efficacy of individualized neoadjuvant androgen deprivation (AD) to maximal response followed by external beam radiotherapy (RT) with continued AD for a total of 9 months in a prospective phase II trial.

Patients and Methods

One hundred twenty-three patients received a total of 9 months of flutamide and luprolide combined with RT. RT initiation was individualized to begin after maximum response to AD as assessed by monthly digital rectal examination and prostate-specific antigen (PSA). The neoadjuvant phase was restricted to no more than 6 months.

Results

Median time to initiation of RT was 4.7 months. Indications to begin RT (and their rates) were undetectable PSA (28%), PSA unchanged from one month to the next (46%), PSA rising from one month to the next (10%), 6 months of AD (14%), and other (2%). Five-year outcomes were biochemical disease-free survival, (DFS) 63% ± 7%; clinical DFS, 75% ± 5%; cancer-specific survival, 99% ± 1%; and overall survival, 89% ± 3%. Patients initiating RT after 6 months of AD had significantly lower biochemical and clinical DFS. Those patients whose testosterone recovered to normal after completion of AD had a significantly superior survival rate. Of those patients potent before treatment, 65% remained so at last follow-up.

Conclusion

The combination of 9 months of AD and RT, with initiation of RT individualized on the basis of maximum response to AD, achieves disease control rates comparable with past studies, while preserving potency in many patients. Further studies are warranted to determine the optimal combination of AD and RT in this patient population.
Cancer Rates After Year 2000 Significantly Decrease in Children With Perinatal HIV Infection: A Study by the Italian Register for HIV Infection in Children
Authors: Chiappini Elena , Galli Luisa , Tovo Pier-Angelo , Gabiano Clara , Lisi Catiuscia , Giaquinto Carlo , Rampon Osvalda , Gattinara Guido Castelli , De Marco Giulio , Osimani Patrizia , Manzionna Mariano , Miniaci Angela , Pintor Carlo , Rosso Raffaella , Esposito Susanna , Viganò Alessandra , Dodi Icilio , Maccabruni Anna , Fundarò Carlo , de Martino Maurizio
Published: December 2006

Purpose

To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period.

Patients and Methods

An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%.

Results

Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004).

Conclusion

Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.
Pharmacokinetics of Gemcitabine in Japanese Cancer Patients: The Impact of a Cytidine Deaminase Polymorphism
Authors: Sugiyama Emiko , Kaniwa Nahoko , Kim Su-Ryang , Kikura-Hanajiri Ruri , Hasegawa Ryuichi , Maekawa Keiko , Saito Yoshiro , Ozawa Shogo , Sawada Jun-ichi , Kamatani Naoyuki , Furuse Junji , Ishii Hiroshi , Yoshida Teruhiko , Ueno Hideki , Okusaka Takuji , Saijo Nagahiro
Published: December 2006

Purpose

Gemcitabine is rapidly metabolized to its inactive metabolite, 2′,2′-difluorodeoxyuridine (dFdU), by cytidine deaminase (CDA). We previously reported that a patient with homozygous 208A alleles of CDA showed severe adverse reactions with an increase in gemcitabine plasma level. This study extended the investigation of the effects of CDA genetic polymorphisms on gemcitabine pharmacokinetics and toxicities.

Patients and Methods

Genotyping of CDA was performed by a direct sequencing of DNA obtained from the peripheral blood of Japanese gemcitabine-naïve cancer patients (n = 256). The patients recruited to the association study received a 30-minute intravenous infusion of gemcitabine at a dose of either 800 or 1,000 mg/m2, and eight blood samples were periodically collected (n = 250). Plasma levels of gemcitabine and dFdU were measured by high-performance liquid chromatography. Plasma CDA activities toward cytidine and gemcitabine were also measured (n = 121).

Results

Twenty-six genetic variations, including 14 novel ones and two known nonsynonymous single nucleotide polymorphisms (SNPs), were detected. Haplotypes harboring the nonsynonymous SNPs 79A>C (Lys27Gln) and 208G>A (Ala70Thr) were designated *2 and *3, respectively. The allelic frequencies of the two SNPs were 0.207 and 0.037, respectively. Pharmacokinetic parameters of gemcitabine and plasma CDA activities significantly depended on the number of haplotype *3. Haplotype *3 was also associated with increased incidences of grade 3 or higher neutropenia in the patients who were coadministered fluorouracil, cisplatin, or carboplatin. Haplotype *2 showed no significant effect on gemcitabine pharmacokinetics.

Conclusion

Haplotype *3 harboring a nonsynonymous SNP, 208G>A (Ala70Thr), decreased clearance of gemcitabine, and increased incidences of neutropenia when patients were coadministered platinum-containing drugs or fluorouracil.
Comparison of Intensive Chemotherapy, Allogeneic, or Autologous Stem-Cell Transplantation As Postremission Treatment for Children With Very High Risk Acute Lymphoblastic Leukemia: PETHEMA ALL-93 Trial
Authors: Ribera Jose-Maria , Ortega Juan-José , Oriol Albert , Bastida Pilar , Calvo Carlota , Pérez-Hurtado José-María , González-Valentín María-Elvira , Martín-Reina Victoria , Molinés Antonio , Ortega-Rivas Fernando , Moreno Maria-José , Rivas Concepción , Egurbide Izaskun , Heras Inmaculada , Poderós Concepción , Martínez-Revuelta Eva , Guinea José-Maria , del Potro Eloy , Deben Guillermo
Published: December 2006

Purpose

The optimal postremission therapy for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is not well established. This randomized trial compared three options of postremission therapy: chemotherapy and allogeneic or autologous stem-cell transplantation (SCT).

Patients and Methods

All 106 VHR-ALL patients received induction with five drugs followed by intensification with three cycles of chemotherapy. Patients in complete remission (CR) with an HLA-identical family donor were assigned to allogeneic SCT (n = 24) and the remaining were randomly assigned to autologous SCT (n = 38) or to delayed intensification followed by maintenance chemotherapy up to 2 years in CR (n = 38).

Results

Overall, 100 patients achieved CR (94%). With a median follow-up of 6.5 years, 5-year disease-free survival (DFS) and overall survival (OS) probabilities were 45% (95% CI, 37% to 54%) and 48% (95% CI, 40% to 57%), respectively. The three groups were comparable in the main pretreatment ALL characteristics. Intention-to-treat analysis showed no differences for donor versus no donor in DFS (45%; 95% CI, 27% to 65% v 45%; 95% CI, 37% to 55%) and OS (48%; 95% CI, 30% to 67% v 51%; 95% CI, 43% to 61%), as well as for autologous SCT versus chemotherapy comparisons (DFS: 44%; 95% CI, 29% to 60% v 46%; 95% CI, 32% to 62%; OS: 45%; 95% CI, 31% to 62% v 57%; 95% CI, 43% to 73%). No differences were found within the different subgroups of ALL and neither were differences observed when the analysis was made by treatment actually performed.

Conclusion

This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in children with VHR-ALL.