bluuebunny/crossref_metadata_2025 huggingface dataset:
fMRI Demonstrates Diaschisis in the Extrastriate Visual Cortex
Authors: Brodtmann Amy , Puce Aina , Darby David , Donnan Geoffrey
Published: June 2007

Background and Purpose—

Diaschisis may play a critical role in motor recovery, but in other cortical networks its role is unclear. Some visual system regions, such as the fusiform gyri, depend on intact striate regulation for their function. We evaluated visual cortical diaschisis by serial functional magnetic resonance imaging.

Methods—

Using a high-level visual activation task, we studied patients with visual system stroke by functional magnetic resonance imaging within 10 days and at 6 months. Their activation data were compared with those of age-appropriate healthy control subjects.

Results—

Three patients were studied. In the short term, patients displayed absent or significantly reduced activation in ventral extrastriate sites. All displayed a restitution of activation to these sites at 6 months.

Conclusions—

Functional magnetic resonance imaging revealed evidence of ipsilesional cortical diaschisis within ventral extrastriate sites. Diaschisis may play an underrecognized role in visual recovery after stroke.
Stent-Assisted Endovascular Thrombolysis Versus Intravenous Thrombolysis in Internal Carotid Artery Dissection With Tandem Internal Carotid and Middle Cerebral Artery Occlusion
Authors: Lavallée Philippa C. , Mazighi Mickaël , Saint-Maurice Jean-Pierre , Meseguer Elena , Abboud Halim , Klein Isabelle F. , Houdart Emmanuel , Amarenco Pierre
Published: June 2007

Background and Purpose—

Tandem internal carotid and middle cerebral artery occlusion independently predicts poor outcome after intravenous thrombolysis. Recanalization of internal carotid artery dissection by stent-assisted angioplasty has recently been proposed when anticoagulation fails to prevent a new ischemic event. We recently reported a case of tandem internal carotid and middle cerebral artery occlusion with dissection of the internal carotid artery successfully treated with endovascular stent-assisted thrombolysis.

Methods—

We compared clinical outcomes in consecutive patients presenting with tandem internal carotid and middle cerebral artery occlusion with internal carotid artery dissection within 3 hours of symptom onset who were eligible for intravenous thrombolysis, treated by either endovascular stent-assisted thrombolysis or intravenous recombinant tissue-type plasminogen activator (rtPA) when an endovascular therapist was unavailable. National Institutes of Health Stroke Scale scores were obtained at baseline and after 24 hours. The modified Rankin Scale score was used to assess outcomes at 3 months. Arterial recanalization was assessed by magnetic resonance imaging.

Results—

Of 10 patients screened, 6 were treated with endovascular therapy and 4 with intravenous rtPA. Before treatment, mean National Institutes of Health Stroke Scale scores were high and comparable in the 2 groups (17 and 16, respectively). In the endovascular group, all patients achieved middle cerebral artery recanalization with subsequent dramatic improvement versus only 1 patient with middle cerebral artery recanalization in the intravenous rtPA group. At 3 months, 4 patients in the endovascular group had a favorable outcome (modified Rankin Scale score=0). In the intravenous rtPA group, 3 patients had a poor outcome (modified Rankin Scale score≥3).

Conclusions—

Endovascular stent-assisted thrombolysis is a promising treatment in tandem internal carotid and middle cerebral artery occlusion due to internal carotid artery dissection and compares favorably with intravenous rtPA.
Seasonal-to-Interannual Forecasting of Tropical Indian Ocean Sea Surface Temperature Anomalies: Potential Predictability and Barriers
Authors: Wajsowicz Roxana C.
Published: June 2007

Whether seasonally phased-locked persistence and predictability barriers, similar to the boreal spring barriers found for El Niño–Southern Oscillation (ENSO), exist for the tropical Indian Ocean sector climate is investigated using observations and hindcasts from two coupled ocean–atmosphere dynamical ensemble forecast systems: the National Centers for Environmental Prediction (NCEP) Coupled Forecast System (CFS) for 1990–2003, and the NASA Seasonal-to-Interannual Prediction Project (NSIPP) system for 1993–2002. The potential predictability of the climate is also assessed under the “perfect model/ensemble” assumption.

Lagged correlations of the indices calculated over the east and west poles of the Indian Ocean dipole mode (IDM) index show weak sea surface temperature anomaly (SSTA) persistence barriers in boreal spring at both poles, but the major decline in correlation at the east pole occurs in boreal midwinter for all start months with an almost immediate recovery, albeit negative correlations, until summer approaches. Processes responsible for the change in sign of SSTAs associated with a major IDM event effect a similar change on much weaker SSTAs. At the west pole, a major decline occurs at the end of boreal summer for fall and winter starts when the thermocline deepens with the seasonal cycle and coupling between the ocean and atmosphere is weak.

A decline in skillful prediction of SSTA at the east pole over boreal winter is also found in the hindcasts, but the relatively large thermocline depth anomalies are skillfully predicted through this time and skill in SSTA prediction returns. A predictability barrier at the onset of the boreal summer monsoon is found at both IDM poles with some return of skill in late fall. Potential predictability calculations suggest that this barrier may be overcome at the west pole with improvements to the forecast systems, but not at the east pole for forecasts initiated in boreal winter unless the ocean is initialized with a memory of fall conditions.
A Model-Based Assessment and Design of a Tropical Indian Ocean Mooring Array
Authors: Oke Peter R. , Schiller Andreas
Published: June 2007

A series of observing system simulation experiments (OSSEs) are performed for the tropical Indian Ocean (±15° from the equator) using a simple analysis system. The analysis system projects an array of observations onto the dominant empirical orthogonal functions (EOFs) derived from an intermediate-resolution (2° × 0.5°) ocean circulation model. This system produces maps of the depth of the 20°C isotherm (D20), representing interannual variability, and the high-pass-filtered mixed layer depth (MLD), representing intraseasonal variability. The OSSEs are designed to assess the suitability of the proposed Indian Ocean surface mooring array for resolving intraseasonal to interannual variability. While the proposed array does a reasonable job of resolving the interannual time scales, it may not adequately resolve the intraseasonal time scales. A procedure is developed to rank the importance of observation locations by determining the observation array that best projects onto the EOFs used in the analysis system. OSSEs using an optimal array clearly outperform the OSSEs using the proposed array. The configuration of the optimal array is sensitive to the number of EOFs considered. The optimal array is also different for D20 and MLD, and depends on whether fixed observations are included that represent an idealized Argo array. Therefore, a relative frequency map of observation locations identified in 24 different OSSEs is compiled and a single, albeit less optimal, array that is referred to as a consolidated array is objectively determined. The consolidated array reflects the general features of the individual optimal arrays derived from all OSSEs. It is found that, in general, observations south of 8°S and off of the Indonesian coast are most important for resolving the interannual variability, while observations a few degrees south of the equator, and west of 75°E, and a few degrees north of the equator, and east of 75°E, are important for resolving the intraseasonal variability. In a series of OSSEs, the consolidated array is shown to outperform the proposed array for all configurations of the analysis system for both D20 and MLD.
Civil–Military Relations—Who Are the Real Principals? A Response to “Courage in the Service of Virtue: The Case of General Shinseki's Testimony before the Iraq War”
Authors: Camacho Paul R. , Hauser William Locke
Published: June 2007

This response to Coletta's “Courage in the Service of Virtue: The Case of General Shinseki's Testimony before the Iraq War” argues that too much significance is attributed to Shinseki's remarks. The larger question is whether military leaders should speak up when their civilian leadership's plan is grossly inadequate. Second, the response considers questions about the middle levels of power. The authors suggest that the principal–agent argument is Shinseki's defense and the ultimate principals are the American public. Third, a table is offered as a means of comparing and contrasting the Huntington–Janowitz positions with new theoretical focuses. Fourth, the conclusion suggests that concerns touched on in the tables (the obligation to speak up, the public space, the implications of economic development, and the changing nature of warfare) overshadow the Shinseki issue and that social action theory and type construction methodology are of service in addressing civil–military relations.
Effects of Union Type on Division of Household Labor
Authors: Davis Shannon N. , Greenstein Theodore N. , Gerteisen Marks Jennifer P.
Published: June 2007

Using data from 17,636 respondents in 28 nations, this research uses multilevel modeling to compare the reported division of household labor and factors affecting it for currently married and currently cohabiting couples. Cohabiting men report performing more household labor than do married men, and cohabiting women report performing less household labor than do married women. The findings provide support for the time-availability, relative-resources, and gender-ideology perspectives. The effects of time availability and relative resources on the division of household labor are substantially the same for both union types, but gender ideology is more influential on the division of labor reported by cohabiting than by married respondents. Implications and suggestions for future research are discussed.
China's Juvenile Delinquency Prevention Law
Authors: Lening Zhang  , Jianhong Liu
Published: June 2007

The present study introduces and discusses the Juvenile Delinquency Prevention Law of the People's Republic of China. The law was promulgated in the context of Chinese socioeconomic reforms and legal reforms in response to the rising delinquency since the early 1980s. The study explains the social and political background of the law with respect to the patterns of delinquency in China. The law has several main features that reflect the Chinese philosophical underpinnings of crime prevention and control, and the study discusses the connection between the law and the traditional Chinese philosophy and thinking. Finally, the study discusses the challenges to the enforcement of the law in Chinese society, which has lacked a legal tradition in its history.
Somatization Disorder, a Cause of Difficult Pain: A Case Report
Authors: Gupta Deepak , Mishra Seema , Bhatnagar Sushma
Published: June 2007

Presented is a case report of a 55-year-old man with a suspected diagnosis of pancreatic malignancy who was referred for pain management to the pain and palliative care clinic. A diagnosis of pain originating from a malignancy was later ruled out. The patient was referred for psychiatric evaluation, where his pain symptoms were confirmed to be somatoform in origin. This case highlights the importance of ruling out somatization as the cause of symptoms in difficult pain patients.
Nursing Autonomy Plays an Important Role in Nurses' Attitudes Toward Caring for Dying Patients
Authors: Miyashita Mitsunori , Nakai Yuko , Sasahara Tomoyo , Koyama Yurie , Shimizu Yoichi , Tsukamoto Naoko , Kawa Masako
Published: June 2007

The aim of this study was to clarify the relationship of nursing autonomy and other factors related to attitudes toward caring for dying patients. A cross-sectional survey of nurses was conducted in November 2003 using a self-administered questionnaire. We collected demographic data from 178 (75%) participants and used the Frommelt Attitude Toward Care of the Dying scale, Form B, Japanese version (FATCOD-Form B-J), the Pankratz Nursing Questionnaire (PNQ), and the Death Attitude Inventory (DAI). FATCOD-Form B-J measures nurse's attitude toward caring for dying patients. It includes two subscales: positive attitude toward caring for the dying patient and perception of patient- and family-centered care. The PNQ measures nursing autonomy of individual nurses and has three subscales: nursing autonomy and advocacy, patients' rights, and rejection of traditional role limitations. The DAI measures attitudes toward death in context of Japanese cultural characteristics. It includes seven subscales: afterlife beliefs, death anxiety, death relief, death avoidance, life purpose, death concern, and supernatural beliefs. We investigated the factors associated with the FATCOD-Form B-J. Support of a mentor regarding end-of-life issues (β = .19, P = .001), death avoidance domain of the DAI (β = —.14, P = 0.03), life purpose domain of the DAI (β = .23, P = .001), and rejection of traditional role limitations domain of the PNQ (β = .51, P = .001) were selected as significant independent variables by multivariate analysis to evaluate nurses' positive attitudes toward caring for dying patients. Death anxiety domain of the DAI (β = —.17, P = .02), patients' rights domain of the PNQ (β =.46, P = .001), and rejection of traditional role limitations domain of the PNQ (β = .34, P = .001) were selected as significant independent variables by multivariate analysis to evaluate the nurses' perception of patient-and family-centered care. In conclusion, nursing autonomy plays an important role in the attitudes of Japanese nurses who care for dying patients. Educational and administrative efforts to strengthen nursing autonomy are necessary.
Measuring Tobacco Smoke Exposure Among Smoking and Nonsmoking Bar and Restaurant Workers
Authors: Okoli Chizimuzo T. C. , Hall Lynne A. , Rayens Mary Kay , Hahn Ellen J.
Published: June 2007

Purpose: This study assesses the validity of hair nicotine as a biomarker for secondhand smoke (SHS) exposure. Although most biomarkers of tobacco-smoke exposure have a relatively short half-life, hair nicotine can measure several months of cumulative SHS exposure. Design: A cross-sectional study of hospitality-industry workers. Method: Hair samples were obtained from 207 bar and restaurant workers and analyzed by the reversed-phase high-performance liquid chromatography with electrochemical detection (HPLC-ECD) method. Self-reported tobacco use and sources of SHS exposure were assessed. Findings: Higher hair-nicotine levels were associated with more cigarettes smoked per day among smokers and a greater number of SHS-exposure sources among nonsmokers. Number of SHS exposure sources, gender, number of cigarettes smoked per day, and type of establishment predicted hair-nicotine levels. Discussion: Hair nicotine is a valid measure of SHS exposure. It may be used as an alternative biomarker to measure longer term SHS exposure.
Trusted Information Sources: The Preferred Option for Complementary and Alternative Medicine Users
Authors: Robinson Anske , Cooper Simon
Published: June 2007

The objective of this article is to explore complementary and alternative medicine (CAM) users' reliance on health service providers, different forms of media, and interpersonal contacts for their health-needs information. To explore this information, a survey was posted to a random sample of 1,308 people in five rural and two metropolitan localities in Victoria, Australia. The response rate was 40% ( n = 459). The overall current CAM use was 52% and lifetime use was 85%. We found that the CAM users obtained most of their health needs information from doctors and CAM practitioners, whereas the Internet and health food shops served as the least useful sources of information. The respondents who used the modalities we labeled as natural remedy modalities accessed the most health information. The study results show that although conventional medicine may question some types of health care information that forms the basis of respondents' decision making, their health care decisions are nevertheless informed decisions.
End-of-life decision-making in respiratory intermediate care units: a European survey
Authors: Nava S. , Sturani C. , Hartl S. , Magni G. , Ciontu M. , Corrado A. , Simonds A.
Published: June 2007

A survey was performed on behalf of the European Respiratory Society to assess end-of-life practices in patients admitted to European respiratory intermediate care units and high dependency units over a 6-month period.

A 33-item questionnaire was sent by e-mail to physicians throughout Europe and the response rate was 28 (29.5%) out of 95. A total of 6,008 patients were admitted and an end-of-life decision was taken in 1,292 (21.5%). The mortality rate in these patients was 68% (884 out of 1,292).

The patients received similar proportions of withholding of treatment (298 (23%) out of 1292), do-not-resuscitate or do-not-intubate orders (442 (34%) out of 1,292) and noninvasive mechanical ventilation as the ceiling of ventilatory care (402 (31%) out of 1,292). Withdrawal of therapy was employed in 149 (11%) out of 1,292 patients and euthanasia in one. Do-not-intubate/do-not-resuscitate orders were more frequently used in North compared with South Europe. All of the 473 competent patients directly participated in the decision, whereas, in 722 (56%) out of 1,292 cases, decision-making was reported to be shared with the nurses.

In European respiratory intermediate care units and high dependency units, an end-of-life decision is taken for 21.5% of patients admitted. Withholding of treatment, do-not-intubate/do-not-resuscitate orders and noninvasive mechanical ventilation as the ventilatory care ceiling are the most common procedures. Competent patients are often involved, together with nurses.
CD8+ T-cell alveolitis in familial pulmonary alveolar microlithiasis
Authors: de Laurentiis G. , Vitiello L. , Racioppi L. , Perna F. , Galgani M. , Merola G. , Carratù P. , Maniscalco M. , Marsico S. , Sofia M.
Published: June 2007

Pulmonary alveolar microlithiasis (PAM) is a rare diffuse lung disease characterised by the accumulation of calcium phosphate microliths within the alveoli.

The causative mechanism of PAM has only recently been discovered, and involves a gene mutation of sodium phosphate co-transporter, which is expressed by alveolar epithelial cells. This mutation may have variable consequences on the clinical phenotype. However, pulmonary cell immune phenotyping in familial PAM has not previously been assessed.

In the present article, the analysis of bronchoalveolar lavage fluid of two siblings with PAM diagnosis revealed a pattern of lymphocytic alveolitis with accumulation of CD8+ T-cells. The clonal complexity of this lymphocyte’s population was assayed by spectratyping, which showed an oligoclonal accumulation of T-cells with a restricted variable beta T-cell receptor (TCR) gene usage. TCR analysis in peripheral blood lymphocytes revealed no abnormal patterns of T-lymphocytes.

In the pulmonary alveolar microlithiasis familial cases reported, CD8-mediated maladaptive immune response may have taken place in the bronchoalveolar compartment. The relationship between this immune dysregulation and genetic background in pulmonary alveolar microlithiasis warrants further investigation.
Gene expression of lung squamous cell carcinoma reflects mode of lymph node involvement
Authors: Larsen J. E. , Pavey S. J. , Bowman R. , Yang I. A. , Clarke B. E. , Colosimo M. L. , Hayward N. K. , Fong K. M.
Published: June 2007

Tumour, node, metastasis staging is essential for lung cancer management. However, similarly staged cancers may have markedly different prognoses, indicating that stage cannot completely explain tumour behaviour. While ipsilateral hilar node involvement is designated N1, the current authors hypothesised that primary tumours involving nodes by direct extension are biologically distinct from those involving nodes through lymphatic metastasis.

Microarrays were used to investigate the gene expression profiles of 59 primary lung squamous cell carcinomas, comparing N0 tumours (n = 35), N1 tumours by direct extension (N1d; n = 8), and N1/N2 tumours by lymphatic metastasis (N1/N2m; n = 16).

Hierarchical clustering using 125 genes differentially expressed between N0 and N1/N2mtumours found N1dtumours clustered with N0 tumours. Class prediction modelling found the expression profiles of all eight N1dtumours were more similar to N0 than to N1/N2mtumours.

The present study demonstrates for the first time that N1 tumours directly invading hilar nodes are genomically different to those that metastasisevialymphatics. Independent reports suggest that tumours with direct, rather than metastatic node involvement have better outcomes. Consequently, the data suggest that there is a need to re-evaluate the N1 staging definition in lung cancer. This is relevant for prognosis prediction and also for clinical management, particularly in selecting those patients most likely to benefit from adjuvant chemotherapy.
New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK
Authors: Fujiwara Kyoko , Igarashi Jun , Irahara Natsumi , Kimura Makoto , Nagase Hiroki
Published: June 2007

Background

A variety of skin cancer susceptibility among mouse strains has allowed identification of genes responsible for skin cancer development. FifteenSktsloci for skin tumour susceptibility have been mapped so far by using the two-stage skin carcinogenesis model [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)]. A few responsible genes have been identified using wild-derived dominant resistantMus spretusmice, and one has been confirmed as a low penetrance cancer susceptibility gene in a variety of human cancers.

Results

In the present study, we found that wild-derived PWK mice developed no tumour by treatment with the two-stage skin carcinogenesis protocol. This phenotype is dominant resistant when crossed with the highly susceptible strain FVB. By analyzing the F1 backcross generation between PWK and FVB, we found empirical evidence of significant linkage at the new lociSkts-fp1on chromosome 4 and suggestive linkage on chromosomes 1, 3, 11, 12 and 14 for skin tumour susceptibility.Skts-fp1includes theSkts7interval, which was previously mapped by aMus spretusand NIH backcross. We also observed suggestive linkage on chromosomes 1 and 2 in the female population only, while suggestive linkage on chromosomes 14 and 15 only was observed in the male population. A significant genetic interaction was seen between markers ofD11Mit339andD16Mit14.

Conclusion

Analysis of this new cross may facilitate the identification of genes responsible for mouse skin cancer susceptibility and may reveal their biological interactions.
Gibberellins and heterosis of plant height in wheat (Triticum aestivum L.)
Authors: Zhang Yi , Ni Zhongfu , Yao Yingyin , Nie Xiuling , Sun Qixin
Published: June 2007

Background

Heterosis in internode elongation and plant height are commonly observed in hybrid plants, and higher GAs contents were found to be correlated with the heterosis in plant height. However, the molecular basis for the increased internode elongation in hybrids is unknown.

Results

In this study, heterosis in plant height was determined in two wheat hybrids, and it was found that the increased elongation of the uppermost internode contributed mostly to the heterosis in plant height. Higher GA4 level was also observed in a wheat hybrid. By using the uppermost internode tissues of wheat, we examined expression patterns of genes participating in both GA biosynthesis and GA response pathways between a hybrid and its parental inbreds. Our results indicated that among the 18 genes analyzed, genes encoding enzymes that promote synthesis of bioactive GAs, and genes that act as positive components in the GA response pathways were up-regulated in hybrid, whereas genes encoding enzymes that deactivate bioactive GAs, and genes that act as negative components of GA response pathways were down-regulated in hybrid. Moreover, the putative wheat GA receptor gene TaGID1, and two GA responsive genes participating in internode elongation, GIP and XET, were also up-regulated in hybrid. A model for GA and heterosis in wheat plant height was proposed.

Conclusion

Our results provided molecular evidences not only for the higher GA levels and more active GA biosynthesis in hybrid, but also for the heterosis in plant height of wheat and possibly other cereal crops.
Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators
Authors: Yaklichkin Sergey , Vekker Alexander , Stayrook Steven , Lewis Mitchell , Kessler Daniel S
Published: June 2007

Background

The Fox gene family comprises a large and functionally diverse group offorkhead-related transcriptional regulators, many of which are essential for metazoan embryogenesis and physiology. Defining conserved functional domains that mediate the transcriptional activity of Fox proteins will contribute to a comprehensive understanding of the biological function of Fox family genes.

Results

Systematic analysis of 458 protein sequences of the metazoan Fox family was performed to identify the presence of the engrailed homology-1 motif (eh1), a motif known to mediate physical interaction with transcriptional corepressors of the TLE/Groucho family. Greater than 50% of Fox proteins contain sequences with high similarity to the eh1 motif, including ten of the nineteen Fox subclasses (A, B, C, D, E, G, H, I, L, and Q) and Fox proteins of early divergent species such as marine sponge. The eh1 motif is not detected in Fox proteins of the F, J, K, M, N, O, P, R and S subclasses, or in yeast Fox proteins. The eh1-like motifs are positioned C-terminal to the winged helix DNA-binding domain in all subclasses except for FoxG proteins, which have an N-terminal motif. Two similar eh1-like motifs are found in the zebrafish FoxQ1 and in FoxG proteins of sea urchin and amphioxus. The identification of eh1-like motifs by manual sequence alignment was validated by statistical analyses of the Swiss protein database, confirming a high frequency of occurrence of eh1-like sequences in Fox family proteins. Structural predictions suggest that the majority of identified eh1-like motifs are short α-helices, and wheel modeling revealed an amphipathicity that supports this secondary structure prediction.

Conclusion

A search for eh1 Groucho interaction motifs in the Fox gene family has identified eh1-like sequences in greater than 50% of Fox proteins. The results predict a physical and functional interaction of TLE/Groucho corepressors with many members of the Fox family of transcriptional regulators. Given the functional importance of the eh1 motif in transcriptional regulation, our annotation of this motif in the Fox gene family will facilitate further study of the diverse transcriptional and regulatory roles of Fox family proteins.
Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells
Authors: Li Jinghuan , Smyth Paul , Flavin Richard , Cahill Susanne , Denning Karen , Aherne Sinead , Guenther Simone M , O'Leary John J , Sheils Orla
Published: June 2007

Background

Archival formalin-fixed paraffin-embedded (FFPE) tissues have limited utility in applications involving analysis of gene expression due to mRNA degradation and modification during fixation and processing. This study analyzed 160 miRNAs in paired snap frozen and FFPE cells to investigate if miRNAs may be successfully detected in archival specimens.

Results

Our results show that miRNA extracted from FFPE blocks was successfully amplified using Q-RT-PCR. The levels of expression of miRNA detected in total RNA extracted from FFPE were higher than that extracted from snap frozen cells when the quantity of total RNA was identical. This phenomenon is most likely explained by the fact that larger numbers of FFPE cells were required to generate equivalent quantities of total RNA than their snap frozen counterparts.

Conclusion

We hypothesise that methylol cross-links between RNA and protein which occur during tissue processing inhibit the yield of total RNA. However, small RNA molecules appear to be less affected by this process and are recovered more easily in the extraction process. In general miRNAs demonstrated reliable expression levels in FFPE compared with snap frozen paired samples, suggesting these molecules might prove to be robust targets amenable to detection in archival material in the molecular pathology setting.
Farber disease: clinical presentation, pathogenesis and a new approach to treatment
Authors: Ehlert Karoline , Frosch Michael , Fehse Natalja , Zander Axel , Roth Johannes , Vormoor Josef
Published: June 2007

Background

Farber Disease is an autosomal-recessively inherited, lysosomal storage disorder caused by acid ceramidase deficiency and associated with distinct clinical phenotypes. Children with significant neurological involvement usually die early in infancy, whereas patients without or only mild neurological findings suffer from progressive joint deformation and contractures, subcutaneous nodules, inflammatory, periarticular granulomas, a hoarse voice and finally respiratory insufficiency caused by granuloma formation in the respiratory tract and interstitial pneumonitis leading to death in the third or fourth decade of live. As the inflammatory component of this disorder is caused by some kind of leukocyte dysregulation, allogeneic hematopoietic stem cell transplantation can restore a healthy immune system and thus may provide a curative option in Farber Disease patients without neurological involvement. Previous stem cell transplantations in two children with severe neurological involvement had resulted in a disappointing outcome, as both patients died of progressive deterioration of their neurological status. As a consequence, stem cell transplantation does not appear to be able to abolish or even reduce the neurotoxic effects of the abundant ceramide storage in the brain.

Methods

After myeloablative, busulfan-based preparative regimens, four Farber Disease patients without neurological involvement received an allogeneic hematopoietic stem cell transplantation from related and unrelated donors. Stem cell source was BM in three patients and PBSC in one patient; GvHD-prophylaxis consisted of CsA and short course MTX.

Results and discussion

In all patients, HSCT resulted in almost complete resolution of granulomas and joint contractures, considerable improvement of mobility and joint motility without relevant therapy-related morbidities. All patients are alive and well at this point with stabile donor cell chimerism and without evidence of chronic GvHD or other late sequelae of stem cell transplantation.

Conclusion

Allogeneic hematopoietic stem cell transplantation provides a promising approach for Farber Disease patients without neurological involvement.
Tau phosphorylation by GSK-3β promotes tangle-like filament morphology
Authors: Rankin Carolyn A , Sun Qian , Gamblin Truman C
Published: June 2007

Background

Neurofibrillary tangles (NFTs) are intraneuronal aggregates associated with several neurodegenerative diseases including Alzheimer's disease. These abnormal accumulations are primarily comprised of fibrils of the microtubule-associated protein tau. During the progression of NFT formation, disperse and non-interacting tau fibrils become stable aggregates of tightly packed and intertwined filaments. Although the molecular mechanisms responsible for the conversion of disperse tau filaments into tangles of filaments are not known, it is believed that some of the associated changes in tau observed in Alzheimer's disease, such as phosphorylation, truncation, ubiquitination, glycosylation or nitration, may play a role.

Results

We have investigated the effects of tau phosphorylation by glycogen synthase kinase-3β (GSK-3β) on tau filaments in an in vitro model system. We have found that phosphorylation by GSK-3β is sufficient to cause tau filaments to coalesce into tangle-like aggregates similar to those isolated from Alzheimer's disease brain.

Conclusion

These results suggest that phosphorylation of tau by GSK-3β promotes formation of tangle-like filament morphology. The in vitro cell-free experiments described here provide a new model system to study mechanisms of NFT development. Although the severity of dementia has been found to correlate with the presence of NFTs, there is some question as to the identity of the neurotoxic agents involved. This model system will be beneficial in identifying intermediates or side reaction products that might be neurotoxic.
Palliative care in dementia: issues and evidence
Authors: Hughes Julian C. , Jolley David , Jordan Alice , Sampson Elizabeth L.
Published: June 2007

Palliative care is an approach that stands well with the aims of person-centred dementia care. There is no doubt that the standards of care for many people with advanced dementia are poor. There is a lack of good-quality evidence, however, to support any particular approach for palliative care in dementia. Still, there are a number of areas in relation to caring for people with severe dementia where a palliative approach might be beneficial. In general, the relevant decisions have to be made on an individual basis but within a palliative framework. Advance care planning is likely to be crucial in encouraging this process. There is certainly a moral imperative behind the idea that care at the end of life for people with dementia should be improved.
Cost-effectiveness of first-v.second-generation antipsychotic drugs: results from a randomised controlled trial in schizophrenia responding poorly to previous therapy
Authors: Davies Linda M. , Lewis Shôn , Jones Peter B. , Barnes Thomas R. E. , Gaughran Fiona , Hayhurst Karen , Markwick Alison , Lloyd Helen
Published: June 2007

Background

There are claims that the extra costs of atypical (second-generation) antipsychotic drugs over conventional (first-generation) drugs are offset by improved health-related quality of life.

Aims

To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia.

Method

Cost-effectiveness acceptability analysis integrated clinical and economic randomised controlled trial data of conventional and atypical antipsychotics in routine practice.

Results

Conventional antipsychotics had lower costs and higher quality-adjusted life-years (QALYs) than atypical antipsychotics and were more than 50% likely to be cost-effective.

Conclusions

The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics.
Brain opioid receptor binding in early abstinence from opioid dependence
Authors: Williams Tim M. , Daglish Mark R. C. , Lingford-Hughes Anne , Taylor Lindsay G. , Hammers Alexander , Brooks David J. , Grasby Paul , Myles Judith S. , Nutt David J.
Published: June 2007

Background

Although opioid receptor function in humans is clearly reduced during opioid dependence, what happens to the receptor in early abstinence is not understood.

Aims

This study sought to examine changes in opioid receptor availability in early abstinence from opioid dependence.

Method

Ten people with opioid dependence who had completed inpatient detoxification and 20 healthy controls underwent [11C]-diprenorphine positron emission tomography. Clinical variables were assessed with structured questionnaires. Opioid receptor binding was characterised as the volume of distribution of [11C]-diprenorphine using a template of predefined brain volumes and an exploratory voxel-by-voxel analysis.

Results

Compared with controls, participants with opioid dependence had increased [11C]-diprenorphine binding in the whole brain and in 15 of the 21 a priori regions studied.

Conclusions

This study suggests that opioid receptor binding is increased throughout the brain in early abstinence from dependent opioid use. These data complement the findings in cocaine and alcohol dependence.
Metabolic disease and cardiovascular risk in people treated with antipsychotics in the community
Authors: Mackin Paul , Bishop David , Watkinson Helen , Gallagher Peter , Ferrier I. Nicol
Published: June 2007

Background

Prevalence of physical comorbidity in severe mental illness is a significant public health concern, but comparative data in people with diagnoses other than schizophrenia are sparse.

Aims

To investigate the prevalence of metabolic disease and cardiovascular risk in people with severe mental illness treated with antipsychotics in the community.

Methods

Case – control study of 90 people treated with antipsychotics in the community and 92 age- and gender-matched controls. The prevalence of metabolic syndrome and 10-year cardiovascular risk were calculated.

Results

People on antipsychotics had a significantly worse metabolic profile than controls (F=6.583, d.f. = 15,161, P<0.0001). Moreover, metabolic syndrome was more prevalent (OR=3.68, 95% CI 1.71–7.93, P=0.001), as was cardiovascular risk across a number of outcomes. These results are consistent across diagnostic groups.

Conclusions

People with severe mental illness treated with antipsychotics have excess metabolic dysfunction and heightened risk for cardiovascular disease.
Patient choice in psychiatry
Authors: Samele Chiara , Lawton-Smith Simon , Warner Lesley , Mariathasan Jeevi
Published: June 2007

The government has embarked on an ambitious plan to make patient choice central to the way healthcare and treatment are delivered. Mental healthcare is incorporated into this agenda. This editorial considers the implications of patient choice for psychiatry and some of the main challenges associated with this policy.
Theory of mind in schizophrenia
Authors: Sprong Mirjam , Schothorst Patricia , Vos Ellen , Hox Joop , Van Engeland Herman
Published: June 2007

Background

Mentalising impairment (an impaired ability to think about people in terms of their mental states) has frequently been associated with schizophrenia.

Aims

To assess the magnitude of the deficit and analyse associated factors.

Method

Twenty-nine studies of mentalising in schizophrenia (combined n = 1518), published between January 1993 and May 2006, were included to estimate overall effect size. Study descriptors predicted to influence effect size were analysed using weighted regression-analysis techniques. Separate analyses were performed for symptom subgroups and task types.

Results

The estimated overall effect size was large and statistically significant (d= –1.255, P < 0.001) and was not significantly affected by sample characteristics. All symptom subgroups showed significant mentalising impairment, but participants with symptoms of disorganisation were significantly more impaired than the other subgroups (P<0.01).

Conclusions

This meta-analysis showed significant and stable mentalising impairment in schizophrenia. The finding that patients in remission are also impaired favours the notion that mentalising impairment represents a possible trait marker of schizophrenia.
Implementing evidence-based supported employment
Authors: Rinaldi Miles , Perkins Rachel
Published: June 2007

Aims and Method

We evaluated the impact of implementing the individual placement and support (IPS) approach within eight community mental health teams (CMHTs) in two London boroughs. Demographic, clinical and vocational data were collected enabling a comparison of the number of people supported in work/education and individual client outcomes at 6 and 12 months.

Results

Following the integration of employment specialists there were significant increases in the number and proportion of clients engaged in mainstream work or educational activity at 6 months and 12 months. The employment specialists supported 38% in open employment at 6 months and 39% at 12 months.

Clinical Implications

The results support the use of IPS in clinical practice in CMHTs.
Podcasts for psychiatrists: a new way of learning
Authors: Agrawal Vishal
Published: June 2007

Digitalisation of the world is a fast-growing reality and the world of medicine, or indeed psychiatry, has not been left behind. Internet and the World Wide Web revolutionised the way we access information, and the medical profession has taken full advantage of it. But now, podcasts are set to change the way information is delivered. The Royal College of Psychiatrists has already started its podcasts and seems to be at the forefront of this revolution in mass communication within the medical community.
Impact of Psychotherapeutic Support for Patients With Gastrointestinal Cancer Undergoing Surgery: 10-Year Survival Results of a Randomized Trial
Authors: Küchler Thomas , Bestmann Beate , Rappat Stefanie , Henne-Bruns Doris , Wood-Dauphinee Sharon
Published: June 2007

Purpose

The impact of psychotherapeutic support on survival for patients with gastrointestinal cancer undergoing surgery was studied.

Patients and Methods

A randomized controlled trial was conducted in cooperation with the Departments of General Surgery and Medical Psychology, University Hospital of Hamburg, Germany, from January 1991 to January 1993. Consenting patients (N = 271) with a preliminary diagnosis of cancer of the esophagus, stomach, liver/gallbladder, pancreas, or colon/rectum were stratified by sex and randomly assigned to a control group that received standard care as provided on the surgical wards, or to an experimental group that received formal psychotherapeutic support in addition to routine care during the hospital stay. From June 2003 to December 2003, the 10-year follow-up was conducted. Survival status for all patients was determined from our own records and from three external sources: the Hamburg cancer registry, family doctors, and the general citizen registration offices.

Results

Kaplan-Meier survival curves demonstrated better survival for the experimental group than the control group. The unadjusted significance level for group differences was P = .0006 for survival to 10 years. Cox regression models that took TNM staging or the residual tumor classification and tumor site into account also found significant differences at 10 years. Secondary analyses found that differences in favor of the experimental group occurred in patients with stomach, pancreatic, primary liver, or colorectal cancer.

Conclusion

The results of this study indicate that patients with gastrointestinal cancer, who undergo surgery for stomach, pancreatic, primary liver, or colorectal cancer, benefit from a formal program of psychotherapeutic support during the inpatient hospital stay in terms of long-term survival.
Single Versus Sequential High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Tumors: A Prospective Randomized Multicenter Trial of the German Testicular Cancer Study Group
Authors: Lorch Anja , Kollmannsberger Christian , Hartmann Joerg Thomas , Metzner Bernd , Schmidt-Wolf Ingo G.H. , Berdel Wolfgang E. , Weissinger Florian , Schleicher Jan , Egerer Gerlinde , Haas Antje , Schirren Rebekka , Beyer Jörg , Bokemeyer Carsten , Rick Oliver
Published: June 2007

Purpose

To compare single versus sequential high-dose chemotherapy (HDCT) as first or subsequent salvage treatment in patients with relapsed or refractory germ cell tumors (GCTs).

Patients and Methods

Between November 1999 and November 2004, 230 patients were planned to be recruited in a prospective, randomized, multicenter trial comparing one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2, and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE; arm A) versus three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2, and cyclophosphamide 6,400 mg/m2 (CEC; arm B).

Results

The study was stopped prematurely after recruitment of 216 patients as a result of excess treatment-related mortality in arm B. One hundred eleven (51%) of 216 patients were randomly assigned to sequential HDCT, and 105 (47%) of 216 patients were randomly assigned to single HDCT. Five (2%) of 216 patients had to be excluded because of non-GCT histologies at review. With a median follow-up time of 36 months, 109 (52%) of 211 patients were alive, and 91 (43%) of 211 patients were progression free. At 1 year, event-free, progression-free, and overall survival rates were 40%, 53%, and 80%, respectively, in arm A compared with 37%, 49%, and 61%, respectively, in arm B (P > .05 for all comparisons). Treatment-related deaths, mainly as a result of sepsis and cardiac toxicity, were less frequent in arm A (four of 108 patients, 4%) compared with arm B (16 of 103 patients, 16%; P < .01).

Conclusion

We found no difference in survival probabilities between single HDCT using CE and sequential HDCT using CEC. Sequential HDCT was better tolerated and resulted in fewer treatment-related deaths.
STAT3 Polymorphism Predicts Interferon-Alfa Response in Patients With Metastatic Renal Cell Carcinoma
Authors: Ito Noriyuki , Eto Masatoshi , Nakamura Eijiro , Takahashi Atsushi , Tsukamoto Taiji , Toma Hiroshi , Nakazawa Hayakazu , Hirao Yoshihiko , Uemura Hirotsugu , Kagawa Susumu , Kanayama Hiroomi , Nose Yoshiaki , Kinukawa Naoko , Nakamura Tsuyoshi , Jinnai Nobuyoshi , Seki Toyokazu , Takamatsu Masanobu , Masui Yoshihiro , Naito Seiji , Ogawa Osamu
Published: June 2007

Purpose

To clarify the effect of genetic polymorphisms on the response to interferon alfa (IFN-α) for metastatic renal cell carcinoma (MRCC), and to find a reliable molecular marker to select those patients with MRCC who would benefit from IFN-α immunotherapy.

Patients and Methods

We carried out an association study in which 463 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in 75 Japanese patients who had received IFN-α for MRCC.

Results

After adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-α. Linkage disequilibrium mapping revealed that the SNP in the 5′ region of STAT3, rs4796793, was the most significant predictor of IFN-α response (odds ratio [OR] = 2.73; 95% CI, 1.38 to 5.78). The highest OR was shown in the CC genotype at rs4796793 compared to the GG + GC genotypes (OR = 8.38, 95% CI, 1.63 to 42.96). Genotype-dependent expressions of STAT3 in B lymphocyte cell lines and the enhanced growth inhibitory effects of IFN-α by STAT3 suppression in an RCC cell line supported the results of the present association study.

Conclusion

The present study suggested that the STAT3 polymorphism is a useful diagnostic marker to predict the response to IFN-α therapy in patients with MRCC. An efficient response marker for IFN-α needs to be utilized to establish individual optimal treatment strategies, even when newer drug therapies are used as first line treatments for MRCC.