bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial
Authors: Pérez-Bárcena Jon , Llompart-Pou Juan A , Homar Javier , Abadal Josep M , Raurich Joan M , Frontera Guillem , Brell Marta , Ibáñez Javier , Ibáñez Jordi 
Published: August 2008

Abstract
Introduction
Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment.

Methods
This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation ≤ 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines.

Results
A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis – undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital – thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection.

Conclusions
Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups.

Trial Registration
(Trial registration: US Clinical Trials registry NCT00622570.)
Anti-stigma films and medical students' attitudes towards mental illness and psychiatry: randomised controlled trial
Authors: Kerby Jane , Calton Tim , Dimambro Ben , Flood Caroline , Glazebrook Cristine 
Published: August 2008

Aims and MethodTo explore the feasibility of a randomised controlled trial of the effects of two anti-stigma films on medical students' attitudes to serious mental illness and psychiatry. Attitudes to serious mental illness, perceived dangerousness, social distance and psychiatry, were measured before and after watching the films and at 8 weeks.ResultsIntervention films significantly improved general attitudes to serious mental illness and social distance, with a trend towards reducing perceived dangerousness. These effects appeared to attenuate during the students' clinical placements, suggesting a possible interaction with their clinical experiences.Clinical ImplicationsOur results suggest both that it may be possible to conduct a substantive trial of the effects of the intervention films on a larger cohort of medical students and that the films may be effective in reducing stigmatising attitudes in medical students.
National service for adolescents and adults with severe obsessive–compulsive and body dysmorphic disorders
Authors: Drummond L. M. , Fineberg N. A. , Heyman I. , Kolb P. J. , Pillay A. , Rani S. , Salkovskis P. , Veale D. 
Published: August 2008

Aims and MethodNational guidelines for the assessment and treatment of obsessive–compulsive disorder (OCD) and body dysmorphic disorder were published in 2005 by the National Institute for Health and Clinical Excellence (NICE). Local services are unable to treat a small but significant number of the most severely ill patients successfully, and the guidelines recommend that such patients should have access to highly specialised care. From 1 April 2007, the Department of Health decided to centrally fund treatment services for severe, chronic, refractory OCD and BDD. We describe a new National Service for Refractory OCD; its rationale, treatments offered, referral criteria and expected clinical outcomes.ResultsInitial results from one centre show an average 42% reduction in OCD symptoms at the end of treatment.Clinical ImplicationsThe operational challenges and potential generalisability of this model of healthcare delivery are discussed. We present a summary of the progress made so far in establishing a new, coherent National Service for Refractory OCD, 18 months after the NICE guideline was published. the aim of the paper is to educate clinicians about the service and describe its rationale, treatments offered, referral criteria and expected clinical outcomes.
The repentant sinner: methods to reduce stigmatised attitudes towards mental illness
Authors: Luty Jason , Rao Harish , Arokiadass Sujaa Mary Rajagopal , Easow Joby Maducolil , Sarkhel Arghya 
Published: August 2008

Aims and MethodTo devise a simple technique to reduce stigmatised attitudes of the general public towards those with mental disorder (schizophrenia and substance misuse). Members of the general public (n=400) completed a questionnaire to measure stigmatised attitudes towards people with schizophrenia and substance misuse disorders. Participants were randomised to receive either a short, ‘upbeat’ leaflet with a description of a patient in remission and a photograph of a man in a business suit; or a simple description of a fictional patient. the 5-item Attitudes to Mental Illness Questionnaire (AMIQ) was used to measure the effect of the various procedures on stigmatised attitudes (score range −10 to +10).ResultsResults were received for 310 (77%) participants. the leaflet produced a large, statistically significant reduction in stigmatised attitudes towards people with opiate dependence (effect size 1.53, CI 1.23–1.82, P < 0.0001; median change 4 units) and alcohol dependence (effect size 1.41, CI 1.12–1.70, P < 0.0001; median change 4 units) but less so towards people with schizophrenia (effect size 0.54, CI 0.27–0.80, P=0.0002; median change 2 units). There was no difference between participants in respect of the control group at 4-week follow-up (233 responses received; 78% response rate).Clinical ImplicationsA short illustrated leaflet can be used to reduce stigmatised attitudes towards substance misuse disorders if patients are presented in a positive manner. This is less effective for attitudes towards people with schizophrenia, possibly because people have a more generous attitude towards patients who have overcome substance misuse disorders.
Junior psychiatrists' electrocardiogram interpretation skills
Authors: Collins Noel , Mandal Uttara , Pendlebury Gabrielle , Drife Jenny 
Published: August 2008

Aims and MethodWe checked whether psychiatric junior doctors could identify common electrocardiogram (ECG) abnormalities. Participants were directly approached at three London sites during induction or teaching programmes.ResultsThe survey had a total response rate of 65% (36/55). Psychiatry junior doctors displayed an overall success rate of 97% in detecting whether an ECG is grossly abnormal, but were much less competent in specifying exact ECG diagnoses (success rate of 41%). Accuracy rates for some diagnoses (e.g. paced rhythm) fell to as low as 11%. General practitioners performed no better than psychiatry trainees.Clinical ImplicationsThere is little consensus about minimum acceptable standards in medical skills such as ECG reporting in junior doctors. These competencies are generally ignored in new curriculums. Questions regarding the appropriate remit of psychiatry doctors in this area are raised and the need for more monitoring and education of these skills is queried.
Is psychiatry torn in different ethical directions?
Authors: Lepping Peter 
Published: August 2008

SummaryPsychiatry is the only specialty that uses legislation which is torn between utilitarian and rights-focused approaches. Although on the one hand this improves the opportunity for good outcome, on the other it reduces autonomous decision-making. Because psychiatry is the only medical speciality in this situation, this may cause stigmatisation and an inappropriate expectation on psychiatry to fulfil some kind of social policing role.
Defects of Prostate Development and Reproductive System in the Estrogen Receptor-α Null Male Mice
Authors: Chen Ming , Hsu Iawen , Wolfe Andrew , Radovick Sally , Huang KuoHsiang , Yu Shengqiang , Chang Chawnshang , Messing Edward M. , Yeh Shuyuan 
Published: August 2008

The estrogen receptor-α knockout (ERαKO, ERα−/−) mice were generated via the Cre-loxP system by mating floxed ERα mice with β-actin (ACTB)-Cre mice. The impact of ERα gene deletion in the male reproductive system was investigated. The ACTB-Cre/ERα−/− male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERα−/− male mice are 2-fold elevated. The ACTB-Cre/ERα−/− testes consist of atrophic and degenerating seminiferous tubules with less cellularity in the disorganized seminiferous epithelia. Furthermore, the ventral and dorsal-lateral prostates of ACTB-Cre/ERα−/− mice display reduced branching morphogenesis. Loss of ERα could also be responsible for the decreased fibroblast proliferation and changes in the stromal content. In addition, we found bone morphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERα−/− prostates. Collectively, these results suggest that ERα is required for male fertility, acts through a paracrine mechanism to regulate prostatic branching morphogenesis, and is involved in the proliferation and differentiation of prostatic stromal compartment.Newly generated ACTB-Cre/Estrogen receptor alpha knockout (ERα-/-) male mice show that ERα acts through a paracrine mechanism to regulate prostatic branching morphogenesis and is involved in the proliferation and differentiation of prostatic stoma.
Laminin-511 but Not -332, -111, or -411 Enables Mouse Embryonic Stem Cell Self-Renewal In Vitro
Authors: Domogatskaya Anna , Rodin Sergey , Boutaud Ariel , Tryggvason Karl 
Published: August 2008

Abstract
We tested specific laminin (LN) isoforms for their ability to serve as substrata for maintaining mouse embryonic stem (ES) cells pluripotent in vitro in the absence of leukemia inhibitory factor or any other differentiation inhibitors or feeder cells. Recombinant human LN-511 alone was sufficient to enable self-renewal of mouse ES cells for up to 169 days (31 passages). Cells cultured on LN-511 maintained expression of pluripotency markers, such as Oct4, Sox2, Tert, UTF1, and Nanog, during the entire period, and cells cultured for 95 days (17 passages) were used to generate chimeric mice. LN-332 enabled ES cells proliferation but not pluripotency. In contrast, under the same conditions LN-111, Matrigel, and gelatin caused rapid differentiation, whereas LN-411 and poly-d-lysine did not support survival. ES cells formed a thin monolayer on LN-511 that differed strikingly from typical dense cluster ES cell morphology. However, expression of pluripotency markers was not affected by morphological changes. The effect was achieved at low ES cell density (&lt;200 cell/mm2). The ability of LN-511 and LN-332 to support ES cell proliferation correlated with increased cell contact area with those adhesive substrata. ES cells interacted with LN-511 via β1-integrins, mostly α6β1 and αVβ1. This is the first demonstration that certain extracellular matrix molecules can support ES cell self-renewal in the absence of differentiation inhibitors and at low cell density. The results suggest that recombinant laminin isoforms can provide a basis for defined surface coating systems for feeder-free maintenance of undifferentiated mammalian ES cells in vitro.
Disclosure of potential conflicts of interest is found at the end of this article.
A Cross-Talk Between Stromal Cell-Derived Factor-1 and Transforming Growth Factor-β Controls the Quiescence/Cycling Switch of CD34+ Progenitors Through FoxO3 and Mammalian Target of Rapamycin
Authors: Chabanon Aurélie , Desterke Christophe , Rodenburger Emilie , Clay Denis , Guerton Bernadette , Boutin Laetitia , Bennaceur-Griscelli Annelise , Pierre-Louis Olivier , Uzan Georges , Abecassis Lucile , Bourgeade Marie-Françoise , Lataillade Jean-Jacques , Le Bousse-Kerdilès Marie-Caroline 
Published: August 2008

Abstract
Cell cycle regulation plays a fundamental role in stem cell biology. A balance between quiescence and proliferation of hematopoietic stem cells in interaction with the microenvironment is critical for sustaining long-term hematopoiesis and for protection against stress. We analyzed the molecular mechanisms by which stromal cell-derived factor-1 (SDF-1) exhibited a cell cycle-promoting effect and interacted with transforming growth factor-β (TGF-β), which has negative effects on cell cycle orchestration of human hematopoietic CD34+ progenitor cells. We demonstrated that a low concentration of SDF-1 modulated the expression of key cell cycle regulators such as cyclins, cyclin-dependent kinase inhibitors, and TGF-β target genes, confirming its cell cycle-promoting effect. We showed that a cross-talk between SDF-1- and TGF-β-related signaling pathways involving phosphatidylinositol 3-kinase (PI3K)/Akt phosphorylation participated in the control of CD34+ cell cycling. We demonstrated a pivotal role of two downstream effectors of the PI3K/Akt pathway, FoxO3a and mammalian target of rapamycin, as connectors in the SDF-1-/TGF-β-induced control of the cycling/quiescence switch and proposed a model integrating a dialogue between the two molecules in cell cycle progression. Our data shed new light on the signaling pathways involved in SDF-1 cell cycle-promoting activity and suggest that the balance between SDF-1- and TGF-β-activated pathways is critical for the regulation of hematopoietic progenitor cell cycle status.
Disclosure of potential conflicts of interest is found at the end of this article.
Enhanced Reprogramming of Xist by Induced Upregulation of Tsix and Dnmt3a
Authors: Do Jeong Tae , Han Dong Wook , Gentile Luca , Sobek-Klocke Inge , Stehling Martin , Schöler Hans R. 
Published: August 2008

Abstract
Reactivation of Oct4 gene expression occurs within 2 days of fusion of somatic cells with pluripotent stem cells and within 9 days of postinfection of four transcription factors. We sought to determine whether somatic genome reprogramming is completed by the onset of Oct4 reactivation. The complex regulation of the reactivation of inactive X chromosome (Xi) serves as a model for studying reprogramming of chromatin domains. A time-course analysis of the DNA methylation, gene expression, and X inactivation-specific transcript (Xist)/Tsix RNA fluorescence in situ hybridization revealed that expression of pluripotency- and tissue-specific marker genes was reset to the level of pluripotent stem cells within 2 days of fusion, whereas reprogramming of Xist/reactivation of Xi took at least 9 days. We found that trichostatin A, which normally activates gene expression, results in downregulation of Xist. This is due to activation of Dnmt3a and Tsix, two negative regulators of Xist. Moreover, delayed reprogramming of Xist/reactivation of inactive X chromosome after cell fusion was accelerated by DNA methylation and histone deacetylation of Xist, which follow upregulation of Dnmt3a and Tsix.
Disclosure of potential conflicts of interest is found at the end of this article.
Don't Look: Growing Clonal Versus Nonclonal Neural Stem Cell Colonies
Authors: Coles-Takabe Brenda L.K. , Brain Ian , Purpura Kelly A. , Karpowicz Phillip , Zandstra Peter W. , Morshead Cindi M. , van der Kooy Derek 
Published: August 2008

Abstract
Recent reports have challenged the clonality of the neurosphere assay in assessing neural stem cell (NSC) numbers quantitatively. We tested the clonality of the neurosphere assay by culturing mixtures of differently labeled neural cells, watching single neural cells proliferate using video microscopy, and encapsulating single NSCs and their progeny. The neurosphere assay gave rise to clonal colonies when using primary cells plated at 10 cells/μl or less; however, when using passaged NSCs, the spheres were clonal only if plated at 1 cell/μl. Most important, moving the plates during the growth phase (to look at cultures microscopically) greatly increased the incidence of nonclonal colonies. To ensure clonal sphere formation and investigate nonautonomous effects on clonal sphere formation frequencies, single NSCs were encapsulated in agarose and proliferated as clonal free-floating spheres. We demonstrate that clonal neurospheres can be grown by avoiding movement-induced aggregation, by single-cell tracking, and by encapsulation of single cells.
Disclosure of potential conflicts of interest is found at the end of this article.
Absence of electroencephalographic seizure activity in patients treated for head injury with an intracranial pressure–targeted therapy
Authors: Olivecrona Magnus , Zetterlund Bo , Rodling-Wahlström Marie , Naredi Silvana , Koskinen Lars-Owe D. 
Published: August 2008

Object
The authors prospectively studied the occurrence of clinical and nonclinical electroencephalographically verified seizures during treatment with an intracranial pressure (ICP)–targeted protocol in patients with traumatic brain injury (TBI).

Methods
All patients treated for TBI at the Department of Neurosurgery, University Hospital Umeå, Sweden, were eligible for the study. The inclusion was consecutive and based on the availability of the electroencephalographic (EEG) monitoring equipment. Patients were included irrespective of pupil size, pupil reaction, or level of consciousness as long as their first measured cerebral perfusion pressure was > 10 mm Hg. The patients were treated in a protocol-guided manner with an ICP-targeted treatment based on the Lund concept. The patients were continuously sedated with midazolam, fentanyl, propofol, or thiopental, or combinations thereof. Five-lead continuous EEG monitoring was performed with the electrodes at F3, F4, P3, P4, and a midline reference. Sensitivity was set at 100 μV per cm and filter settings 0.5–70 Hz. Amplitude-integrated EEG recording and relative band power trends were displayed. The trends were analyzed offline by trained clinical neurophysiologists.

Results
Forty-seven patients (mean age 40 years) were studied. Their median Glasgow Coma Scale score at the time of sedation and intubation was 6 (range 3–15). In 8.5% of the patients clinical seizures were observed before sedation and intubation. Continuous EEG monitoring was performed for a total of 7334 hours. During this time neither EEG nor clinical seizures were observed.

Conclusions
Our protocol-guided ICP targeted treatment seems to protect patients with severe TBI from clinical and subclinical seizures and thus reduces the risk of secondary brain injury.
WingSpan Stent System in the endovascular treatment of intracranial aneurysms: clinical experience with midterm follow-up results
Authors: Yavuz Kivilcim , Geyik Serdar , Saatci Isil , Cekirge H. Saruhan 
Published: August 2008

Object
The WingSpan stent is a new self-expandable neurovascular stent designed for endovascular treatment of intracranial atheromatous lesions. The authors report their experience with the use of this stent for the endovascular treatment of intracranial aneurysms.

Methods
Thirty-seven patients with 40 wide-necked intracranial aneurysms were treated using the WingSpan stent. Twenty-two aneurysms (55%) were small and 18 (45%) were large or giant. In all but 4 aneurysms, embolization was completed by packing the aneurysm sac with platinum coils. In 4 dissecting aneurysms that were fusiform or too small and wide necked to be catheterized, the stent was used alone. In these cases, the stent bridged the aneurysm neck to allow for flow redirection and the potential stent-induced endothelization effect.

Results
Follow-up angiograms obtained in 3 of 4 aneurysms, treated with only stent placement, demonstrated aneurysmal thrombosis and parent artery remodeling in 2 patients and moderate decrease in size in 1. Follow-up angiography obtained at 6 months to 1 year in 31 aneurysms after stent-supported coil embolization demonstrated complete occlusion in 23 aneurysms (74.2%) with a progressive thrombosis rate of 66.7% (10 of 15 aneurysms), and a recanalization rate of 16.1%.

Conclusions
In treating wide-necked intracranial aneurysms, the WingSpan Stent System is very flexible, secure, and effective. Its delivery system is very easy and exact in that it exerts higher outward radial force, thus providing an excellent conformability and a strong scaffold to hold the coils in place. It may offer an effective treatment when used alone in some fusiform or very wide-necked, small dissecting aneurysms in which other surgical or endovascular treatment strategies are not deemed feasible.
Results using a self-expanding stent alone in the treatment of severe symptomatic carotid bifurcation stenosis
Authors: Bussière Miguel , Pelz David M. , Kalapos Paul , Lee Donald , Gulka Irene , Leung Andrew , Lownie Stephen P. 
Published: August 2008

Object
Conventional endovascular therapy for carotid stenosis involves placement of an embolic protection device followed by stent insertion and angioplasty. A simpler approach may be placement of a stent alone. The authors determined how often this approach could be used to treat patients with carotid stenosis, and assessed which factors would preclude this approach.

Methods
Over a period of 6 years, 97 patients with symptomatic carotid stenosis were treated with the intention of using a “stent-only” approach. Arteries in 77 patients (79%) were treated with stents alone, 13 required preinsertion balloon dilation, 6 postinsertion dilation, and 1 both pre- and postinsertion dilation.

Results
The mean stenosis according to North American Symptomatic Carotid Endarterectomy Trial criteria was reduced from 82 to 40% in the stent-only group and from 89 to 37% in the stent and balloon angioplasty group. The 30-day stroke and death rate was 7.2%. Patients were followed for a mean of 15 months. In the stent-alone group, the mean preoperative Doppler peak systolic velocity (PSV) was 409 cm/second, with an internal carotid artery/common carotid artery (ICA/CCA) ratio of 7.2. At follow-up review, the PSV decreased to 153 cm/second and the ICA/CCA ratio to 2.1. In the angioplasty group the mean preoperative PSV was 496 cm/second and the ICA/CCA ratio was 9.2, decreasing to 163 cm/second and 2, respectfully, at follow-up evaluation. Restenosis occurred in 12.8% of patients at 6 months and in 15.9% at 1 year. One stroke occurred during the follow-up period in each group. Using multivariable analysis, factors precluding the “stent-only” approach were as follows: severity of stenosis, circumferential calcification, and no history of hyperlipidemia.

Conclusions
Balloons may not be required to treat all patients with carotid stenosis. A stent alone was feasible in 79% of patients, and 79% of patients were alive and free from ipsilateral stroke or restenosis at 1 year. Restenosis rates with this approach are higher than with conventional angioplasty and stent insertion. Carotid arteries with very severe stenoses (> 90%) and circumferential calcification may be more successfully treated with angioplasty combined with stent placement.