bluuebunny/crossref_metadata_2025 huggingface dataset:
Naturally occurring genotype 2b/1a hepatitis C virus in the United States
Authors: Bhattacharya Dipankar , Accola Molly A , Ansari Israr H , Striker Rob , Rehrauer William M
Published: November 2011

Background

Hepatitis C Virus (HCV) infected patients are frequently repeatedly exposed to the virus, but very few recombinants between two genotypes have been reported.

Findings

We describe the discovery of an HCV recombinant using a method developed in a United States clinical lab for HCV genotyping that employs sequencing of both 5' and 3' portions of the HCV genome. Over twelve months, 133 consecutive isolates were analyzed, and a virus from one patient was found with discordant 5' and 3' sequences suggesting it was a genotype 2b/1a recombinant. We ruled out a mixed infection and mapped a recombination point near the NS2/3 cleavage site.

Conclusions

This unique HCV recombinant virus described shares some features with other recombinant viruses although it is the only reported recombinant of a genotype 2 with a subtype 1a. This recombinant represents a conundrum for current clinical treatment guidelines, including treatment with protease inhibitors. This recombinant is also challenging to detect by the most commonly employed methods of genotyping that are directed primarily at the 5' structural portion of the HCV genome.
DnaJ homolog Hdj2 Facilitates Japanese Encephalitis Virus Replication
Authors: Wang Robert Yung-Liang , Huang Yu-Ru , Chong Ka-Man , Hung Chun-Yu , Ke Zhi-Long , Chang Ruey-Yi
Published: November 2011

Background

Japanese encephalitis virus (JEV) is a member of the mosquito-borne Flaviviridae family of viruses that causes human encephalitis. Upon infection of a new host, replication of viral RNA involves not only the viral RNA-dependent RNA polymerase (RdRp), but also host proteins. Host factors involved in JEV replication are not well characterized.

Results

We identified Hdj2, a heat-shock protein 40 (Hsp40)/DnaJ homolog, from a mouse brain cDNA library interacting with JEV nonstructural protein 5 (NS5) encoding viral RdRp using yeast two-hybrid system. Specific interaction of Hdj2 with NS5 was confirmed by coimmunoprecipitation and colocalization in JEV-infected cells. Overexpression of Hdj2 in JEV-infected cells led to an increase of RNA synthesis, and the virus titer was elevated approximately 4.5- to 10-fold. Knocking down of Hdj2 by siRNA reduced the virus production significantly.

Conclusions

We conclude that Hdj2 directly associates with JEV NS5 and facilitates viral replication. This study is the first to demonstrate Hdj2 involved in JEV replication, providing insight into a potential therapeutic target and cell-based vaccine development of JEV infection.
Cough management: a practical approach
Authors: De Blasio Francesco , Virchow Johann C , Polverino Mario , Zanasi Alessandro , Behrakis Panagiotis K , Kilinç Gunsely , Balsamo Rossella , De Danieli Gianluca , Lanata Luigi
Published: November 2011

Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists. Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. Therapeutic suppression of cough may be either disease-specific or symptom related. The potential benefits of an early treatment of cough could include the prevention of the vicious cycle of cough. There has been a long tradition in acute cough, which is frequently due to upper respiratory tract infections, to use symptom-related anti-tussives. Suppression of cough (during chronic cough) may be achieved by disease-specific therapies, but in many patients it is often necessary to use symptomatic anti-tussives, too. According to the current guidelines of the American College of Chest Physician on "Cough Suppressants and Pharmacologic Protussive Therapy" and additional clinical trials on the most frequent anti-tussive drugs, it should be possible to diagnose and treat cough successfully in a majority of cases. Among drugs used for the symptomatic treatment of cough, peripherally acting anti-tussives such as levodropropizine and moguisteine show the highest level of benefit and should be recommended especially in children. By improving our understanding of the specific effects of these anti-tussive agents, the therapeutic use of these drugs may be refined. The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action.
The genome diversity and karyotype evolution of mammals
Authors: Graphodatsky Alexander S , Trifonov Vladimir A , Stanyon Roscoe
Published: November 2011

The past decade has witnessed an explosion of genome sequencing and mapping in evolutionary diverse species. While full genome sequencing of mammals is rapidly progressing, the ability to assemble and align orthologous whole chromosome regions from more than a few species is still not possible. The intense focus on building of comparative maps for companion (dog and cat), laboratory (mice and rat) and agricultural (cattle, pig, and horse) animals has traditionally been used as a means to understand the underlying basis of disease-related or economically important phenotypes. However, these maps also provide an unprecedented opportunity to use multispecies analysis as a tool for inferring karyotype evolution. Comparative chromosome painting and related techniques are now considered to be the most powerful approaches in comparative genome studies. Homologies can be identified with high accuracy using molecularly defined DNA probes for fluorescencein situhybridization (FISH) on chromosomes of different species. Chromosome painting data are now available for members of nearly all mammalian orders. In most orders, there are species with rates of chromosome evolution that can be considered as 'default' rates. The number of rearrangements that have become fixed in evolutionary history seems comparatively low, bearing in mind the 180 million years of the mammalian radiation. Comparative chromosome maps record the history of karyotype changes that have occurred during evolution. The aim of this review is to provide an overview of these recent advances in our endeavor to decipher the karyotype evolution of mammals by integrating the published results together with some of our latest unpublished results.
Passive leg raising can predict fluid responsiveness in patients placed on venovenous extracorporeal membrane oxygenation
Authors: Guinot Pierre-Grégoire , Zogheib Elie , Detave Mathieu , Moubarak Mona , Hubert Vincent , Badoux Louise , Bernard Eugénie , Besserve Patricia , Caus Thierry , Dupont Hervé
Published: November 2011

Introduction

In ICUs, fluid administration is frequently used to treat hypovolaemia. Because volume expansion (VE) can worsen acute respiratory distress syndrome (ARDS) and volume overload must be avoided, predictive indicators of fluid responsiveness are needed. The purpose of this study was to determine whether passive leg raising (PLR) can be used to predict fluid responsiveness in patients with ARDS treated with venovenous extracorporeal membrane oxygenation (ECMO).

Methods

We carried out a prospective study in a university hospital surgical ICU. All patients with ARDS treated with venovenous ECMO and exhibiting clinical and laboratory signs of hypovolaemia were enrolled. We measured PLR-induced changes in stroke volume (ΔPLRSV) and cardiac output (ΔPLRCO) using transthoracic echocardiography. We also assessed PLR-induced changes in ECMO pump flow (ΔPLRPO) and PLR-induced changes in ECMO pulse pressure (ΔPLRPP) as predictors of fluid responsiveness. Responders were defined by an increase in stroke volume (SV) > 15% after VE.

Results

Twenty-five measurements were obtained from seventeen patients. In 52% of the measurements (n = 13), SV increased by > 15% after VE (responders). The patients' clinical characteristics appeared to be similar between responders and nonresponders. In the responder group, PLR significantly increased SV, cardiac output and pump flow (P < 0.001). ΔPLRSV values were correlated with VE-induced SV variations (r2 = 0.72, P = 0.0001). A 10% increased ΔPLRSV predicted fluid responsiveness with an area under the receiver operating characteristic curve (AUC) of 0.88 ± 0.07 (95% confidence interval (CI95): 0.69 to 0.97; P < 0.0001), 62% sensitivity and 92% specificity. On the basis of AUCs of 0.62 ± 0.11 (CI95: 0.4 to 0.8; P = 0.31) and 0.53 ± 0.12 (CI95: 0.32 to 0.73, P = 0.79), respectively, ΔPLRPP and ΔPLRPO did not predict fluid responsiveness.

Conclusions

In patients treated with venovenous ECMO, a > 10% ΔPLRSV may predict fluid responsiveness. ΔPLRPP and ΔPLRPO cannot predict fluid responsiveness.
Payment by results for learning disability services: a model for the future?
Authors: Bhaumik Sabyasachi , Devapriam John , Gangadharan Satheesh , Hiremath Avinash , Roy Ashok
Published: November 2011

Payment by results (PbR) for mental health services is currently being piloted with the aim of arriving at a national tariff for mental health by 2013/2014. The Department of Health has also established two pilot sites to consider applicability of PbR for learning disability services. This article outlines the concept of PbR in learning disability services and describes the progress of the pilot work being undertaken in this area.
Implementing legislative changes on young people's consent to treatment: a guide for trainers
Authors: Huline-Dickens Sarah
Published: November 2011

This article reviews the recent changes in the law in England and Wales relating to consent to treatment for young people, in particular the Mental Capacity Act 2005 and the 2007 amendments to the Mental Health Act 1983. Using a fictitious case study, it offers a structured approach to the application of these new items of legislation that could be useful to trainers and their trainees.
Early intervention in psychosis: strengths and limitations of services
Authors: Murphy Brendan P. , Brewer Warrick J.
Published: November 2011

Early intervention services were established on the basis of a number of fundamental principles, including the notions that intervening in the early stages of psychosis alters illness trajectory and prognosis, that multicomponent interventions promote psychosocial recovery and reduce iatrogenic damage, and that early targeting of non-responders reduces treatment resistance. There is growing evidence of the benefits of specialised early intervention services. These include improved clinical, social and vocational outcomes, reduced in-patient stays and better engagement. Early intervention services can also significantly reduce the risk of a second episode and are highly valued by service users and carers. Duration of treatment appears to determine long-term outcome and there remains uncertainty about how long such intensive intervention should last and whether all patients need the same length of care. Budgetary constraints are pervasive and are particularly likely to affect prodrome clinics and community awareness programmes.
Transference: keeping mum or mummified?
Authors: Johnston James
Published: November 2011

Transference reveals the mental state of the other to us through our countertransference. Our emotional responses to the transference relationship are different depending on the degree of disturbance evoked in us. Reflecting on our countertransference can convey emotional insight into the nature and meaning of the transference as a way of understanding the emotional experiences of the other.
Low serotonergic tone and elevated risk for substance misuse
Authors: Nutt David
Published: November 2011

Cox et al's paper addresses an issue that has long been assumed to be a central aspect of brain function – the interplay of different neurotransmitters – but for which we have very little evidence so far. It is currently unclear whether these findings will have implications for the treatment of those with cocaine or other substance dependence.
Clinical and cognitive characteristics of children with attention-deficit hyperactivity disorder, with and without copy number variants
Authors: Langley Kate , Martin Joanna , Agha Sharifah Shameem , Davies Charlotte , Stergiakouli Evangelia , Holmans Peter , Williams Nigel , Owen Michael , O'Donovan Michael , Thapar Anita
Published: November 2011

Background

Submicroscopic, rare chromosomal copy number variants (CNVs) contribute to neurodevelopmental disorders but it is not known whether they define atypical clinical cases.

Aims

To identify whether large, rare CNVs in attention-deficit hyperactivity disorder (ADHD) are confined to a distinct clinical subgroup.

Method

A total of 567 children with ADHD aged 5–17 years were recruited from community clinics. Psychopathology was assessed using the Child and Adolescent Psychiatric Assessment. Large, rare CNVs (>500 kb, <1% frequency) were defined from single nucleotide polymorphism data.

Results

Copy number variant carriers (13.6%) showed no differences from non-carriers in ADHD symptom severity, symptom type, comorbidity, developmental features, family history or pre-/ perinatal markers. The only significant difference was a higher rate of intellectual disability (24% v. 9%, χ2 = 15.5, P = 0.001). Most CNV carriers did not have intellectual disability.

Conclusions

Large, rare CNVs are not restricted to an atypical form of ADHD but may be more highly enriched in children with cognitive problems.
Improving end-of-life care for people with dementia
Authors: Sampson Elizabeth L. , Burns Alistair , Richards Mike
Published: November 2011

One in three adults over the age of 60 years will die with dementia. Most will have complex physical and psychological needs. Despite this, many people with dementia receive poor-quality end-of-life care. Recent government strategies have highlighted the importance of improved coordination and provision of services.
A centenarian extraordinaire
Authors: Tyrer Peter
Published: November 2011

Henry Rollin, a distinguished Member, Fellow and now Honorary Fellow of the Royal College of Psychiatrists, has attained his 101st year. The achievements of this remarkable man are described and speculations made about the reasons for his longevity and his plans for the future.
Factors that discourage medical students from pursuing a career in psychiatry
Authors: Curtis-Barton Marie T. , Eagles John M.
Published: November 2011

Aims and method

This cross-sectional study investigated the evolution of intentions among medical students to pursue a career in psychiatry and the factors that might discourage them from becoming a psychiatrist. A questionnaire survey was sent to medical students in years 1–5 at Aberdeen University.

Results

From 918 students, 467 (51%) returned useable responses. Proportions of students across the 5-year groups who definitely or probably intended to become psychiatrists remained fairly stable at 4–7%. In their final year, psychiatry remained a possible career option for a further 17% of students. The most potent discouraging factor was the perception of poor prognoses among psychiatric patients. Perceptions of a lack of scientific/evidence base reduced enthusiasm for becoming a psychiatrist. Issues relating to the prestige of the specialty were also important.

Implications

If recruitment to the specialty is to improve, these negative perceptions among students should be addressed by their teachers and more widely within psychiatry.
Longer-Term Outcomes of Letrozole Versus Placebo After 5 Years of Tamoxifen in the NCIC CTG MA.17 Trial: Analyses Adjusting for Treatment Crossover
Authors: Jin Huan , Tu Dongsheng , Zhao Naiqing , Shepherd Lois E. , Goss Paul E.
Published: November 2011

Purpose

The interim analysis of the National Cancer Institute of Canada Clinical Trials Group MA.17 trial showed that letrozole was significantly better than placebo in disease-free survival (DFS) for postmenopausal women with hormone receptor–positive breast cancer following about 5 years of tamoxifen therapy. When patients were unblinded, those on placebo were offered letrozole. Longer-term efficacy of letrozole, especially survival, was of particular interest because the median follow-up of the first interim analysis was only 2.5 years. Efficacy was difficult to assess because more than 60% of placebo patients crossed over to letrozole after being unblinded.

Patients and Methods

Two statistical approaches were used to adjust for the potential effects of treatment crossover: one was based on the inverse probability of censoring weighted (IPCW) Cox model and the other on a Cox model with time-dependent covariates.

Results

With a median follow-up of 64 months, the hazard ratios (HRs) of letrozole and placebo from the IPCW analyses were HR of 0.52 (95% CI, 0.45 to 0.61; P < .001) for DFS, HR of 0.51 (95% CI, 0.42 to 0.61; P < .001) for distant disease-free survival (DDFS), and HR of 0.61 (95% CI, 0.52 to 0.71; P < .001) for overall survival (OS). The results from the analyses based on the Cox model with time-dependent covariates were similar for letrozole and placebo: HR of 0.58 (95% CI, 0.47 to 0.72; P < .001) for DFS, HR of 0.68 (95% CI, 0.52 to 0.88; P = .004) for DDFS, and HR of 0.76 (95% CI, 0.60 to 0.96; P = .02) for OS.

Conclusion

Exploratory analyses based on longer follow-up and adjusting for treatment crossover suggest that extended adjuvant letrozole was superior to placebo in DFS, DDFS, and OS.
MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib
Authors: Lennerz Jochen K. , Kwak Eunice L. , Ackerman Allison , Michael Michael , Fox Stephen B. , Bergethon Kristin , Lauwers Gregory Y. , Christensen James G. , Wilner Keith D. , Haber Daniel A. , Salgia Ravi , Bang Yung-Jue , Clark Jeffrey W. , Solomon Benjamin J. , Iafrate A. John
Published: November 2011

Purpose

Amplification of the MET proto-oncogene in gastroesophageal cancer (GEC) may constitute a molecular marker for targeted therapy. We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an expanded phase I cohort study.

Patients and Methods

From 2007 to 2009, patients with GEC were genetically screened as a consecutive series of 489 tumors (stages 0, I, and II, 39%; III, 25%; IV, 36%; n = 222 esophageal, including n = 21 squamous carcinomas). MET, EGFR, and HER2 amplification status was assessed by using fluorescence in situ hybridization.

Results

Ten (2%) of 489 patients screened harbored MET amplification; 23 (4.7%) harbored EGFR amplification; 45 (8.9%) harbored HER2 amplification; and 411 (84%) were wild type for all three genes (ie, negative). MET-amplified tumors were typically high-grade adenocarcinomas that presented at advanced stages (5%; n = 4 of 80). EGFR-amplified tumors showed the highest fraction of squamous cell carcinoma (17%; n = 4 of 23). HER2, MET, and EGFR amplification were, with one exception (MET and EGFR positive), mutually exclusive events. Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFR-amplified groups, with a rank order for all groups by median survival (from most to least aggressive): MET (7.1 months; P < .001) less than EGFR (11.2 months; P = .16) less than HER2 (16.9 months; P = .89) when compared with the negative group (16.2 months). Two of four patients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage (−30% and −16%) and experienced progression after 3.7 and 3.5 months.

Conclusion

MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib (PF-02341066).
Use of Zidovudine and Interferon Alfa With Chemotherapy Improves Survival in Both Acute and Lymphoma Subtypes of Adult T-Cell Leukemia/Lymphoma
Authors: Hodson Andrew , Crichton Siobhan , Montoto Silvia , Mir Naheed , Matutes Estella , Cwynarski Kate , Kumaran Thurai , Ardeshna Kirit M. , Pagliuca Antonio , Taylor Graham P. , Fields Paul A.
Published: November 2011

Purpose

Adult T-cell leukemia/lymphoma (ATLL) is a mature (post-thymic) T-cell lymphoma associated with human T-lymphotropic virus type 1 infection. Survival in aggressive subtypes remains poor, and treatment resistance is frequent. Use of zidovudine (ZDV) and interferon alfa (IFN-α) has been associated with improved response rates in small studies and prolonged overall survival in leukemic ATLL subtypes in a recent meta-analysis.

Patients and Methods

We report the clinicopathologic characteristics, treatment, and outcome of 73 patients with aggressive ATLL (acute ATLL, 29; lymphoma ATLL, 44) diagnosed and treated in England between 1999 and 2009. The impact of ZDV/IFN-α on treatment response and survival was assessed.

Results

The overall response rate ranged from 49% with chemotherapy alone to 81% with combined first-line therapy (chemotherapy with concurrent/sequential ZDV/IFN-α). Median overall survival (OS) was 9 months: 7.5 months for acute ATLL and 10 months for lymphoma ATLL. Use of ZDV/IFN-α at any time prolonged survival in acute (P < .001) and lymphoma ATLL (P < .001) and was the sole factor associated with reduction in risk of death in aggressive ATLL (hazard ratio, 0.23; 95% CI, 0.09 to 0.60; P = .002). Combined first-line therapy prolonged median OS in acute (P = .0081) and lymphoma ATLL (P = .001) compared with chemotherapy alone.

Conclusion

These data support the use of low-dose ZDV/IFN-α with chemotherapy in first-line treatment of acute and lymphoma ATLL.
Genetic Activation of the MET Pathway and Prognosis of Patients With High-Risk, Radically Resected Gastric Cancer
Authors: Graziano Francesco , Galluccio Nadia , Lorenzini Paola , Ruzzo Annamaria , Canestrari Emanuele , D'Emidio Silvia , Catalano Vincenzo , Sisti Valerio , Ligorio Claudia , Andreoni Francesca , Rulli Eliana , Di Oto Enrico , Fiorentini Giammaria , Zingaretti Costantino , De Nictolis Michele , Cappuzzo Federico , Magnani Mauro
Published: November 2011

Purpose

To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF.

Patients and Methods

A single-institution cohort of 230 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction. Quantitative polymerase chain reaction (qPCR) for MET CNG and sequencing for HGF DATE truncation (< 25 deoxyadenosines instead of 30) were used. Results were analyzed for association with disease-free survival (DFS) and overall survival (OS). To assess the reliability of the qPCR measurement, a random sample of cases was reanalyzed using an alternative assay (fluorescent in situ hybridization [FISH]) with calculation of the intracorrelation coefficient (ICC).

Results

In 216 assessable patients, MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients (10%) and 30 patients (13%), respectively. Patients with MET CNG five or more copies (MET-positive) showed significantly worse prognosis with multivariate hazard ratio (HR) of 3.02 (95% CI, 1.71 to 5.33; P < .001) for DFS and multivariate HR of 2.91 (95% CI, 1.65 to 5.11; P < .001) for OS. The agreement between qPCR and FISH was high, with ICC = 0.9% (95% CI, 0.81% to 0.95%; the closer the ICC is to 1, the greater is the agreement). HGF-truncated DATE did not show relevant prognostic effect.

Conclusion

In this study, qPCR revealed approximately 10% of white patients with gastric cancer harboring MET CNG of five or more copies. This marker was significantly associated with unfavorable prognosis. This information is relevant to the current clinical development of anti-MET compounds.
Evaluating Survivorship Care Plans: Results of a Randomized, Clinical Trial of Patients With Breast Cancer
Authors: Grunfeld Eva , Julian Jim A. , Pond Gregory , Maunsell Elizabeth , Coyle Douglas , Folkes Amy , Joy Anil A. , Provencher Louise , Rayson Daniel , Rheaume Dorianne E. , Porter Geoffrey A. , Paszat Lawrence F. , Pritchard Kathleen I. , Robidoux André , Smith Sally , Sussman Jonathan , Dent Susan , Sisler Jeffrey , Wiernikowski Jennifer , Levine Mark N.
Published: November 2011

Purpose

An Institute of Medicine report recommends that patients with cancer receive a survivorship care plan (SCP). The trial objective was to determine if an SCP for breast cancer survivors improves patient-reported outcomes.

Patients and Methods

Women with early-stage breast cancer who completed primary treatment at least 3 months previously were eligible. Consenting patients were allocated within two strata: less than 24 months and ≥ 24 months since diagnosis. All patients were transferred to their own primary care physician (PCP) for follow-up. In addition to a discharge visit, the intervention group received an SCP, which was reviewed during a 30-minute educational session with a nurse, and their PCP received the SCP and guideline on follow-up. The primary outcome was cancer-related distress at 12 months, assessed by the Impact of Event Scale (IES). Secondary outcomes included quality of life, patient satisfaction, continuity/coordination of care, and health service measures.

Results

Overall, 408 survivors were enrolled through nine tertiary cancer centers. There were no differences between groups on cancer-related distress or on any of the patient-reported secondary outcomes, and there were no differences when the two strata were analyzed separately. More patients in the intervention than control group correctly identify their PCP as primarily responsible for follow-up (98.7% v 89.1%; difference, 9.6%; 95% CI, 3.9 to 15.9; P = .005).

Conclusion

The results do not support the hypothesis that SCPs are beneficial for improving patient-reported outcomes. Transferring follow-up to PCPs is considered an important strategy to meet the demand for scarce oncology resources. SCPs were no better than a standard discharge visit with the oncologist to facilitate transfer.
Duration of Short-Course Androgen Suppression Therapy and the Risk of Death As a Result of Prostate Cancer
Authors: D'Amico Anthony V. , Chen Ming-Hui , Crook Juanita , Armstrong John G. , Malone Shawn , Steigler Allison , Dunne Mary , Kantoff Philip W. , Denham James W.
Published: November 2011

Purpose

We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer–specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.

Patients and Methods

Between February 2, 1996, and December 27, 2001, 761 men with unfavorable-risk PC were treated in Australia, New Zealand, Ireland, or the United States in a randomized trial with radiotherapy and 3, 4, or 6 months of AST (the study cohort). Competing risks regression was used to evaluate whether the duration of AST interacted with GS and was significantly associated with the risk of PCSM, adjusting for age, trial site, and PC prognostic factors.

Results

After a median follow-up of 10.9 years, 263 men died, 111 (42%) from PC. For all men, 6 versus 3 or 4 months of AST was associated with a reduced risk of PCSM (adjusted hazard ratio [AHR], 0.55; 95% CI, 0.36 to 0.82; P = .004). AHRs evaluating the impact of the duration of AST on the risk of PCSM were 0.67 (95% CI, 0.29 to 1.56; P = .35), 0.47 (95% CI, 0.25 to 0.85; P = .01), and 0.59 (95% CI, 0.30 to 1.19; P = .14) for men with GS ≤ 6, 7, and 8 to 10 PC, respectively. Therefore, the strongest evidence for this benefit was in men with GS 7 PC.

Conclusion

AST durations of no less than 6 months should be considered when treating GS 7 PC with conventional dose RT.
Growth Hormone Secretion After Conformal Radiation Therapy in Pediatric Patients With Localized Brain Tumors
Authors: Merchant Thomas E. , Rose Susan R. , Bosley Christina , Wu Shengjie , Xiong Xiaoping , Lustig Robert H.
Published: November 2011

Purpose

Growth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors.

Patients and Materials

Between 1997 and 2008, 192 pediatric patients with localized primary brain tumors (ependymoma, n = 88; low-grade glioma, n = 51; craniopharyngioma, n = 28; high-grade glioma, n = 23; and other tumor types, n = 2) underwent provocative testing of GH secretion by using the secretogogues arginine and l-dopa before and after (6, 12, 36, and 60 months) conformal radiation therapy (CRT). A total of 664 arginine/l-dopa test procedures were performed.

Results

Baseline testing revealed preirradiation GHD in 22.9% of tested patients. On the basis of data from 118 patients, peak GH was modeled as an exponential function of time after CRT and mean radiation dose to the hypothalamus. The average patient was predicted to develop GHD with the following combinations of the time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 to 30 Gy; and 60 months and 15 to 20 Gy. A cumulative dose of 16.1 Gy to the hypothalamus would be considered the mean radiation dose required to achieve a 50% risk of GHD at 5 years (TD50/5).

Conclusion

GH secretion after CRT can be predicted on the basis of dose and time after irradiation in pediatric patients with localized brain tumors. These findings provide an objective radiation dose constraint for the hypothalamus.
Expression of hindbrain boundary markers is regulated by FGF3
Authors: Weisinger Karen , Kohl Ayelet , Kayam Galya , Monsonego-ornan Efrat , Sela-donenfeld Dalit
Published: November 2011

Compartment boundaries act as organizing centers that segregate adjacent areas into domains of gene expression and regulation, and control their distinct fates via the secretion of signalling factors. During hindbrain development, a specialized cell-population forms boundaries between rhombomeres. These boundary cells demonstrate unique morphological properties and express multiple genes that differs them from intra-rhombomeric cells. Yet, little is known regarding the mechanisms that controls the expression or function of these boundary markers.

Multiple components of the FGF signaling system, including ligands, receptors, downstream effectors as well as proteoglycans are shown to localize to boundary cells in the chick hindbrain. These patterns raise the possibility that FGF signaling plays a role in regulating boundary properties. We provide evidence to the role of FGF signaling, particularly the boundary-derived FGF3, in regulating the expression of multiple markers at hindbrain boundaries. These findings enable further characterization of the unique boundary-cell population, and expose a new function for FGFs as regulators of boundary-gene expression in the chick hindbrain.
Improvement and validation of 125I-high-performance liquid chromatography method for determination of total human serum choline and ethanolamine plasmalogens
Authors: Maeba Ryouta , Yamazaki Yuya , Nezu Toru , Okazaki Tomoki
Published: November 2011

Background

Serum plasmalogens (Pls) have gained interest in several clinical symptoms such as metabolic syndrome/atherosclerosis or Alzheimer's disease possibly because of their antioxidant properties. We have developed a highly sensitive and simple method to determine plasmenylcholine (PlsCho; choline plasmalogen) and plasmenylethanolamine (PlsEtn; ethanolamine plasmalogen) separately, using a radioactive iodine and high-performance liquid chromatography (125I-HPLC method). The present study reports the improvement and validation of 125I-HPLC method by introducing a quantitative standard (QS) and online detection with a flow γ-counter.

Methods

1-Alkenyl 2,3-cyclic glycerophosphate was prepared as QS from l- α-lyso plasmenylcholine by enzymatic treatment with phospholipase D. Online detection with a flow γ-counter was investigated to be available to quantify Pls. The method validation was carried out in terms of selectivity, sensitivity, linearity, precision, accuracy and recovery.

Results

Linearity was established over the concentration range 5–300 μmol/L for Pls and QS with regression coefficients >0.99. The accuracy and reliability were satisfactory. The method has been applied to the determination of human serum Pls from healthy subjects and the elderly with dementia or artery stenoses.

Conclusions

The improved 125I-HPLC method is useful as an autoanalytical system for a routine diagnostic test of human serum Pls.
Clinical quality indicators in laboratory medicine
Authors: Barth Julian H
Published: November 2011

Clinical laboratories have an important role in improving patient care. The past decades have seen enormous changes with unpredictable improvements in analytical performance, range of tests and capacity to manage large volumes of work. At the same time, there has been a dramatic fall in the rate of laboratory errors. However, there is now a growing awareness that the testing process includes the time before samples reach the laboratory and after reports have been printed and that these areas need to be included in the quality assessment of the total testing process. Laboratory quality should include a focus on patient safety and clinical effectiveness. Services should be patient-centred, timely, efficient and equitable, and finally, should be moulded to ensure optimal outcomes. There is a need to define quality indicators that will ensure there is appropriate choice and selection of tests, use of the appropriate assay standardization and the correct interpretation of the assay results at the appropriate time. These are the areas in which a quality laboratory can, and should, now involve itself.
Directional connectivity of resting state human fMRI data using cascaded ICA-PDC analysis
Authors: Silfverhuth Minna J , Remes Jukka , Starck Tuomo , Nikkinen Juha , Veijola Juha , Tervonen Osmo , Kiviniemi Vesa
Published: November 2011

Background

Directional connectivity measures, such as partial directed coherence (PDC), give us means to explore effective connectivity in the human brain. By utilizing independent component analysis (ICA), the original data-set reduction was performed for further PDC analysis.

Purpose

To test this cascaded ICA-PDC approach in causality studies of human functional magnetic resonance imaging (fMRI) data.

Material and Methods

Resting state group data was imaged from 55 subjects using a 1.5 T scanner (TR 1800 ms, 250 volumes). Temporal concatenation group ICA in a probabilistic ICA and further repeatability runs ( n = 200) were overtaken. The reduced data-set included the time series presentation of the following nine ICA components: secondary somatosensory cortex, inferior temporal gyrus, intracalcarine cortex, primary auditory cortex, amygdala, putamen and the frontal medial cortex, posterior cingulate cortex and precuneus, comprising the default mode network components. Re-normalized PDC (rPDC) values were computed to determine directional connectivity at the group level at each frequency.

Results

The integrative role was suggested for precuneus while the role of major divergence region may be proposed to primary auditory cortex and amygdala.

Conclusion

This study demonstrates the potential of the cascaded ICA-PDC approach in directional connectivity studies of human fMRI.
Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting
Authors: Senore Carlo , Ederle Andrea , Fantin Alberto , Andreoni Bruno , Bisanti Luigi , Grazzini Grazia , Zappa Marco , Ferrero Franco , Marutti Anna , Giuliani Orietta , Armaroli Paola , Segnan Nereo
Published: November 2011

Objective

Quantitative information on adverse reactions associated with colorectal cancer (CRC) screening tests is useful to estimate the balance between benefit and risk in different strategies.

Setting

Six Italian screening centres.

Methods

Thirty-day active follow-up (interview about side-effects and acceptability of the screening procedure and review of hospital admissions) among average-risk people undergoing flexible sigmoidoscopy (FS), total colonoscopy (TC), fecal immunochemical test (FIT) in a multicentre randomized trial of CRC screening. Multivariable logistic models were used to assess determinants of completion rate and self-reported pain.

Results

The attendance rate following the first invitation and mail reminder was 28.2% (1696/6018) in the FS and 23.0% (1382/6021) in the TC arm. Response rate to the 30-day follow-up questionnaire was 88.6% (1502/1696) among people undergoing FS, and 86.7% (1198/1382) among those undergoing TC. The proportion of people complaining of serious reactions following bowel preparation (odds ratio [OR], 5.17; 95% confidence interval [CI] 3.70–7.24) or reporting severe pain immediately after the exam (OR, 1.86; 95% CI 1.47–2.34) was higher for TC than for FS. The most common post-procedural complaints were abdominal distension and pain. People mentioning pain or bowel distension following preparation were more likely to report severe pain both after FS (OR, 2.13; 95% CI 1.52–2.97) and TC (OR: 2.03; 95% CI 1.41–2.90). The 30-day hospitalization rate was similar after FS, TC and FIT.

Conclusions

Screenees reported higher pain levels after TC than FS. The proportion of people complaining of severe side effects after discharge was similar. Bowel preparation was poorly tolerated by people undergoing TC. Subjects’ reactions to the bowel preparation was predictive of post-procedural discomfort. A commitment of at least 48 hours was required of people undergoing TC, compared with 3–4 for FS.
Evaluation of the nationwide cervical screening programme in Thailand: a case-control study
Authors: Kasinpila Chananya , Promthet Supannee , Vatanasapt Patravoot , Sasieni Peter , Parkin D Maxwell
Published: November 2011

Objectives

To evaluate the effectiveness of the Pap smear screening programme in Thailand in the prevention of invasive cervical cancer.

Setting

Four tertiary hospitals, in two provinces of north-east Thailand.

Methods

A hospital-based case-control study of women aged 30–64, who were resident in north-east Thailand. A total of 130 women with a diagnosis of invasive cervical cancer were compared with two groups of controls: a) hospital controls, b) hospital patient companions. Information on risk factors for cervical cancer and history of screening by cytology (Pap smear) were collected using a structured interview.

Results

Eighty percent of control subjects reported having had a Pap test in the past, and some two-thirds within the three years before interview. There was a significant protective effect for multiple (6+) previous screening tests as reported by 20% of controls. When women who had tests less than six months prior to the study were excluded, there was a strong, significant protective effect of the number of tests (for 1–5 tests: OR = 0.45 95% CI = 0.25 to 0.84, and for 6+ tests: OR = 0.29 95% CI = 0.11 to 0.82). Tests carried out 1–2 years and 3+ years before diagnosis were associated with an OR of 0.27 (95% CI = 0.13–0.56) and 0.42 (95% CI = 0.20–0.88), respectively.

Conclusions

The cervical screening programme in north-east Thailand has achieved excellent coverage and is preventing cervical cancer. Women who have been screened multiple times are at substantially lower risk than those only screened a few times suggesting that the quality of the screening could be improved.
My Patient is Short of Breath: Have They Got a Pneumothorax?
Authors: Lewis David
Published: November 2011

Clinical diagnosis of pneumothorax in the emergency department (ED) resuscitation room can be difficult and in certain circumstances chest radiography is either impractical or the delay is unacceptable. The diagnosis must also be considered in other clinical areas such as critical care, theatres, respiratory units and acute medical units. Erect chest radiography is the standard first-line diagnostic test for pneumothorax in the ED, but the sensitivity is low (59–81%). For many patients in ED, critical care and theatre, an erect chest radiograph is not possible as the patient must remain supine. The sensitivity for a supine chest radiograph has been reported as being 45–75%. Ultrasound has been shown to be more sensitive than chest radiography in the diagnosis of pneumothorax in certain settings. This paper outlines the evidence for ultrasound in the diagnosis of pneumothorax in the point of care setting; it describes the technique and discusses the clinical application of this imaging modality.
Spontaneous Resolution of Small Bowel Obstruction in a Child following Rupture of a Small Bowel Duplication Cyst
Authors: Patel K , Jacob J , Flavill J , Sellars M
Published: November 2011

Duplication cysts are rare congenital malformations that can present with a variety of symptoms that may change during the course of an acute admission. We report a case in which a four-year-old boy presented with signs of small bowel obstruction that following imaging were found to be secondary to bowel compression by a large duplication cyst. The symptoms changed when the cyst ruptured. We highlight the importance of ultrasound in establishing the diagnosis of enteric duplication cysts in the symptomatic paediatric population. We also explore the differential diagnosis and complications that can be caused by these congenital anomalies.
The influence of the tibial slope and the size of the intercondylar notch on rupture of the anterior cruciate ligament
Authors: Sonnery-Cottet B. , Archbold P. , Cucurulo T. , Fayard J.-M. , Bortolletto J. , Thaunat M. , Prost T. , Chambat P.
Published: November 2011

It has been suggested that an increased posterior tibial slope (PTS) and a narrow notch width index (NWI) increase the risk of anterior cruciate ligament (ACL) injury. The aim of this study was to establish why there are conflicting reports on their significance. A total of fifty patients with a ruptured ACL and 50 patients with an intact ACL were included in the study. The group with ACL rupture had a statistically significantly increased PTS (p < 0.001) and a smaller NWI (p < 0.001) than the control group. When a high PTS and/or a narrow NWI were defined as risk factors for an ACL rupture, 80% of patients had at least one risk factor present; only 24% had both factors present. In both groups the PTS was negatively correlated to the NWI (correlation coefficient = -0.28, p = 0.0052). Using a univariate model, PTS and NWI appear to be correlated to rupture of the ACL. Using a logistic regression model, the PTS (p = 0.006) and the NWI (p < 0.0001) remain significant risk factors. From these results, either a steep PTS or a narrow NWI predisposes an individual to ACL injury. Future studies should consider these factors in combination rather than in isolation.
Displaced fracture of the waist of the scaphoid
Authors: Dias J. J. , Singh H. P.
Published: November 2011

A displaced fracture of the scaphoid is one in which the fragments have moved from their anatomical position or there is movement between them when stressed by physiological loads. Displacement is seen in about 20% of fractures of the waist of the scaphoid, as shown by translation, a gap, angulation or rotation. A CT scan in the true longitudinal axis of the scaphoid demonstrates the shape of the bone and displacement of the fracture more accurately than do plain radiographs. Displaced fractures can be treated in a plaster cast, accepting the risk of malunion and nonunion. Surgically the displacement can be reduced, checked radiologically, arthroscopically or visually, and stabilised with headless screws or wires. However, rates of union and deformity are unknown. Mild malunion is well tolerated, but the long-term outcome of a displaced fracture that healed in malalignment has not been established.

This paper summarises aspects of the assessment, treatment and outcome of displaced fractures of the waist of the scaphoid.
Physical, mechanical and pharmacological properties of coloured bone cement with and without antibiotics
Authors: Galasso O. , Mariconda M. , Calonego G. , Gasparini G.
Published: November 2011

Coloured bone cements have been introduced to make the removal of cement debris easier at the time of primary and revision joint replacement. We evaluated the physical, mechanical and pharmacological effects of adding methylene blue to bone cement with or without antibiotics (gentamicin, vancomycin or both). The addition of methylene blue to plain cement significantly decreased its mean setting time (570 seconds (sd 4) vs 775 seconds (sd 11), p = 0.01), mean compression strength (95.4 MPa (sd 3) vs 100.1 MPa (sd 6), p = 0.03), and mean bending strength (65.2 MPa (sd 5) vs 76.6 MPa (sd 4), p < 0.001) as well as its mean elastic modulus (2744 MPa (sd 97) vs 3281 MPa (sd 110), p < 0.001). The supplementation of the coloured cement with vancomycin and gentamicin decreased its mean bending resistance (55.7 MPa (sd 4) vs 65.2 MPa (sd 5), p < 0.001).The methylene blue significantly decreased the mean release of gentamicin alone (228.2 µg (sd 24) vs 385.5 µg (sd 26), p < 0.001) or in combination with vancomycin (498.5 µg (sd 70) vs 613 µg (sd 25), p = 0.018) from the bone cement. This study demonstrates several theoretical disadvantages of the antibiotic-loaded bone cement coloured with methylene blue.
Unmasking Potential Intracellular Roles For Dysferlin through Improved Immunolabeling Methods
Authors: Roche Joseph A. , Ru Lisa W. , O’Neill Andrea M. , Resneck Wendy G. , Lovering Richard M. , Bloch Robert J.
Published: November 2011

Mutations in the DYSF gene that severely reduce the levels of the protein dysferlin are implicated in muscle-wasting syndromes known as dysferlinopathies. Although studies of its function in skeletal muscle have focused on its potential role in repairing the plasma membrane, dysferlin has also been found, albeit inconsistently, in the sarcoplasm of muscle fibers. The aim of this article is to study the localization of dysferlin in skeletal muscle through optimized immunolabeling methods. We studied the localization of dysferlin in control rat skeletal muscle using several different methods of tissue collection and subsequent immunolabeling. We then applied our optimized immunolabeling methods on human cadaveric muscle, control and dystrophic human muscle biopsies, and control and dysferlin-deficient mouse muscle. Our data suggest that dysferlin is present in a reticulum of the sarcoplasm, similar but not identical to those containing the dihydropyridine receptors and distinct from the distribution of the sarcolemmal protein dystrophin. Our data illustrate the importance of tissue fixation and antigen unmasking for proper immunolocalization of dysferlin. They suggest that dysferlin has an important function in the internal membrane systems of skeletal muscle, involved in calcium homeostasis and excitation-contraction coupling.
Deficiency of Pro-apoptotic Hrk Attenuates Programmed Cell Death in the Developing Murine Nervous System but Does Not Affect Bcl-x Deficiency-Induced Neuron Apoptosis
Authors: Ghosh Arindam P. , Cape Jennifer D. , Klocke Barbara J. , Roth Kevin A.
Published: November 2011

The BCL-2 family includes both pro- and anti-apoptotic proteins, which regulate programmed cell death during development and in response to various apoptotic stimuli. The BH3-only subgroup of pro-apoptotic BCL-2 family members is critical for the induction of apoptotic signaling, by binding to and neutralizing anti-apoptotic BCL-2 family members. During embryonic development, the anti-apoptotic protein BCL-XL plays a critical role in the survival of neuronal populations by regulating the multi-BH domain protein BAX. In this study, the authors investigated the role of Harakiri (HRK), a relatively recently characterized BH3-only molecule in disrupting the BAX-BCL-XL interaction during nervous system development. Results indicate that HRK deficiency significantly reduces programmed cell death in the nervous system. However, HRK deficiency does not significantly attenuate the widespread apoptosis seen in the Bcl-x−/− embryonic nervous system, indicating that other BH3-only molecules, alone or in combination, may regulate BAX activation in immature neurons.