bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of cloned pigs expressing human thrombomodulin in endothelial cells
Authors: Yazaki Satoko , Iwamoto Masaki , Onishi Akira , Miwa Yuko , Hashimoto Michiko , Oishi Takatsugu , Suzuki Shunichi , Fuchimoto Dai‐ichiro , Sembon Shoichiro , Furusawa Tadashi , Liu DaGe , Nagasaka Takaharu , Kuzuya Takafumi , Ogawa Haruko , Yamamoto Koji , Iwasaki Kenta , Haneda Masataka , Maruyama Shoichi , Kobayashi Takaaki 
Published: April 2012

Yazaki S, Iwamoto M, Onishi A, Miwa Y, Hashimoto M, Oishi T, Suzuki S, Fuchimoto D‐I, Sembon S, Furusawa T, Liu DG, Nagasaka T, Kuzuya T, Ogawa H, Yamamoto K, Iwasaki K, Haneda M, Maruyama S, Kobayashi T. Production of cloned pigs expressing human thrombomodulin in endothelial cells. Xenotransplantation 2012; 19: 82–91. © 2012 John Wiley & Sons A/S.Abstract:  For long‐term xenograft survival, coagulation control is one of the remaining critical issues. Our attention has been directed toward human thrombomodulin (hTM), because it is expected to exhibit the following beneficial effects on coagulation control and cytoprotection: (i) to solve the problem of molecular incompatibility in protein C activation; (ii) to exert a role as a physiological regulator, only when thrombin is formed; (iii) to suppress direct prothrombinase activity; and (iv) to have anti‐inflammatory properties. hTM gene was transfected into pig (Landrace/Yorkshire) fibroblasts using pCAGGS expression vector and pPGK‐puro vector. After puromycin selection, only fibroblasts expressing a high level of hTM were collected by cell sorting and then applied to nuclear transfer. Following electroactivation and subsequent culture, a total of 1547 cleaved embryos were transferred to seven surrogate mother pigs. Two healthy cloned piglets expressing hTM were born, successfully grew to maturity and produced normal progeny. Immunohistochemical staining of organs from F1 generation pigs demonstrated hTM expression in endothelial cells as well as parenchymal cells. High expression was observed particularly in endothelial cells of kidney and liver. Aortic endothelial cells from cloned pigs were found to express hTM levels similar to human umbilical vein endothelial cells (HUVEC) and to make it possible to convert protein C into activated protein C. The blockade of human endothelial cell protein C receptor (hEPCR) significantly reduced APC production in HUVEC, but not in hTM‐PAEC. Although no bleeding tendency was observed in hTM‐cloned pigs, activated partial thromboplastin time (APTT) was slightly prolonged and soluble hTM was detected in pig plasma. hTM was expressed in platelets and mononuclear cells, but not in RBC. Cloned pigs expressing hTM in endothelial cells at a comparable level to HUVEC were produced. As complete suppression of antigen‐antibody reaction in the graft is essential for accurate assessment of transgene related to coagulation control, production of genetically engineered pigs expressing hTM and complement regulatory protein based on galactosyltransferase knockout is desired.
What is the role of the (1→3)‐β‐d‐glucan assay in the screening of patients undergoing autologous haematopoietic stem‐cell transplantation?
Authors: Metan Gökhan , Koç A. N. , Kaynar Leyla G. , Atalay Altay , Öztürk Ahmet , Eser Bülent , Çetin Mustafa 
Published: April 2012

SummaryThe aim of this study is to determine the clinical contribution of (1→3)‐β‐d‐glucan (BDG) screening in the case of patients undergoing autologous haematopoietic stem‐cell transplantation (HSCT). The records at our stem‐cell transplantation centre were reviewed to identify the patients who underwent autologous HSCT between April 2009 and December 2010. Patients were classified as having proven invasive aspergillosis (IA), probable IA, or possible IA on the basis of the criteria established by the European Organization for Research and Treatment of Cancer and Mycoses Study Group (independent of the BDG results). During the study period, the patients were screened for BDG twice a week from transplant (day 0) until engraftment. Three patients were diagnosed with probable IA and five were diagnosed with possible IA. A total of 354 serum samples from79 patients who met the study inclusion criteria were used for statistical analysis. At the cut‐off value of 80 pg ml−1, the sensitivity was 27.2% [95% confidence interval (CI); 7.3–60.6]; specificity, 94.4% (95% CI; 91.3–96.5); positive predictive value, 6.2%; and negative predictive, 93.7%. The clinical contribution of the BDG assay as a screening test was relatively limited in this cohort of patients undergoing autologous HSCT.
Inflammatory bowel disease in Asia: A systematic review
Authors: Prideaux Lani , Kamm Michael A , De Cruz Peter P , Chan Francis K L , Ng Siew C 
Published: April 2012

AbstractThe incidence and prevalence of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are lower in Asia than in the West. However, across Asia the incidence and prevalence of IBD has increased rapidly over the last two to four decades. These changes may relate to increased contact with the West, westernization of diet, increasing antibiotics use, improved hygiene, vaccinations, or changes in the gut microbiota. Genetic factors also differ between Asians and the Caucasians. In Asia, UC is more prevalent than CD, although CD incidence is rapidly increasing in certain areas. There is a male predominance of CD in Asia, but a trend towards equal sex distribution for UC. IBD is diagnosed at a slightly older age than in the West, and there is rarely a second incidence peak as in the West. A positive family history is much less common than in the West, as are extra‐intestinal disease manifestations. There are clear ethnic differences in incidence within countries in Asia, and an increased incidence in IBD in migrants from Asia to the West. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.
Can the 1.8 mm transnasal biopsy forceps instead of standard 2.2 mm alter rapid urease test and histological diagnosis?
Authors: Jeon Su Jin , Shin Sung Jae , Lee Kee Myung , Lim Sun Kyu , Lee Yoon Chul , Lee Myung Hee , Hwang Jae Cheol , Cheong Jae Youn , Yoo Byung Moo , Kim Jin Hong 
Published: April 2012

AbstractBackground and Aim:  Biopsy specimens are taken during transnasal esophagogastroduodenoscopy with 1.8 mm forceps. The aims of this study were to compare the concordance of the Campylobacter‐like organism (CLO) test and histological diagnoses between biopsies taken with 1.8 mm and 2.2 mm forceps and to determine whether the concordance of the CLO test could be improved by increasing the number of specimens using 1.8 mm forceps.Methods:  A total of 200 patients were enrolled. We first performed the CLO test twice using each sample taken with both forceps in 100 patients. The CLO test was conducted three times again after confirming the difference in the CLO test between two forceps: (i) one sample with 1.8 mm forceps; (ii) two with 1.8 mm; and (iii) one with 2.2 mm in the other 100 patients. Additionally, each specimen was taken from the same gastric lesions in 200 patients for the histological diagnosis using both forceps types.Results:  The concordance rate of the CLO test between each sample with 1.8 mm and 2.2 mm forceps was 83% (κ‐value, 0.64), and that between two samples with 1.8 mm and one with 2.2 mm was 92% (κ‐value, 0.83). The concordance rate of the histological diagnosis with 1.8 and 2.2 mm was 97% (κ‐value, 0.84).Conclusions:  At least two samples using 1.8 mm forceps might be needed to obtain similar results on the CLO test using 2.2 mm. But, the size difference between two forceps did not influence the histological diagnosis.
Wegener's granulomatosis: treatment and survival characteristics in a high‐prevalence southern hemisphere region
Authors: Khan A. R. , Chapman P. T. , Stamp L. K. , Wells J. E. , O'Donnell J. L. 
Published: April 2012

AbstractOur aim was to describe the treatment and survival characteristics of Wegener's granulomatosis (WG) in Canterbury, New Zealand. The medical records of 48 patients diagnosed between 1 July 1997 and 31 December 2008 and fulfilling validated classification criteria for WG were reviewed to characterise survivorship in the province of Canterbury, New Zealand. The age at diagnosis was 61 years (range 20 to 83 years) with an equal number of males and females. Using Kaplan–Meier product‐limit analysis, the probability of survival at 1 and 10 years was 91% and 62% respectively. Of the 12 deaths in the cohort, four occurred within 12 months of diagnosis: two from pulmonary haemorrhage and two from renal failure. Beyond 12 months, two patients died of renal failure, two of myocardial infarction and one from cardiac arrhythmia, one from cerebrovascular disease and two from colorectal carcinoma. The median time to relapse was 6.75 years, and the probability of relapse within 10 years was 67%. Survivorship, treatment response rate and the rate of relapse from WG in a cohort of patients from this high‐prevalence southern hemisphere region were similar to that reported for northern hemisphere cohorts with a similar prevalence.
How to select the doctors of the future
Authors: Oates K. , Goulston K. 
Published: April 2012

AbstractAlthough previous academic performance is acknowledged as the best predictor of achievement in medical school, no one has succeeded in finding a selection method which will choose students who will become doctors with the qualities the community expect. Australian medical schools use various selection methods. It could well be argued that the most important phase in the selection process is informed decision‐making by potential applicants. More effort should be made by medical schools to achieve this.
Intravenous immunoglobulins as treatment of severe cutaneous polyarteritis nodosa
Authors: Marie I. , Miranda S. , Girszyn N. , Soubrane J.‐C. , Vandhuick T. , Levesque H. 
Published: April 2012

AbstractWe describe three patients with severe refractory cutaneous polyarteritis nodosa, resulting in painful ulcers involving the lower limbs and causing toe necrosis. Due to the severity of the cutaneous manifestations, the three patients received intravenous immunoglobulins at a dose of 1 g/kg/day for 2 days monthly. After the second intravenous immunoglobulin infusion, skin signs dramatically improved and completely healed after the third intravenous immunoglobulin infusion. Our findings indicate that intravenous immunoglobulins can be included in a therapeutic strategy to treat refractory cutaneous polyarteritis nodosa.
Utility, or not, of estimates of glomerular filtration rate in modifying drug dosage, with particular reference to enoxaparin
Authors: Adam W. R. 
Published: April 2012

AbstractA reduced clearance of some drugs in renal failure is a problem, particularly with drugs that are excreted by the kidney substantially unmetabolised and also have significant toxicity and a low therapeutic ratio. The problem is compounded by the significant inaccuracy of estimated glomerular filtration rate (eGFR). The aim was to develop general recommendations to reduce the risk of drug toxicity in renal failure, with particular reference to enoxaparin.The substantial inaccuracies in eGFR (eGFR in 32% of patients is different from measured GFR by 20–30%) are compounded when using a dichotomous decision tree (renal failure or not). As the eGFR approaches the GFR decision boundary, for classification as renal failure or not, misclassification approaches 50%.Recommendations, when patients are at risk, include the following: acknowledge inaccuracies of eGFR, particularly in anthropometrically diverse populations; measure drug levels wherever possible; realise that drug levels after early doses relate more to volume of distribution, rather than renal function, allowing time for modification of the drug dose; where accurate urine collection is feasible, use creatinine clearance as an estimate of GFR; and use eGFR as a (more) continuous, rather than dichotomous, variable to adjust dosage, exampled by enoxaparin.
Cancer and quackery
Authors: Irving K. B. 
Published: April 2012

AbstractThe Internal Medicine Journal published an article by two senior oncologists who were contesting the supposed miracle cure of a cancer survivor. This paper draws on the history of medicine to explore the conflict between biomedicine and alternative therapies. I suggest that the Internal Medicine Journal article, written about an episode that occurred more than 30 years ago, can best be explained by some oncologists' discomfort with losing their authority to dictate patient choices. I propose a compromise that rejects paternalism but accepts the possibility of worse patient outcomes.
Mental health education programmes for generalist health professionals: An integrative review
Authors: Brunero Scott , Jeon Yun‐Hee , Foster Kim 
Published: April 2012

ABSTRACTMainstreaming of mental health services has led to an increase in the presentation and care of mental health patients in generalist health settings. The lack of adequate mental health educational preparation of general health professionals (GHP) has been identified as a major barrier to meeting the health‐care needs of mental health patients. This study aimed to review and synthesize research evidence on mental health education programmes (MHEP) that have been designed to develop the knowledge, skills, and attitudes of GHP. An integrative literature review was conducted following a search of key electronic databases and hand searching of references of relevant papers, and 25 papers met the study inclusion criteria. Knowledge, skill, and attitudinal improvements in GHP post MHEP were shown in most studies. MHEP that included supervised clinical experience, role play, and case scenarios were reported as being more effective. Issues such as patient participation in education, interprofessional education models, and the willingness, interest and, motivation for GHP to be involved in MHEP warrant further research.
High cellular organization of pyoverdine biosynthesis in Pseudomonas aeruginosa: clustering of PvdA at the old cell pole
Authors: Guillon Laurent , El Mecherki Maher , Altenburger Stephan , Graumann Peter L. , Schalk Isabelle J. 
Published: April 2012

SummaryPyoverdine I (PVDI) is the major siderophore produced by Pseudomonas aeruginosa PAO1 to import iron. Its biosynthesis requires the coordinated action of cytoplasmic, periplasmic and membrane proteins. The individual enzymatic activities of these proteins are well known. However, their subcellular distribution in particular areas of the cytoplasm, periplasm, or within the membrane has never been investigated. We used chromosomal replacement to generate P. aeruginosa strains producing fluorescent fusions with PvdA, one of the initial enzymes in the biosynthetic pathway of PVDI in the cytoplasm, and PvdQ, involved in the maturation of PVDI in the periplasm. Cellular fractionation indicated that a substantial amount of PvdA‐YFP was located in the membrane fraction. Epifluorescence microscopy imaging showed that PvdA‐YFP was mainly clustered at the old cell pole of bacteria, indicating a polar segregation of the protein. Epifluorescence and TIRF imaging on cells expressing labelled PvdQ showed that this enzyme was uniformly distributed in the periplasm, in contrast with PvdA‐YFP. The description of the intracellular distribution of these enzymes contributes to the understanding of the PVDI biosynthetic pathway.
Practice‐setting and surgeon characteristics heavily influence the decision to perform partial nephrectomy among American Urologic Association surgeons
Authors: Weight Christopher J. , Crispen Paul L. , Breau Rodney H. , Kim Simon P. , Lohse Christine M. , Boorjian Stephen A. , Thompson R. Houston , Leibovich Bradley C. 
Published: April 2012

What's known on the subject? and What does the study add?
There is great variability in the utilization of partial nephrectomy, but the causes of these variations are not well understood.
The present study underscores the already observed phenomenon of surgical volume influencing surgical planning and outcomes, but it gets at why this might be so. We observe that high‐volume renal surgeons have different thresholds of ‘technical feasibility’.
Objective
To investigate why there continues to be wide variability in the application of partial nephrectomy (PN) for treating small renal masses despite guidelines in the US and Europe stating that a PN is a standard of care for a patient with a T1 renal mass.
Patients and Methods
In June 2009, 764 surgeon‐members of the American Urologic Association (AUA) participated in a survey evaluating the management of renal masses.
Renal mass complexity was graded by nephrometry score (NS).
Multivariable logistic regression models with generalized estimating equations were constructed to evaluate how tumour, surgeon and practice‐setting characteristics influence the use of PN.
Results
The survey response rate was 19%. Each urological surgeon responded to eight scenarios, providing 6112 evaluable cases.
Tumour NS ranged from 4 to 10, and each unit increase in NS was associated with 59% increased likelihood of a surgeon offering RN on multivariable analysis (odds ratio [OR] = 1.59; 95% CI: 1.52–1.64).
When holding patient and tumour characteristics constant, the following surgeon and practice‐setting characteristics significantly increased the odds of offering a PN: increasing renal case volume (OR = 1.57; 95% CI: 1.27–1.95), academic practice (OR = 1.80; 95% CI: 1.42–2.29), increasing PN % volume (OR = 3.7; 95% CI: 2.46–5.55) and younger surgeon age (≤40 vs >50 years) (OR = 1.64; 95% CI: 1.35–1.96).
Conclusion
The characteristics of a surgeon and the setting in which he or she practices influence the utilization of PN, the adherence to professional guidelines, and the threshold of tumour complexity at which a surgeon stops offering PN.
Prognostic role of tumour multifocality in renal cell carcinoma
Authors: Siracusano Salvatore , Novara Giacomo , Antonelli Alessandro , Artibani Walter , Bertini Roberto , Carini Marco , Carmignani Giorgio , Ciciliato Stefano , Cunico Sergio Cosciani , Lampropoulou Nikolitsa , Longo Nicola , Martorana Giuseppe , Minervini Andrea , Mirone Vincenzo , Simeone Claudio , Simonato Alchiede , Valotto Claudio , Zattoni Filiberto , Ficarra Vincenzo ,   members of the SATURN Project – LUNA Foundation
Published: April 2012

Study Type – Therapy (multi‐centre cohort)Level of Evidence 3bWhat's known on the subject? and What does the study add?In RCC about 5% of the patients presented multifocal disease. Prevalence of tumour multifocality was associated with a higher percentage of symptomatic RCC, higher pathological TNM stages, higher tumour grade and higher prevalence of tumour necrosis.Although in univariable analysis multifocal tumours had lower probability of CSS, tumour multifocality did not retain an independent predictive role in multivariable analysis. Patient age at surgery, gender, mode of presentation, pathological N stage and presence of metastases were independent predictors of CSS in multivariable analyses.OBJECTIVE
To evaluate the prevalence and the prognostic role of multifocality in a large multi‐institutional series of patients who underwent radical or partial nephrectomy for renal cell carcinoma (RCC).
METHODS
We retrospectively collected the data of 5378 patients who were surgically treated for RCC in 16 academic centres involved in the Surveillance and Treatment Update Renal Neoplasms (SATURN) project.
Univariable and multivariable Cox regression models addressed time to cancer‐specific survival (CSS) after surgery.
RESULTS
Tumour multifocality was identified in 249 patients (5%). The median follow‐up of the whole cohort was 42 months. At last follow‐up, 786 (14.6%) were dead of cancer and 336 (6.2%) had experienced non‐cancer‐related death.
The 5‐ and 10‐year CSS estimates were 84.1% and 77.3%, respectively, in patients with monofocal RCC, compared with 71.1% and 63.6%, respectively, in patients with multifocal disease (P < 0.001).
In univariable Cox regression analysis, tumour multifocality was significantly associated with CSS (hazard ratio [HR]= 1.83; P < 0.001).
On multivariate Cox regression analysis adjusted for the effects of other covariates, tumour multifocality did not retain an independent predictive value (HR = 1.24; P= 0.291).
CONCLUSIONS
In the present multi‐institutional collaboration, about 5% of the patients presented multifocal RCC.
The presence of multifocal cancer was associated with some unfavourable clinical and pathological features.
Although in univariable analysis multifocal tumours had lower CSS probabilities, tumour multifocality did not retain an independent predictive role in multivariable analysis, once adjusted for the effect of the other clinical and pathological covariates.
Role of magnetic resonance imaging in bladder cancer: current status and emerging techniques
Authors: Green David A. , Durand Matthieu , Gumpeni Naveen , Rink Michael , Cha Eugene K. , Karakiewicz Pierre I. , Scherr Douglas S. , Shariat Shahrokh F. 
Published: April 2012

What's known on the subject? and What does the study add?According to current treatment guidelines, magnetic resonance imaging (MRI) or computed tomography (CT) can be used to assist in staging bladder cancer patients being considered for radical surgery.In this article, we review the evidence supporting the use of MRI for bladder cancer staging. The ability of MRI to differentiate non‐muscle invasive from muscle‐invasive bladder cancer, to differentiate organ‐confined from non‐organ‐confined bladder cancer, and to identify lymph node metastases is described in detail. Additionally, the role of MRI as a biomarker of chemotherapeutic response in bladder cancer is reviewed and summarized.OBJECTIVES
• To evaluate the current status of magnetic resonance imaging (MR) as a staging tool for bladder cancer.
• To investigate the role of MR in assessing chemotherapeutic response in bladder cancer patients.
PATIENTS AND METHODS
• A Pubmed/MEDLINE search was conducted to identify original articles, review articles, and editorials regarding the use of MR in bladder cancer.
RESULTS
• Contrast‐enhanced MR and diffusion weighted MR (DW‐MRI) can likely distinguish between non‐muscle invasive bladder cancer and muscle invasive cancer with >80% accuracy.
• Some advantages of DW‐MRI are the differentiation of benign versus malignant tissue involvement without the need for intravenous contrast, and the possibility of obtaining information on histologic grade and T stage.
• Traditional MR sequence have low sensitivity for identifying small lymph node metastases but MR lymphography (MRL) using ultra‐small paramagnetic iron oxide (USPIO) may enhance their detectin.
• There may be a role for DW‐MRI in the evaluation of chemotherapeutic response in bladder cancer patients.
CONCLUSION
• To date, sample sizes and study designs are insufficient to clearly establish the role of MR in bladder cancer management, and to this end, well designed prospective trials are needed.