bluuebunny/crossref_metadata_2025 huggingface dataset:
Latex Agglutination Test Based on Single‐Chain Fv Recombinant Antibody Fragment
Authors: Golchin M. , Khalili‐Yazdi A. , Karamouzian M. , Abareghi A.
Published: September 2011

Recombinant antibodies have been proposed as invaluable tools for various therapeutic and diagnostic purposes. Here, we describe the development of a novel latex agglutination test (LAT) using single‐chain Fv recombinant antibody fragment for the detection of K99+ enterotoxigenic Escherichia coli strains. For the production of a single‐chain Fv antibody fragment (scFv) against the major colonization factor (FanC) of K99 antigen, the scFv gene was integrated into a bacterial expression vector under the control of T7 promoter. After high‐level expression of soluble scFv (approximately 50 mg/l) in flask cultivation of E. coli DE3 and purification, scFv was immobilized on different latex particles, and then, these sensitized beads were used in LAT. Results obtained with our latex reagents revealed that the recombinant antibody–coated particles were able to give a good agglutination signal with purified antigen, intact cells displaying this protein and clinical specimens. The strength of agglutination of scFv‐coated beads for antigen was comparable to that of polyclonal anti‐K99–coated particles. However, the assay proved to be simple and rapid, similar to conventional LATs, and owing to more convenient and economical production of recombinant antibodies, they can be considered as a useful reagent for replacing monoclonal antibodies in LATs.
Autoantigen‐Specific Memory B Cells in Primary Sjögren’s Syndrome
Authors: Aqrawi L. A. , Skarstein K. , Bredholt G. , Brun J. G. , Brokstad K. A.
Published: September 2011

Sjögren’s syndrome (SS) is a systemic rheumatic autoimmune disease affecting the exocrine glandular function and is characterized by the presence of autoantibodies against the ribonucleoprotein particles, SS‐A/Ro and SS‐B/La, and mononuclear cell infiltration of exocrine tissues. Our aim is to characterize memory B cell pattern and function in relation to the progression of the disease, by analysing samples from a well‐defined cohort of patients with primary SS. We have measured the number of Ro/La‐specific plasma cells in peripheral blood mononuclear cells (PBMC) from 23 patients and 20 healthy controls by direct enzyme‐linked immunospot (ELISPOT) assay. Furthermore, we quantified the Ro‐ and La‐specific memory B cells in these individuals by a 6‐day in vitro polyclonal stimulation of PBMC followed by an antigen‐specific ELISPOT assay for the detection of memory B cells. In addition to this, ELISA profiling of autoantibodies was carried out using patients’ plasma and supernatant, collected post‐mitogen stimulation of PBMC. The average Ro60‐, Ro52‐ and La48‐specific plasma cells in PB was 9, 17 and 13 cells in 105 PBMC, respectively. After in vitro stimulation, these numbers increased to 43, 50 and 26 for Ro60, Ro52 and La48, correspondingly. However, the fraction of memory B cells activated into antibody‐secreting cells was lower than the overall IgG B cell population. We conclude that these lower Ro/La‐specific memory B cell levels may indicate that a greater portion of the Ro‐ and La‐specific B cells are in an activated stage. This is in tune with previous reports.
Immunomodulatory Effects of Palifermin (Recombinant Human Keratinocyte Growth Factor) in an SLE‐Like Model of Chronic Graft‐Versus‐Host Disease
Authors: Ellison C. A. , Lissitsyn Y. V. , Gheorghiu I. , Gartner J. G.
Published: September 2011

Keratinocyte growth factor (KGF) promotes epithelial cell proliferation and survival. Recombinant human KGF, also known as palifermin, protects epithelial cells from injury induced by chemicals, irradiation and acute murine graft‐versus‐host disease (GVHD). Findings from our studies and others have shown that palifermin also has immunomodulatory properties. In a model of acute GVHD, we showed that it shifts the immune response from one in which Th1 cytokines dominate to mixed Th1 and Th2 cytokine profile. Using the DBA/2→(C57BL/6 × DBA/2)F1‐hybrid model of chronic, systemic lupus erythematosus‐like GVHD, we showed that palifermin treatment is associated with higher levels of Th2 cytokines, the production of anti‐nuclear antibodies, cryoglobulinemia and the development of more severe pathological changes in the kidney. The aim of our current study was to gain a better understanding of the immunobiology of KGF by further characterizing the palifermin‐mediated effects in this model of chronic GVHD. Because the pathological changes we observed resemble those seen in thymic stromal lymphopoietin (TSLP) transgenic mice, we had originally hypothesized that palifermin might augment TSLP levels. Surprisingly, we did not observe an increase in thymic TSLP mRNA expression in palifermin‐treated recipients. We did, however, observe some differences in the percentages of CD4+CD25+Foxp3+ regulatory T cells in the spleen at some time points in palifermin‐treated recipients. Most importantly, we found that TGFβ levels were higher in palifermin‐treated recipients early in the GVH reaction, raising the possibility that KGF might indirectly induce the development of fibrosis and glomerulonephritis through a pathway involving TGFβ.
Subcutaneous Administration of Modified Vaccinia Virus Ankara Expressing an Ag85B‐ESAT6 Fusion Protein, but Not an Adenovirus‐Based Vaccine, Protects Mice Against Intravenous Challenge with Mycobacterium tuberculosis
Authors: You Q. , Jiang C. , Wu Y. , Yu X. , Chen Y. , Zhang X. , Wei W. , Wang Y. , Tang Z. , Jiang D. , Wu Y. , Wang C. , Meng X. , Zhao X. , Kong W.
Published: September 2011

Recombinant virus‐based tuberculosis (TB) vaccines that are strongly immunogenic and elicit robust cellular immunity are considered ideal vaccine candidates. Here, we engineered a poxvirus‐based vaccine, MVA85B‐E6, and an adenovirus‐based vaccine, AD85B‐E6, both of which express the fusion protein Ag85B‐ESAT6. Subcutaneous vaccination of AD85B‐E6 generated strong interferon (IFN)‐γ production by both CD4 and CD8 T cells and CD8 cytotoxic T lymphocyte activity; these results indicate that strong T‐helper type 1 immune responses were elicited in mice, which is in contrast to the moderate responses induced by vaccination with MVA85B‐E6. However, MVA85B‐E6 given subcutaneously led to levels of protection comparable with that induced by the bacillus Calmette–Guérin vaccine in the lungs and spleens, whereas AD85B‐E6 given subcutaneously did not show any protective efficacy after intravenous challenge of BALB/c mice with Mycobacterium tuberculosis H37Rv. Our study emphasizes that more efficient biomarkers for vaccine efficacy and more appropriate routes of vaccine administration are necessary for the development of a successful TB vaccine.
Climbing‐ripple successions in turbidite systems: depositional environments, sedimentation rates and accumulation times
Authors: JOBE ZANE R. , LOWE DONALD R. , MORRIS WILLIAM R.
Published: September 2011

Climbing‐ripple cross‐lamination is most commonly deposited by turbidity currents when suspended load fallout and bedload transport occur contemporaneously. The angle of ripple climb reflects the ratio of suspended load fallout and bedload sedimentation rates, allowing for the calculation of the flow properties and durations of turbidity currents. Three areas exhibiting thick (>50 m) sections of deep‐water climbing‐ripple cross‐lamination deposits are the focus of this study: (i) the Miocene upper Mount Messenger Formation in the Taranaki Basin, New Zealand; (ii) the Permian Skoorsteenberg Formation in the Tanqua depocentre of the Karoo Basin, South Africa; and (iii) the lower Pleistocene Magnolia Field in the Titan Basin, Gulf of Mexico. Facies distributions and local contextual information indicate that climbing‐ripple cross‐lamination in each area was deposited in an ‘off‐axis’ setting where flows were expanding due to loss of confinement or a decrease in slope gradient. The resultant reduction in flow thickness, Reynolds number, shear stress and capacity promoted suspension fallout and thus climbing‐ripple cross‐lamination formation. Climbing‐ripple cross‐lamination in the New Zealand study area was deposited both outside of and within channels at an inferred break in slope, where flows were decelerating and expanding. In the South Africa study area, climbing‐ripple cross‐lamination was deposited due to a loss of flow confinement. In the Magnolia study area, an abrupt decrease in gradient near a basin sill caused flow deceleration and climbing‐ripple cross‐lamination deposition in off‐axis settings. Sedimentation rate and accumulation time were calculated for 44 climbing‐ripple cross‐lamination sedimentation units from the three areas using TDURE, a mathematical model developed by Baas et al. (2000). For Tc divisions and Tbc beds averaging 26 cm and 37 cm thick, respectively, average climbing‐ripple cross‐lamination and whole bed sedimentation rates were 0·15 mm sec−1 and 0·26 mm sec−1 and average accumulation times were 27 min and 35 min, respectively. In some instances, distinct stratigraphic trends of sedimentation rate give insight into the evolution of the depositional environment. Climbing‐ripple cross‐lamination in the three study areas is developed in very fine‐grained to fine‐grained sand, suggesting a grain size dependence on turbidite climbing‐ripple cross‐lamination formation. Indeed, the calculated sedimentation rates correlate well with the rate of sedimentation due to hindered settling of very fine‐grained and fine‐grained sand–water suspensions at concentrations of up to 20% and 2·5%, respectively. For coarser grains, hindered settling rates at all concentrations are much too high to form climbing‐ripple cross‐lamination, resulting in the formation of massive/structureless S3 or Ta divisions.
Corumbella and in situ Cloudina in association with thrombolites in the Ediacaran Itapucumi Group, Paraguay
Authors: Warren Lucas V. , Fairchild Thomas R. , Gaucher Claudio , Boggiani Paulo C. , Poiré Daniel G. , Anelli Luís E. , Inchausti Julio C. G.
Published: September 2011

Terra Nova, 23, 382–389, 2011

An in situ assemblage of Cloudina, thrombolites and an ichnofossil (cf. Archaeonassa), together with fragments of Corumbella werneri, is reported here, from a tidally influenced, shallow, lagoonal setting on a carbonate ramp within the Itapucumi Group, Paraguay. The association of Cloudina with thrombolites is comparable to other terminal Neoproterozoic occurrences, but the coexistence of shelly fossils in situ with trace fossils and microbially induced sedimentary structures is apparently unique. This discovery extends the record of Cloudina and Corumbella in South America and further elucidates the diversity, distribution and palaeoecology of shelled organisms in late Ediacaran time.
Simultaneous resetting of the muscovite K‐Ar and monazite U‐Pb geochronometers: a story of fluids
Authors: Tartèse Romain , Ruffet Gilles , Poujol Marc , Boulvais Philippe , Ireland Trevor R.
Published: September 2011

Terra Nova, 23, 390–398, 2011

Although water is ubiquitous in the continental crust, its effect on geochronometers through mineral reequilibration is rarely taken into account. Herein, we present 40Ar/39Ar analyses on muscovite and U‐Pb isotopic data on zircon and monazite from a Variscan syn‐tectonic granite from western France. Both the K‐Ar in the muscovite and U‐Pb in the monazite isotopic systems were hydrothermally reset, whereas the U‐Pb radiogenic system in most of the zircons was unaffected and dates the granite emplacement age. Titanium chemical maps obtained on muscovites from various dated samples display a spectacular overprinting of their magmatic zoning resulting from increasing fluid‐rock interaction. These results reiterate the need to combine geochronological data with petrological, mineralogical and geochemical studies to accurately interpret ages obtained in this type of geodynamical settings.
Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis
Authors: Bruhn S. , Barrenäs F. , Mobini R. , Andersson B. A. , Chavali S. , Egan B. S. , Hovig E. , Sandve G. K. , Langston M. A. , Rogers G. , Wang H. , Benson M.
Published: September 2011

To cite this article: Bruhn S, Barrenäs F, Mobini R, Andersson BA, Chavali S, Egan BS, Hovig E, Sandve GK, Langston MA, Rogers G, Wang H, Benson M. Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis. Allergy 2012; 67: 33–40.

Background:  The transcription factor (TF) IRF4 is involved in the regulation of Th1, Th2, Th9, and Th17 cells, and animal studies have indicated an important role in allergy. However, IRF4 and its target genes have not been examined in human allergy.

Methods:  IRF4 and its target genes were examined in allergen‐challenged CD4+ cells from patients with IAR, using combined gene expression microarrays and chromatin immunoprecipitation chips (ChIP‐chips), computational target prediction, and RNAi knockdowns.

Results:  IRF4 increased in allergen‐challenged CD4+ cells from patients with IAR, and functional studies supported its role in Th2 cell activation. IRF4 ChIP‐chip showed that IRF4 regulated a large number of genes relevant to Th cell differentiation. However, neither Th1 nor Th2 cytokines were the direct targets of IRF4. To examine whether IRF4 induced Th2 cytokines via one or more downstream TFs, we combined gene expression microarrays, ChIP‐chips, and computational target prediction and found a putative intermediary TF, namely ETS1 in allergen‐challenged CD4+ cells from allergic patients. ETS1 increased significantly in allergen‐challenged CD4+ cells from patients compared to controls. Gene expression microarrays before and after ETS1 RNAi knockdown showed that ETS1 induced Th2 cytokines as well as disease‐related pathways.

Conclusions:  Increased expression of IRF4 in allergen‐challenged CD4+ cells from patients with intermittent allergic rhinitis leads to activation of a complex transcriptional program, including Th2 cytokines.
Hyperbilirubinemia after hematopoietic stem cell transplantation: comparison of clinical and pathologic findings in 41 autopsied cases
Authors: Kagoya Yuki , Takahashi Tsuyoshi , Nannya Yasuhito , Shinozaki Aya , Ota Satoshi , Fukayama Masashi , Kurokawa Mineo
Published: September 2011

Kagoya Y, Takahashi T, Nannya Y, Shinozaki A, Ota S, Fukayama M, Kurokawa M. Hyperbilirubinemia after hematopoietic stem cell transplantation: comparison of clinical and pathologic findings in 41 autopsied cases. Clin Transplant 2011: 25: E552–E557. © 2011 John Wiley & Sons A/S.

Abstract:  Hyperbilirubinemia is often associated with morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Diagnosis of its etiology is usually made clinically among various possible causes, and analysis of histological findings as compared with the clinical diagnosis has not been performed sufficiently. We retrospectively analyzed clinical and pathological findings in 41 autopsied patients who died with hyperbilirubinemia (>2 mg/dL). Overall, liver graft‐versus‐host disease (GVHD) showed the most prominent discordance between clinical and pathological diagnoses. Only 11 of the 22 patients, considered to have liver GVHD clinically, had GVHD findings at autopsy. Serum gamma‐glutamyl transpeptidase (GGT), GGT/aspartate aminotransferase (AST) ratio, and alkaline phosphatase (ALP)/AST ratio in GVHD patients were significantly higher compared with those without GVHD (p = 0.02, <0.01, and 0.03, respectively), which was useful in clinical diagnosis of liver GVHD. Other major findings include liver invasion of the primary malignancies in 8 patients, post‐transplant lymphoproliferative disorder of the liver in two patients, and disseminated liver invasion by fungus or varicella‐zoster virus in one patient, respectively. Although analysis of clinical data is useful for narrowing diagnosis, histological analysis by liver biopsy is crucially important, especially in cases suspected of having GVHD.
Validation of genetic variants associated with early acute rejection in kidney allograft transplantation
Authors: Oetting William S. , Zhu Yanni , Brott Marcia J. , Matas Arthur J. , Cordner Gretchen K. , Pan Wei
Published: September 2011

Oetting WS, Zhu Y, Brott MJ, Matas AJ, Cordner GK, Pan W. Validation of genetic variants associated with early acute rejection in kidney allograft transplantation.  Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01522.x.  © 2011 John Wiley & Sons A/S.

Abstract:  Numerous reports have identified genetic variants associated with kidney transplant outcome, but only a few have been validated in subsequent studies. We analyzed the association of 21 previously reported genetic variants associated with acute rejection (AR), in an effort to validate these associations in our kidney transplant population. All recipients (n = 585) received Ab induction, rapid discontinuation of prednisone, and calcineurin inhibitors with either mycophenolate mofetil or sirolimus. Both univariate analysis and logistic regression were used for determining the association between the genotypes and AR. Univariate analysis detected one significant single‐nucleotide polymorphism (p = 0.03), rs1801133, within the methylenetetrahydrofolate reductase (MTHFR) gene associated with AR. Logistic regression analysis identified two variants associated with AR, the 32‐bp deletion within chemokine (C‐C motif) receptor 5 gene (rs333) and the p.222A/V variant (rs1801133) within the MTHFR gene. Although our analysis utilized a much larger cohort than used in previous reports, we were only able to detect an association with two of these variants. The lack of validation for the other 19 variants may be due to the small effect size, or that, they are not associated with AR. These results stress the need for larger cohorts for both future studies as well as for validation studies.
Sublingual immunotherapy in children with allergic rhinitis: quality of systematic reviews
Authors: de Bot Cindy M. A. , Moed Heleen , Berger Marjolein Y. , Röder Esther , van Wijk Roy G. , van der Wouden Johannes C.
Published: September 2011

To cite this article: de Bot CMA, Moed H, Berger MY, Röder E, van Wijk RG, van der Wouden JC. Sublingual immunotherapy in children with allergic rhinitis: quality of systematic reviews. Pediatr Allergy Immunol 2011; 22: 548–558.

Systematic reviews have gained popularity as a way to combine the increasing amount of research information. This study assessed the quality of systematic reviews and meta‐analyses of sublingual immunotherapy (SLIT) for allergic rhinitis in children, published since 2000. Eligible reviews were identified by searching Medline/Pubmed, Embase, and the Cochrane Library, from 2000 through 2008. Methodological quality was assessed using the assessment of multiple systematic reviews instrument. Ten systematic reviews were included, one of which was published in the Cochrane Library. Eight reviews gave some details about the search strategy. None of the reviews included measures to avoid selection bias. In 60% of the reviews, the methodological quality of the included studies was (partly) assessed. Four reviews pooled the results of individual studies, neglecting clinical heterogeneity. Three of the 10 reviews provided information about sources of funding or grants from industry. Of the 10 reviews, the six reviews with the highest overall score scored 5–8 points, indicating moderate quality. Systematic reviews are useful to evaluate the efficacy of SLIT in children. Although more reviews have become available, the methodological quality could be improved. SLIT for children could be promising, but methodological flaws in the reviews and individual studies are too serious to draw definite conclusions.
Development of Collagen Fibres and Lysyl Oxidase Expression in the Presumptive Dermis of Chick Limb Bud
Authors: Yamazaki Y. , Mikami Y. , Yuguchi M. , Namba Y. , Isokawa K.
Published: September 2011

With 4 figures and 1 table

Lysyl oxidase (LOX) plays a critical role in the formation of cross‐linkages in extracellular matrix molecules. Thus, it is essential for the biogenesis and homeostasis of the connective tissue matrix. During development, collagen fibres and elastic system fibres emerge and accumulate in a temporospatial manner in the presumptive dermis of chicks. In this study, we investigated LOX mRNA expression by laser capture microdissection and RT‐qPCR and LOX protein localization by immunohistochemistry. The picrosirius polarization method was used to investigate a relation between collagen accumulation and LOX expression. PCR analysis showed that the expression of LOX mRNA in the presumptive dermis became apparent at embryonic day 13 and increased considerably by ED17. Immunohistochemical staining for LOX in the dermis was very low at all stages of development. Accumulation of collagen fibres was seen in the dermis on ED10, and higher wavelengths of birefringence became evident by ED13. Our findings suggest that the temporal pattern of LOX mRNA expression correlates with collagen fibre accumulation in the dermis of the developing chick limb bud, whereas LOX expression was relatively constant at the protein level.
Prevalence of gastroesophageal reflux disease in Korea and associated health‐care utilization: A national population‐based study
Authors: Kim Kyoung‐Min , Cho Yu Kyung , Bae Seung Jin , Kim Dong‐Sook , Shim Ki‐Nam , Kim Jie‐Hyun , Jung Sung Woo , Kim Nayoung
Published: September 2011

Background and Aim:  Few studies have reported temporal trends in the prevalence of gastroesophageal reflux disease (GERD) and associated health‐care utilization in Asia. The aim of this study was to investigate temporal changes in the prevalence of GERD and associated health‐care utilization.

Methods:  Patients with a primary or secondary disease code for GERD, according to the Korean Standard Classification of Diseases, were defined as having “doctor‐diagnosed GERD”. The prevalence of GERD from 2005 to 2008 was evaluated using Korean National Health Insurance claim data. Claims for proton pump inhibitors (PPI) over this period were also evaluated. Complications of GERD and health‐care utilization characteristics, such as the use of diagnostic tests and prescriptions, were investigated.

Results:  The prevalence of doctor‐diagnosed GERD increased rapidly from 4.6% to 7.3% between 2005 and 2008. Over the same period, the amount of PPI claims increased by 56%. People aged 30–39 years and females had a high frequency of GERD‐related visits. Esophageal stricture was rare, and 23% of patients with GERD had peptic ulcers. Endoscopy was used as a diagnostic test in 34% of cases. Seventy‐seven percent of patients with GERD were treated with PPI or H2 receptor antagonists.

Conclusions:  The prevalence of GERD increased rapidly from 2005 to 2008. The rapid increase of PPI use reflects the real increase in the prevalence of GERD and demand for health care. Middle‐aged people and women had a high frequency of GERD visits. Therefore, GERD might be a significant disease burden in Korea.
Newly‐developed, forward‐viewing echoendoscope: A comparative pilot study to the standard echoendoscope in the imaging of abdominal organs and feasibility of endoscopic ultrasound‐guided interventions
Authors: Iwashita Takuji , Nakai Yousuke , Lee John G , Park Do Hyun , Muthusamy V Raman , Chang Kenneth J
Published: September 2011

Background and Aim:  Multiple diagnostic and therapeutic endoscopic ultrasound (EUS) procedures have been widely performed using a standard oblique‐viewing (OV) curvilinear array (CLA) echoendoscope. Recently, a new, forward‐viewing (FV) CLA was developed, with the advantages of improved endoscopic viewing and manipulation of devices. However, the FV–CLA echoendoscope has a narrower ultrasound scanning field, and lacks an elevator, which might represent obstacles for clinical use. The aim of this study was to compare the FV–CLA echoendoscope to the OV–CLA echoendoscope for EUS imaging of abdominal organs, and to assess the feasibility of EUS‐guided interventions using the FV–CLA echoendoscope.

Methods:  EUS examinations were first performed and recorded using the OV–CLA echoendoscope, followed immediately by the FV–CLA echoendoscope. Video recordings were then assessed by two independent endosonographers in a blinded fashion. The EUS visualization and image quality of specific abdominal organs/structures were scored. Any indicated fine‐needle aspiration (FNA) or intervention was performed using the FV–CLA echoendoscope, with the OV–CLA echoendoscope as salvage upon failure.

Results:  A total of 21 patients were examined in the study. Both echoendoscopes had similar visualization and image quality for all organs/structures, except the common hepatic duct (CHD), which was seen significantly better with the FV–CLA echoendoscope. EUS interventions were conducted in eight patients, including FNA of pancreatic mass (3), pancreatic cyst (3), and cystgastrostomy (2). The FV–CLA echoendoscope was successful in seven patients. One failed FNA of the pancreatic head cyst was salvaged using the OV–CLA echoendoscope.

Conclusions:  There were no differences between the FV–CLA echoendoscope and the OV–CLA echoendoscope in visualization or image quality on upper EUS, except for the superior image quality of CHD using the FV–CLA echoendoscope. Therefore, the disadvantages of the FV–CLA echoendoscope appear minimal in light of the potential advantages.
Success rate and cannulation time between precut sphincterotomy and double‐guidewire technique in truly difficult biliary cannulation
Authors: Angsuwatcharakon Phonthep , Rerknimitr Rungsun , Ridtitid Wiriyaporn , Ponauthai Yuwadee , Kullavanijaya Pinit
Published: September 2011

Background and Aim:  Precut sphincterotomy (PS) is usually indicated in failed standard biliary cannulation (BC). PS requires experienced endoscopists, and contains significant risk. Double‐guidewire (DG) cannulation seems to be easier, and might be useful after failed standard BC. We aimed to compare cannulation time, success rate, and complication rates between the two techniques.

Methods:  Patients who failed standard BC within 10 min by the expert were defined as truly difficult BC and randomized into both groups. In the DG group, the first guidewire was left in the pancreatic duct, and then a catheter, pre‐inserted with another guidewire, was used for the BC. In the PS group, a fistulotomy technique was used.

Results:  From June 2008 to October 2009, 534 patients underwent endoscopic retrograde cholangiopancreatography. Forty‐four patients (8.2%) who failed standard BC were randomized into the DG group (n = 23) and the PS group (n = 21). Median cannulation times and success rates in the DG and PS groups were 172 versus 394 s (P < 0.001), and 73.9% versus 80.9% (P = 0.724), respectively. The pancreatitis rate and serum amylase at 24 h in the DG and PS groups were 21.7% versus 14.3% (P = 0.701) and 937 versus 195 mg/dL (P = 0.020), respectively. Two from each group developed mild bleeding. No perforation occurred.

Conclusion:  In truly difficult BC, the DG technique requires a significant shorter duration for BC, with a comparable success rate to the PS technique. The post‐procedure serum amylase level in the DG group was significantly higher, and there was a trend of more pancreatitis.
Identification of the putative intestinal stem cell marker doublecortin and CaM kinase‐like‐1 in Barrett's esophagus and esophageal adenocarcinoma
Authors: Vega Kenneth J , May Randal , Sureban Sripathi M , Lightfoot Stan A , Qu Dongfeng , Reed Alessandra , Weygant Nathaniel , Ramanujam Rama , Souza Rhonda , Madhoun Mohammad , Whorton Joshua , Anant Shrikant , Meltzer Stephen J , Houchen Courtney W
Published: September 2011

Background and Aim:  In Barrett's esophagus (BE), the normal esophageal squamous epithelium is replaced with a specialized metaplastic columnar epithelium. BE is a premalignant lesion that can progress to esophageal adenocarcinoma (EAC). Currently, there are no early molecular indicators that would predict progression from BE to EAC. As the only permanent residents of the epithelium, stem cells have been implicated in this metaplastic progression. The aim of the present study was to determine the expression of doublecortin and CaM kinase‐like‐1 (DCAMKL‐1) and other putative gastrointestinal stem cell markers in normal esophageal mucosa (NEM), BE, and EAC.

Methods:  Human NEM, BE, EAC, and multitissue microarrays were analyzed for DCAMKL‐1, and immunohistochemically scored based on staining intensity and tissue involvement, with epithelia and stroma scored separately. Total RNA isolated from BE and paired NEM was subjected to real‐time reverse‐transcription–polymerase chain reaction analysis for DCAMKL‐1, leucine‐rich repeat‐containing G‐protein‐coupled receptor (LGR5), and Musashi‐1 (Msi‐1) mRNA expression.

Results:  DCAMKL‐1 was minimally expressed in squamous NEM, but increased in BE (with and without dysplasia) and EAC tissues. In EAC, we found increased stromal DCAMKL‐1 staining compared to adjacent epithelia. Within the submucosa of dysplastic BE tissues, an increase in the endothelial cell expression of DCAMKL‐1 was observed. Finally, an upregulation of DCAMKL‐1, LGR5, and Msi‐1 mRNA was seen in BE compared to squamous NEM.

Conclusions:  In the present study, we report the progressive increase of DCAMKL‐1 expression in BE from dysplasia to EAC. Furthermore, there was an increase in putative stem cell markers DCAMKL‐1, LGR5, and Msi‐1 mRNA. Taken together, these data suggest that the regulation of resident stem cells might play an important role in the progression of BE to EAC.
New opportunity for vaccinating older people: Well‐child clinic visits
Authors: Arslan Ismail , Beyazova Ufuk , Aksakal Nur , Polat Selda , Camurdan Aysu Duyan , Sahin Figen
Published: September 2011

Background:  Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. As aging of the population is making the health of the elderly a universal priority, preventive measures, such as vaccination, will become increasingly important.

Methods:  We designed a prospective interventional study to determine whether recommendations to vaccinate grandparents of children attending well‐child clinics would increase the pneumococcal vaccination rate in the elderly. Children younger than 5 years of age, attending a university well‐child clinic from 1 May to 31 September 2008 who had grandparents over 65 years of age were eligible. A survey including the questions about the demographic characteristics of children, their parents and grandparents over 65 was carried out by face‐to‐face interview with the parents. High‐risk medical conditions and vaccination history of grandparents was also noted and the benefits and necessity of pneumococcal vaccination (23vPPV) for the elderly was emphasized. Four months later these families were contacted to determine whether this intervention had increased the pneumococcal vaccination rates of the elderly.

Results:  Information was obtained from 938 grandparents of 545 children. Before the interview, among all grandparents, only 0.9% were vaccinated with 23vPPV. Four months after this intervention, immunization coverage increased to 19.1%. The sex of the grandchild (OR: 1.99) and previous hepatitis B or influenza immunization of the grandparents (OR: 2.73) were the significant parameters accounting for higher immunization rates.

Conclusion:  Reminding elderly grandparents about vaccines in well‐child clinics could be an opportunity in this field.
Comparison of the histopathological diagnoses of preoperative dilatation and curettage and hysterectomy specimens
Authors: Barut Aykut , Barut Figen , Arikan Ilker , Harma Muge , Harma Mehmet Ibrahim , Ozmen Bayar Ulku
Published: September 2011

Aim:  A biopsy is often taken as part of the preoperative workup, regardless of the indication for hysterectomy. Some authors believe that dilatation and curettage is a poor diagnostic procedure for intrauterine pathologies, but dilatation and curettage has been the method of choice for obtaining an endometrial sample. The aim of this study was to investigate the concordance between endometrial histopathological diagnoses from preoperative dilatation and curettage and hysterectomy specimens. The differences between premenopausal and postmenopausal women were also investigated.

Methods:  Histopathological results for dilatation and curettage specimens from 645 women (401 premenopausal and 244 postmenopausal) who underwent a hysterectomy between 2003 and 2009 were analyzed retrospectively.

Results:  High sensitivity (87.8%), specificity (100%), positive (100%) and negative (98.7%) predictive values, and accuracy (98.8%) were observed for all malignant endometrial pathologies obtained at dilatation and curettage. In postmenopausal women, eight malignancies were missed when the preoperative diagnosis from the dilatation and curettage sample indicated inadequate tissue or premalignant lesions. For premenopausal women, we found only two missed malignancies. The accuracy was 99.5% and 96.8% for malignant pathologies diagnosed from curettage material for pre‐ and postmenopausal women, respectively.

Conclusions:  Dilatation and curettage remains the ‘gold standard’ for diagnosing endometrial pathologies, especially malignancies.
Carcinomatous meningitis during systematic chemotherapy in a patient with advanced small‐cell neuroendocrine carcinoma of the uterine cervix
Authors: Watanabe Yoh , Nakai Hidekatsu , Imaoka Izumi , Murakami Takamichi , Hoshiai Hiroshi
Published: September 2011

Carcinoma meningitis with uterine cervical cancer is an extremely rare event. We present the clinicopathologic characteristics and diagnostic imaging findings of a patient with advanced small‐cell neuroendocrine carcinoma of the cervix who had developed carcinoma meningitis during systematic chemotherapy.
Urinary pathogens and drug susceptibility patterns of urinary tract infections among antenatal clinic attendees in Ibadan, Nigeria
Authors: Kehinde Aderemi , Adedapo Kayode , Aimakhu Chris , Odukogbe Akin‐Tunde , Olayemi Oladapo , Salako Babatunde
Published: September 2011

Aim:  To determine the bacterial agents involved in urinary tract infections in pregnant women and their antibiotic susceptibility patterns in Ibadan, Nigeria.

Methods:  All consenting subjects who attended antenatal clinics of the University College Hospital and Adeoyo Maternity Hospital, Ibadan, Nigeria, from 1 April 2007 and 30 March 2009 were interviewed to obtain demographic and pregnancy health data. Mid‐stream urine samples obtained were processed by standard methods. Confirmed bacterial isolates were tested against seven antibiotics using the Kirby–Bauer disc diffusion technique.

Results:  Of the 473 specimens processed, 136 (28.8%) were positive for microscopy, 118 (25.0%) were culture positive, while 18 (3.8%) were microscopy positive but negative for culture. More than 90% of the bacterial isolates were Gram‐negative bacilli, of which approximately 80% were members of the family Enterobacteriaceae. Klebsiella oxytoca accounted for 45 (38.1%) of the causative agents identified, followed by Escherichia coli (31.3%), Pseudomonas aeruginosa (9.3%) and Proteus mirabilis (6.8%). Candida albicans accounted for three (2.6%) of the isolates. Ten isolates (22.2%) of K. oxytoca were resistant to cefuroxime while three (6.7%) were resistant to ofloxacin. The only Gram‐positive bacterium isolated, Staphylococcus saprophyticus, accounted for four (4.3%) of all pathogens, of which three (75.0%) were susceptible to nitrofurantoin, ofloxacin, cefuroxime and the amoxicillin–clavulanic acid combination.

Conclusions:  In conclusion, the incidence of culture‐positive urinary tract infection in pregnancy is common in Ibadan. More studies are needed to evaluate the susceptibility profile of uropathogens to commonly used antibiotics in our environment.
Ultrasound for evaluation of adnexal malignancy: From 2D to 3D ultrasound
Authors: Hata Toshiyuki , Hata Kohkichi , Noguchi Junko , Kanenishi Kenji , Shiota Atsuko
Published: September 2011

Conventional two‐dimensional (2D) ultrasound has been widely used for the evaluation of adnexal malignancy in gynecologic fields. This 2D ultrasound evaluation includes a morphological assessment, color/power and pulsed Doppler sonographic assessment, scoring system, and contrast agent assessment of adnexal masses. The introduction of three‐dimensional (3D) ultrasound would facilitate the novel assessment of adnexal masses. With the recent advance in 3D power Doppler (3DPD) ultrasound as well as quantitative 3DPD histogram analysis, quantitative and qualitative assessments of the vascularization and blood flow of adnexal masses have become feasible. These novel techniques may assist in the evaluation of adnexal malignancy, and offer potential advantages relative to conventional 2D sonographic assessments. 3D ultrasound may be an important modality in future gynecologic oncology research and in the evaluation of adnexal malignancy in clinical practice, although some limitations regarding the assessment of adnexal malignancy employing 3D ultrasound remain unresolved.
Robot‐assisted extended pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP): a video‐based illustration of technique, results, and unmet patient selection needs
Authors: Davis John W. , Shah Jay B. , Achim Mary
Published: September 2011

What's known on the subject? and What does the study add?

Extending the pelvic lymph node dissection template for radical prostatectomy to include the hypogastric and sub‐obturator zones increases the number of lymph nodes retrieved and the chance of finding metastases.

This study demonstrates how to modify the robot‐assisted technique to accomplish the extended template and demonstrates the short‐term impact of this approach.

OBJECTIVE

To describe the differences in technique and results between standard vs extended template pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP) using a robot‐assisted (RA) technique.

PATIENTS AND METHODS

Using extended templates illustrated for the open surgical technique, a RA technique was developed to solve obstacles related to surgical exposure, identification of key landmarks, proper sequencing of operative steps, and prevention of complicationsshown in the accompanying video.

From May 2006 to October 2007, 261 patients underwent a standard PLND, and from November 2007 to November 2010, 670 underwent an extended PLND (E‐PLND) by one surgeon.

RESULTS

The lymph node (LN) yield increased from a median(interquartile range) of 8 (5–11) to 16 (11–21) with the extended technique (P < 0.001).

The ratio of positive LNs increased from 7% to 18%. Among E‐PLND cases by risk group, positive LNs were found in 39%, 9%, and 3% of high‐, intermediate‐, and low‐risk cases, and the later two groups strongly associated with upgrading and/or upstaging.

Extensive clipping appears necessary to avoid postoperative lymphoceles, and peritoneal fenestration for the extraperitoneal technique.

The median operative duration for E‐PLND was 42 min, roughly double that of a standard PLND.

CONCLUSIONS

E‐PLND is feasible with a RA technique, and increases the LN yield and positive LN ratio;the latter especially in high‐risk disease.

The procedure takes twice as long and requires several updates in technique shown in the video.
Robotic partial nephrectomy: surgical technique
Authors: Sukumar Shyam , Rogers Craig G.
Published: September 2011

What's known on the subject? and What does the study add?

Robotic partial nephrectomy has equivalent oncological outcomes, and possibly better functional outcomes in the short‐to‐intermediate term, when compared to laparoscopic partial nephrectomy. Robotic partial nephrectomy has a less prohibitive learning curve, better ergonomics, and improved vision when compared to laparoscopic partial nephrectomy. We describe our standard transperitoneal technique for robotic partial nephrectomy and also highlight the essential steps in an accompanying video. Novel approaches are discussed, including robotic bulldog clamps for hilar clamping, robotic ultrasound probe for tumour identification, flexible Doppler probe for vessel identification, and barbed suture renorrhaphy. Tips and tricks to avoid common pitfalls and manage complications are discussed.

Kidney sparing approaches have become the ‘gold standard’ for the management of small renal masses and have been shown to be equivalent to radical nephrectomy for oncological outcomes.

Robotic partial nephrectomy (RPN) has emerged as a feasible alternative to other minimally invasive approaches for patients requiring nephron‐sparing surgery.

Several reports have highlighted the benefits of RPN, including a less demanding learning curve and shorter warm ischaemia time.

We describe our operative technique for transperitoneal RPN, discuss contemporary outcomes and suggest tips to avoid complications.
Gestational diabetes and cardiovascular risk factors in the offspring: Results from a cross‐sectional study
Authors: Beyerlein A. , Nehring I. , Rosario A. Schaffrath , von Kries R.
Published: September 2011

Diabet. Med. 29, 378–384 (2012)

Background  While the association of gestational diabetes mellitus and abnormal glucose tolerance is beyond doubt, its associations with other cardiovascular disease risk factors in the offspring are less clearly established. Some of these associations, in particular overweight in the offspring, might be confounded by maternal overweight.

Methods  Data on 12 542 children in the age of 3–17 years with full information about gestational diabetes mellitus and maternal BMI were available from the German nationwide KiGGS study. We calculated linear and logistic regression models for measurements of body composition, blood pressure, HbA1c and cholesterol values in the offspring with gestational diabetes mellitus as the explanatory variable, with and without adjustment for maternal BMI.

Results  The prevalence of gestational diabetes mellitus in the dataset was 2.2%. Unadjusted regression analyses suggested weak positive effects of gestational diabetes mellitus on body composition measurements [e.g. a mean increase in BMI standard deviation scores (SDS) of 0.17 units (95% confidence interval: 0.03, 0.30)]. After adjustment for maternal BMI, the observed associations almost disappeared [e.g. BMI SDS: 0.07 (−0.06, 0.20)]. With respect to blood pressure and cholesterol, no potential effects of gestational diabetes mellitus were observed in both unadjusted and adjusted models.

Conclusion  Gestational diabetes mellitus does not appear to have a relevant effect on cardiovascular disease correlates such as blood pressure or cholesterol levels in children, and the potential effect of gestational diabetes mellitus on body composition seems to be widely explainable by maternal BMI.
Association between HbA1c and cardiovascular disease mortality in older Hong Kong Chinese with diabetes
Authors: Xu L. , Chan W. M. , Hui Y. F. , Lam T. H.
Published: September 2011

Diabet. Med. 29, 393–398 (2012)

Objective  To examine the association between baseline HbA1c level and mortality attributable to all‐cause, cardiovascular disease, coronary heart disease and stroke.

Methods  A total of 2137 Chinese aged 65 years or above attending the Elderly Health Service, Department of Health, Hong Kong, with diagnosed diabetes had HbA1c measured during 1998 to 2000 and were followed up to 2009. Information on socio‐economic position, lifestyle factors and disease history was collected. Hazard ratios and 95% confidence intervals with adjustment for potential confounders were calculated using Cox’s proportional hazards models.

Results  After an average of 7.9 years of follow‐up, 540 participants had died. After adjusting for potential confounders, higher HbA1c (≥ 69 mmol/mol, 8.5%) increased the risk of cardiovascular disease (hazard ratio 2.11;95% CI 1.37–3.25) and stroke mortality (hazard ratio 2.43; 95% CI 1.06–5.55) compared with HbA1c of 58–68 mmol/mol (7.5–8.4%), and increased the risk of all‐cause (hazard ratio 1.41; 95% CI 1.06–1.86) and coronary heart disease mortality (hazard ratio 2.44; 95% CI 1.11–5.37) compared with HbA1c of 48 mmol/mol (6.5%) or less. Analysis of HbA1c as a continuous variable showed that every XX mmol/mol (1%) increase in HbA1c decreased stroke mortality risk by 51% in those with HbA1c level less than 48 mmol/mol (6.5%) and increased stroke mortality risk by 30% in those with an HbA1c level of 48 mmol/mol (6.5%) or higher, suggesting a U‐shaped association between HbA1c and stroke mortality.

Conclusion  High HbA1c predicted excess risk of all‐cause, cardiovascular disease, coronary heart disease and stroke mortality. The question of whether low HbA1c increases mortality in older patients with diabetes needs further investigation.
How to fail as a family therapist working with adults with learning disabilities: a paradoxical literature review
Authors: Purdy Lloyd
Published: September 2011

Over the past 15 years there has been a growing interest in the application of systemic family therapy approaches, methods and techniques to problems encountered by those living with learning disabilities and their social networks. As reports of success in this area increase, however, it is clear that this marginalized group of people continue to suffer from a lack of a ‘theory of failure’. In order to overcome this deficit, a review of the literature as at December 2010 forms the basis of such a paradoxical description, welcoming those living with learning disabilities into a family therapy tradition.
Sarcasm, Pretense, and The Semantics/Pragmatics Distinction*
Authors: Camp Elisabeth
Published: September 2011

Traditional theories of sarcasm treat it as a case of a speaker's meaning the opposite of what she says. Recently, ‘expressivists’ have argued that sarcasm is not a type of speaker meaning at all, but merely the expression of a dissociative attitude toward an evoked thought or perspective. I argue that we should analyze sarcasm in terms of meaning inversion, as the traditional theory does; but that we need to construe ‘meaning’ more broadly, to include illocutionary force and evaluative attitudes as well as propositional content. I distinguish four subclasses of sarcasm, individuated in terms of the target of inversion. Three of these classes raise serious challenges for a standard implicature analysis.
A model of canine leukocyte telomere dynamics
Authors: Benetos Athanase , Kimura Masayuki , Labat Carlos , Buchoff Gerald M. , Huber Shell , Labat Laura , Lu Xiaobin , Aviv Abraham
Published: September 2011

Recent studies have found associations of leukocyte telomere length (TL) with diseases of aging and with longevity. However, it is unknown whether birth leukocyte TL or its age‐dependent attrition – the two factors that determine leukocyte TL dynamics – explains these associations because acquiring this information entails monitoring individuals over their entire life course. We tested in dogs a model of leukocyte TL dynamics, based on the following premises: (i) TL is synchronized among somatic tissues; (ii) TL in skeletal muscle, which is largely postmitotic, is a measure of TL in early development; and (iii) the difference between TL in leukocytes and muscle (ΔLMTL) is the extent of leukocyte TL shortening since early development. Using this model, we observed in 83 dogs (ages, 4–42 months) no significant change with age in TLs of skeletal muscle and a shorter TL in leukocytes than in skeletal muscle (P < 0.0001). Age explained 43% of the variation in ΔLMTL (P < 0.00001), but only 6% of the variation in leukocyte TL (P = 0.035) among dogs. Accordingly, muscle TL and ΔLMTL provide the two essential factors of leukocyte TL dynamics in the individual dog. When applied to humans, the partition of the contribution of leukocyte TL during early development vs. telomere shortening afterward might provide information about whether the individual’s longevity is calibrated to either one or both factors that define leukocyte TL dynamics.