bluuebunny/crossref_metadata_2025 huggingface dataset:
Results of a 2-Week Inpatient Stay at the Department for Internal and Integrative Medicine: An Observational Study
Authors: Lauche Romy , Cramer Holger , Moebus Susanne , Paul Anna , Michalsen Andreas , Langhorst Jost , Dobos Gustav
Published: October 2012

Introduction. The Department for Internal and Integrative Medicine in Essen utilizes mind/body medical elements in order to empower patients with chronic diseases to better cope with their symptoms and to adopt a healthy lifestyle. This study explored the influence and predictors of a 2-week integrative treatment program on patients’ quality of life.Methods. This observational study was conducted with inpatients as part of the quality assurance program. Patients’ quality of life, psychological symptoms, and health locus of control were measured on admission and discharge and again 3, 6, and 12 months after discharge. Regression analyses were conducted to determine the factors predicting improved quality of life.Results. Data from 2486 inpatients treated in 2001–2004 were included (80% female, mean age 53.9 ± 14.3 years). Response rates decreased to 50% at 12 months. Small-to-moderate effects were found on patients’ quality of life, anxiety, and depression. Patients’ internal locus of control significantly increased. Improved quality of life was mainly predicted by lower baseline scores.Conclusion. Results of this study suggest that a 2-week inpatient treatment might sustainably reduce patients’ symptoms and increase their quality of life; however, conclusions are only preliminary. More research is needed to enable the effectiveness to be judged conclusively.
Using the K-Nearest Neighbor Algorithm for the Classification of Lymph Node Metastasis in Gastric Cancer
Authors: Li Chao , Zhang Shuheng , Zhang Huan , Pang Lifang , Lam Kinman , Hui Chun , Zhang Su
Published: October 2012

Accurate tumor, node, and metastasis (TNM) staging, especially N staging in gastric cancer or the metastasis on lymph node diagnosis, is a popular issue in clinical medical image analysis in which gemstone spectral imaging (GSI) can provide more information to doctors than conventional computed tomography (CT) does. In this paper, we apply machine learning methods on the GSI analysis of lymph node metastasis in gastric cancer. First, we use some feature selection or metric learning methods to reduce data dimension and feature space. We then employ the K-nearest neighbor classifier to distinguish lymph node metastasis from nonlymph node metastasis. The experiment involved 38 lymph node samples in gastric cancer, showing an overall accuracy of 96.33%. Compared with that of traditional diagnostic methods, such as helical CT (sensitivity 75.2% and specificity 41.8%) and multidetector computed tomography (82.09%), the diagnostic accuracy of lymph node metastasis is high. GSI-CT can then be the optimal choice for the preoperative diagnosis of patients with gastric cancer in the N staging.
Relationship between Plasma Ferritin Level and Siderocyte Number in Splenectomizedβ-Thalassemia/HbE Patients
Authors: Tripatara A. , Srichana N. , Lamool P. , Amnuaykan S. , Hongart P. , Jetsrisuparb A.
Published: October 2012

Introduction. In iron overload status, excess iron deposits in reticuloendothelial cells and tissues and can be detected using Prussian blue staining. The aim of this paper was to investigate the relationship between siderocyte numbers and plasma ferritin levels (a practically standard marker of iron overload) in the blood of the splenectomized and nonsplenectomizedβ-thalassemia/HbE patients, who are at risk of iron overload.Methods. EDTA blood samples from 64 patients with 35 splenectomized and 29 nonsplenectomizedβ-thalassemia/HbE patients, who received regular blood transfusions, and 20 normal individuals were investigated for siderocyte numbers, plasma ferritin levels, and complete blood counts.Results. The average percent siderocytes in splenectomized and nonsplenectomizedβ-thalassemia/HbE patients were 11.5% and 0.08%, respectively, and plasma ferritin levels of 2,332 μg/L and 1,279 μg/L, respectively. Percent siderocytes showed a good correlation with plasma ferritin levels only in splenectomized patients (r=0.69,P<0.001). A receiver operating curve analysis from splenectomized patients’ data indicated that siderocytes at 3% cut-off are the best predictor for plasma ferritin level ≥1,000 μg/L with 92.9% sensitivity and 42.9% specificity.Conclusion. Circulating siderocyte numbers can be used as a screening test for the assessment of the iron overload in splenectomizedβ-thalassemia/HbE patients in the place where serum ferritin is not available.
Performance Evaluation of Warm- and Hot-Mix Asphalt Mixtures Based on Laboratory and Accelerated Pavement Tests
Authors: Kim Yongjoo , Lee Jaejun , Baek Cheolmin , Yang Sunglin , Kwon Sooahn , Suh Youngchan
Published: October 2012

A number of warm-mix asphalt (WMA) technologies are used to reduce the temperature at which the asphalt mixtures are produced and compacted, apparently without compromising the performance of the pavement. The main objective of this study is to determine whether the use of an innovative wax-based LEADCAP WMA additive influences the performance of the asphalt mixture, which is produced and compacted at significantly low temperatures. The WMA pavement using LEADCAP additive (WMA-LEADCAP) along with a control HMA pavement was evaluated with respect to their performances of rutting resistance, crack resistance, and viscoelastic property based on the laboratory dynamic modulus test, indirect tensile strength test, and in-door accelerated pavement test (APT) results. With the limited data carried out, the LEADCAP additive is effective in producing and paving asphalt mixture at approximately 30°C lower temperature than a control HMA mixture, and the performances of WMA-LEADCAP pavement are comparable to a control HMA pavement.
Diaphragm Used with Replens Gel and Risk of Bacterial Vaginosis: Results from a Randomized Controlled Trial
Authors: Cohen Craig R. , Cheng Su-Chun , Shiboski Stephen , Chipato Tsungai , Matu Martin , Mwangi James , Mutimutema Monalisa E. S. , Tuveson Jennifer , Kamba Mavis , Padian Nancy , van der Straten Ariane
Published: October 2012

Background. Bacterial vaginosis (BV) has been linked to female HIV acquisition and transmission. We investigated the effect of providing a latex diaphragm with Replens and condoms compared to condom only on BV prevalence among participants enrolled in an HIV prevention trial.Methods. We enrolled HIV-seronegative women and obtained a vaginal swab for diagnosis of BV using Nugent’s criteria; women with BV (score 7–10) were compared to those with intermediate (score 4–6) and normal flora (score 0–3). During quarterly follow-up visits over 12–24 months a vaginal Gram stain was obtained. The primary outcome was serial point prevalence of BV during followup.Results. 528 participants were enrolled; 213 (40%) had BV at enrollment. Overall, BV prevalence declined after enrollment in women with BV at baseline (OR=0.4, 95% CI 0.29–.56) but did not differ by intervention group. In the intention-to-treat analysis BV prevalence did not differ between the intervention and control groups for women who had BV (OR=1.01, 95% CI 0.52–1.94) or for those who did not have BV (OR=1.21, 95% CI 0.65–2.27) at enrollment. Only 2.1% of participants were treated for symptomatic BV and few women (5–16%) were reported using anything else but water to cleanse the vagina over the course of the trial.Conclusions. Provision of the diaphragm, Replens, and condoms did not change the risk of BV in comparison to the provision of condoms alone.
Coherent Network Optimizing of Rail‐Based Urban Mass Transit
Authors: Zhang Ying
Published: October 2012

An efficient public transport is more than ever a crucial factor when it comes to the quality of life and competitiveness of many cities and regions in Asia. In recent years, the rail‐based urban mass transit has been regarded as one of the key means to overcoming the great challenges in Chinese megacities. The purpose of this study is going to develop a coherent network optimizing for rail‐based urban mass transit to find the best alternatives for the user and to demonstrate how to meet sustainable development needs and to match the enormous capacity requirements simultaneously. This paper presents an introduction to the current situation of the important lines, and transfer points in the metro system Shanghai. The insufficient aspects are analyzed and evaluated; while the optimizing ideas and measurements are developed and concreted. A group of examples are used to illustrate the approach. The whole study could be used for the latest reference for other megacities which have to be confronted with the similar situations and processes with enormous dynamic travel and transport demands.
Massive Hemoptysis in a Case of Intralobar Pulmonary Sequestration Associated with Pulmonary Hypoplasia and Meandering Right Pulmonary Vein: Diagnosis and Management
Authors: Mohapatra Manoranjan , Mishra Sanjeet , Jena Paresh
Published: October 2012

Pulmonary sequestration is a congenital malformation characterized by focal area of dysplastic lung tissue that lacks normal communication with tracheobronchial tree and receives blood supply from systemic arteries. Surgical resection has been the conventional method of treatment of pulmonary sequestration. In recent years transarterial embolization of the anomalous systemic arteries has emerged as a suitable alternative to surgery. In this paper, we describe transarterial coil embolization for control of massive life-threatening hemoptysis in a rare case of intralobar sequestration in right lung associated with ipsilateral pulmonary hypoplasia and meandering right inferior pulmonary vein. A 3-year follow-up computed tomographic (CT) angiography revealed complete regression of the sequestration along with altered pulmonary arterial contour. To the best of our knowledge, transarterial coil embolization for control of massive life-threatening hemoptysis in such a complex pulmonary anomaly has not yet been reported.
Vibrational Spectroscopic Studies of Tenofovir Using Density Functional Theory Method
Authors: Ramkumaar G. R. , Srinivasan S. , Bhoopathy T. J. , Gunasekaran S.
Published: October 2012

A systematic vibrational spectroscopic assignment and analysis of tenofovir has been carried out by using FTIR and FT‐Raman spectral data. The vibrational analysis was aided by electronic structure calculations—hybrid density functional methods (B3LYP/6‐311++G(d,p), B3LYP/6‐31G(d,p), and B3PW91/6‐31G(d,p). Molecular equilibrium geometries, electronic energies, IR intensities, and harmonic vibrational frequencies have been computed. The assignments proposed based on the experimental IR and Raman spectra have been reviewed and complete assignment of the observed spectra have been proposed. UV‐visible spectrum of the compound was also recorded and the electronic properties such as HOMO and LUMO energies and λmax were determined by time‐dependent DFT (TD‐DFT) method. The geometrical, thermodynamical parameters, and absorption wavelengths were compared with the experimental data. The B3LYP/6‐311++G(d,p)‐, B3LYP/6‐31G(d,p)‐, and B3PW91/6‐31G(d,p)‐based NMR calculation procedure was also done. It was used to assign the 13C and 1H NMR chemical shift of tenofovir.
Catalytic Properties and Immobilization Studies of Catalase from Malva sylvestris L.
Authors: Arabaci G. , Usluoglu A.
Published: October 2012

Catalase was partially purified from Malva sylvestris L. and immobilized onto chitosan. Then, its catalytic properties were investigated. (NH4)2SO4 precipitation and dialysis were performed in the extracted enzyme. Further purification was performed with sephadex G‐200 column. Kinetic studies of the purified enzyme activity were measured and characterized. The inhibitory effects of KCN, NaN3, CuSO4, and EDTA on M. sylvestris L. catalase activity were observed except NaCl. Furthermore, M. sylvestris L. catalase was immobilized covalently with glutaraldehyde onto chitosan particles. The pH and temperature optima as well as the changes in the kinetics (Km, Vmax) of the immobilized and free M. sylvestris L. catalase were determined. The Km value for immobilized catalase (23.4 mM) was higher than that of free enzyme (17.6 mM). Optimum temperature was observed higher than that of the free enzyme. The optimum pH was the same for both free and immobilized catalases (pH 7.50). Immobilized catalase showed higher storage and thermal stabilities than free catalases. Free catalase lost all its activity within 60 days whereas immobilized catalase lost 45% of its activity during the same incubation period at 4°C. The remaining immobilized catalase activity was about 70% after 8 cycles of batch operations.
A Novel Therapeutic Regimen to Eradicate Established Solid Tumors with an Effective Induction of Tumor-Specific Immunity
Authors: Tysome James R. , Li Xiaozhu , Wang Shengdian , Wang Pengju , Gao Dongling , Du Pan , Chen Dong , Gangeswaran Rathi , Chard Louisa S. , Yuan Ming , Alusi Ghassan , Lemoine Nicholas R. , Wang Yaohe
Published: October 2012

Purpose: The efficacy of oncolytic viruses depends on multiple actions including direct tumor lysis, modulation of tumor perfusion, and stimulation of tumor-directed immune responses. In this study, we investigated whether a sequential combination of immunologically distinct viruses might enhance antitumor efficacy through the induction of tumor-specific immunity and circumvention or mitigation of antiviral immune responses.

Experimental Design: The Syrian hamster as an immune-competent model that supports replication of both adenovirus and vaccinia virus was evaluated in vitro and in vivo. The antitumor efficacy of either virus alone or sequential combination of the two viruses was examined in pancreatic and kidney cancer models. The functional mechanism of the regimen developed here was investigated by histopathology, immunohistochemistry staining, CTL assay, and T-cell depletion.

Results: The Syrian hamster is a suitable model for assessment of oncolytic adenovirus and vaccinia virus. Three low doses of adenovirus followed by three low doses of vaccinia virus resulted in a superior antitumor efficacy to the reverse combination, or six doses of either virus alone, against pancreatic and kidney tumors in Syrian hamsters. A total of 62.5% of animals bearing either tumor type treated with the sequential combination became tumor-free, accompanied by the induction of effective tumor-specific immunity. This enhanced efficacy was ablated by CD3+ T-cell depletion but was not associated with humoral immunity against the viruses.

Conclusion: These findings show that sequential treatment of tumors with oncolytic adenovirus and vaccinia virus is a promising approach for cancer therapy and that T-cell responses play a critical role. Clin Cancer Res; 18(24); 6679–89. ©2012 AACR.
Do Imaging Biomarkers Relate to Outcome in Patients Treated with VEGF Inhibitors?
Authors: O'Connor James P.B. , Jayson Gordon C.
Published: October 2012

The management of solid tumors has been transformed by the advent of VEGF pathway inhibitors. Early clinical evaluation of these drugs has used pharmacodynamic biomarkers derived from advanced imaging such as dynamic MRI, computed tomography (CT), and ultrasound to establish proof of principle. We have reviewed published studies that used these imaging techniques to determine whether the same biomarkers relate to survival in renal, hepatocellular, and brain tumors in patients treated with VEGF inhibitors. Data show that in renal cancer, pretreatment measurements of Ktrans and early pharmacodynamic reduction in tumor enhancement and density have prognostic significance in patients treated with VEGF inhibitors. A weaker, but significant, relationship is seen with subtle early size change (10% in one dimension) and survival. Data from high-grade glioma suggest that pretreatment fractional blood volume and Ktrans were prognostic of overall survival. However, lack of control data with other therapies prevents assessment of the predictive nature of these biomarkers, and such studies are urgently required. Clin Cancer Res; 18(24); 6588–98. ©2012 AACR.
Cabazitaxel: More Than a New Taxane for Metastatic Castrate-Resistant Prostate Cancer?
Authors: Mita Alain C. , Figlin Robert , Mita Monica M.
Published: October 2012

The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness. Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel showed linear pharmacokinetics and a terminal elimination half-life comparable with that of docetaxel, findings which support dosing as a single infusion in three-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m2 every three weeks. Antitumor activity was shown in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24% and sustained tumor stabilizations were also observed. The TROPIC phase III study, conducted in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support. Clin Cancer Res; 18(24); 6574–9. ©2012 AACR.
Frequent Mutational Activation of the PI3K-AKT Pathway in Trastuzumab-Resistant Breast Cancer
Authors: Chandarlapaty Sarat , Sakr Rita A. , Giri Dilip , Patil Sujata , Heguy Adriana , Morrow Monica , Modi Shanu , Norton Larry , Rosen Neal , Hudis Clifford , King Tari A.
Published: October 2012

Purpose: HER2-amplified breast cancer is sometimes clinically insensitive to HER2-targeted treatment with trastuzumab. Laboratory models of resistance have causally implicated changes in HER2 expression and activation of the phosphoinositide 3-kinase (PI3K)–AKT pathway. We conducted a prospective tissue acquisition study to determine if there is evidence for these lesions in metastatic tumors that have progressed on trastuzumab-containing therapy.

Experimental Design: From 2/2007 to 11/2011, 63 patients with HER2-amplified breast cancer with recurrence of disease after adjuvant trastuzumab therapy or World Health Organization–defined progression of metastatic disease on a trastuzumab-containing regimen were prospectively enrolled and underwent tumor biopsy. Specimens were analyzed for activating mutations in PIK3CA and HER2 by Sequenom and analyzed for HER2 and PTEN status by immunohistochemistry.

Results: In 53/60 cases (88%, 3 cases not evaluable for HER2), HER2 overexpression persisted in the metastatic tumor following trastuzumab exposure. Among the 7 cases lacking HER2 overexpression, repeat analysis of the pretreatment tumor failed to confirm HER2 overexpression in five cases. Among cases evaluable for PTEN (56) or PI3K mutation (45), absent or significantly diminished PTEN expression was noted in 33 (59%) and activating mutations in PIK3CA in 13 (29%). The combined rate of PTEN loss and PIK3CA mutation in the trastuzumab-refractory tumors was 71% compared with 44% (P = 0.007) in an unexposed cohort of 73 HER2-amplified tumors.

Conclusions: In this series of prospectively collected trastuzumab-refractory human breast cancers, loss of HER2 overexpression was rare, whereas activation of the PI3K-AKT pathway through loss of PTEN or PIK3CA mutation was frequently observed. Clin Cancer Res; 18(24); 6784–91. ©2012 AACR.
Sequence Dependence of MEK Inhibitor AZD6244 Combined with Gemcitabine for the Treatment of Biliary Cancer
Authors: Xu Junyao , Knox Jennifer J. , Ibrahimov Emin , Chen Eric , Serra Stefano , Tsao Ming , Cao Pinjiang , Vines Douglass , Green David E. , Metran-Nascente Cristiane , McNamara Mairead G. , Hedley David W.
Published: October 2012

Purpose: MEK inhibition has clinical activity against biliary cancers and might therefore be successfully combined with gemcitabine, one of the most active chemotherapy agents for these cancers. As gemcitabine is active in S-phase, and the extracellular signal-regulated kinase (ERK) pathway has a major role driving cell-cycle progression, concurrent use of a MEK inhibitor could potentially antagonize the effect of gemcitabine. We therefore tested the sequence dependence of the combination of gemcitabine and the MEK inhibitor AZD6244 using a series of biliary cancer models.

Experimental Design: Primary xenografts were established from patients with gallbladder and distal bile duct cancer and grown in severe combined immunodeficient (SCID) mice at the subcutaneous site. Plasma and tumor drug levels and the time course for recovery of ERK signaling and S-phase were measured in tumor-bearing mice treated for 48 hours with AZD6244 and then monitored for 48 hours off treatment. On the basis of these results, two different treatment schedules combining AZD6244 with gemcitabine were tested in four different biliary cancer models.

Results: DNA synthesis was suppressed during treatment with AZD6244, and reentry into S-phase was delayed by approximately 48 hours after treatment. Strong schedule dependence was seen in all four biliary cancer models tested, suggesting that combined treatment with AZD6244 plus gemcitabine would be more active in patients with biliary cancer when gemcitabine is given following a 48-hour interruption in AZD6244 dosing, rather than concurrently.

Conclusions: The combination of AZD6244 plus gemcitabine is highly schedule dependent, and predicted to be more effective in the clinic using sequential rather than simultaneous dosing protocols. Clin Cancer Res; 19(1); 118–27. ©2012 AACR.
Metabolic Syndrome Components and Risk Factors for Pancreatic Adenocarcinoma: A Case-Control Study in China
Authors: Wu Qiao , Chen Ge , Wu Wen-ming , Zhou Li , You Lei , Zhang Tai-ping , Zhao Yu-pei
Published: October 2012

Background: Metabolic syndrome is a complex collection of interrelated conditions. Recent data have shown that metabolic syndrome may play a role in several cancers. Pancreatic adenocarcinoma is the fourth most common cause of death from cancer in the United States and the fifth in Europe. Despite the increasing numbers of published studies, the etiology of pancreatic adenocarcinoma is incompletely defined. Therefore, this paper aims to evaluate the risk factors for pancreatic adenocarcinoma. Methods: This was a case-control study of pancreatic adenocarcinoma patients who were referred to the Peking Union Medical College Hospital. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center. Data on metabolic syndrome, pancreatic diseases, liver diseases, and a history of diabetes and history of hypertension were collected either by conducting a retrospective review of the patients’ records and health examination reports or by interview. Results: A history of smoking (OR = 2.981), diabetes (OR = 2.421), cholecystolithiasis (OR = 5.453), or chronic pancreatitis (OR = 28.264) as well as the levels of fasting blood glucose (OR = 4.241), total cholesterol (OR = 1.793), and apolipoprotein A (OR = 36.065) were significantly related to pancreatic adenocarcinoma. Conclusions: Cholelithiasis, chronic pancreatitis, and certain metabolic syndrome components are potential risk factors for the development of pancreatic adenocarcinoma.
Factors Associated with Dietary Adherence in Celiac Disease: A Nationwide Study
Authors: Kurppa Kalle , Lauronen Olli , Collin Pekka , Ukkola Anniina , Laurila Kaija , Huhtala Heini , Mäki Markku , Kaukinen Katri
Published: October 2012

Aims: Diagnostics and follow-up of celiac disease have gradually shifted from tertiary centers to secondary and primary health care. In order to establish whether this has affected the success of treatment, and to identify predictors for dietary non-adherence, we carried out a study in a nationwide cohort of treated celiac patients. Patients and Methods: 843 biopsy-proven patients, 94 children and 749 adults, were enrolled and interviewed. Adherence to a gluten-free diet was determined by means of an interview and serological testing. Results: Altogether, 88% were on a strict gluten-free diet; the rest had occasional dietary transgressions. Younger age at diagnosis, being currently a teenager, and current symptoms were associated with non-adherence. There was no association between non-adherence and place of diagnosis, gender, disease phenotype or severity of symptoms before diagnosis, presence of comorbidities, family history of celiac disease, smoking, duration of diet, use of oats, self-efficacy for the diet or lack of follow-up. Conclusions: Good dietary adherence can be achieved also in patients diagnosed and followed in primary health care. In a country with a high prevalence and good general knowledge of celiac disease, only age at diagnosis and age at present would appear to be major determinants for adherence.
The Barts ‘Flank-Free’ Modified Supine Position for Percutaneous Nephrolithotomy
Authors: Bach C. , Goyal A. , Kumar P. , Kachrilas S. , Papatsoris A.G. , Buchholz N. , Masood J.
Published: October 2012

Background: The last decade has seen the emergence of a variety of supine positions for carrying out percutaneous nephrolithotomy (PCNL). These positions all differ with regard to ease of puncture under image guidance, operative field availability, ability to make and dilate multiple tracts and ease of combining retrograde intrarenal surgery (RIRS). As all of these positions have their limitations regarding the important parameters mentioned above, there is a need for a supine position which addresses some of the difficulties. Methods: We describe and illustrate our flank-free modified supine position, which we believe addresses a number of the issues. Results: Our position allows easy percutaneous access under fluoroscopy (torso only tilted to around 15°), space for placing (flank free of support) and dilating multiple tracts (kidney lies in a fairly neutral position and hence less mobile), a fairly horizontal tract allowing low intrarenal pressures and easy washout of fragments as well as allowing RIRS in a position of relative familiarity. The lesser torso rotation compared with the Valdivia, Galdakao modified and the Barts modified Valdivia positions also means it is more comfortable for patients. Conclusions: Our results are encouraging and easily comparable with published series on prone position, Valdivia, complete supine and the Barts modified Valdivia positions. We would like to highlight the Barts ‘flank-free’ modified supine position as one of the standard positions for carrying out supine PCNL.
Encephalocystocele – Uncommon Diagnosis in Prenatal Medicine
Authors: Dankovcik Robert , Vyhnalkova Vlasta , Muranska Stela , Kucera Eduard , Korpova Maria , Plichtova Anna , Miklosova Maria , Ferianec Vladimir , Evangelista Jirasek Jan , Dudas Marek
Published: October 2012

Encephalocystocele is a developmental malformation characterized by brain herniation accompanied with extracranial cystic protrusion of the ventricular system. This nosological unit is often overlooked and insufficiently classified merely as encephalocele. Herein, two exceptionally clear cases of the parieto-occipital cranioschisis with encephalocystocele and congenital hydrocephalus of the lateral ventricles are documented with 2-dimensional/3-dimensional sonographic images and the corresponding MRI findings. In both cases, prenatal diagnosis was confirmed by autopsy.
Advances in Peritoneal Dialysis in Acute Kidney Injury
Authors: Ponce Daniela , Balbi André Luís , Amerling Richard
Published: October 2012

Peritoneal dialysis (PD) is a simple, safe, cheap, and efficient renal replacement therapy method. It can correct metabolic disorders and fluid overload in acute kidney injury (AKI) patients both in and out of the intensive care unit. Use of PD in AKI is enhanced by placement of a Tenckhoff catheter, which can be safely accomplished at the bedside. Some PD modalities, such as high-volume PD and continuous-flow PD, can provide dialysis doses and efficiency comparable to extracorporeal blood purification methods. PD is particularly suitable for neonates, children, and patients with refractory heart failure or who are otherwise hemodynamically unstable. PD should be considered in situations where systemic anticoagulation and/or vascular access are problematic. PD is limited by a lower efficiency that may produce inadequate renal replacement in larger and/or severely hypercatabolic patients. Fluid removal can be unpredictable, there is a risk of infection, and possible issues with mechanical ventilation. In this article, we discuss the use of PD in AKI, with emphasis on recent advances.
Colitis and Colorectal Cancer
Authors: Foersch Sebastian , Waldner Maximilian J. , Neurath Markus F.
Published: October 2012

Inflammatory bowel diseases (IBD) are accompanied by an increased risk of developing colitis-associated carcinoma (CAC). These tumors are one of the most important causes of morbidity and mortality in patients with IBD and distinctly differ from sporadic colorectal cancer in their biology and underlying mechanisms. First, this review discusses risk factors for the development of CAC and summarizes some of the most important genetic alterations and molecular pathways involved in inflammatory carcinogenesis. Then, new endoscopic techniques, such as chromoendoscopy and confocal laser endomicroscopy, and their contribution to surveillance and early detection of CAC are presented. Last, we briefly address different types of concepts for prevention (i.e. anti-inflammatory agents) and treatment (i.e. surgical resection) of CAC and give an outlook on this important aspect of IBD.
Cellular Immune Suppressor Mechanisms in Patients with Hepatocellular Carcinoma
Authors: Zhao Fei , Korangy Firouzeh , Greten Tim F.
Published: October 2012

Hepatocellular carcinoma (HCC) has been shown to induce several immune suppressor mechanisms in patients. Our laboratory has been investigating different cellular mechanisms of immune suppression in patients with HCC. These suppressor mechanisms range from CD4+ regulatory T cells, functionally impaired dendritic cells, neutrophils, and monocytes to myeloid-derived suppressor cells. In vitro as well as in vivo studies have demonstrated that abrogation of the suppressor cells enhances or unmasks tumor-specific anti-tumor immune responses. We performed a literature search for immune suppressor cells in HCC, and here we provide a comprehensive summary of the latest studies in this field.
Cellular Immune Responses to Hepatocellular Carcinoma: Lessons for Immunotherapy
Authors: Schmidt Nathalie , Neumann-Haefelin Christoph , Thimme Robert
Published: October 2012

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a continuously high mortality. Thus, the development of new therapeutic strategies is crucial to decrease recurrence rates and to improve the overall survival rates of HCC patients. The rationale for immunotherapy is based on the findings of several studies showing specific CD8+ T-cell responses against various tumor-associated antigens (TAAs) in HCC patients and a clinical benefit of T-cell infiltration in the tumor tissue. However, the impact of TAA-specific CD8+ T-cell responses on tumor control seems to be rather weak. Several different mechanisms contribute to the failure of the cellular immune response and will be summarized in this review. The aim of immune-based therapies is to overcome these mechanisms of T-cell failure and to induce or boost TAA-specific CD8+ and CD4+ T-cell responses. Several preclinical and clinical studies of immune-based therapeutic approaches show encouraging results and will be discussed in this review.
Interleukin-6 Trans-Signaling and Colonic Cancer Associated with Inflammatory Bowel Disease
Authors: Chalaris Athena , Schmidt-Arras Dirk , Yamamoto Kosuke , Rose-John Stefan
Published: October 2012

Interleukin-6 (IL-6) is a cytokine largely induced during infection, inflammation, and cancer. In the liver, IL-6 induces the synthesis of acute-phase proteins, which are believed to support the response of the body during infection and inflammation. Moreover, IL-6 has been reported to be a growth factor in multiple myeloma. IL-6 on cells binds to an IL-6 receptor (IL-6R) forming an IL-6/IL-6R complex, which associates with a homodimer of a second receptor subunit, gp130, to initiate signaling. Gp130 is present on all cells of the body, whereas IL-6R is only expressed on hepatocytes, some leukocytes, and some epithelial cells. Since gp130 has no measurable affinity for IL-6, cells which do not express IL-6R are unresponsive to the cytokine. A soluble form of IL-6R, which is found in the blood, can still bind IL-6 and the complex of IL-6/sIL-6R can bind to cellular gp130 also on cells without IL-6R expression. This signaling mechanism has been called trans-signaling. Interestingly, a soluble form of gp130 (sgp130) blocks IL-6 trans-signaling without affecting classic IL-6 signaling via the membrane-bound IL-6R. We used a dimerized version of sgp130 fused to the Fc portion of an IgG1 antibody (sgp130Fc) to discriminate between classic and trans-signaling of IL-6. It turned out that proinflammatory activities of IL-6 are mediated via trans-signaling, whereas anti-inflammatory or regenerative activities are mediated via classic signaling. These results are important for strategies to inhibit IL-6 signaling in autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and inflammation-associated colorectal cancer.
Prevention and Management of Dialysis Catheter Complications in the Intensive Care Unit
Authors: Wilson Patrick , Lertdumrongluk Paungpaga , Leray-Moragués Hélène , Chenine-Koualef Leila , Patrier Laure , Canaud Bernard
Published: October 2012

Dialysis dependence at hospital discharge after acute kidney injury (AKI) requiring renal replacement therapy (RRT) in the intensive care unit (ICU) is found in 10–15% of survivors. In case of severe AKI in the ICU, it is necessary to reconcile two objectives: the creation of an adequate temporary angioaccess for RRT and the preservation of the patient’s vascular network in case of evolution to end-stage renal disease. A central venous catheter (CVC) is the best option for RRT in the ICU setting. Most catheter-related hazards can be prevented by following best clinical practices for insertion and handling of the CVC, and by knowing the advantages and disadvantages of the different types of catheters, the sites and techniques of insertion, the types of RRT modality for choosing the best CVC option, and the prophylactic and therapeutic measures to prevent and to manage the complications. We review here some important aspects of the CVC for the treatment of AKI in the ICU.
Renal Replacement Therapy in the End-Stage Renal Disease Patient with Critical Illness
Authors: Thompson Stephanie , Pannu Neesh
Published: October 2012

Dialysis patients account for 1–9% of all intensive care unit (ICU) admissions. As a result of the increasing prevalence of patients with end-stage renal disease (ESRD) and the changing demographics of this population, the number of dialysis patients requiring hospitalization and ICU support is expected to increase. Critically ill ESRD patients have more comorbidity and higher severity of illness than the general population resulting in higher ICU and in-hospital mortality rates. ESRD patients have been excluded from trials evaluating renal replacement therapy in the ICU, therefore little information is available about the optimal management of renal replacement therapy for dialysis patients in this setting. This review focuses on the epidemiology of chronic dialysis patients admitted to the ICU and discusses an approach to providing renal replacement therapy for critically ill patients with ESRD.
The Acute Salivary Ghrelin Response to a Psychosocial Stress Is Enhanced in Symptomatic Patients with Bulimia Nervosa: A Pilot Study
Authors: Monteleone Palmiero , Tortorella Alfonso , Scognamiglio Pasquale , Serino Ismene , Monteleone Alessio Maria , Maj Mario
Published: October 2012

Background: Stress is a precipitating factor for both binge eating and bulimia nervosa (BN); however, the biological mechanisms through which it may trigger binge eating are poorly understood. There is evidence that the adrenal hormone cortisol and the gastric peptide ghrelin might be involved in stress-induced food ingestion. We hypothesized that symptomatic patients with BN might disclose deranged responses of ghrelin and/or cortisol to stressors and that this could be related to their binge-eating behaviour. Methods: Here we investigated salivary cortisol and ghrelin responses to the Trier Social Stress Test (TSST) in 10 women with acute BN and 10 age-matched healthy females. Eating-related psychopathology and behaviours were assessed by self-report measures. Results: No significant differences emerged between bulimic patients and healthy controls in the pre-stress salivary levels of both cortisol and ghrelin. The BN patients displayed normal cortisol but enhanced ghrelin responses to TSST. No significant correlations emerged between stress-induced salivary hormone changes and self-report measures of binge eating. Conclusion: To our knowledge, this is the first study showing deranged salivary ghrelin reactivity to a psychosocial stressor in symptomatic patients with BN. The extent to which this could contribute to the binge-eating behaviour of BN subjects awaits clarification.
Complex Motor Sequence Skills Profit from Sleep
Authors: Genzel Lisa , Quack Amelie , Jäger Eugen , Konrad Boris , Steiger Axel , Dresler Martin
Published: October 2012

Simple motor memory has been shown to benefit from sleep; however, more complex motor skills have rarely been investigated so far. We investigated complex motor learning using a dance mat and choreographies in 36 healthy, young male subjects. Subjects performed one song and two new songs in three sessions distributed over 24 h to test sequence-specific learning and skill transfer. Each song had a unique choreography. One group learned the main song in the evening and was retested 12 and 24 h later on the main song and each one new song (PM-AM-PM). The second group underwent the same procedure; however, the first session was in the morning (AM-PM-AM). Thus, one group slept before the first retest (PM-AM-PM) while the other group slept between the first and the second retest (AM-PM-AM). Regarding sequence-specific learning, sleep induced a significant difference between the groups, which disappeared after both groups had slept. A significant transfer effect occurred independent of sleep. During both new songs, no difference between the groups was seen; however, the second and third songs were learned significantly faster than the first song. This study could show that complex motor sequence learning benefits from sleep while skill transfer seems to occur independently of sleep.
Comparison of Superoxide Dismutase, Glutathione Peroxidase and Adenosine Deaminase Activities between Respiratory and Nocturnal Subtypes of Patients with Panic Disorder
Authors: Ozdemir Osman , Selvi Yavuz , Ozkol Halil , Tuluce Yasin , Besiroglu Lutfullah , Aydin Adem
Published: October 2012

Objective: There is mounting evidence indicating that oxidative and inflammatory processes may have an important role in the pathogenesis of panic disorder (PD). PD is a heterogeneous disease, and panic attacks are divided according to the different symptom clusters as respiratory, nocturnal, non-fearful, cognitive, or vestibular subtypes. The aim of this study was to compare whole-blood and serum superoxide dismutase (SOD), glutathione peroxidase and adenosine deaminase activities in PD patients with/without nocturnal, respiratory subtypes and healthy subjects. Methods: The study was conducted including 60 patients with PD and 30 healthy control subjects. The Panic Attack Symptom Checklist, Panic and Agoraphobia Scale, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were administered to the patients. Biochemical analyses were performed after all the blood samples were collected. Results: We found that whole-blood SOD and glutathione peroxidase activities of patients were significantly lower and adenosine deaminase activities of patients were higher than those of healthy controls. There were no statistically significant differences between respiratory and nocturnal subtypes. In addition, there were no marked relationships between the duration of illness and panic-agoraphobia scores of patients with nocturnal subtypes. Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores of patients with the nocturnal subtype were markedly higher than those of patients without the nocturnal subtype. Conclusion: The results suggest that oxidative and inflammatory processes may play a role in the pathophysiology of PD. These findings may support the idea that both nocturnal and respiratory subtypes of PD have different symptom clusters of the same disease.
The Impact of High-Frequency Repetitive Transcranial Magnetic Stimulation on Fine Motor Functions in Medication-Resistant Major Depression
Authors: Schrijvers Didier L. , Baeken Chris , De Raedt Rudi , Sabbe Bernard G.C.
Published: October 2012

Objectives: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been reported to improve mood symptoms in major depressive disorder (MDD), research on its impact on psychomotor symptoms is scarce. This study assessed the psychomotor effects of 1 and 10 sessions, respectively, of HF-rTMS over the left DLPFC. Methods: Ten HF-rTMS sessions were applied in 21 medication-free MDD patients over a 2-week period. At the beginning, one placebo (sham)-controlled rTMS session was also applied in a cross-over, single-blind design. Psychomotor variables were digitally recorded during completion of a Fitts’ task, at baseline, after the first and second real/sham session and at the end point. Results: The total 10-session treatment period resulted in a decrease of depression severity. One HF-rTMS session resulted in improvements on the Fitts’ task, without a difference between active and sham stimulation, however. No further improvements occurred from session 2 to session 10. Conclusions: No evidence was provided to link the observed psychomotor improvements to HF-rTMS stimulation, as a practice effect could have impacted the significant psychomotor outcomes.
Extracorporeal Carbon Dioxide Removal: The Future of Lung Support Lies in the History
Authors: Kaushik Manish , Wojewodzka-Zelezniakowicz Marzena , Cruz Dinna N. , Ferrer-Nadal A. , Teixeira Catarina , Iglesias Elena , Kim Jeong Chul , Braschi Antonio , Piccinni Pasquale , Ronco Claudio
Published: October 2012

Extracorporeal organ support in patients with dysfunction of vital organs like the kidney, heart, and liver has proven helpful in bridging the patients to recovery or more definitive therapy. Mechanical ventilation in patients with respiratory failure, although indispensable, has been associated with worsening injury to the lungs, termed ventilator-induced lung injury. Application of lung-protective ventilation strategies are limited by inevitable hypercapnia and hypercapnic acidosis. Various alternative extracorporeal strategies, proposed more than 30 years ago, to combat hypercapnia are now more readily available. In particular, the venovenous approach to effective carbon dioxide removal, which involves minimal invasiveness comparable to renal replacement therapy, appears to be very promising. The clinical applications of these extracorporeal carbon dioxide removal therapies may extend beyond just lung protection in ventilated patients. This article summarizes the rationale, technology and clinical application of various extracorporeal lung assist techniques available for clinical use, and some of the future perspectives in the field.
Measurement of Brain Edema by Noninvasive Cerebral Electrical Impedance in Patients with Massive Hemispheric Cerebral Infarction
Authors: Lou Jin He , Wang Jian , Liu Li Xu , He Lan Ying , Yang Hao , Dong Wei Wei
Published: October 2012

Background: Malignant cerebral infarction often occurs in patients with massive cerebral infarction. Monitoring brain edema is therefore helpful to make correct clinical decisions. Our previous studies have confirmed that cerebral electrical impedance (CEI) can sensitively reflect the brain edema after stroke. Methods: The CEI was measured consecutively by a noninvasive brain edema monitor in 69 patients with massive hemispheric cerebral infarction (MHCI). The results of the CEI were converted into the perturbation index (PI). The characteristics of dynamic changes of the CEI after MHCI were analyzed. Receiver-operating characteristics analysis was used to calculate predictive values for PI and other known parameters including NIHSS score and infarct volume. Results: (1) The overall rate of positive CEI was 88.4% (61/69) in all patients with MHCI. (2) The PI on the infarct side increased significantly within 24 h after stroke onset and reached a peak level 3–5 days after stroke onset (p < 0.01). (3) Age, NIHSS score at admission, infarct volume, and the PI at 24 h after stroke onset were significantly different between the malignant and nonmalignant groups. The best predictor of a malignant MHCI was the PI at 24 h after stroke onset with a cut-off value of 10.02 (90.9% sensitivity, 87.2% specificity, 76.9% positive predictive value, 95.3% negative predictive value). Conclusions: The noninvasive CEI can sensitively reflect the brain edema in patients with MHCI. Monitoring the CEI may help to predict malignant MHCI and guide treatment decisions.
Predicting and Managing Complications of Renal Replacement Therapy in the Critically Ill
Authors: Selby Nicholas M. , McIntyre Christopher W.
Published: October 2012

Renal replacement therapy (RRT) remains associated with a significant risk of serious complications, and critically ill patients requiring RRT continue to manifest particularly poor overall survival rates. These poor outcomes persist despite improvements in the modalities employed as well as an enhanced understanding of the effects of the extracorporeal circuit, anticoagulation, treatment doses, fluid replacement and dialysis membrane. More recently, there has been an emerging appreciation that intermittent RRT (in the chronic maintenance haemodialysis setting) is capable of generating sufficient circulatory stress to propagate additional widespread end-organ injury. The mitigation of this plethora of risks by the correct identification of complications, targeting of therapy refinements and prediction, whilst problems still remain occult, is desirable and becoming increasingly possible in the pursuit of improved outcomes in this high-mortality therapeutic field.
Handling Continuous Renal Replacement Therapy-Related Adverse Effects in Intensive Care Unit Patients: The Dialytrauma Concept
Authors: Maynar Moliner J. , Honore P.M. , Sánchez-Izquierdo Riera J.A. , Herrera Gutiérrez M. , Spapen H.D.
Published: October 2012

Continuous renal replacement therapy (CRRT) is increasingly used for the management of critically ill patients. As a consequence, the incidence of complications that accompany CRRT is also rising. However, a standardized approach for preventing or minimizing these adverse events is lacking. Dialytrauma is a newly proposed concept that encompasses all harmful adverse events related to CRRT while providing a framework for prevention or, at the least, early recognition of these events in order to attenuate the consequences. A mainstay of this approach is the utilization of a dedicated checklist for improving CRRT quality and patient safety. In this context, we discuss the most important adverse effects of CRRT and review current strategies to minimize them.