bluuebunny/crossref_metadata_2025 huggingface dataset:
Encapsulation of Diclofenac Molecules into Poly(ε‐Caprolactone) Electrospun Fibers for Delivery Protection
Authors: Tammaro Loredana , Russo Giuseppina , Vittoria Vittoria
Published: December 2009

Mg‐Al Hydrotalcite‐like clay (LDH) intercalated with diclofenac anions (HTlc‐DIC) was introduced into poly(ε‐caprolactone) (PCL) in different concentrations by the electrospinning technique, and mats of nonwoven fibers were obtained and compared to the pristine pure electrospun PCL. The fibers, characterized by X‐ray diffraction, thermogravimetric analysis, and differential scanning calorimetry, show an exfoliated clay structure up to 3 wt%, a good thermal stability of the diclofenac molecules and a crystallinity of PCL comparable to the pure polymer. The scanning electron microscopy revealed electrospun PCL and PCL composite fibers diameters ranging between 500 nm to 3.0 μm and a generally uniform thickness along the fibers. As the results suggested the in vitro drug release from the composite fibers is remarkably slower than the release from the corresponding control spun solutions of PCL and diclofenac sodium salt. Thus, HTlc‐DIC/PCL fibrous membranes can be used as an antinflammatory scaffold for tissue engineering.
Biologic Agents—A Panacea for Inflammatory Arthritis or Not?
Authors: Ninan J. , Smith Malcolm D. , Dugar M. , O'Brien Karen , Ahern Michael
Published: December 2009

Aim.To describe the retention rates for biological therapies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in a clinical setting.Methods.All patients managed in a dedicated biological therapy clinic in a teaching hospital in Australia were assessed for continuation on biological treatments and reasons for switching to an alternative biological agent or cessation of treatment.Results.There was a lower retention rate for RA patients on biological therapies compared to PsA and AS patients and the retention rate for RA patients was lower than that reported in RCTs.Conclusions.The retention rate on biological therapies for RA patients was lower in the clinic setting than what is reported in RCTs. The reasons for the lower retention rate in the clinical setting are discussed but no clear determinants for nonresponse to biological agents were identifiable. These agents have very limited steroid sparing effects.
Architectural Synthesis of Fixed‐Point DSP Datapaths Using FPGAs
Authors: Caffarena Gabriel , López Juan A. , Leyva Gerardo , Carreras Carlos , Nieto-Taladriz Octavio
Published: December 2009

We address the automatic synthesis of DSP algorithms using FPGAs. Optimized fixed‐point implementations are obtained by means of considering (i) a multiple wordlength approach; (ii) a complete datapath formed of wordlength‐wise resources (i.e., functional units, multiplexers, and registers); (iii) an FPGA‐wise resource usage metric that enables an efficient distribution of logic fabric and embedded DSP resources. The paper shows (i) the benefits of applying a multiple wordlength approach to the implementation of fixed‐point datapaths and (ii) the benefits of a wise use of embedded FPGA resources. The use of a complete fixed‐point datapath leads to improvements up to 35%. And, the wise mapping of operations to FPGA resources (logic fabric and embedded blocks), thanks to the proposed resource usage metric, leads to improvements up to 54%.
Field Synergy Principle for Energy Conservation Analysis and Application
Authors: Chen Qun , Wang Moran , Guo Zeng-Yuan
Published: December 2009

Optimization of mass and energy transfer process is critical to improve energy efficiency. In this contribution we introduce the field synergy principle as a unified principle for analyzing and improving the performance of the transfer process. Three field synergy numbers are introduced for heat, mass, and momentum transfer, respectively, and three cases are demonstrated for validation. The results indicate that the field synergy numbers will increase when reducing the angle between the velocity vector and the temperature gradient or the species concentration gradient fields in the convective heat or mass transfer, and the overall heat or mass transfer capability is therefore enhanced. In fluid flows, it will reduce the fluid flow drag to decrease the synergy number between the velocity and the velocity gradient fields over the entire domain and to decrease the product between the fluid viscosity and the velocity gradient at the boundary simultaneously.
MicroRNA-145 Suppresses Cell Invasion and Metastasis by Directly Targeting Mucin 1
Authors: Sachdeva Mohit , Mo Yin-Yuan
Published: December 2009

MicroRNAs are important gene regulators that could play a profound role in tumorigenesis. Our previous studies indicate that miR-145 is a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that miR-145 exerts its function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145–mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β-catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis. Cancer Res; 70(1); 378–87
Biomarkers Predictp53Gene Therapy Efficacy in Recurrent Squamous Cell Carcinoma of the Head and Neck
Authors: Nemunaitis John , Clayman Gary , Agarwala Sanjiv S. , Hrushesky William , Wells James R. , Moore Charles , Hamm John , Yoo George , Baselga Jose , Murphy Barbara A. , Menander Kerstin A. , Licato Laura L. , Chada Sunil , Gibbons Robert D. , Olivier Magali , Hainaut Pierre , Roth Jack A. , Sobol Robert E. , Goodwin W. Jarrard
Published: December 2009

Purpose: Most recurrent squamous cell carcinomas of the head and neck have a dysfunctional p53 tumor suppressor pathway contributing to treatment resistance. We hypothesized that tumor p53 biomarkers may predict the efficacy of normal p53 delivered by gene therapy in these patients.

Experimental Design: Tumor p53 biomarkers were evaluated in 116 patients, including 29 treated with methotrexate in a phase III randomized controlled trial. Profiles favorable for p53 gene therapy efficacy were hypothesized to have either normal p53 gene sequences or low-level p53 protein expression, whereas unfavorable p53 inhibitor profiles were predicted to have high-level expression of mutated p53 that can inhibit normal p53 protein function.

Results: A statistically significant increase in tumor responses was observed for patients with favorable p53 efficacy profiles compared with those with unfavorable p53 inhibitor profiles [phase I/II trials: favorable (34 of 46, 74%) versus unfavorable (1 of 5, 20%), P = 0.0290; phase III trial: favorable (17 of 24, 71%) versus unfavorable (2 of 11, 18%), P = 0.0088]. In the phase III trial, there was statistically significant increased time to progression (TTP) and survival following p53 gene therapy in patients with favorable p53 profiles compared with unfavorable p53 inhibitor profiles (median TTP, 2.7 months versus 1.4 months, P = 0.0121; median survival, 7.2 months versus 2.7 months, P < 0.0001). In contrast, the biomarker profiles predictive of p53 gene therapy efficacy did not predict methotrexate response, TTP, or survival outcomes.

Conclusions: These results indicate that tumor p53 biomarker profiles may predict p53 gene therapy efficacy in recurrent squamous cell carcinoma of the head and neck. (Clin Cancer Res 2009;15(24):7719–25)
Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer
Authors: Jorissen Robert N. , Gibbs Peter , Christie Michael , Prakash Saurabh , Lipton Lara , Desai Jayesh , Kerr David , Aaltonen Lauri A. , Arango Diego , Kruhøffer Mogens , Ørntoft Torben F. , Andersen Claus Lindbjerg , Gruidl Mike , Kamath Vidya P. , Eschrich Steven , Yeatman Timothy J. , Sieber Oliver M.
Published: December 2009

Purpose: Colorectal cancer prognosis is currently predicted from pathologic staging, providing limited discrimination for Dukes stage B and C disease. Additional markers for outcome are required to help guide therapy selection for individual patients.

Experimental Design: A multisite single-platform microarray study was done on 553 colorectal cancers. Gene expression changes were identified between stage A and D tumors (three training sets) and assessed as a prognosis signature in stage B and C tumors (independent test and external validation sets).

Results: One hundred twenty-eight genes showed reproducible expression changes between three sets of stage A and D cancers. Using consistent genes, stage B and C cancers clustered into two groups resembling early-stage and metastatic tumors. A Prediction Analysis of Microarray algorithm was developed to classify individual intermediate-stage cancers into stage A–like/good prognosis or stage D–like/poor prognosis types. For stage B patients, the treatment adjusted hazard ratio for 6-year recurrence in individuals with stage D–like cancers was 10.3 (95% confidence interval, 1.3-80.0; P = 0.011). For stage C patients, the adjusted hazard ratio was 2.9 (95% confidence interval, 1.1-7.6; P = 0.016). Similar results were obtained for an external set of stage B and C patients. The prognosis signature was enriched for downregulated immune response genes and upregulated cell signaling and extracellular matrix genes. Accordingly, sparse tumor infiltration with mononuclear chronic inflammatory cells was associated with poor outcome in independent patients.

Conclusions: Metastasis-associated gene expression changes can be used to refine traditional outcome prediction, providing a rational approach for tailoring treatments to subsets of patients. (Clin Cancer Res 2009;15(24):7642–51)
miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis in Adrenocortical Cancer
Authors: Soon Patsy Siok Hwa , Tacon Lyndal J. , Gill Anthony J. , Bambach Christopher P. , Sywak Mark S. , Campbell Peter R. , Yeh Michael W. , Wong Steven G. , Clifton-Bligh Roderick J. , Robinson Bruce G. , Sidhu Stan B.
Published: December 2009

Purpose: Adrenocortical adenomas are common, whereas adrenocortical carcinomas are rare. Discriminating between benign and malignant adrenocortical tumors using conventional histology can be difficult. In addition, adrenocortical carcinomas generally have poor prognosis and limited treatment options. MicroRNAs are short noncoding RNAs that are involved in regulation of gene transcription.

Experimental Design: To identify microRNAs involved in the pathogenesis of adrenocortical tumors, expression profiling of microRNAs was done on a cohort of 22 adrenocortical carcinomas, 27 adrenocortical adenomas, and 6 normal adrenal cortices.

Results: Twenty-three microRNAs were found to be significantly differentially expressed between adrenocortical carcinomas and adrenocortical adenomas. miR-335 and miR-195 were significantly downregulated in adrenocortical carcinomas compared with adrenocortical adenomas. This result was further validated in an external cohort of six adrenocortical carcinomas and four adrenocortical adenomas. Using Kaplan-Meier analysis, downregulation of miR-195 and upregulation of miR-483-5p in adrenocortical carcinomas were significantly associated with poorer disease-specific survival.

Conclusions: These findings indicate that deregulation of microRNAs is a recurring event in human adrenocortical carcinomas and that aberrant expression of miR-195 and miR-483-5p identifies a subset of poorer prognosis adrenocortical carcinomas. (Clin Cancer Res 2009;15(24):7684–92)
Integrated Molecular and Clinical Analysis of AKT Activation in Metastatic Melanoma
Authors: Davies Michael A. , Stemke-Hale Katherine , Lin E. , Tellez Carmen , Deng Wanleng , Gopal Yennu N. , Woodman Scott E. , Calderone Tiffany C. , Ju Zhenlin , Lazar Alexander J. , Prieto Victor G. , Aldape Kenneth , Mills Gordon B. , Gershenwald Jeffrey E.
Published: December 2009

Purpose: Activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway has been implicated in melanoma based primarily on the prevalence of mutations in PTEN and NRAS. To improve our understanding of the regulation and clinical significance of the PI3K-AKT pathway in melanoma, we quantitatively measured the levels of phosphorylated AKT, its substrate GSK3α/β, and its negative regulator PTEN in clinical metastases. Results were compared with mutational status, clinical outcomes, and sites of metastasis.

Experimental Design: DNA and protein were isolated from dissected frozen melanoma metastases (n = 96). Activating mutations of BRAF, NRAS, AKT, PIK3CA, and KIT were detected by mass spectroscopy genotyping. Phosphorylated AKT (Ser473 and Thr308), P-GSK3α/β, and PTEN protein expression were measured by reverse-phase protein array. A panel of human melanoma cells lines (n = 58) was analyzed for comparison.

Results: BRAF-mutant tumors had higher levels of P-AKT-Ser473 (P = 0.01), P-AKT-Thr308 (P = 0.002), and P-GSK3α/β (P = 0.08) than NRAS-mutant tumors. Analysis of individual tumors showed that almost all tumors with elevated P-AKT had low PTEN levels; NRAS-mutant tumors had normal PTEN and lower P-AKT. Similar results were observed in melanoma cell lines. Stage III melanoma patients did not differ in overall survival based on activation status of the PI3K-AKT pathway. Brain metastases had significantly higher P-AKT and lower PTEN than lung or liver metastases.

Conclusions: Quantitative interrogation of the PI3K-AKT pathway in melanoma reveals unexpected significant differences in AKT activation by NRAS mutation and PTEN loss, and hyperactivation of AKT in brain metastases. These findings have implications for the rational development of targeted therapy for this disease. (Clin Cancer Res 2009;15(24):7538–46)
Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas
Authors: Schaaij-Visser Tieneke B.M. , Graveland A. Peggy , Gauci Sharon , Braakhuis Boudewijn J.M. , Buijze Marijke , Heck Albert J.R. , Kuik Dirk J. , Bloemena Elisabeth , Leemans C. René , Slijper Monique , Brakenhoff Ruud H.
Published: December 2009

Purpose: The 5-year survival rates of head and neck squamous cell carcinomas (HNSCC) remain disappointing. HNSCCs develop in precursor fields of genetically altered cells that are often not completely resected when the tumor is excised, causing local relapse. These precursor fields are mostly recognized as dysplasia, but histologic grading cannot reliably predict malignant transformation. Our aim was to discover and validate protein biomarkers that can detect precursor fields and predict local relapse in HNSCC using immunostaining of surgical margins.

Experimental Design: We compared paired and genetically characterized normal, precursor, and tumor tissues of eight patients by proteome analysis to identify differentially expressed proteins. The prognostic value of candidate protein biomarkers was evaluated by immunohistochemical analysis of 222 surgical margins of 46 HNSCC patients who developed local relapse or remained disease free. Significant associations were determined by Kaplan-Meier survival analysis and Cox-proportional hazards models.

Results: Forty proteins showed significant differential expression (false discovery rate–corrected P < 0.05). Most discriminative markers suited for immunostaining were keratin 4 and cornulin. Low expression in the surgical margins of keratin 4 (hazard ratio, 3.8; P = 0.002), cornulin (hazard ratio, 2.7; P = 0.025), and their combination (hazard ratio, 8.8; P = 0.0005) showed a highly significant association with the development of local relapse. Dysplasia grading had no prognostic relevance.

Conclusions: Immunohistochemical assessment of keratin 4 and cornulin expression in surgical margins of HNSCC patients outperforms histopathologic grading in predicting the risk for local relapse. These markers can be used to initiate more frequent and lifelong surveillance of patients at high risk of local relapse, and enable selection for adjuvant treatment or tertiary prevention trials. (Clin Cancer Res 2009;15(24):7666–75)
Toll-Like Receptor Triggering and T-Cell Costimulation Induce Potent Antitumor Immunity in Mice
Authors: Westwood Jennifer A. , Haynes Nicole M. , Sharkey Janelle , McLaughlin Nicole , Pegram Hollie J. , Schwendener Reto A. , Smyth Mark J. , Darcy Phillip K. , Kershaw Michael H.
Published: December 2009

Purpose: To determine the antitumor activity of a novel combination of two immunomodulatory agents that simultaneously direct multiple components of immunity against cancer.

Experimental Design: We combined the Toll-like receptor agonist CpG 1826 with a T-cell costimulatory antibody specific for CD137 in an optimal treatment route and dosing schedule against established tumors in two mouse models. Mechanistic insight was gained using gene-deficient mice and cell-depleting antibodies.

Results: The combination was shown to eradicate tumors in a large proportion of mice. Crucial roles for CD8+ T cells, natural killer cells, and IFNs were shown. CpG and anti-CD137 injection led to activation of dendritic cells and optimal expansion of activated T cells in the blood. Macrophages were not necessary for therapeutic effect, and indeed depletion of macrophages in vivo enhanced therapy leading to tumor rejection in 100% of mice, which has not been previously reported in the immunotherapeutic setting. Long-term surviving mice were resistant to tumor rechallenge, demonstrating immunologic memory. In addition, we show, for the first time, that mice lacking B cells have a total loss of a recall response against tumor, suggesting a role for B cells in the induction of antitumor immunologic memory.

Conclusion: This study provides support for the use of a novel combination of immunomodulatory agents stimulating multiple facets of immunity for the effective immunotherapy of cancer. (Clin Cancer Res 2009;15(24):7624–33)
Angiotensin type 2 receptor–mediated apoptosis of human prostate cancer cells
Authors: Li Hongwei , Qi Yanfei , Li Chengyao , Braseth Leah N. , Gao Yongxin , Shabashvili Arseniy E. , Katovich Michael J. , Sumners Colin
Published: December 2009

Angiotensin II (Ang II) type 1 receptor blocking drugs have been shown to inhibit the growth of prostate cancer cells and delay the development of prostate cancer. Functional Ang II type 2 receptors (AT2R) are present in these cells and inhibit growth induced by epidermal growth factor. The present studies report apoptosis of prostate cancer cells induced by AT2R overexpression. A recombinant adenoviral vector expressing AT2R (Ad-G-AT2R-EGFP) was transduced into prostate cancer cells, including androgen-independent (DU145 and PC3) and androgen-dependent cell lines (LNCaP). Following AT2R transduction, apoptosis was analyzed by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining and caspase-3 activity assays. The results indicate that increased expression of AT2R alone induced apoptosis in the prostate cancer lines, an effect that did not require Ang II. AT2R overexpression in DU145 cells induced inhibition of proliferation, a significant reduction of S-phase cells, and an enrichment of G1-phase cells. The data also indicate that overexpression of AT2R led to apoptosis via an extrinsic cell death signaling pathway that is dependent on activation of p38 mitogen-activated protein kinase, caspase-8, and caspase-3. Finally, the apoptosis induced by AT2R overexpression is partially dependent on the activation of p53, but not on p21. The observations presented here suggest that the ability of increased AT2R expression to induce apoptosis in prostate cancer cells may have potential therapeutic implications for this disease, and suggest that AT2R is a promising novel target gene for prostate cancer gene therapy. [Mol Cancer Ther 2009;8(12):3255–65]
G-quadruplex ligand SYUIQ-5 induces autophagy by telomere damage and TRF2 delocalization in cancer cells
Authors: Zhou Wen-Jun , Deng Rong , Zhang Xiao-Yue , Feng Gong-Kan , Gu Lian-Quan , Zhu Xiao-Feng
Published: December 2009

Agents stabilizing G-quadruplexes have the potential to destroy the functional structure of telomere and could therefore act as antitumor agents. We previously reported that SYUIQ-5 could stabilize G-quadruplex, induce senescence, and inhibit c-myc gene promoter activity. In this study, we showed that SYUIQ-5 inhibited proliferation of CNE2 and HeLa cancer cells, triggered a rapid and potent telomere DNA damage response characterized by the formation of telomeric foci γ-H2AX, and obviously induced autophagy with the features of increased LC3-II and a punctuated pattern of YFP-LC3 fluorescence. These phenomena may primarily depend on the delocalization of TRF2 from telomere, which was further degraded by proteasomes. Furthermore, overexpression of TRF2 inhibited SYUIQ-5–induced γ-H2AX expression. Also, ATM was activated following SYUIQ-5 treatment. The pretreatment with ATM inhibitor ku55933 and ATM siRNA effectively reduced the production of γ-H2AX and LC3-II. ATM knockdown partially antagonized the anticancer effects of SYUIQ-5. Moreover, inhibition of autophagy by short hairpin RNA against the autophagy-related gene ATG5 attenuated the cytotoxicity of SYUIQ-5. These results indicated that SYUIQ-5 triggered potent telomere damage through TRF2 delocalization from telomeres, and eventually induced autophagic cell death in cancer cells. Our findings exhibit a novel mechanism that is responsible for the antitumor effects of SYUIQ-5. [Mol Cancer Ther 2009;8(12):3203–13]
Basal c-Jun NH2-terminal protein kinase activity is essential for survival and proliferation of T-cell acute lymphoblastic leukemia cells
Authors: Cui Jian , Wang Qingyang , Wang Jing , Lv Ming , Zhu Ning , Li Yan , Feng Jiannan , Shen Beifen , Zhang Jiyan
Published: December 2009

Hyperactivation of c-Jun NH2-terminal protein kinase (JNK) has been found in various malignant lymphocytes and inhibition of JNK activity leads to cell cycle arrest and apoptosis. However, the role of JNK activity in the oncogenic growth of T-cell acute lymphoblastic leukemia (T-ALL) cells remains largely unknown. Here, we report that treatment of T-ALL cells with JNK inhibitors led to cell cycle arrest and apoptosis and increased sensitivity to Fas-mediated apoptosis, whereas weak ectopic expression of MKK7-JNK1 fusion protein, which shows constitutive JNK activity, in T-ALL cells resulted in accelerated cell cycle progression and resistance to Fas-mediated apoptosis. The protein levels of c-Myc and Bcl-2 were reduced in the presence of JNK inhibitors but were enhanced with MKK7-JNK1. Small interfering RNA against JNK1, but not JNK2, exhibited similar effects to JNK inhibitors. These findings suggest that targeting JNK, especially JNK1 isoform, may have some important therapeutic implications in the treatment of T-ALL. Further exploration revealed that JNK protein and basal JNK activity in T-ALL cells showed aberrant subcellular localization, but no hyperactivation of JNK was observed. Thus, our work suggests that there might be novel mechanism(s) other than hyperactivation underlying the protumorigenic role of JNK activity. [Mol Cancer Ther 2009;8(12):3214–22]
Hepatocyte Nuclear Factor-4–Independent Synthesis of Coagulation Factor VII in Breast Cancer Cells and Its Inhibition by Targeting Selective Histone Acetyltransferases
Authors: Koizume Shiro , Yokota Naho , Miyagi Etsuko , Hirahara Fumiki , Nakamura Yoshiyasu , Sakuma Yuji , Yoshida Akira , Kameda Yoichi , Tsuchiya Eiju , Ruf Wolfram , Miyagi Yohei
Published: December 2009

Tissue factor/coagulation factor VII (fVII) complex formation on the surface of cancer cells plays important roles in cancer biology, such as cell migration and invasion, angiogenesis, and antiapoptotic effects. We recently found that various cancer cells ectopically synthesize fVII, resulting in activation of cell motility and invasion. Here, we characterized mechanisms of hepatic and ectopic fVII (FVII) gene expression to identify molecular targets enabling selective inhibition of the ectopic expression. Unlike hepatic expression, hepatocyte nuclear factor-4 binding to the promoter is not required for ectopic FVII expression, although Sp1 binding is essential. Furthermore, we found novel nuclear targets of basal hepatocytic and ectopic FVII expression. Notably, histone acetyltransferases p300 and cyclic AMP–responsive element binding protein–binding protein (CBP) are exclusively recruited to the promoter region of the FVII gene specifically in breast cancer cells. We further show that curcumin, a dietary compound, can selectively inhibit ectopic fVII expression by targeting p300/CBP activity. These results suggest a strategy to inhibit ectopic fVII-induced tumor progression without impairment of the physiologic hemostatic process. (Mol Cancer Res 2009;7(12):1928–36)
Impact of Perinatal Outcome of the Presence of Fused or Separate Placentas in Dichorionic Twins
Authors: Suzuki Shunji
Published: December 2009

Objective: The aim of this study was to investigate the influence of fusion of the placentas on various obstetric and neonatal findings in dichorionic twin pregnancies. Methods: Medical charts of the total population of women who gave birth to dichorionic twin babies at the Japanese Red Cross Katsushika Maternity Hospital between 2002 and 2007 were reviewed. Data were collected from 158 deliveries with dichorionic fused placentas and from 261 deliveries with separate placentas. Results: There were no significant differences in various obstetric and neonatal findings between dichorionic twin pregnancies with fused placentas and those with separate placentas. Conclusion: The current findings indicate that there is no significant influence of fusion of placentas in dichorionic twin pregnancies.
Evaluation of the Effect of Acetyl L-Carnitine on Experimental Cisplatin Nephrotoxicity
Authors: Tufekci Ozlem , Gunes Dilek , Özoğul Candan , Kolatan Efsun , Altun Zekiye , Yılmaz Osman , Aktaş Safiye , Erbayraktar Zübeyde , Kırkım Günay , Mutafoğlu Kamer , Soylu Alper , Şerbetçioğlu Bülent , Güneri Enis Alpin , Olgun Nur
Published: December 2009

Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.
Doppler Velocimetry of the Ductus Arteriosus in Normal Fetuses and Fetuses Suspected for Pulmonary Hypoplasia
Authors: Gerards F.A. , Twisk J.W.R. , van Vugt J.M.G.
Published: December 2009

Objective: The purpose of this study was to determine whether the pulsatility index (PI) of the ductus arteriosus could predict the occurrence of pulmonary hypoplasia secondary to congenital disorders or complications during pregnancy. Sample and Methods: In this longitudinal study, 78 uncomplicated pregnancies and 43 pregnancies complicated by various disorders or complications with regard to pulmonary hypoplasia were studied by Doppler sonography between 18 and 35 weeks of gestation. A PI >97.5th percentile was considered abnormal. Results: Using a multilevel modelling, the reference curve of the PI of the ductus arteriosus was created based on 301 measurements. Of the 43 complicated pregnancies, 21 infants (49%) were diagnosed with pulmonary hypoplasia on postmortem examination and/or the clinical and radiological presentation. Using the PI, a sensitivity of 38%, a specificity of 95%, a positive predictive value of 89% and a negative predictive value of 62% were found. Conclusion: The PI of the ductus arteriosus is not useful in predicting the occurrence of pulmonary hypoplasia secondary to congenital disorders or complications during pregnancy.
Intracranial Injection with KCI: An Alternative Method in Selected Cases of Multifetal Pregnancy Reduction
Authors: Lembet Arda , Selam Belgin , Bodur Harika , Ergin Tolga , Demirel Cem
Published: December 2009

Multifetal pregnancy reduction (MFPR) offers a therapeutic option which reduces the maternal, prenatal, neonatal morbidity and mortality associated with multifetal pregnancies. In certain cases of MFPR, where difficulty is encountered in reaching the thorax due to the fetal position as well as the location of membranes and placenta, an alternative approach may be the insertion of the needle to the fetal cranium. We describe a new technique for MFPR performed by fetal intracranial injection of potassium chloride. To our knowledge, the current case series is the first report describing the technique of intracranial injection of potassium chloride during MFPR and selective termination. This approach enables a technically easier procedure than the intrathoracic approach. However, the use of this technique should be reserved for selected cases of MFPR only by experienced operators and centers.
Preoperative MUCP and VLPP Did Not Predict Long-Term (4-Year) Outcome after Transobturator Mid-Urethral Sling
Authors: Costantini Elisabetta , Lazzeri Massimo , Giannantoni Antonella , Bini Vittorio , del Zingaro Michele , Porena Massimo
Published: December 2009

Objective: Maximum urethral closure pressure (MUCP) and Valsalva leak point pressure (VLPP) have been considered objective parameters for studying the urethral integrity and predicting outcome after surgery for stress urinary incontinence (SUI). We test the hypothesis that preoperative MUCP and/or VLPP may predict long-term outcome after out-in transobturator tape (TOT) surgery for female SUI. Methods: 65 patients affected by stress or mixed urinary incontinence were enrolled in a prospective observational descriptive study conducted from May 2002 to November 2005 at a single tertiary urban teaching university urogynecological department. Preoperative MUCP and VLPP, stratified as ≤ or >40 cm H2O and ≤ or >60 cm H2O, respectively, were separately or in combination correlated with primary (continence status: dry or wet) and secondary outcome variables (quality of life questionnaires) after surgery. Results: Out of 65 patients, 6 (9.2%) did not attend the follow-up. The median follow-up was 46 months (mean 52 ± 18; range 36–82). The overall objective cure rates (dry) were 74.4% for patients with VLPP >60 cm H2O and 65% for VLPP ≤60 cm H2O (p < 0.654). The overall objective cure rates (dry) were 75% for patients with MUCP >40 cm H2O and 68.6% for MUCP ≤40 cm H2O (p < 0.808). The overall objective cure rates (dry) were 82.4% for patients with MUCP >40 cm H2O and VLPP >60 cm H2O and 69.2% for MUCP ≤40 cm H2O and VLPP ≤60 cm H2O (p < 0.956). Conclusions: These data seem to cast doubts on the predictive value of MUCP and VLPP in patients who underwent TOT.
Outline of 3,830 Male Patients Referred to Urodynamic Evaluation for Lower Urinary Tract Symptoms: How Common Is Infravesical Outlet Obstruction?
Authors: Rodrigues Paulo , Hering Flávio , Meller Alex , D’Império Márcio
Published: December 2009

Introduction: The prevalence of bladder outlet obstruction in men has been overestimated leading to improper clinical results after transurethral resection of the prostate. Patients and Methods: 3,830 consecutive male cases submitted for urodynamic evaluation were prospectively analyzed using a Schaefer nomogram. The prevalence of detrusor overactivity and the occurrence of obstruction were prospectively studied using standardized urodynamic practice. Results: Infravesical obstruction was diagnosed in 44.8% of the studied population: 0.7% of the obstructed cases were obstructed at the sphincter zone and 7.9% showed obstruction as a high-pressure, high-flow-rate pattern. Detrusor overactivity was demonstrated in 73.9% of the obstructed cases and in 22% of the unobstructed. Older patients (>60 years) seemed more likely (odds ratio: 2.8) to present detrusor overactivity, but at the same time showed less frequent obstruction. The oldest subjects (>80 years) showed a lower prevalence of obstruction, although overactive bladder was a common finding. Conclusion: Infravesical obstruction is less frequent than previously stated. The common assumption that obstruction is the cause of lower urinary tract symptoms in older men is wrong. Older men are more likely to suffer from detrusor overactivity resulting from lower urinary tract symptoms rather than infravesical obstruction. Urodynamic studies seem to be crucial for a proper diagnosis in men considered candidates for surgical treatment.
Effects of Retroperitoneal or Transperitoneal Laparoscopic Surgery on Hemodynamic and Respiratory Function in Old Patients
Authors: Ji Qing , Zhang Lidong , Li Weiyan , Jia Hongbin , Wang Yongguang
Published: December 2009

Purpose: To compare the effects of retroperitoneal laparoscopic surgery (RPL) and transperitoneal laparoscopic surgery (TPL) on the hemodynamic and ventilatory functions in old patients. Methods: Thirty-two senior patients underwent either RPL or TPL. Swan-Ganz and radial artery catheters were placed to monitor hemodynamic functions. Artery blood samples were obtained to analyze ventilatory functions. Results: For hemodynamic changes in both TPL and RPL, central venous pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure significantly increased 10 min after CO2 insufflation and decreased to preanesthesia levels roughly 30 min after insufflation relief. For ventilatory functions, in both TPL and RPL, peak airway pressure, partial pressure of arterial carbon dioxide (PaCO2), end-tidal carbon dioxide tension (PetCO2), carbon dioxide output (VCO2), and the difference between PaCO2 and PetCO2 (Pa-PetCO2) all increased significantly 10 min after CO2 insufflation and returned to the preanesthesia level 20 min after CO2 desufflation. However, increments of PaCO2, VCO2 and Pa-PetCO2 were significantly higher in RPL than in TPL, and did not return to the preanesthesia level until 30 min after CO2 desufflation. Conclusion: For senior patients, TPL and RPL have similar effects on hemodynamic functions. However, RPL tends to cause much more change in the respiratory measurements.
Long-Term Testicular Growth and Position after Orchidopexy for Congenital Undescended Testis
Authors: Sijstermans K. , Hack W.W.M. , van der Voort-Doedens L.M. , Meijer R.W.
Published: December 2009

Aim: We aimed to investigate long-term testicular growth and the position of congenital undescended testes (UDT) after orchidopexy (ORP), taking into account that nowadays UDT has to be divided into congenital and acquired forms. Methods: This study included 181 patients with 199 congenital UDT (91 right-sided, 72 left-sided, 18 bilateral), in whom ORP had been carried out (1986–2006). Long-term testicular position and growth were assessed by clinical examination and ultrasound (US). Results: In 44.5% (65/146), testicular volume of the unilaterally operated congenital UDT was >50th percentile for age. In 55.5% (81/146), the volume was ≤50th percentile, and 13.0% (19/146) of these were ≤10th percentile. In 7 of 34 (20.6%) bilaterally operated congenital UDT, testicular volume was ≤10th percentile. The difference in size between the operated congenital UDT and the contralateral non-operated testes measured by both Prader orchidometer (p = 0.00) and US (p = 0.00) was statistically significant. There was a strong correlation between the orchidometer and US. On examination, 87.9% (175/199) of the operated testes were located in the lower scrotum. Conclusion: The findings of this study suggest that ORP for congenital UDT is safe, and even when performed later than current recommendations did not result in severe growth retardation.
Ureteral Triplication Combined with Right Renal Ectopia and Ureteral Cyst
Authors: Xu Zhe , Li Zuoqing , Wang Daohu , Deng Gaoyan , Su Cheng , Pan Jing , Li Suisheng
Published: December 2009

Ureteral triplication is one of the rarest malformations of the upper urinary tract. We report the case of a 12-year-old girl with right ureteral triplication combined with renal ectopia and ureteral cyst with stenosis at the junction of the ureteral cyst and distal ureter. The ureteral cyst was tailored and tubularized, and the tight junction was removed, as in Hynes-Anderson ureteropyeloplasty; on reevaluation almost 4 years later, kidney function was normal and computed tomography showed a normal kidney and ureter.
Delayed Infection of a Pelvic Lymphocele following Robotic Radical Prostatectomy and Pelvic Lymphadenectomy: Two Cases
Authors: Tremp Mathias , Sulser Tullio , Seifert Hans-Helge
Published: December 2009

Pelvic lymphocele is an infrequent complication of pelvic surgery, usually presenting shortly after surgery. We report 2 cases with a delayed infected pelvic lymphocele presenting after transperitoneal pelvic lymphadenectomy and robotic radical prostatectomy for adenocarcinoma of the prostate. These cases illustrate that late infection of pelvic lymphoceles may occur following radical prostatectomy and pelvic lymphadenectomy. The practicing urologist should be aware of this possibility and look for an infected lymphocele in postoperative pelvic lymphadenectomy patients presenting with fever and leukocytosis of uncertain etiology, regardless of the time elapsed since surgery. To date, there is a paucity of data in the literature on robotic- assisted laparoscopic resection of a lymphocele after radical prostatectomy. The minimally invasive technique can be considered as a possible alternative to lymphocele percutaneous drainage. It is effective, results in minimal patient morbidity and allows for rapid recovery.
Optimizing Vascular Risk Reduction in the Stroke Patient with Atherothrombotic Disease
Authors: Ovbiagele Bruce
Published: December 2009

Introduction: With mounting evidence underscoring the multifactorial pathogenesis of atherothrombotic cerebrovascular disease, it is becoming increasingly obvious that an early and aggressive multimodal treatment of the underlying atherosclerotic disease process is the most effective approach towards preventing recurrent vascular events in the majority of ischemic stroke patients. Knowledge of the evidence behind this strategy and the effective means for implementing it could be useful to the healthcare practitioner caring for stroke and transient ischemic attack (TIA) patients. Review Summary: This review presents the evidence behind the broadening therapeutic options for recurrent vascular event prevention in ischemic stroke patients whose underlying stroke pathophysiologic mechanism is presumed to be due to atherosclerosis. The paper identifies modifiable vascular risk factors associated with recurrent stroke, as well as the clinical trial data on which the latest clinical practice guidelines on recurrent stroke prevention have been based. Therapies discussed include antithrombotics, statins, antihypertensives, revascularization procedures and lifestyle modification (smoking cessation, exercise and diet education). Finally, successful hospital-based quality improvement programs for initiating and maintaining these evidence-based recurrent stroke prevention treatments are also described. Conclusions: A timely, systematic, evidence-based multimodal preventive approach to atherothrombotic disease in ischemic stroke and TIA patients that transcends the continuum of care will enhance treatment rates and improve clinical outcomes.
Lingual Nerve Morbidity and Mandibular Third Molar Surgery: A Prospective Study
Authors: Baqain Zaid H. , Abukaraky Ashraf , Hassoneh Yazan , Sawair Faleh
Published: December 2009

Objective: The objective of this study was to estimate the frequency of postoperative lingual nerve (LN) impairment after the surgical removal of mandibular third molars (M3) and to identify potential risk indicators. Subjects and Methods: A prospective cohort study involving 321 subjects who had 443 mandibular M3 surgically extracted at the University Hospital, Amman, Jordan. Predictor variables were categorized as patient-, anatomy- and operation-specific. The outcome variable was the presence or absence of LN impairment. Bivariate and multivariate analyses were performed to identify independent predictors. Results: The prevalence of temporary LN hypoesthesia was 2.5% and all 11 cases resolved within 6 months. Factors that predicted LN injury by univariate analysis were horizontal and mesioangular tooth angulation, bone removal, tooth sectioning, longer operations, lingual flap retraction and bleeding into the socket. In the multivariate logistic regression model, lingual flap retraction (p = 0.002, OR = 26.790) and bleeding into the socket (p = 0.044, OR = 4.918) were the independent predictors. Conclusion: Operative variables were the main predictors of temporary LN damage.
Disease Activity and Cytokine Production in Mitogen-Stimulated Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis
Authors: Uppal Sukhbir S. , Raghupathy Raj , Hayat Sawsan J. , Longenecker Joseph C. , Abraham Mini , Rawoot Parvez
Published: December 2009

Objective: To test whether there are differences in the levels and ratios of 6 pro- and 3 anti-inflammatory cytokines produced by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) subjects compared to controls. Subjects and Methods: 79 participants (42 seropositive RA patients and 37 healthy controls) were enrolled in this study. The production levels in mitogen-stimulated PBMCs of the 6 proinflammatory cytokines (IFN-γ, TNF-α, TNF-β, IL-8, IL-17, IL-18) and 3 anti-inflammatory cytokines (IL-4, IL-10, IL-13) were assayed by ELISA using kits obtained from Immunotech SA. The ratios of pro- to anti-inflammatory cytokines were calculated for all participants. Results: There were significantly elevated levels of IL-8 and IL-10, and reduced levels of IFN-γ, IL-4, and IL-17 in mitogen-stimulated PBMC culture supernatants of RA subjects compared to controls. Of the 18 pro-/anti-inflammatory cytokine ratios, 3 ratios (TNF-α/IL13, IL-8/IL-4 and IL-8/IL-13) were significantly higher in RA patients compared to controls; and 6 were higher in controls (IFN-γ/IL-4; IFN-γ/IL-10; IFN-γ/IL-13; TNF-β/IL10; IL-17/IL-10; IL-18/IL-10). Conclusions:Activated PBMCs of RA patients, regardless of disease activity, showed higher-level production of IL-8 and IL-10 compared to controls; lower-level production of IFN-γ, IL-4, and IL-17; and elevated ratios of TNF-α/IL-13, IL-8/IL-4 and IL-8/IL-13.
Signet Ring Cell Adenoma of the Thyroid: A Very Rare Entity
Authors: Yalta Tulin , Elagoz Sahende , Uyar Meral , Topuz Omer , Ozer Hatice , Tuncer Ersin
Published: December 2009

Objectives: To report a case of signet ring cell adenoma of the thyroid which is an extremely rare thyroid lesion. Clinical Presentation and Intervention: A 25-year-old female patient presented with a goiter and dysphagia that had been present for the last 1 year before admission. Physical examination revealed a palpable solitary nodule in the right lobe of the thyroid. The ultrasonogram demonstrated multiple nodules among which the most remarkable one was 15 × 24 mm in size, in the right lobe of the thyroid. After surgical excision, the lesion was found to be consistent withsignet ring cell adenomacharacterized by the presence of round to oval signet ring cells with large cytoplasmic vacuoles and hyperchromatic eccentric nuclei. Intracytoplasmic thyroglobulin, periodic acid-Schiff (PAS) with and without diastase and combined Alcian-blue-PAS were all positive. Conclusions: Pathologists should keep this rare primary tumor of the thyroid in mind when examining thyroid lesions and should not confound it with metastatic signet ring cell carcinoma of the thyroid.
Sex-Dependent Species Discrimination in Auditory Forebrain of Naturally Hybridizing Birds
Authors: Gee Jennifer M. , Tomaszycki Michelle L. , Adkins-Regan Elizabeth
Published: December 2009

Pairs of individuals breed together only if they recognize each other as the same species, but the process of recognizing conspecifics can depend on flexible criteria even when species-specific signals are innate and fixed. This study examines species recognition in naturally hybridizing sister species, California and Gambel’s quail (Callipepla californica and Callipepla gambelii), that have vocalizations which are not learned. Specifically, this study tests whether being raised in a vocalizing mixed-species cohort affects neural activity in the adult auditory forebrain in response to heterospecific and conspecific calls. After hatching, quail chicks were raised either with their own kind or with both species. Once reaching reproductive condition, each adult was played a recording that was one of three types: Gambel’s quail opposite-sex contact calls; California quail opposite-sex contact calls; or synthetic tones. Brains were collected following playback and assessed for neuronal activity by quantifying expression of the protein of the immediate early gene, ZENK, in two brain regions, the caudomedial nidopallium (NCM) and the caudomedial mesopallium (CMM). ZENK levels were greater in NCM of males than females, but female NCM cells responded differentially to conspecific compared to heterospecific calls. Namely, females had more immuno-positive NCM cells when they heard conspecific calls rather than heterospecific male calls. Early experience with heterospecific broodmates did not alter neural responses in the NCM or CMM to heterospecific vocalizations. This study suggests that the NCM plays a role in species discrimination but that rearing condition does not alter the response in these non-vocal-learning species.