bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical staging and cytoreductive surgery of epithelial ovarian cancer
Authors: Hoskins William J.
Published: March 2011

Background. Surgery remains the cornerstone of the treatment for epithelial ovarian cancer. In early ovarian cancer, the initial operation is a complete assessment of the spread of disease. In this staging operation, 33% of patients thought to have either Stage I or II tumors will be found to have advanced‐stage disease. The correct diagnosis of advanced disease prevents improper treatment of patients originally thought to have early disease. For patients with advanced disease, the initial cytoreductive operation reduces tumor bulk and produces increased sensitivity to chemotherapy for the remaining tumor. The principles of cellular kinetics provide good theoretic evidence for the benefit of cytoreductive surgery.

Methods. Current studies relating to primary and secondary surgical cytoreduction of epithelial ovarian cancer were reviewed.

Results. Current indirect evidence indicates a significant survival benefit for patients with epithelial ovarian cancer who undergo successful surgical cytoreduction. Several recent studies also have shown the importance of the biology of the tumor, the extent of tumor spread, the location of the tumor, the cell type, the histologic grade, and the age of the patient. Although the literature contains fewer reports of secondary cytoreductive surgery than of primary cytoreductive surgery at the time of second‐look, surgical reassessment appears to provide a survival benefit.

Conclusions. The potential benefit of secondary cytoreduction will be increasingly important as new salvage therapies become available.
Mechanisms and modulation of resistance to chemotherapy in ovarian cancer
Authors: Perez Raymond P. , Hamilton Thomas C. , Ozols Robert F. , Young Robert C.
Published: March 2011

Chemotherapy for advanced ovarian cancer remains sub‐optimal. Despite the improvements in objective response rates realized with cisplatin‐based combination chemotherapeutic regimens, most patients still die of refractory cancer. Drug resistance has emerged as the single most important determinant of treatment outcome. Laboratory studies have provided substantial insights into the cellular mechanisms of resistance to the commonly used chemotherapeutic agents. Decreased drug accumulation, metabolic drug inactivation, and repair or tolerance to drug‐induced cellular injury all contribute to resistance at the cellular level. Identification of these mechanisms has facilitated the development of specific treatment strategies, many of which are in or nearing clinical trials. These strategies include dose intensification, inhibition of P‐glycoprotein function, inhibition of cellular glutathione synthesis, and inhibition of cellular DNA repair. The initial results from clinical trials that use these strategies provide reasonable grounds for optimism. In addition, efforts to identify new drugs with activity against resistant cells continue. One such drug, taxol, has significant activity in tumors refractory to conventional therapy. These approaches offer hope that intensive laboratory and clinical efforts ultimately will translate into real improvements in the efficacy of chemotherapy for ovarian cancer.
Cell growth regulation in epithelial ovarian cancer
Authors: Bast Robert C. , Boyer Cinda M. , Jacobs Ian , Xu Feng Ji , Wu Shu , Wiener Jon , Kohler Matt , Berchuck Andrew
Published: March 2011

Background. As in the case of other epithelial neoplasms, most ovarian cancers arise from single clones of cells that have undergone multiple genetic alterations. A comparison of normal and malignant ovarian epithelium has identified several differences in growth regulation by peptide growth factors, protooncogenes, and tumor suppressor genes.

Methods. Recent articles and abstracts have been reviewed.

Results. The malignant ovarian epithelial phenotype has been associated with (1) autocrine growth stimulation by transforming growth factor‐alpha, (2) loss of autocrine growth inhibition by transforming growth factor‐beta, (3) mutation or amplification of ras in 2–12% of cases, (4) amplification of myc in 23% of specimens, (5) expression of fms in 56% of cases with potential autocrine stimulation by macrophage colony stimulating factor, (6) paracrine stimulation by macrophage products including interleukin‐1, interleukin‐6 and tumor necrosis factor, (7) overexpression of c‐erhB‐2 (HER‐2/neu) in 30% of cases, and (8) mutation with consequent overexpression of p53 in 50% of advanced ovarian cancers. A poor clinical prognosis is associated with expression or overexpression of the epidermal growth factor receptor, fms, and HER‐2/neu. Antibodies against the extracellular domain of the HER‐2/neu gene product p185 inhibit the growth of tumor cells that overexpress HER‐2/neu and are associated with marked decreases in diacyl‐glycerol levels. The intracellular kinase domain is required for growth inhibition. Antibodies that inhibit growth stimulate phosphorylation of intracellular substrates. Ricin A chain monoclonal antibody conjugates that react with p185 also inhibit the growth of tumor cells that overexpress p185. The intracellular kinase region is not required for immunotoxin‐mediated killing. Coexpression of HER‐2/neu and the epidermal growth factor receptor has been observed in 65% of epithelial ovarian cancers and in a limited number of normal tissue from a fraction of donors.

Conclusions: Multiple alterations in growth factors, protooncogenes and growth factors have been detected in different epithelial ovarian cancers. Inappropriate signalling from receptor tyrosine kinases may be particularly important for ovarian oncogenesis. Drugs that affect tyrosine kinase and phosphatase activity deserve attention as potential therapeutic agents for ovarian cancer. The extracellular domains of the HER‐2/neu gene product p185 and the epidermal growth factor receptor may provide useful targets for serotherapy.
Monoclonal antibodies in the management of ovarian cancer: A clinical perspective
Authors: Rubin Stephen C.
Published: March 2011

Despite recent advances in the conventional management of ovarian cancer, this disease remains the leading cause of death among the gynecologic malignancies, killing more American women each year than all other gynecologic cancers combined. As a tumor arising from a nonessential organ that remains primarily confined to the peritoneal cavity, ovarian cancer makes an attractive target for monoclonal antibodies (MoAb). Several MoAb have been developed that have actual or potential clinical use in the management of ovarian cancer. Serum assays using a MoAb against an ovarian cancer‐associated antigen (CA 125) are currently in routine clinical use for monitoring the course of disease in women with known ovarian cancer. Such assays may play a role in multi‐technique screening programs. Radiolabeled antibodies are under study for use in external imaging or intraoperative detection of ovarian cancer. Isotope‐labeled antibodies also are being evaluated in the treatment of ovarian cancer as are antibodies coupled to drugs or biologic toxins. Some antibodies may have direct antitumor effects through binding to biologically active receptors or through immune effector functions. The use of antibody fragments, chimeric antibodies, human antibodies, and genetically engineered antibodies is under active investigation. MoAb have important potential for improving the diagnosis, monitoring of response to therapy, and treatment of ovarian cancer.
Diagnosis and management of gestational trophoblastic disease
Authors: Lewis John L.
Published: March 2011

Gestational trophoblastic disease is a term that describes a group of tumors that share several characteristics as follows: (1) they arise in fetal chorion, (2) they produce human chorionic gonadotropin (hCG), and (3) they respond extremely well to chemotherapy. Although rare, they have received a disproportionate amount of attention because they were the first metastatic solid tumor to be cured using chemotherapy. Also, hCG was the first reliable tumor marker. Finally, because they arise in fetal tissue, they have the potential for a strong immune response against paternal antigens in the tumor. This potential for immunologic rejection was thought initially to explain the success of chemotherapy in this disease. The early detection of gestational trophoblastic disease is successful in patients who have had a hydatidiform mole as the pregnancy event that begins the process but unsuccessful in the early detection of the development of choriocarcinoma after a normal term delivery, abortion (spontaneous or elective), or ectopic pregnancy. Surveillance after evacuation of a molar pregnancy (whether complete or a partial mole) consists of regular evaluation of hCG production and the detection of metastatic disease. However, the development of gestational choriocarcinoma after term pregnancy or an abortion (no molar tissue can develop as a consequence of these pregnancies) is detectable only by signs or symptoms of metastatic disease in any of the many organs to which this tissue can spread. Unlike most staging classifications in gynecologic cancers, which are based on histologic findings and tumor location, the classification used in gestational trophoblastic disease stresses other features that are more useful for treatment selection. Both the National Institutes of Health and the World Health Organization classifications emphasize the importance of recognizing factors that predict the likelihood of a tumor responding to chemotherapy. Currently available treatment can cure all patients except those who are in the very high‐risk group, which usually is characterized by metastasis to the brain or liver or a history of prior chemotherapy. Even in this category, approximately 80% of patients are curable.
New advances in radiation oncology for gynecologic cancer
Authors: Brady Luther W. , Rotman Marvin , Calvo Felipe A.
Published: March 2011

In 1992, the American Cancer Society anticipates that there will be 1,130,000 new cases of invasive cancer diagnosed in the United States. About 66,500 will be invasive cancers of the cervix, uterus, and ovary. About 22,400 patients will die during 1992, with 50–60% of those deaths being due to persistent local regional disease. Data are available to suggest that a reduction in local failure will be reflected by an increase in survival free of disease. In 1992, major efforts are being made to reduce the incidence of local failure. Three areas in this regard are innovative uses of brachytherapy, intraarterial chemotherapy and radiation therapy, and continuous infusion chemotherapy and radiation therapy.

These new techniques show significant reduction in local failure with associated improvement in survival. The data will be presented to illustrate the impact of these techniques.
Conservative management of early vulvar cancer
Authors: Hacker Neville F. , Van Der Velden Jacobus
Published: March 2011

There is a definite trend toward vulvar conservation and individualized management of patients with early vulvar cancer. This approach initially was used only for patients with T1 disease, but with increasing experience with conservative surgery and the integration of postoperative adjuvant radiation when appropriate, some investigators have broadened the indications to include carefully selected patients with T2 lesions. A recent literature review suggests that the local invasive recurrence rate for T1 disease is 7.2% (12 of 165) after radical local excision compared with 6.3% (23 of 365) after radical vulvectomy (P = 0.85). Surgical margins must be at least 1 cm, and the rest of the vulva must be healthy if an increased local recurrence rate is to be avoided. Local recurrences usually can be treated successfully if diagnosed early, but recurrence in the groin is usually fatal. Inguinal‐femoral lymphadenectomy should be done on all patients if the primary tumor is more than 2 cm in diameter and in patients with T1 disease in whom the depth of invasion is greater than 1 mm. Separate groin incisions may be used, but pelvic and groin irradiation should be given if there is at least one large node replaced with tumor or multiple nodes containing micrometastases. Careful patient selection is critical if modified operations are used, or an increased rate of recurrence will follow.
Prognostic factors in early‐stage uterine sarcoma: A gynecologic oncology group study
Authors: Major Francis J. , Blessing John A. , Silverberg Steven G. , Morrow C. Paul , Creasman William T. , Currie John L. , Yordan Edgardo , Brady Mark F.
Published: March 2011

Background. A clinicopathologic evaluation of clinical Stage I and II uterine sarcoma was done by the Gynecologic Oncology Group from 1979–1988.

Methods. After all eligibility criteria were met, 453 cases were evaluable and analyzed for prognostic factors.

Results. Of the 301 mixed mesodermal tumors (MMT), 167 were homologous (HO), and 134 were heterologous (HE). Fifty‐nine tumors were leiomyosarcomas (LM). The remaining 93 sarcomas were predominantly stromal cell and adenosarcomas. For this study, only the MMT or LM tumors were analyzed. The recurrence rate for all MMT was 53% (HO, 44%; HE, 63%). The recurrence rate for LM was 71%. The site of the first recurrence included the pelvis in 21% of MMT and 14% in LM. Factors significantly related to progression‐free interval (PFI) by univariate analysis among MMT were adnexal spread, lymph node metastases, tumor size, lymphatic‐vascular space involvement, histologic grade, cell type, age, peritoneal cytologic findings, and depth of uterine tumor site of invasion. The prognostic factors based on multivariate analysis were adnexal spread, lymph node metastases, histologic cell type (HO versus HE), and grade of sarcoma. For LM, the mitotic index was the only factor significantly related to PFI.
Integrating radiation therapy into the management of ovarian cancer
Authors: Thomas Gillian M. , Dembo Alon J.
Published: March 2011

Several studies during the last 15 years have elucidated the role of postoperative external beam radiation therapy as curative management of some subsets of patients with ovarian cancer. Despite this, the use of radiation therapy in patients with ovarian cancer has remained a controversial subject. Substantially improved cure rates have not been realized during the past decade despite the early promise of high response rates to cisplatin chemotherapy. Thus, it is important that all currently effective therapies be used for maximum therapeutic gain. This article will review the evidence that radiation therapy is curative in ovarian cancer and highlight the criteria, including stage and grade of disease and tumor residuum, by which patients suitable for such therapy are selected. The rationale for the use of whole abdominopelvic irradiation rather than pelvic or lower abdominal treatment will be discussed, as will the optimal radiation technique and its attendant morbidity. Limited data pertinent to the controversy over the use of radiation therapy versus chemotherapy in early disease, will be reviewed. The possible benefits of consolidation abdominopelvic radiation therapy after chemotherapy in highly selected patients with well‐differentiated microscopic residual disease at second‐look laparotomy or with no residual disease but high a risk for relapse will be considered.
EGFR gene status in cytological samples of nonsmall cell lung carcinoma
Authors: da Cunha Santos Gilda , Saieg Mauro Ajaj , Geddie William , Leighl Natasha
Published: March 2011

BACKGROUND:

In nonsmall cell lung cancer (NSCLC), the development and clinical application of tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) has required the investigation of EGFR status by gene copy number and/or mutation analysis. This review aimed to present the current knowledge of the use of cytological specimens for EGFR testing in lung cancer.

METHODS:

A systematic computerized search was performed of the MEDLINE(R) and EMBASE databases to identify articles reporting the use of cytological samples for determining EGFR status in NSCLC.

RESULTS:

Data were extracted from 30 original articles. An additional 19 reviews, consensus statements, and editorials were selected from 175 retrieved papers. Different techniques using cell blocks, scraped cells from archival slides, and fresh cells have shown promising results and include fluorescent in situ hybridization (FISH), direct sequencing, and quantitative polymerase chain reaction (PCR), with similar or higher accuracy and sensitivity than surgical specimens. Preservation and quality of the extracted DNA seem to matter more than the actual number of tumor cells present in the samples. However, major issues still reside in the amount of material, the interference from background non‐neoplastic cells, and standardization of parameters for cytological samples.

CONCLUSIONS:

This analysis provided evidence that cytological material is suitable for detecting EGFR status using several different methodologies and preparations. New prospective, clinical studies are encouraged for collection and handling of cytological samples as well as for validation of novel techniques in large cohorts. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
EGFR and KRAS mutations in lung carcinoma
Authors: Billah Shahreen , Stewart John , Staerkel Gregg , Chen Su , Gong Yun , Guo Ming
Published: March 2011

BACKGROUND:

The aim of this study was to validate clinical utilization of routinely prepared cytology specimens for molecular testing to detect EGFR or KRAS mutations in lung cancer.

METHODS:

From September 2009 to April 2010, the authors collected 209 cytology specimens from patients with lung cancer at the MD Anderson Cancer Center Department of Pathology. The specimens included 99 cases of endobronchial ultrasound‐guided (EBUS) fine‐needle aspiration (FNA), 67 cases of computed tomography (CT)‐guided FNA, 27 cases of body fluid, 10 cases of ultrasound‐guided of superficial FNA, and 6 cases of other cytology specimens. DNA sequencing for EGFR exons 18‐21 and KRAS codons 12, 13, and 61 was performed.

RESULTS:

The overall specimen insufficiency rate was low (6.2%). EBUS (4%) and body‐fluid cases (3.7%) showed lower insufficiency rates than the other cases. Similar insufficiency rates were observed in smears (6.1%) and cell‐block sections (6.4%). EGFR mutations were detected in 19.4% (34 of 175) of nonsmall cell lung carcinoma (NSCLC) with a significantly higher frequency in adenocarcinoma (29%, 29 of 100) than in nonadenocarcinoma (7%, 5 of 75, P = .002). KRAS mutations were detected in 23.6% (41 of 174) of NSCLCs with no statistical differences between adenocarcinoma (26%, 26 of 102) and nonadenocarcinoma (21%, 17 of 72, P = .86). Higher frequencies of EGFR mutations in exons 19 and 21 (65%) than in exons 18 and 20 were detected.

CONCLUSIONS:

Our findings support clinical utilization of routinely prepared cytology specimens, including EBUS, CT/US. FNAs and body fluid specimens, as a reliable source for molecular testing to detect EGFR or KRAS mutations in patients with NSCLC. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
Digital image‐based colourimetric tests for amphetamine and methylamphetamine
Authors: Choodum Aree , Nic Daeid Niamh
Published: March 2011

Digital image analysis was applied to the products of simple colourimetric tests for amphetamine and methylamphetamine. Adobe Photoshop software was used for colour analysis to obtain analytical data in the form of a Red Green Blue (RGB) value. Calibration curves were developed for each compound and a number of illicit amphetamine samples were analyzed to demonstrate the application of the technique. A wide linear range and low detection limit for both drugs under test facilitated the application to illicit samples. Good agreement with gas chromatographic quantification results was obtained for the illicit samples analyzed by this method. The results show great potential for use as a semi‐quantitative field test for illicit drug compounds. Copyright © 2011 John Wiley & Sons, Ltd.
Simultaneous spectrophotometric determination of paracetamol and para‐aminophenol in pharmaceutical dosage forms using two novel multivariate standard addition methods based on net analyte signal and rank annihilation factor analysis
Authors: Yousefinejad Saeed , Hemmateenejad Bahram
Published: March 2011

Recently we proposed two multivariate standard addition methods using net analyte signal concept and rank annihilation factor analysis, which we named SANAS and SARAF, respectively. These methods could model both indirect sample matrix effects and direct interference effects of the coexisting analytes. Here, the potential of these methods for simultaneous determination of paracetamol and para‐aminophenol in the synthetic mixtures and pharmaceutical products was examined. It was found that both models could predict the concentration of analytes in synthetic mixtures with relative errors of prediction lower than 7%. Moreover, the employed methods exhibited the recoveries in the range of 93.11 and 108.67 for analysis of the drugs in the real matrices. From SANAS plots, the figures of merit including sensitivity, selectivity and limit of detection were calculated as 0.143 µg/ml, 0.587 and 0.018 µg/ml for paracetamol and 0.128 µg/ml, 0.547 and 0.020 µg/ml for para‐aminophenol, respectively. Copyright © 2011 John Wiley & Sons, Ltd.
Hydrological and biogeochemical controls on plant species distribution within calcareous fens
Authors: Duval Tim P. , Waddington J. Michael , Branfireun Brian A.
Published: March 2011

This study determines spatial patterns of plant species richness and diversity in three calcareous fens and quantifies individual species response and range/tolerance to hydrological, peat physical, and porewater nutrient gradients using nonlinear quantile regression. Species richness and diversity were highly variable across the sites, with no single species occupying more than 25% of the area surveyed. Variable hydrological regime was related to distance from the principal source area of water to the fens. Surface peat organic matter and calcium carbonate content ranged from 11 to 91% and 2 to 83%, respectively. Dissolved inorganic nitrogen (DIN) and potassium concentrations from the shallow porewater ranged from 0 to 4 mg l−1, whereas available phosphorus was < 100 µg l−1. Species exhibited various response shapes to the environmental gradients, which produced segregated realized ranges. The duration of initial saturation of the peat from the start of the growing season and the peat organic matter content produced the greatest number of complete species responses and ranges. Aggregation of species across growth types based on environmental responses mirrored visually described communities, demonstrating the applicability of the method of analysis. The generation of species response curves for a suite of readily measured environmental variables can be a useful tool for assessing conceptual models of ecosystem functioning and wetland restoration/creation success. Copyright © 2011 John Wiley & Sons, Ltd.
Four New Compounds Constructed from Bis‐Antimony‐Capped Keggin Polyoxoanions {PMo12Sb2O40} and Different Coordination Fragments
Authors: Xiao Li‐Na , Peng Yu , Wang Yan , Xu Jia‐Ning , Gao Zhong‐Min , Liu Ya‐Bing , Zheng Da‐Fang , Cui Xiao‐Bing , Xu Ji‐Qing
Published: March 2011

Four new heteropolyanions {[PMo12Sb2O40][Cu(Im)2]2}·Im (1), {[PMo12Sb2O40][(Cd(Phen)2)2Cl]} (2), [Cu(Phen)2]2[PMo12Sb2O40] (3) and [Cd(bpy)4(H2O)2][PMo12Sb2O40]·bpy·2H2O (4) (Im = imidazole, Phen = 1,10‐phenanthroline, bpy = 4,4′‐bipyridine) have been synthesized and characterized by IR, UV/Vis spectrophotometry, X‐ray photoelectron spectroscopy, powder XRD analyses and elemental analyses. Single‐crystal X‐ray diffraction analyses revealed that these four compounds represent examples of compounds based on the bis‐antimony‐capped Keggin polyoxoanion {PMo12Sb2O40} and different transition‐metal coordination complexes. Compound 1 exhibits a novel 1D chain structure, compound 2 is the first example of an extended structure constructed from polyoxoanions, transition‐metal coordination complexes and halide ions and compounds 3 and 4 are supramolecular structures constructed from {PMo12Sb2O40} polyoxoanions and different transition‐metal coordination fragments.
Direct Organocatalytic Asymmetric Approach to Baylis–Hillman‐Type Products Through a Push–Pull Dienamine Platform
Authors: Ramachary Dhevalapally B. , Ramakumar Kinthada
Published: March 2011

A general process for the asymmetric synthesis of highly substituted 3‐alkyl‐Hagemann's esters was achieved for the first time through organocatalytic Michael or Baylis–Hillman‐type (BH‐type) reaction of Hagemann's esters with β‐nitrostyrenes in the presence of a catalytic amount of L‐(3,5‐Me2)2DPP/thiourea. We have discovered, for the first time, the chiral BH‐type products from Hagemann's esters with β‐nitrostyrenes by utilizing the push–pull dienamine platform.
Defection in the dark? A randomized‐response investigation of cooperativeness in social dilemma games
Authors: Moshagen Morten , Hilbig Benjamin E. , Musch Jochen
Published: March 2011

As previous research has demonstrated numerous times, humans show a robust tendency for cooperation. However, part—or indeed all—of this cooperativeness may be due to socially desirable responding. To address this problem, we propose and apply a new approach for the unbiased measurement of cooperativeness in social dilemma games. Specifically, we employ an extension of the randomized‐response technique (RRT). The RRT protects the privacy of respondents by adding random noise to their responses. It thus encourages more honest responding and thereby provides less biased estimates of sensitive attributes. In a large‐scale study with 2043 respondents we maximized anonymity in a one‐shot prisoner's dilemma game through use of the RRT. Comparing the prevalence rates for cooperation obtained via the RRT with those from direct self‐report showed that traditional direct questioning formats overestimate cooperation rates, with a relative bias of 18%. This finding suggests that to a considerable extent, self‐reported cooperation is due to socially desirable responding, rather than actual cooperativeness. However, our results also demonstrate that cooperation remains substantial even under conditions of maximized anonymity. Copyright © 2011 John Wiley & Sons, Ltd.
Determination of ciclopirox olamine in pharmaceutical products by capillary electrophoresis with capacitively coupled contactless conductivity detection
Authors: Felix Fabiana Silva , do Lago Claudimir Lucio , Angnes Lúcio
Published: March 2011

This paper describes the determination of ciclopirox olamine in pharmaceutical formulations using capillary electrophoresis with capacitively coupled contactless conductivity detection. In an alkaline medium, ciclopirox olamine is converted into an anionic species and its detection is possible in capillary electrophoresis with capacitively coupled contactless conductivity detection without an electroosmotic flow modifier, because it is a low‐mobility species. A linear working range from 2.64 to 264 μg/mL in sodium hydroxide electrolyte as well as low detection limit (0.39 μg/mL) and a good repeatability (RSD=3.4% for 264 μg/mL ciclopirox solution (n=10)) were achieved. It was also possible to determine olamine in its cationic form when acetic acid was used as the electrolyte solution. The results obtained include a linear range from 26.4 to 184.8 μg/mL and a detection limit of 2.6 μg/mL olamine. The proposed methods were applied to the analysis of commercial pharmaceutical products and the results were compared with the values indicated by the manufacturer as well as those obtained using a titrimetric method recommended by American Pharmacopoeia.
Childhood sexual and physical abuse in Spanish female undergraduates: Does it affect eating disturbances?
Authors: Villarroel Ana M. , Penelo Eva , Portell Mariona , Raich Rosa M.
Published: March 2011

Objective

To assess the relationship between childhood sexual and physical abuse, and key attitudinal and behavioural aspects of eating disorders (ED).

Method

Participants included 708 female undergraduates in a Spanish public university, aged from 18 to 30. Abuse was measured by the Traumatic Life Events Questionnaire, and ED by the Eating Disorders Examination Questionnaire (EDE‐Q).

Results

14.3% of the sample had suffered childhood sexual abuse (CSA) and 3.8% childhood physical abuse (CPA). With respect to ED attitudinal features, we observed an increased Weight Concern score among CSA survivors. No association was found between this kind of abuse and disordered eating behaviours, after adjusting for depression, anxiety, self‐esteem, body mass index, age and socioeconomic status. An inverse relationship was found between CPA and ED attitudes measured by EDE‐Q (Restraint, Weight Concern, Shape Concern and the Overall Score), whereas no association was found with the behavioural aspects of eating disturbances.

Discussion

After controlling for different risk factors, CSA appears to be related to an increased Weight Concern, whilst other ED attitudinal features and behaviours do not seem to be related to childhood abuse. The inverse relationship found is discussed. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.
Who was the agent? The neural correlates of reanalysis processes during sentence comprehension
Authors: Hirotani Masako , Makuuchi Michiru , Rüschemeyer Shirley‐Ann , Friederici Angela D.
Published: March 2011

Sentence comprehension is a complex process. Besides identifying the meaning of each word and processing the syntactic structure of a sentence, it requires the computation of thematic information, that is, information about who did what to whom. The present fMRI study investigated the neural basis for thematic reanalysis (reanalysis of the thematic roles initially assigned to noun phrases in a sentence) and its interplay with syntactic reanalysis (reanalysis of the underlying syntactic structure originally constructed for a sentence). Thematic reanalysis recruited a network consisting of Broca's area, that is, the left pars triangularis (LPT), and the left posterior superior temporal gyrus, whereas only LPT showed greater sensitivity to syntactic reanalysis. These data provide direct evidence for a functional neuroanatomical basis for two linguistically motivated reanalysis processes during sentence comprehension. Hum Brain Mapp , 2011. © 2010 Wiley‐Liss, Inc.
Effect of D‐amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency
Authors: Prata Diana P. , Papagni Sergio A. , Mechelli Andrea , Fu Cynthia H.Y. , Kambeitz Joseph , Picchioni Marco , Kane Fergus , Kalidindi Sridevi , McDonald Colm , Kravariti Eugenia , Toulopoulou Timothea , Bramon Elvira , Walshe Muriel , Murray Robin , Collier David A. , McGuire Philip K.
Published: March 2011

Background. The D‐Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D‐amino acid oxidase (DAO), which metabolizes D‐serine, a co‐agonist of NMDA‐type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder. Aims. To examine the influence of G72 variation on brain function in the healthy population. Method. Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task‐dependent functional connectivity during word generation was compared between different rs746187 genotypes. Results. G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task‐dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05). Conclusions. Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D‐amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Abnormal resting state corticolimbic blood flow in depressed unmedicated patients with major depression: A 15O‐H2O PET study
Authors: Monkul E. Serap , Silva Leandro A.P. , Narayana Shalini , Peluso Marco A.M. , Zamarripa Frank , Nery Fabiano G. , Najt Pablo , Li John , Lancaster Jack L. , Fox Peter T. , Lafer Beny , Soares Jair C.
Published: March 2011

We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H215O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET‐MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI‐free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM‐D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic‐frontal structures in depressed patients compared to healthy volunteers. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Diffusion tensor imaging of the hippocampus and verbal memory performance: The RUN DMC Study
Authors: van Norden Anouk G.W. , de Laat Karlijn F. , Fick Ilma , van Uden Inge W.M. , van Oudheusden Lucas J.B. , Gons Rob A.R. , Norris David G. , Zwiers Marcel P. , Kessels Roy P.C. , de Leeuw Frank‐Erik
Published: March 2011

Background: Cerebral small vessel disease (SVD) and hippocampal atrophy are related to verbal memory failures and may ultimately result in Alzheimer's disease. However, verbal memory failures are often present before structural changes on conventional MRI appear. Changes in microstructural integrity of the hippocampus, which cannot be detected with conventional MRI, may be the underlying pathological substrate. With diffusion tensor imaging (DTI), we investigated the relation between the microstructural integrity of the hippocampus and verbal memory performance in 503 nondemented elderly with SVD. Methods: The Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study is a prospective cohort study among 503 nondemented elderly with cerebral SVD aged between 50 and 85 years. All participants underwent T1 MPRAGE, fluid‐attenuated inversion recovery, DTI scanning and the Rey Auditory Verbal Learning Test. After manual segmentation of the hippocampi, we calculated the mean diffusivity (MD) and fractional anisotropy in both hippocampi. The relation between memory performance and hippocampal DTI parameters was adjusted for age, sex, education, depressive symptoms, hippocampal, and white‐matter lesions volume and lacunar infarcts. Results: We found inverse relations between hippocampal MD and verbal memory performance (β = −0.22; P < 0.001), immediate recall (β = −0.22; P < 0.001), delayed recall (β = −0.20; P < 0.001), and forgetting rate (β = −0.13; P = 0.025), most pronounced in participants with a normal hippocampal volume. Conclusion: Microstructural integrity of the hippocampus assessed by DTI is related to verbal memory performance in elderly with SVD, also in participants with an intact appearing hippocampus. Changes in hippocampal microstructure may be an early marker of underlying neurodegenerative disease, before macrostructural (i.e., volumetric) changes occur. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Transoral robotic surgery of the tongue base in obstructive sleep Apnea‐Hypopnea syndrome: Anatomic considerations and clinical experience
Authors: Vicini Claudio , Dallan Iacopo , Canzi Pietro , Frassineti Sabrina , Nacci Andrea , Seccia Veronica , Panicucci Erica , Grazia La Pietra Maria , Montevecchi Filippo , Tschabitscher Manfred
Published: March 2011

Background

The purpose of our work was to describe, through cadaveric dissection, the anatomy of the tongue base with a robotic perspective and to demonstrate the feasibility of this approach in case of tongue base hypertrophy in Obstructive Sleep Apnea‐Hypopnea Syndrome (OSAHS).

Methods

Forty‐four patients with OSAHS underwent tongue base resection in the last 2 years. Twenty patients with a 10‐month minimum follow‐up were evaluated. The anatomic details of 3 tongue bases dissected from above are illustrated.

Results

The cadaveric study shows that no constant landmarks are identifiable, with no significant neurovascular structures present in the midline. Clinically, transoral robotic surgery (TORS) for the tongue base was feasible, with no major complications and satisfaction of the majority of patients. Mean apnea hypopnea index (AHI) improvement was 24.6 ± 22.2 SD, mean Epworth Sleepiness Scale (ESS) improvement was 5.9 ± 4.4 SD.

Conclusion

Tongue base hypertrophy can be safely and effectively managed by TORS in OSAHS. Our midterm data are encouraging and worthy of further evaluation. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Induction of vesicular steatosis by amiodarone and tetracycline is associated with up-regulation of lipogenic genes in heparg cells
Authors: Anthérieu Sébastien , Rogue Alexandra , Fromenty Bernard , Guillouzo André , Robin Marie-Anne
Published: March 2011

Drug-induced liver injury occurs in general after several weeks and is often unpredictable. It is characterized by a large spectrum of lesions that includes steatosis and phospholipidosis. Many drugs such as amiodarone and tetracycline have been reported to cause phospholipidosis and/or steatosis. In this study, acute and chronic hepatic effects of these two drugs were investigated using well-differentiated human hepatoma HepaRG cells. Accumulation of typical lipid droplets, labeled with Oil Red O, was observed in hepatocyte-like HepaRG cells after repeat exposure to either drug. Amiodarone caused the formation of additional intracytoplasmic vesicles that did not stain in all HepaRG cells. At the electron microscopic level, these vesicles appeared as typical lamellar bodies and were associated with an increase of phosphatidylethanolamine and phosphatidylcholine. A dose-dependent induction of triglycerides (TG) was observed after repeat exposure to either amiodarone or tetracycline. Several genes known to be related to lipogenesis were induced after treatment by these two drugs. By contrast, opposite deregulation of some of these genes (FASN, SCD1, and THSRP) was observed in fat HepaRG cells induced by oleic acid overload, supporting the conclusion that different mechanisms were involved in the induction of steatosis by drugs and oleic acid. Moreover, several genes related to lipid droplet formation (ADFP, PLIN4) were up-regulated after exposure to both drugs and oleic acid.

Conclusion:

Our results show that amiodarone causes phospholipidosis after short-term treatment and, like tetracycline, induces vesicular steatosis after repeat exposure in HepaRG cells. These data represent the first demonstration that drugs can induce vesicular steatosis in vitro and show a direct relationship between TG accumulation and enhanced expression of lipogenic genes. (HEPATOLOGY 2011;)
Azacitidine has limited activity in ‘real life’ patients with MDS and AML: a single centre experience
Authors: Ozbalak Murat , Cetiner Mustafa , Bekoz Huseyin , Atesoglu Elif Birtas , Ar Cem , Salihoglu Ayse , Tuzuner Nukhet , Ferhanoglu Burhan
Published: March 2011

Myelodysplastic syndrome (MDS) represents a heterogeneous group of potentially malignant diseases of bone‐marrow stem cells. Acute myelogenous leukaemia (AML) is an inevitable outcome for many patients with MDS. Azacitidine has been reported to result in comparably higher response rates and improved survival than other treatment strategies. In this retrospective study, we report the results on 25 ‘real life’ patients with MDS, CMML or AML treated with azacitidine between 2005 and 2009. All patients fulfilled the World Health Organization criteria for MDS and AML. No eligibility criteria other than diagnosis were considered. Complete response (CR) rate was observed in three of the 25 ‘real life’ patients (12%) with a median duration of CR of 5 months (4–6 months). Seven patients (28%) had mono‐ or bi‐lineage haematologic improvement and 15 patients (60%) showed neither morphologic nor haematologic response. Among 17 non‐AML patients, the median time from onset of Aza‐C treatment to AML transformation was 10 months (4–15 months). Overall death rate was 72%. All of the eight AML patients died. The death rate under Aza‐C among non‐AML patients was 59%. Unlike the results of the clinical trials, our data show that Aza‐C has a limited activity in ‘real‐life’ patients with MDS and AML. It is obvious that Aza‐C can induce complete or partial responses in a considerable number of MDS patients but responses are usually not durable as we observed in our patients. Copyright © 2011 John Wiley & Sons, Ltd.
The effect of treatment with ketoconazole on central CRH systems of depressed patients
Authors: Paslakis Georgios , Lecei Olivera , Stalla Günther K. , Landgraf Rainer , Uhr Manfred , Hamann Bettina , Luppa Peter , Gilles Maria , Heuser Isabella , Deuschle Michael
Published: March 2011

Objectives

Steroid‐synthesis inhibitors are reported to reduce psychopathology in treatment‐resistant depressed patients.

Methods

We studied the effect of a 3‐week treatment with ketoconazole on the evening plasma concentrations of cortisol, corticosteroid‐binding globulin (CBG), dehydroepiandrosterone‐sulfate (DHEA‐S) and adrenocorticotrope hormone (ACTH) as well as morning cerebrospinal fluid (CSF) concentrations of cortisol, corticotropin‐releasing hormone (CRH) and arginine‐vasopressin (AVP) in six elderly treatment‐resistant depressed patients.

Results

While we found plasma cortisol concentrations to be unchanged, a decline in plasma DHEA‐S concentrations indicated effective steroid‐synthesis inhibition. In morning CSF we found CRH concentrations that did not change.

Conclusions

Our preliminary observations indicate that the treatment of depressed patients with the steroid‐synthesis inhibitor ketoconazole does not lead to a major increase in CSF CRH secretion. Copyright © 2011 John Wiley & Sons, Ltd.
Characterization of water quality variation in the Mekong River at Vientiane by frequent observations
Authors: Iida Toshiaki , Inkhamseng Somphone , Yoshida Koshi , Tanji Hajime
Published: March 2011

To better understand the variation of water quality in the Mekong River, sampling and measurement were scheduled twice a week for about 3 years at Vientiane, followed by basic statistical analysis of the observed data. The frequent measurement revealed detailed characteristics of the water quality variation, which had not been detected by monthly observation in the previous studies. The variation in total ionic content was considered to be governed by dilution of the amount of water. Increases in turbidity could be attributed to physical effects including surface soil erosion and bed material resuspension at the time of discharge increase. Nitrogen concentrations were stably low during the low flow period and abruptly increased in May. After the annual maximum in late May, the nitrate concentration steadily decreased regardless of the remarkable rise in the discharge from mid‐July, whereas the ammonium concentration remained at a similar level until October. It was considered that the first small discernable runoff after the long dry season flushed the accumulated nitrogen in the surface soil and mobilized the nitrogen in the riverbed. The variation in phosphorus concentrations was different from that in nitrogen concentrations. During the high flow period, continual dilutions at discharge peaks and occasional large additions of phosphorus by surface runoff were suggested. Copyright © 2011 John Wiley & Sons, Ltd.
A comparison of simulated and measured lake ice thickness using a Shallow Water Ice Profiler
Authors: Brown Laura C. , Duguay Claude R.
Published: March 2011

In northern regions where observational data is sparse, lake ice models are ideal tools as they can provide valuable information on ice cover regimes. The Canadian Lake Ice Model was used to simulate ice cover for a lake near Churchill, Manitoba, Canada throughout the 2008/2009 and 2009/2010 ice covered seasons. To validate and improve the model results, in situ measurements of the ice cover through both seasons were obtained using an upward‐looking sonar device Shallow Water Ice Profiler (SWIP) installed on the bottom of the lake. The SWIP identified the ice‐on/off dates as well as collected ice thickness measurements. In addition, a digital camera was installed on shore to capture images of the ice cover through the seasons and field measurements were obtained of snow depth on the ice, and both the thickness of snow ice (if present) and total ice cover. Altering the amounts of snow cover on the ice surface to represent potential snow redistribution affected simulated freeze‐up dates by a maximum of 22 days and break‐up dates by a maximum of 12 days, highlighting the importance of accurately representing the snowpack for lake ice modelling. The late season ice thickness tended to be under estimated by the simulations with break‐up occurring too early, however, the evolution of the ice cover was simulated to fall between the range of the full snow and no snow scenario, with the thickness being dependant on the amount of snow cover on the ice surface. Copyright © 2011 John Wiley & Sons, Ltd.
MEG3 imprinted gene contribution in tumorigenesis
Authors: Benetatos Leonidas , Vartholomatos George , Hatzimichael Eleftheria
Published: March 2011

Maternally expressed gene 3 (MEG3) is a maternally expressed imprinted gene representing a large noncoding RNA in which microRNAs (miRNAs) and small nucleolar RNAs are also hosted. It is capable of interacting with cyclic AMP, p53, murine double minute 2 (MDM2) and growth differentiation factor 15 (GDF15) playing a role in cell proliferation control. MEG3 expression is under epigenetic control, and aberrant CpG methylation has been observed in several types of cancer. Moreover, gene copy number loss has been reported as additional mechanism associated with tumorigenesis. MEG3 deletion seems to upregulate the paternally expressed genes and on the other hand downregulate the expression of downstream maternally expressed genes and tumor suppressor miRNAs, although there are conflicting data on the topic. MEG3 could represent a tumor suppressor gene located in chromosome 14q32 and its association with tumorigenesis is growing every day.