bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of ZEB2 at the Invasion Front of Colorectal Cancer Is an Independent Prognostic Marker and Regulates Tumor Invasion In Vitro
Authors: Kahlert Christoph , Lahes Saleh , Radhakrishnan Praveen , Dutta Shamik , Mogler Carolin , Herpel Esther , Brand Karsten , Steinert Gunnar , Schneider Martin , Mollenhauer Martin , Reissfelder Christoph , Klupp Fee , Fritzmann Johannes , Wunder Christina , Benner Axel , Kloor Matthias , Huth Cathrin , Contin Pietro , Ulrich Alexis , Koch Moritz , Weitz Jürgen
Published: November 2011

Purpose: Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and dissemination. EMT occurs predominantly at the tumor edge where it is induced by cytokines, the extracellular matrix environment, or hypoxia. In the tumor cell, it is further mediated by several transcription factors and microRNAs. The aim of this study was to explore the expression of EMT-associated genes at the invasive front in colorectal cancer and to evaluate their prognostic significance.

Experimental Design: We evaluated the expression of 13 EMT-associated genes at the invasion front of 30 colorectal liver metastases by quantitative real-time PCR. Immunostaining against zinc finger E-box–binding homeobox 2 (ZEB2) was carried out on 175 primary colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathologic data. DLD-1 cells were transfected with siRNA and subjected to migration and invasion assays.

Results: Gene expression analysis and immunohistochemistry showed an upregulation of ZEB2 at the invasion front in primary colorectal cancer and liver metastases. Overexpression of ZEB2 at the invasion front correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed overexpression of ZEB2 at the invasion front as an independent prognostic marker for cancer-specific survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells in vitro.

Conclusions: Overexpression of ZEB2 at the invasion front correlates with tumor progression and predicts cancer-specific survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer. Clin Cancer Res; 17(24); 7654–63. ©2011 AACR.
Adaptive Clinical Trial Designs for Simultaneous Testing of Matched Diagnostics and Therapeutics
Authors: Scher Howard I. , Nasso Shelley Fuld , Rubin Eric H. , Simon Richard
Published: November 2011

A critical challenge in the development of new molecularly targeted anticancer drugs is the identification of predictive biomarkers and the concurrent development of diagnostics for these biomarkers. Developing matched diagnostics and therapeutics will require new clinical trial designs and methods of data analysis. The use of adaptive design in phase III trials may offer new opportunities for matched diagnosis and treatment because the size of the trial can allow for subpopulation analysis. We present an adaptive phase III trial design that can identify a suitable target population during the early course of the trial, enabling the efficacy of an experimental therapeutic to be evaluated within the target population as a later part of the same trial. The use of such an adaptive approach to clinical trial design has the potential to greatly improve the field of oncology and facilitate the development of personalized medicine. Clin Cancer Res; 17(21); 6634–40. ©2011 AACR.
Identification and Elucidation of the Biology of Adverse Events: The Challenges of Safety Assessment and Translational Medicine
Authors: Turteltaub Kenneth W. , Davis Myrtle A. , Burns-Naas Leigh Ann , Lawton Michael P. , Clark Adam M. , Reynolds Jack A.
Published: November 2011

There has been an explosion of technology-enabled scientific insight into the basic biology of the causes of adverse events. This has been driven, in part, by the development of the various “omics” tools (e.g., genomics, proteomics, and metabolomics) and associated bioinformatics platforms. Meanwhile, for decades, changes in preclinical testing protocols and guidelines have been limited. Preclinical safety testing currently relies heavily on the use of outdated animal models. Application of systems biology methods to evaluation of toxicities in oncology treatments can accelerate the introduction of safe, effective drugs. Systems biology adds insights regarding the causes and mechanisms of adverse effects, provides important and actionable information to help understand the risks and benefits to humans, focuses testing on methods that add value to the safety testing process, and leads to modifications of chemical entities to reduce liabilities during development. Leveraging emerging technologies, such as genomics and proteomics, may make preclinical safety testing more efficient and accurate and lead to better safety decisions. The development of a U.S. Food and Drug Administration guidance document on the use of systems biology in clinical testing would greatly benefit the development of drugs for oncology by communicating the potential application of specific methodologies, providing a framework for qualification and application of systems biology outcomes, and providing insight into the challenges and limitations of systems biology in the regulatory decision-making process. Clin Cancer Res; 17(21); 6641–5. ©2011 AACR.
Using Patient-Initiated Study Participation in the Development of Evidence for Personalized Cancer Therapy
Authors: Ambrose Laurie Fenton , Freedman Jamie , Buetow Kenneth , Friend Stephen , Schilsky Richard L.
Published: November 2011

Personalized cancer therapy offers the promise of delivering the right treatments to the right patients to improve patient outcomes and quality of life, while reducing exposure to ineffective therapies and the cost of cancer care. Realizing this promise depends in large part on our ability to generate timely and sufficiently detailed information regarding factors that influence treatment response. Generating this evidence through the traditional physician investigator-initiated clinical trial system has proved to be challenging, given poor recruitment rates and low compliance with requests for biospecimen collection. As a result, our current understanding of treatment response is inadequate, particularly for cancer therapies that have been in use for many years. Patient-initiated study participation may offer a new model for evidence generation that capitalizes on strong patient interest in furthering research to inform better and more tailored cancer therapies. In this approach, patients are engaged and recruited directly by the sponsor of an Institutional Review Board–approved study, and patients subsequently drive the participation of their health care providers to facilitate collection of required data and tissue samples. The ultimate goal of these studies is to generate evidence of sufficient quality to inform regulatory decisions (i.e., labeling changes for marketed therapies to reflect populations most likely to respond) and treatment selection. Here, we describe a hypothetical prospective observational study in non–small cell lung cancer that could serve as a model for patient-initiated study participation applied to understand molecular determinants of treatment response. Key elements discussed include study design, patient engagement, and data/biospecimen collection and management principles. Clin Cancer Res; 17(21); 6651–7. ©2011 AACR.
Genomic and Molecular Characterization of Malignant Peripheral Nerve Sheath Tumor Identifies the IGF1R Pathway as a Primary Target for Treatment
Authors: Yang Jilong , Ylipää Antti , Sun Yan , Zheng Hong , Chen Kexin , Nykter Matti , Trent Jonathan , Ratner Nancy , Lev Dina C. , Zhang Wei
Published: November 2011

Purpose: Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma that lacks effective therapeutic strategies. We gain insight into the most recurrent genetically altered pathways with the purpose of scanning possible therapeutic targets.

Experimental Design: We conducted a microarray-based comparative genomic hybridization profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Cancer Hospital. Immunohistochemistry (IHC) and cell biology detection and validation were carried out on human MPNST tissues and cell lines.

Results: Genomic characterization of 51 MPNST tissue samples identified several frequently amplified regions harboring 2,599 genes and regions of deletion including 4,901 genes. At the pathway level, we identified a significant enrichment of copy number–altering events in the insulin-like growth factor 1 receptor (IGF1R) pathway, including frequent amplifications of the IGF1R gene itself. To validate the IGF1R pathway as a potential target in MPNSTs, we first confirmed that high IGF1R protein correlated with worse tumor-free survival in an independent set of samples using IHC. Two MPNST cell lines (ST88-14 and STS26T) were used to determine the effect of attenuating IGF1R. Inhibition of IGF1R in ST88-14 cells using siRNAs or an IGF1R inhibitor, MK-0646, led to significant decreases in cell proliferation, invasion, and migration accompanied by attenuation of the PI3K/AKT and mitogen-activated protein kinase pathways.

Conclusion: These integrated genomic and molecular studies provide evidence that the IGF1R pathway is a potential therapeutic target for patients with MPNST. Clin Cancer Res; 17(24); 7563–73. ©2011 AACR.
Costs in Surgical Techniques for Radical Prostatectomy: A Review of the Current State
Authors: Gianino Maria Michela , Galzerano Mario , Martin Barbara , Chiadò Piat Simone , Gontero Paolo
Published: November 2011

Introduction: We carried out a mini-review of the literature in order to obtain a snapshot of the present state of the art of surgical techniques costs available for radical prostatectomy. Materials and Methods: We developed a MEDLINE search strategy and one economist assessed the included studies using the NHS EED guidelines for reviewers. Results: When observing costs by the author, it is possible to trace up a trend line of increasing costs which starts off with RPP, passes through RRP and LRP and ends up with robot-assisted radical prostatectomy. Two studies do not agree with this. One author claims that LRP is less costly than radical retropubic prostatectomy whereas another one agrees on radical perineal prostatectomy and radical retropubic prostatectomy but does not on RAP, which he claims to be less costly. Conclusions: The data shown in our study outline a situation by which the observed studies highlight: different costs of the techniques and incapability to achieve a conclusion about the technique with less average costs. These results can be considered in an explorative way and cannot be generalized. They maintain a strictly approximate value in local realities having only an informative purpose.
Surface Display of AcMNPV Occlusion-Derived P74 Does Not Enhance Oral Infectivity of Budded Viruses
Authors: Alfonso Victoria , López María Gabriela , Carrillo Elisa , Taboga Oscar
Published: November 2011

Baculovirus occlusion-derived viruses (ODVs) and budded viruses (BVs) are morphologically and functionally distinct. ODVs are responsible for primary infection in insect hosts because of their high per os infectivity. On the contrary, BVs poorly infect endothelial gut cells, but propagate the infection in the tissues of insects with a high efficiency. P74 is one of the most important proteins from ODVs, and it participates in the attachment of this viral phenotype to endothelial cells in the midgut. We evaluated the possibility of pseudotyping BVs of Autographa californica multiple nucleopolyhedrovirus with two versions of P74 and its effect on their oral infectivity. Both recombinant BVs contained P74 and replicated similarly to wild-type viruses. Nevertheless, the presence of P74 on the BV’s surface does not enhance the oral infectivity of this phenotype, suggesting that the presence of P74 in the membrane of budded virions interferes with their mechanism of infecting midgut cells.
Congenital Omphalocele and Polyhydramnios: A Study of 52 Cases
Authors: Ozawa Katsusuke , Ishikawa Hiroshi , Maruyama Yasuyo , Nagata Tomoko , Nagase Hiromi , Itani Yasufumi , Kurosawa Kenji , Yamanaka Michiko
Published: November 2011

Introduction: Unlike gastroschisis, congenital omphalocele is often associated with other anomalies and is frequently complicated by polyhydramnios. We examined the relationships between polyhydramnios, pregnancy outcome and fetal prognosis.Patients and Methods: Clinical data from cases diagnosed antenatally with congenital omphalocele from 1993 to 2006 were analyzed retrospectively. Results: Fifty-two cases were diagnosed antenatally with congenital omphalocele, and 38 of these pregnancies resulted in delivered infants. Of these 38 pregnancies, 55.3% were preterm births before 37 weeks of gestation. The mean birth weight was 2,148 g (n = 38). Associated anomalies were recognized in 29 cases (76.3%), including 13 cases (34.2%) of chromosomal aberrations. There were 2 cases of trisomy 13, 10 cases of trisomy 18 and 1 case of trisomy 21. Polyhydramnios was detected in 14 cases (36.8%), and other anomalies were present in all of these cases. Discussion: For antenatal evaluation in cases of congenital omphalocele, it is important to examine the fetus for associated anomalies or underlying disease, especially when polyhydramnios is detected.
Transcriptional Response of MxA, PKR and SOCS3 to Interferon-Based Therapy in HCV Genotype 4-Infected Patients and Contribution of p53 to Host Antiviral Response
Authors: Hamdi N. , El-Akel W. , El-Serafy M. , Esmat G. , Sarrazin C. , Abdelaziz A.I.
Published: November 2011

Aims: To investigate the myxovirus-resistance protein A (MxA) and double-stranded RNA-activated protein kinase (PKR) genetic response to interferon (IFN) therapy in hepatitis C virus (HCV) genotype 4-infected patients. Moreover, we studied the association between suppressor of cytokine signaling 3 (SOCS3) gene expression and therapy resistance in genotype 4. Finally, we investigated the novel link between p53 and IFN-stimulated genes (ISGs) in humans. Methods: Gene expression analyses were performed in peripheral blood using TaqMan real-time PCR. Virologic response was assessed with a branched-DNA assay. Genotyping was confirmed. Results: Early virologic responders (EVRs, n = 23) but not non-EVRs (n = 7) showed strong upregulation of PKR at week 12 of therapy compared to baseline. Both EVRs and non-EVRs showed MxA upregulation at week 12 compared to baseline. Baseline SOCS3 expression did not distinguish EVRs from non-EVRs in genotype 4. An association was found between p53 and MxA and PKR gene expression. Conclusion: Measurement of MxA and PKR transcriptional induction during treatment may distinguish EVRs from non-EVRs in genotype 4. SOCS3 gene does not seem to be implicated in therapy resistance in genotype 4. An association between p53 and ISGs expression was shown for the first time in HCV-infected patients, further supporting the contribution of p53 to host antiviral response.
Decrease in High Human Chorionic Gonadotropin in Twin-Twin Transfusion Syndrome following Fetoscopic Laser Surgery
Authors: Hanaoka Masachi , Hayashi Satoshi , Saito Mari , Morita Mineto , Sago Haruhiko
Published: November 2011

Introduction: The purpose of this study was to investigate the concentration of maternal serum human chorionic gonadotropin (hCG) in twin-twin transfusion syndrome (TTTS) before and after fetoscopic laser surgery and to clarify the association between TTTS and hCG. Material and Methods: The concentration of maternal serum hCG was measured before fetoscopic laser surgery and 2 and 4 weeks after laser surgery in 120 patients diagnosed with TTTS. Results: The preoperative serum concentration of hCG was 6.34 multiples of the median (MoM; interquartile range 3.52–9.86). The concentration of hCG was higher in TTTS of Quintero stage III or IV (7.17 MoM, range 4.21–11.0) compared to stage I or II (3.37 MoM, range 2.35–7.74). When laser surgery for TTTS was effective, hCG gradually decreased to less than half the preoperative concentration 2 weeks after laser surgery, and the concentration was further reduced to within the normal range at 4 weeks. However, the concentration of hCG in 3 cases with TTTS recurrence did not decrease. Discussion: A close association was observed between the concentration of hCG and the condition of TTTS. A change in the concentration of hCG after laser surgery could be a useful marker to judge the effectiveness of laser surgery in TTTS.
Procedure-Related Complications and Perinatal Outcome after Intrauterine Transfusions in Red Cell Alloimmunization in Stockholm
Authors: Tiblad Eleonor , Kublickas Marius , Ajne Gunilla , Bui The Hung , Ek Sverker , Karlsson Anita , Wikman Agneta , Westgren Magnus
Published: November 2011

Introduction: We present a review of all cases of intravascular transfusions in red cell alloimmunization over a time span of 20 years in Stockholm. The aim of the study is to compare our results with published results from larger centers and to identify areas that can be further improved. Material and Methods: A retrospective cohort study was conducted of all women treated with intrauterine transfusions due to erythrocyte immunization in our hospital between June 1990 and June 2010. Primary outcome variables were fetal and neonatal survival, procedure-related complications and gestational age at delivery. Results: A total of 284 intrauterine transfusions were performed in 84 pregnancies, with an overall survival rate of 91.8%. Procedure-related and fatal complications occurred in the present study in 4.9 and 1.4% of fetuses or neonates, respectively. Procedure-related complications were significantly more common in free-loop transfusions than in transfusions in the intrahepatic part of the umbilical vein (OR: 5.4, p = 0.025). There was no significant difference between the intrahepatic and the placental cord insertion route (p = 0.83). Gestational age at first transfusion was significantly associated with an increased risk of a procedure-related complication (OR: 0.8, p = 0.019). Of the live-born infants, 24% of the neonates were born before gestational week 34. Discussion: Our study confirms previous studies demonstrating favorable results with intravascular transfusions.
Localization of the Embryo in the Lower Part of the Gestational Sac at 6–7 Weeks’ Gestation Is Associated with Placenta Previa
Authors: Hasegawa Junichi , Mimura Takashi , Hamada Shoko , Nakamura Masamitsu , Matsuoka Ryu , Ichizuka Kiyotake , Sekizawa Akihiko , Okai Takashi
Published: November 2011

Objective: To evaluate whether placenta previa is associated with ultrasonographic findings during the first trimester. Methods: A case-control study with 1:5 (34 and 170 cases with placenta previa and normal placenta) matched pairs was conducted to compare ultrasonographic findings, including the position of the gestational sac (GS), that of the embryo in the GS, and placental cord insertion from 5–11 weeks of gestation. Results: Embryos located in the lower part of the GS at 6–7 weeks of gestation were observed in 83.3 and 17.1% of the cases and the controls, respectively. Placental cord insertion in the lower third of the uterus at 9–11 weeks of gestation was observed in 38.3 and 6.7% of the cases and the controls, respectively. Conclusion: Low embryo localization and low placental cord insertion during the first trimester was associated with placenta previa.
Renal Angiomyolipoma during Pregnancy: Review of the Literature
Authors: Zapardiel Ignacio , Delafuente-Valero Jesus , Bajo-Arenas Jose Manuel
Published: November 2011

The incidence of renal angiomyolipoma (RA) is 0.3% in the general population, and even more infrequent during pregnancy. Pregnancy can increase the risk of rupture, although the causal mechanism is still not clearly defined. We completed a Medline literature search for articles on RA and pregnancy and its complications. We identified 16 articles (all case reports), but selected only 13 because of unavailable data in the 3 other articles. We report the case of a 30-year-old primiparous woman who presented at the emergency ward with a non-reassuring pattern at fetal monitoring; an urgent cesarean section was decided and carried out. After surgery, a wide retroperitoneal hematoma was observed caused by the rupture of an RA. Conservative management by means of arterial embolism was done and the patient was discharged on postoperative day 10. RAs seem to have a higher risk of rupture during pregnancy, but they should be managed conservatively when hemodynamically possible. Individualization of each case is necessary in order to achieve the best outcome for both the mother and fetus.
Comparison between Single-Injection Inferomedial and Inferotemporal Peribulbar Blockades before Cataract Surgery
Authors: Mahdy Reda A. , Ghanem Mohamed T.
Published: November 2011

Purpose: To compare the efficacy and safety of single-injection inferomedial (IM) and conventional inferotemporal (IT) peribulbar blockades. Patients and Methods: This prospective randomized study included 200 patients who were randomly allocated into two equal groups (n = 100 patients); in the first group, patients received IM peribulbar injection (IM group), while IT peribulbar injection was performed for the second group (IT group). The measurement data were patient characteristics, number of patients who required supplementations, total anesthetic volume injected, surgeon’s experience and any recordable complications. Results: The number of patients who required supplemental anesthetics due to inadequate block was significantly higher in the IT group (15 patients, 15%, vs. no patients, 0%, in the IM group). The total anesthetic volume injected was significantly lower in the IM group (5.6 ± 0.8 vs. 9.8 ± 0.7 ml in the IT group). Surgeon’s satisfaction was significantly higher in the IM group (100 vs. 22% in the IT group). The incidences of complications were not significantly different between the two groups. Conclusion: It is safe and effective to conduct single-injection IM peribulbar blockade using a small needle size and low anesthetic volume.
Preschool Neurobehavioral Outcome following Fetal Myelomeningocele Surgery
Authors: Danzer Enrico , Gerdes Marsha , Bebbington Michael W. , Koh Jamie , Adzick N. Scott , Johnson Mark P.
Published: November 2011

Objective: It was the aim of this study to assess the prevalence of preschool neurobehavioral problems in children following fetal myelomeningocele (fMMC) surgery. Methods: Prior to the Management of Myelomeningocele Study, 30 fMMC patients underwent a standardized neurodevelopmental examination at 5 years of age. The prevalence of behavioral problems was assessed by the Child Behavior Check List (CBCL), which includes a total problem score and 2 broad-band indices (internalizing and externalizing problems). fMMC children were classified as having normal, at-risk or clinically significant scores based on calculated T scores. Results: Twenty-two (73%) fMMC families completed the evaluation. Mean age at delivery following fMMC surgery was 35.5 ± 1.6 weeks. The prevalence of ‘at-risk’ or ‘clinically significant’ scores for internalizing, externalizing and total behavioral problems was similar to general population norms. No difference in overall internalizing (p = 0.19), externalizing (p = 0.54) and total behavioral (p = 0.18) scores was found between non-shunted and shunted fMMC children. However, shunted fMMC children were more likely to experience anxiety and depressive (p = 0.02), pervasive developmental (p = 0.03) and withdrawn (p = 0.06) behavior. Oppositional defiant, attention deficit and hyperactivity problems were not found. No correlation was found between overall neurodevelopmental outcome and abnormal CBCL scores. Conclusions: fMMC surgery and subsequent preterm delivery is not associated with increased behavioral problems, impaired social interactions and restricted behavior patterns. Shunted fMMC children were more likely to have scores in the ‘at-risk’ or ‘clinically significant’ range for multiple CBCL subindices. Early detection of behavioral problems following fMMC surgery provides an opportunity for targeted and timely intervention enabling affected fMMC children to be socially successful.
Changes in Fetal Circulation Associated with Congenital Heart Disease and Their Effects on Fetal Growth
Authors: Itsukaichi Mina , Kikuchi Akira , Yoshihara Kosuke , Serikawa Takehiro , Takakuwa Koichi , Tanaka Kenichi
Published: November 2011

Objective: Our aim was to investigate the association between fetal growth and cerebrovascular resistance in fetuses with congenital heart disease (CHD). Methods: Fetal echocardiography was performed to measure the biparietal diameter, abdominal circumference, femur length, estimated fetal body weight, middle cerebral artery (MCA) resistance index (RI) and umbilical artery (UA) RI in 44 fetuses with CHD and 140 normal fetuses at a gestational age of 28–34 weeks. Results: Fetuses with CHD exhibited significantly lower values for femur length, estimated fetal body weight at the third trimester, body weight, length, and chest circumference at birth than normal controls. The percentages of fetuses showing MCA RI values <10th percentile and UA RI values >90th percentile were significantly higher in the CHD group than in the control group. However, there were no significant differences in any biometric parameters measured between cases with MCA RI values ≧10th percentile and values <10th percentile. Conclusions: Growth restriction and blood flow changes were observed significantly more frequently in fetuses with CHD than in those without CHD. Further studies are necessary to clarify the association between fetal growth and dynamic changes in fetal circulation.
Human Cytomegalovirus Glycoprotein B Genotypes in Chinese Hematopoietic Stem Cell Transplant Recipients
Authors: Xia Chang-sheng , Zhao Xiao-tao , Sun Yuan-yuan , Zhang Zheng
Published: November 2011

Objectives: To investigate the distribution of human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes and to explore the possible relationship between gB genotypes and clinical characteristics in Chinese hematopoietic stem cell transplant (HSCT) recipients. Methods: A prospective analysis of gB genotypes was conducted on HCMV clinical isolates obtained from 102 HSCT recipients. Real-time quantitative PCR and PCR-based restriction fragment length polymorphism analysis were applied for the determination of viral loads and gB genotypes, respectively. Results: The distribution of gB genotypes was as follows: gB1, 54/102 (52.9%); gB3, 21/102 (20.6%); and mixtures, 27/102 (26.5%). The rate of viral clearance at day 21 was higher in patients infected with the gB1 genotype than in those infected with the gB3 genotype (56 and 29%, respectively; p = 0.036). In contrast, the rate of HCMV reactivation/reinfection was higher in patients infected with the gB3 genotype than in those infected with the gB1 genotype (81 and 56%, respectively; p = 0.041). Conclusions: The HCMV gB1 genotype is the most prevalent among Chinese HSCT recipients; patients infected with the gB3 genotype have more difficulty eradicating the virus and have a higher risk of reactivation/reinfection than those infected with the gB1 genotype.
Retinal Complications after Damaging the Vitreolenticular Barrier
Authors: Framme Carsten , Wolf Sebastian
Published: November 2011

This article gives an overview of the vitreal anatomy and its changes in ageing, which have a significant impact on the two main retinal complications after damage of the vitreolenticular barrier, namely retinal detachment and cystoid macular edema. The possible reasons and pathomechanisms for this entity of retinal diseases in the context of anterior segment interaction are highlighted, and a summary of references is provided showing the epidemiology and consequences of such interventions.
Observational Study of the Local Tolerability of Injectable Progesterone Microspheres
Authors: Bernardo-Escudero Roberto , Cortés-Bonilla Manuel , Alonso-Campero Rosalba , de Jesús Francisco-Doce María Teresa , Chavarín-González Juan , Pimentel-Martínez Shantal , Zambrano-Tapia Lucía
Published: November 2011

Background: As intramuscular progesterone administration is associated with local intolerance, the purpose of this work was to determine the local tolerability of a new progesterone microsphere suspension, administered by intramuscular injection. Methods: An observational, longitudinal, prospective, analytical, multicenter, active pharmacovigilance study was conducted. Two hundred and seven progesterone microsphere administrations were evaluated. Patients evaluated pain, burning sensation, pruritus and dysesthesia. Physicians evaluated erythema, pallor, petechia, ecchymosis, bleeding, edema, induration, abscess, macule, papule, vesicle and pustule. Local tolerability was evaluated using a visual analog scale (100-mm line) on the day of administration, and subsequently on days 3 and 7. Local symptoms were evaluated by patients and local signs by the attending physicians. Results: On the day of application, 68.4% of the administered doses were associated with ‘absent’ or ‘mild’ pain, rising to 91.2% on the 7th day; 83.0% of doses were associated with ‘absence’ of or a ‘mild’ burning sensation on the day of administration, rising to 99.5% on day 7. On administration day, 13.2% reported ‘mild’ erythema and 1.0% ‘moderate’ erythema, and 3.9% of doses had ‘mild’ induration and 0.5% ‘moderate’ induration, which increased to 16.6 and 2.9% on day 3, respectively. The values for pallor, ecchymosis, bleeding, edema and pustule were lower than 10 mm (of 100 mm) on the application day and behaved similarly in subsequent days. There were no reports of petechia, abscess, macule, papule or vesicle with the dose application. Conclusions: Progesterone microspheres were well tolerated without serious or unexpected adverse effects.
Screening and Differential Diagnosis of Renal Light Chain-Associated Diseases
Authors: Gerth Jens , Sachse Anja , Busch Martin , Illner Nico , Muegge Lars-Olof , Gröne Hermann-Josef , Wolf Gunter
Published: November 2011

Background: Renal involvement in the light chain-associated diseases multiple myeloma (MM), amyloidosis (AL) and monoclonal immune position disease (MIDD) is common and differential diagnosis usually requires renal biopsy. The aim of this study was to investigate if noninvasive methods are viable to identify and differentiate between the various types of kidney diseases. Patients and Methods: All patients with a light chain-associated disease admitted to our center from 1996 to 2008 were retrospectively evaluated. Renal biopsy data were correlated with proteinuria findings. Results: Only the ratio of free ĸ/λ light chains showed a good sensitivity for myeloma cast nephropathy (MCN), AL and MIDD. The λ light chain was characteristic for AL, the ĸ light chain dominated in MIDD. Renal function at the time of diagnosis was worst in MIDD. MCN presented with a proteinuria of >3.5 g/g creatinine. In contrast, a higher proteinuria was found in AL or MIDD. Whereas the ĸ/λ ratio in the urine was pathological for all three diseases, extremely high or low ratios indicated the presence of MCN. However, in AL or MIDD, the ratio was only moderately elevated. Conclusion: A noninvasive differentiation between MCN and other forms of renal light chain disease is possible.
Traumatic Rupture of Horseshoe Kidney
Authors: Molina Escudero R. , Cancho Gil M.J. , Husillos Alonso A. , Lledó García E. , Herranz Amo F. , Ogaya Piniés G. , Ramón Botella E. , Simó G. , Navas Martínez M.C. , Hernández Fernández C.
Published: November 2011

We present the case of a 25-year-old male who came to the emergency room for pain and abdominal distension following trauma to the mesogastrium. A CT scan was performed, revealing a voluminous retroperitoneal hematoma with laceration of both inferior renal poles with regard to rupture of the isthmus of a horseshoe kidney. The patient presented anemization and increased pain, requiring selective embolization by means of arteriography of a branch of the right renal artery and placement of a double J stent due to urinary extravasation in the lower left kidney pole. Following 1 year of monitoring, the patient has maintained normal renal function. Renal affection in blunt abdominal trauma is frequent, occurring in 7% of previously pathological kidneys. The traumatic rupture of horseshoe kidney is facilitated by its particular anatomical characteristics, constituting an infrequent entity, knowledge of which is necessary to achieve conservative management that renders it possible to preserve renal function.
Hypospadias in a Male (78,XY; SRY-Positive) Dog and Sex Reversal Female (78,XX; SRY-Negative) Dogs: Clinical, Histological and Genetic Studies
Authors: Switonski M. , Payan-Carreira R. , Bartz M. , Nowacka-Woszuk J. , Szczerbal I. , Colaço B. , Pires M.A. , Ochota M. , Nizanski W.
Published: November 2011

Hypospadias is rarely reported in dogs. In this study we pre-sent 2 novel cases of this disorder of sexual development and, in addition, a case of hereditary sex reversal in a female with an enlarged clitoris. The first case was a male Moscow watchdog with a normal karyotype (78,XY) and the presence of the SRY gene. In this dog, perineal hypospadias, bilateral inguinal cryptorchidism and testes were observed. The second case, representing the Cocker spaniel breed, had a small penis with a hypospadic orifice of the urethra, bilateral cryptorchidism, testis and a rudimentary gonad inside an ovarian bursa, a normal female karyotype (78,XX) and a lack of the SRY gene. This animal was classified as a compound sex reversal (78,XX, SRY-negative) with the hypospadias syndrome. The third case was a Cocker spaniel female with an enlarged clitoris and internally located ovotestes. Cytogenetic and molecular analyses revealed a normal female karyotype (78,XX) and a lack of the SRY gene, while histology of the gonads showed an ovotesticular structure. This case was classified as a typical hereditary sex reversal syndrome (78,XX, SRY-negative). Molecular studies were focused on coding sequences of the SRY gene (case 1) and 2 candidates for monogenic hypospadias, namely MAMLD1 (mastermind-like domain containing 1) and SRD5A2 (steroid-5-alpha-reductase, alpha polypeptide 2). Sequencing of the entire SRY gene, including 5′- and 3′-flanking regions, did not reveal any mutation. The entire coding sequence of MAMLD1 and SRD5A2 was analyzed in all the intersexes, as well as in 4 phenotypically normal control dogs (3 females and 1 male). In MAMLD1 2 SNPs, including 1 missense substitution in exon 1 (c.128A>G, Asp43Ser), were identified, whereas in SRD5A2 7 polymorphisms, including 1 missense SNP (c.358G>A, Ala120Thr), were found. None of the identified polymorphisms cosegregated with the intersexual phenotype, thus, we cannot confirm that hypospadias may be associated with polymorphism in the coding sequence of the studied genes.
Surgical Stabilization of Postpartum Symphyseal Instability: Two Cases and a Review of the Literature
Authors: Osterhoff Georg , Ossendorf Christian , Ossendorf-Kimmich Nina , Zimmermann Roland , Wanner Guido A. , Simmen Hans-Peter , Werner Clément M.L.
Published: November 2011

During pregnancy, asymptomatic widening of the symphysis pubis by about one third is normal and considered physiological. However, peripartal relaxation of the symphyseal and sacroiliac ligaments may cause significant complaints conditions including pain and gait dysfunction. Usually, patients are treated by the application of pelvic binders and bed rest up to several weeks. Surgical stabilization is performed seldom, though it may be promising in selected patients. Based on 2 cases of postpartum symphyseal instability treated by surgical fixation, the current literature was reviewed systematically to evaluate the outcome and potential complications of surgical fixation of symphyseal instability. Thirteen articles met inclusion criteria and were analyzed in detail. Including the two cases presented, surgical stabilization of postpartum symphyseal instability has been described for 33 patients. In conclusion, though only based on case reports and case series, early surgical stabilization represents a decent treatment option for postpartum symphyseal instability and may be indicated by pain or walking disability alone. In regard to the clinical outcome comparing internal and external fixation, no differences were demonstrable. However, the rate of infection was higher in patients treated by external fixation. Based on these data, we propose a treatment algorithm for this injury.
Comparison of Clinical Outcomes between ‘On-Flap’ and ‘Off-Flap’ Epi-LASIK for Myopia: A Meta-Analysis
Authors: Feng Yi-fan , Chen Shi-hao , Stojanovic Aleksandar , Wang Qin-mei
Published: November 2011

Objective: To examine possible differences in clinical outcomes between off-flap and on-flap epipolis laser in situ keratomileusis (epi-LASIK) for myopia. Methods: Pertinent studies were selected by extensive searches. A total of 9 studies reporting on a total of 958 eyes were included in the present meta-analysis. Statistical analysis was performed using RevMan 5.0 software. Results: There were no significant differences in the final refractive spherical equivalent (p = 0.38), manifest refractive spherical equivalent within ±0.50 D of the target (p = 0.76), final uncorrected visual acuity (p = 0.90), loss of ≧1 line of best spectacle-corrected visual acuity (p = 0.99), and corneal haze at 3 months postoperatively (p = 0.96) or more than 6 months (p = 0.64). More patients felt severe pain in the on-flap group than in the off-flap group, although this finding was not statistically significant (p = 0.05). However, off-flap epi-LASIK had a better mean uncorrected visual acuity at 3 days (p = 0.04) and 5 days (p = 0.01), and faster re-epithelialization (p < 0.00001) after surgery. Conclusions: According to the available data, off-flap and on-flap epi-LASIK had equal visual and refractive outcomes for the treatment of myopia. Off-flap epi-LASIK had more rapid re-epithelialization and visual recovery compared to on-flap epi-LASIK.
Clinical Laboratory Implementation of Cytogenomic Microarrays
Authors: South S.T. , Brothman A.R.
Published: November 2011

Examination of the whole genome for copy number alterations by microarray is now routinely done in many laboratories. The field of cytogenetics has evolved to adapt this technology, and the current phase of transition has resulted in the need for standardization in methodologies and interpretation of data. This review will outline some of the changes addressed in the field over the last several years and briefly discuss some of the trends in data processing, analysis and interpretation.
Contribution of Three-Dimensional Ultrasonography in Depicting Perineal Features in Cloacal Malformation
Authors: Le Borgne H. , Philippe H.J. , Le Vaillant C.
Published: November 2011

Cloacal anomaly is a rare malformation with an incidence of 1 in 50,000 births. The definitive prenatal diagnosis of cloacal dysgenesis sequence is difficult. The use of three-dimensional (3-D) ultrasonography helps to describe the perineum and change diagnosis. In our case report, a large median genital structure was visualized, which was initially considered a penis-like structure, but the 3-D technique showed an enlarged bud. The urethral meatus was at the tip of this smooth structure. The lack of anal structure was clearly demonstrated.
Y-Autosome Translocation Interferes with Meiotic Sex Inactivation and Expression of Autosomal Genes: A Case Study in the Pig
Authors: Barasc H. , Mary N. , Letron R. , Calgaro A. , Dudez A.M. , Bonnet N. , Lahbib-Mansais Y. , Yerle M. , Ducos A. , Pinton A.
Published: November 2011

Y-autosome translocations are rare in humans and pigs. In both species, these rearrangements can be responsible for meiotic arrest and subsequent infertility. Chromosome pairing abnormalities on the SSCX, SSCY and SSC1 chromatin domains were identified by analyzing pachytene spermatocytes from a boar carrying a (Y;1) translocation by immunolocalization of specific meiotic protein combined with FISH. Disturbance of the meiotic sex chromosome inactivation (MSCI) was observed by Cot-RNA-FISH and analysis of ZFY gene expression by sequential RNA- and DNA-FISH on spermatocytes. We hypothesized that the meiotic arrest observed in this boar might be due to the silencing of critical autosomal genes and/or the reactivation of some sex chromosome genes.
Molecular and Cytogenetic Studies in a Case of XX SRY-Negative Sex Reversal in an Arabian Horse
Authors: Ciotola F. , Albarella S. , Pasolini M.P. , Auletta L. , Esposito L. , Iannuzzi L. , Peretti V.
Published: November 2011

An 18-month-old Arabian foal characterized by a stallion-like appearance was submitted for cytogenetic and molecular genetics examinations due to abnormalities of external genitalia and the presence of ovotestis-like structures in the abdominal cavity. By RB-banding the animal showed the normal female equine karyotype (2n = 64,XX). Molecular analysis revealed the absence of the SRY and ZFY genes and the presence of ZFX, a typical female equine condition. The entire RSPO1 coding region was examined to exclude its involvement. Although a SNP was found in exon 3, it was not responsible for an amino acid substitution.
Intra-Abdominal Pulmonary Sequestration: A Case Report and Literature Review
Authors: Liu Liangren , Han Ping , Zhu Yuchun , Gong Jing , Xu Yong , Wei Xin , Li Xiang , Dong Qiang , Wei Qiang
Published: November 2011

Pulmonary sequestration is a rare congenital malformation mostly located in the thorax, while intra-abdominal pulmonary sequestration is an extremely rare type of pulmonary sequestration usually diagnosed during the first 6 months of life. Only 1 case of intra-abdominal pulmonary sequestration in a patient older than 60 years has been reported in the current literature. It is difficult to differentiate an intra-abdominal pulmonary sequestration from other retroperitoneal tumors. A definitive diagnosis is always made by histologi- cal examination. Intra-abdominal pulmonary sequestration commonly responds well to surgical resection and is associated with excellent results and prognosis. The authors present the case of a 74-year-old asymptomatic man with a retroperitoneal mass which was completely excised and revealed by histopathological study to be an intra-abdominal pulmonary sequestration.
Results of a BoNT/A Antibody Study in Children and Adolescents after Onabotulinumtoxin A (Botox®) Detrusor Injection
Authors: Schulte-Baukloh H. , Herholz J. , Bigalke H. , Miller K. , Knispel H.H.
Published: November 2011

Background: Onabotulinumtoxin A (OnaBoNT/A, Botox®) is effective in the treatment of neurogenic detrusor overactivity, however this therapy can fail. In a prospective study, we analyzed patient serum for BoNT/A antibodies (BoNT/A-AB) as a possible cause of therapy failure. Methods: 17 patients (average age 14.5 years) who had neurogenic detrusor overactivity were admitted for repeated OnaBoNT/A injection into the detrusor muscle. We analyzed their serum for BoNT/A-AB. The clinical findings were correlated with the incidence of BoNT/A-AB. Results: Positive BoNT/A-AB were clearly or marginally determined in 6 patients. Therapy had failed in all 6. In 4 of the 6, therapy might have failed because of a low-compliance bladder (3 patients) or tethered-cord syndrome (1), but BoNT/A-AB were found as the only possible cause in 2 patients. Thus, the incidence of BoNT/A-AB in the 17 patients was 35%, and the antibodies were clinically significant in 12%. All patients with BoNT/A-AB had a history of recurrent urinary tract infections. Conclusions: Patients who show a failure of therapy after OnaBoNT/A injections for which no other causes can be determined should have their serum checked for BoNT/A-AB. Recurrent urinary tract infection might be a predisposing factor for BoNT/A-AB.
Hospital and Community Validation of a Screening Instrument for Detection of Neurodisability in Indian Children Aged 6 Months to 2 Years
Authors: Bhave Anupama , Bhargava Roli , Rizvi Anwar , Rizvi Talat , Kumar Rashmi
Published: November 2011

Objective: To develop and validate a screening instrument for neurological disorders in children aged 6 months to 2 years in the community. Methods: A comprehensive parent-administered instrument was developed to screen for hearing, vision, seizures, motor deficits and development in Indian children aged 6–24 months. This was tested for reliability and validated in the hospital setting by comparing with pre-decided gold standards. It was then used in a community survey in a two-phase design in which all screen positives and a random sample of screen negatives were validated. Result: The screening instrument had overall sensitivity, specificity and positive predictive values of 95.8, 68.1 and 76.1%, respectively, in the hospital setting. In the field setting, these figures changed to 95.4, 51.8 and 20.6%, respectively. The reasons for this are discussed. Conclusion: Community surveys must use a two-phase design to get the true prevalence. A falsely high prevalence will be computed if only a single-phase design or hospital validation is used.
Polymyalgia Rheumatica and the Risk of Stroke: A Three-Year Follow-Up Study
Authors: Kang Jiunn-Horng , Sheu Jau-Jiuan , Lin Herng-Ching
Published: November 2011

Background: Polymyalgia rheumatica (PMR) is a relatively common rheumatic disease, particularly in the elderly. Vasculitis is associated with PMR and theoretically makes such patients susceptible to vascular events such as stroke. This study aims to explore the frequency and risk of stroke among patients with PMR through a population-based case-controlled study. Methods: The study included 781 patients with PMR from the Taiwan Longitudinal Health Insurance Database between 2001 and 2005. We randomly extracted 3,905 other patients, matched with the study group in terms of sex and age, as a control population. Each subject was individually tracked for a three-year period to identify those who had strokes. Stratified Cox proportional hazard regression was employed to evaluate the risk of stroke, after adjusting for socio-demographic characteristics and comorbidities. Results: We found that 386 out of 4,686 sampled patients (8.24%) had stroke during the three-year follow-up period, including 113 patients with PMR (14.47% of the PMR group) and 273 controls (6.98% of the control group). The stratified Cox proportional hazard regression showed that the adjusted hazard ratio of stroke for patients with PMR was 2.09 times that of controls (95% CI = 1.63–2.66, p <0.001), after adjusting for socio-demographic characteristics and comorbidities. Conclusions: PMR was associated with a significantly higher risk of stroke in the three-year follow-up period. Physicians should be aware of this potential association in clinical settings.