bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Management of Metastatic Urothelial Carcinoma with Gemcitabine and Paclitaxel Chemotherapy in a Hemodialysis Patient
Authors: Ide Hiroki , Satou Atsuko , Hoshino Katsura , Yasumizu Yota , Uchida Yasumitsu , Tasaka Yuji , Masuda Takeshi
Published: September 2011

This is the first report of urothelial carcinoma (UC) in a hemodialysis (HD) patient treated with almost the same doses of gemcitabine and paclitaxel (GP) as those administered to patients with normal renal function. There have been some reports of UC treated with cisplatin-based chemotherapy in HD patients. However, there have only been a few reports of UC treated with GP in HD patients. Furthermore, to our knowledge, there has not been any report of UC in a HD patient treated with almost the same doses of GP as those in patients with normal renal function. Following cystectomy for bladder cancer, a 73-year-old woman undergoing HD developed lung metastasis and received combination chemotherapy with almost the same doses of GP as those in patients with normal renal function. After three cycles were completed, metastatic tumors disappeared and there has not been any recurrence or metastasis for 1 year to date. Furthermore, there were no grade 3 or 4 adverse effects during this treatment.
The Value of Contrast-Enhanced Transrectal Ultrasound in Predicting the Nature of Prostate Diseases and the Gleason Score of Prostate Cancer by a Subjective Blood Flow Grading Scale
Authors: Zhao Hong Wei , Luo Jun Hang , Xu Hui Xiong , Wang Dao Hu , Lai Ying Rong , Chen Mian Ni , Lv Jian Yao , Xie Xiao Yan , Lu Ming De , Chen Wei
Published: September 2011

Objectives: To investigate the value of contrast-enhanced transrectal ultrasound (CETRUS) in predicting the nature of prostate diseases and prostate cancer Gleason score. Methods: 106 patients suspected of prostate cancer were evaluated with CETRUS followed by systematic biopsy. Prostate blood flow of CETRUS was graded using a subjective 5-point scale. The relationships between ultrasound findings and biopsy outcomes, as well as prostate cancer Gleason score were analyzed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of CETRUS. Results: Biopsy revealed prostate cancer in 43 of 106 patients. The proportions of malignant histology in the groups with CETRUS scores of 1–5 were 0% (0/10), 8.3% (2/24), 31.7% (13/41), 88.9% (16/18) and 92.3% (12/13), respectively. The rate of prostate cancer with a Gleason score ≧7 in the groups with a CETRUS score of 2–5 were 0% (0/2), 15.4% (2/13), 37.5% (6/16) and 91.7% (11/12), respectively. The blood flow grading scale correlated with pathological outcomes and Gleason score significantly (r = 0.66, p < 0.001; and r = 0.61, p < 0.001, respectively). ROC analysis showed the area under the ROC curve to be 0.87. Conclusions: CETRUS-based blood flow grading scale is a reliable tool for predicting the pathological outcome of prostate diseases and prostate cancer Gleason score noninvasively.
Putative Biomarker Genes for Grading Clear Cell Renal Cell Carcinoma
Authors: Maruschke M. , Koczan D. , Reuter D. , Ziems B. , Nizze H. , Hakenberg O.W. , Thiesen H.-J.
Published: September 2011

Objective: The initial objective of this renal cancer study was to identify gene sets in clear cell renal cell carcinoma (ccRCC) to support grading of ccRCC histopathology. Materials and Methods: Preselected ccRCC tumor tissues of grade 1 (G1, n = 14) and grade 3 (G3, n = 15) as well es 14 normal kidney tissues thereof were subjected to microarray expression analysis using Human Genome U133 Plus 2.0 Array. Event ratio scoring, hierarchical clustering and principal component analysis were used to determine gene sets that distinguish expression profiles from normal kidney tissue, G1 and G3 tumor tissues. Results: An initial set of 73 genes provided seven gene subclusters (SC01 to SC07) that distinguish RNA expression profiles from G1, G3 tumor and normal kidney tissues. A ranked list of 24 genes was determined that separated G1 from G3 tumors in high concordance with histopathological grading confirmed by immunohistochemical analysis of ceruloplasmin protein expression. Conclusion: A final set of 24 genes has been determined awaiting further validation on the RNA as well as on the protein level by studying an additional cohort of ccRCC patients. A reliable separation of G1 and G3 tumor grades will be instrumental to foster and direct the administration of upcoming targeted therapeutics of ccRCC tumors in a more predictive and reliable manner.
Gynecomastia as a First Clinical Sign of Nonseminomatous Germ Cell Tumor
Authors: Kolitsas N. , Tsambalas S. , Dimitriadis F. , Baltogiannis D. , Vlachopoulou E. , Vappa S. , Giannakis D. , Tsounapi P. , Takenaka A. , Sofikitis N.
Published: September 2011

Introduction: Gynecomastia is a common clinical sign in several diseases. In this report we present a case of gynecomastia with underlying testicular tumor which remained misdiagnosed for a prolonged period of time. Case Report: A 16-year-old adolescent noticed unilateral painless swelling of the left breast. He was referred to the Department of General Surgery and examined by a breast surgeon. A diagnosis of mastitis was made and a treatment with an oral antibiotic drug began. After failure of the initial antibiotic treatment, the patient was referred to the Department of Endocrinology and left testicular cancer was diagnosed. Unilateral high inguinal orchidectomy and subsequent chemotherapeutic treatment were performed. Conclusion: Primary care physicians should be aware of the possibility of a concomitant presence of gynecomastia and testicular cancer. We suggest a physical examination as well as a laboratory investigation, and testicular ultrasonography of the testes in all patients with gynecomastia.
Oxytocin Immunoreactivity in the Corpus Cavernosum of Patients with Erectile Dysfunction
Authors: Tarhan Fatih , Faydacı Gökhan , Gül Aylin Ege , Kuyumcuoğlu Uğur , Eryıldırım Bilal
Published: September 2011

Objectives: Oxytocin is released by the posterior pituitary gland during male orgasm. Additionally, the presence of an oxytocin receptor gene and protein expression in human corpus cavernosum is demonstrated, and it has contractile activity on the smooth muscle of the animal and human corpus cavernosum in vitro. The aim of this study was to investigate the immunoreactivity of oxytocin in corpus cavernosum of patients with organic erectile dysfunction and to compare it with healthy controls. Methods: Cavernous biopsies were obtained from 31 patients with erectile dysfunction and 11 patients without erectile dysfunction. Oxytocin immunohistochemistry was performed using the streptavidin-biotin immunoperoxidase staining on all cases. Intensity and proportion of stained cells were added for the immunoreactivity score. Results: The mean ages of patients with erectile dysfunction and controls were 41.47 ± 2.08 and 36.50 ± 3.35 years, respectively (p > 0.05). Oxytocin expression was detected in smooth muscle as well as in endothelial cells in both groups. The mean oxytocin immunoreactivity score values of patients with erectile dysfunction and controls were also 2.16 ± 0.12 and 2.30 ± 0.21, respectively (p > 0.05). There was no significant difference in immunoreactivity scores both in arterial and cavernosal failure and also in smoker and nonsmoker groups (p > 0.05). Immunoreactivity scores were not statistically significantly different between patients with concomitant medical disorders and patients with no other medical disorder (p > 0.05). Conclusion: We detected oxytocin immunoreactivity in male corpus cavernosum, but staining was not different between patients with erectile dysfunction and controls. However, further studies are necessary to reach a final conclusion regarding the effects of oxytocin on corpus cavernosum.
Clinical and Radiological Characteristics of 22 Children with SHOX Anomalies and Familial Short Stature Suggestive of Léri-Weill Dyschondrosteosis
Authors: Salmon-Musial Anne-Sophie , Rosilio Myriam , David Michel , Huber Céline , Pichot Emmanuel , Cormier-Daire Valérie , Nicolino Marc
Published: September 2011

Aims: To describe genetic, clinical, anthropometric and radiological characteristics of 22 children with SHOX gene anomalies and familial short stature suggestive of Léri-Weill dyschondrosteosis. Methods: Monocentric retrospective observational study. Results: Six children (27%) presented with deletions located downstream of SHOX (mean height –1.4 ± 0.9 SDS) and 16 (68%) with either deletions encompassing SHOX, intragenic deletions or point mutations of SHOX (mean patient height for the 3 latter types of anomalies: –2.6 ± 0.8 SDS). In our sample, the two most frequently observed dysmorphic signs were clinical and/or radiological Madelung deformity (86%) and high arched palate (77%). Half the girls were born small for gestational age. Sixteen children treated with recombinant growth hormone had an increase in height from –2.7 ± 0.7 to –1.4 ± 0.7 SDS. Four children achieved adult height (–2.0 ± 0.9 SDS) with a gain over baseline height of 1.0 ± 0.5 SDS after a mean treatment duration of 5.8 ± 2.1 years. Conclusion: Patients shared common clinical, anthropometric and radiological signs but their height deficit varied, depending on the type of the SHOX gene anomaly. Due to the small size of our sample, our findings need to be confirmed in a larger population of patients.
Endothelial Nitric Oxide Synthase T(–786)C Polymorphism in Children and Adolescents with Type 1 Diabetes and Impaired Endothelium-Dependent Dilatation
Authors: Battelino Nina , Sebestjen Miran , Keber Irena , Blagus Rok , Hovnik Tinka , Bratina Natasa , Battelino Tadej
Published: September 2011

Background/Aims: This study aimed to investigate the association of endothelial nitric oxide synthase (eNOS) polymorphisms with impaired endothelium-dependent dilatation (EDD) in a cohort of children and adolescents with type 1 diabetes. Methods: Ninety-seven children and adolescents with type 1 diabetes underwent ultrasound assessment of EDD. The association of various factors with EDD was analyzed with multivariate linear regression analysis. Genotypes were determined for the eNOS T(–786)C and 4ab polymorphisms, and their association with EDD was tested with logistic regression analysis. Results: Thirty-three percent of children had impaired EDD. EDD was independently associated with A1c (p = 0.0005) and inversely correlated with A1c (p = 0.0037, OR = 2.14) using logistic regression analysis. The presence of any C allele at eNOS (–786) was significantly more frequent in patients with impaired EDD (OR = 2.97, 95% CI = 1.08–8.87, p = 0.03). Logistic regression analysis revealed OR of 3.09 for impaired EDD for patients with any C allele as compared to TT patients when controlling for all other covariates (p = 0.048). Conclusion:A third of children and adolescents with type 1 diabetes had impaired EDD independently associated with A1c. The presence of any C at (–786) of the eNOS gene conveyed a significantly increased independent risk for impaired EDD.
Telomeres in Trisomy 21 Amniocytes
Authors: Sukenik-Halevy R. , Biron-Shental T. , Sharony R. , Fejgin M.D. , Amiel A.
Published: September 2011

Individuals with trisomy 21 have an increased risk of developing leukemia and premature dementia. They also have a higher rate of telomere loss. The aim of the study was to compare telomere length and the hTERC gene copy number, which encodes the telomerase RNA subunit, in amniocytes of trisomy 21 conceptions and normal pregnancies. A quantitative fluorescence-in-situ protocol (Q-FISH) was used to compare telomere length in amniocytes cultured from 11 trisomy 21 conceptions and from 14 normal pregnancies. Quantification was conducted using novel computer software. Fluorescence in situ hybridization (FISH) was used to assess the percentage of cells with additional copies of hTERC. We found that the immunofluorescence intensity, which represents telomere length, was significantly lower in amniocytes from trisomy 21 conceptions compared to the control group. The trisomy 21 group had a higher number of cells with additional copies of hTERC. This observation could be one of the cytogenetic parameters that represent a state of genetic instability and might play a role in the pathomechanism of typical features of Down syndrome, such as dementia and malignancy.
A Method for Generating Selective DNA Probes for the Analysis of C-Negative Regions in Human Chromosomes
Authors: Morozkin E.S. , Loseva E.M. , Karamysheva T.V. , Babenko V.N. , Laktionov P.P. , Vlassov V.V. , Rubtsov N.B.
Published: September 2011

Linker-adapter polymerase chain reaction (LA-PCR) is among the most efficient techniques for whole genome DNA amplification. The key stage in LA-PCR is the hydrolysis of a DNA sample with restriction endonucleases, and the choice of a restriction endonuclease (or several endonucleases) determines the composition of DNA probes generated in LA-PCR. Computer analysis of the localization of the restriction sites in human genome has allowed us to propose an efficient technique for generating DNA probes by LA-PCR using the restriction endonucleases HaeIII and RsaI. In silico hydrolysis of human genomic DNA with endonucleases HaeIII and RsaI demonstrate that 100- to 1,000-bp DNA fragments are more abundant in the gene-rich regions. Applying in situ hybridization to metaphase chromosomes, we demonstrated that the produced DNA probes predominantly hybridized to the C-negative chromosomal regions, whereas the FISH signal was almost absent in the C-positive regions. The described protocol for generating DNA probes may be successfully used in subsequent cytogenetic analysis of the C-negative chromosomal regions.
Molecular and Cellular Evidence for the Alternative Lengthening of Telomeres (ALT) Mechanism in Chicken
Authors: O’Hare T.H. , Delany M.E.
Published: September 2011

Telomere maintenance is an important genetic mechanism controlling cellular proliferation. Normally, telomeres are maintained by telomerase which is downregulated upon cellular differentiation in most somatic cell lineages. Telomerase activity is upregulated in immortalized cells and cancers to support an infinite lifespan and uncontrolled cell growth; however, some immortalized and transformed cells lack telomerase activity. Telomerase-negative tumors and immortalized cells utilize an alternative mechanism for maintaining telomeres termed alternative lengthening of telomeres (ALT). This research explored evidence for the ALT pathway in chicken cell lines by studying nontransformed immortalized cell lines (DF-1 and OU2) and comparing them to a normal (mortal) cell line and a transformed cell line (DT40). The research consisted of molecular and cellular analyses including profiling of telomeric DNA (array sizing and total content), telomerase activity, and expression of genes involved in the telomerase, recombination, and ALT pathways. In addition, an immunofluorescence analysis for an ALT marker, i.e. ALT-associated promyelocytic leukemia bodies (APBs), was conducted. Evidence for ALT was observed in the telomerase-negative immortalized cell lines. Additionally, the APB marker was also found in the other cell systems. The attributes of the chicken provide an additional vertebrate model for investigation of the ALT pathway.
Cytogenetic Analysis of CpG-Oligonucleotide DSP30 plus Interleukin-2-Stimulated Canine B-Cell Lymphoma Cells Reveals the Loss of One X Chromosome as the Sole Abnormality
Authors: Reimann-Berg N. , Murua Escobar H. , Kiefer Y. , Mischke R. , Willenbrock S. , Eberle N. , Nolte I. , Bullerdiek J.
Published: September 2011

Human and canine lymphoid neoplasms are characterized by non-random cytogenetic abnormalities. However, due to the low mitotic activity of the B cells, cytogenetic analyses of B-cell lymphoid proliferations are difficult to perform. In the present study we stimulated canine B-cell lymphoma cells with the immunostimulatory CpG-oligonucleotide DSP30 in combination with interleukin-2 (IL-2) and obtained an adequate number of metaphases. Cytogenetic analyses revealed the loss of one X chromosome as the sole cytogenetic aberration. Chromosome analysis of the corresponding blood showed a normal female karyotype. Monosomy X as the sole clonal chromosomal abnormality is found in human hematopoietic malignancies as well, thus the dog may serve as a promising animal model.
Frequent Loss of the BLID Gene in Early-Onset Breast Cancer
Authors: Cavalli L.R. , Noone A.-M. , Makambi K.H. , Rone J.D. , Kasid U.N. , Haddad B.R.
Published: September 2011

The BH3-like motif-containing inducer of cell death (BLID) is an intronless gene localized on 11q24.1. Loss of that region has frequently been reported in early-onset breast cancer and is significantly associated with poor prognosis and reduced survival. Downregulation of BLID is associated with younger age, triple-negative phenotype, and reduced disease-free and overall survival of breast cancer patients. In this study, we investigated allelic loss of BLID in breast tumor specimens from 78 women with invasive breast cancer using 2 dinucleotide polymorphic markers closely linked to the BLID gene (no intragenic marker for BLID is available). Seventy-three cases were informative. Overall, loss of heterozygosity (LOH) at the BLID locus was detected in 32% of the informative cases (23/73). However, in patients 40 years old and younger, LOH was detected in 50% of the cases (9/18). Patients aged 40 years and younger were significantly more likely to experience LOH than those aged 41–55 years (p = 0.04). Specifically, the odds of BLID loss for patients aged 40 years and younger were 3.7 times the odds of loss for patients aged 41–55 years (95% CI, 1.1–13). Our findings suggest a tumor suppressor role of the BLID gene in early-onset breast cancer.
Two Candidate Genes (FTO and INSIG2) for Fat Accumulation in Four Canids: Chromosome Mapping, Gene Polymorphisms and Association Studies of Body and Skin Weight of Red Foxes
Authors: Grzes M. , Szczerbal I. , Fijak-Nowak H. , Szydlowski M. , Switonski M.
Published: September 2011

Fat accumulation is a polygenic trait which has a significant impact on human health and animal production. Obesity is also an increasingly serious problem in dog breeding. The FTO and INSIG2 are considered as candidate genes associated with predisposition for human obesity. In this report we present a comparative genomic analysis of these 2 genes in 4 species belonging to the family Canidae – the dog and 3 species which are kept in captivity for fur production, i.e. red fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci by FISH and compared the entire coding sequence of INSIG2 and a fragment of the coding sequence of FTO. The FTO gene was assigned to the following chromosomes: CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24–25 (Chinese raccoon dog), while the INSIG2 was mapped to CFA19q17, VVU5p14, ALA24q15 and NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in INSIG2 and 13 in FTO) and among them 2 were missense substitutions in the dog (23C/T, Thr>Met in the FTO gene and 40C/A, Arg>Ser in INSIG2). The distribution of these 2 SNPs was studied in 14 dog breeds. Two synonymous SNPs, one in the FTO gene (–28T>C in the 5′-flanking region) and one in the INSIG2 (10175C>T in intron 2), were used for the association studies in red foxes (n = 390) and suggestive evidence was observed for their association with body weight (FTO, p < 0.08) and weight of raw skin (INSIG2, p < 0.05). These associations indicate that both genes are potential candidates for growth or adipose tissue accumulation in canids. We also suggest that the 2 missense substitutions found in dogs should be studied in terms of genetic predisposition to obesity.
Karyotype Evolution of Eulipotyphla (Insectivora): The Genome Homology of Seven Sorex Species Revealed by Comparative Chromosome Painting and Banding Data
Authors: Biltueva L. , Vorobieva N. , Perelman P. , Trifonov V. , Volobouev V. , Panov V. , Ilyashenko V. , Onischenko S. , O’Brien P. , Yang F. , Ferguson-Smith M. , Graphodatsky A.
Published: September 2011

The genus Sorex is one of the most successful genera of Eulipotyphla. Species of this genus are characterized by a striking chromosome variability including XY1Y2 sex chromosome systems and exceptional chromosomal polymorphisms within and between populations. To study chromosomal evolution of the genus in detail, we performed cross-species chromosome painting of 7 Sorex species with S. granarius and S. araneus whole-chromosome probes and found that the tundra shrew S. tundrensis has the most rearranged karyotype among these. We reconstructed robust phylogeny of the genus Sorex based on revealed conserved chromosomal segments and syntenic associations. About 16 rearrangements led to formation of 2 major Palearctic groups after their divergence from the common ancestor: the S. araneus group (10 fusions and 1 fission) and the S. minutus group (5 fusions). Further chromosomal evolution of the 12 species inside the groups, including 5 previously investigated species, was accompanied by multiple reshuffling events: 39 fusions, 20 centromere shifts and 10 fissions. The rate of chromosomal exchanges upon formation of the genus was close to the average rate for eutherians, but increased during recent (about 6–3 million years ago) speciation within Sorex. We propose that a plausible ancestral Sorex karyotype consists of 56 elements. It underwent 20 chromosome rearrangements from the boreoeutherian ancestor, with 14 chromosomes retaining the conserved state. The set of genus-specific chromosome signatures was drawn from the human (HSA)-shrew comparative map (HSA3/12/22, 8/19/3/21, 2/13, 3/18, 11/17, 12/15 and 1/12/22). The syntenic association HSA4/20, that was previously proposed as a common trait of all Eulipotyphla species, is shown here to be an apomorphic trait of S. araneus.
Sonographic Alteration of Lenticular Nucleus in Focal Task-Specific Dystonia of Musicians
Authors: Walter Uwe , Buttkus Franziska , Benecke Reiner , Grossmann Annette , Dressler Dirk , Altenmüller Eckart
Published: September 2011

Background/Aims: In distinct movement disorders, transcranial sonography detects alterations of deep brain structures with higher sensitivity than other neuroimaging methods. Lenticular nucleus hyperechogenicity on transcranial sonography, thought to be caused by increased local copper content, has been reported as a characteristic finding in primary spontaneous dystonia. Here, we wanted to find out whether deep brain structures are altered in task-specific dystonia. Methods: The frequency of sonographic brainstem and basal ganglia changes was studied in an investigator-blinded setting in 15 musicians with focal task-specific hand dystonia, 15 musicians without dystonia, and 15 age- and sex-matched nonmusicians without dystonia. Results: Lenticular nucleus hyperechogenicity was found in 12 musicians with task-specific dystonia, but only in 3 nondystonic musicians (Fisher’s exact test, p = 0.001) and 2 nonmusicians (p < 0.001). The degree of lenticular nucleus hyperechogenicity in affected musicians correlated with age, but not with duration of music practice or duration of dystonia. In 2 of 3 affected musicians with normal echogenic lenticular nucleus, substantia nigra hyperechogenicity was found. Conclusions: Our findings support the idea of a pathogenetic link between primary spontaneous and task-specific dystonia. Sonographic basal ganglia alteration might indicate a risk factor that in combination with extensive fine motor training promotes the manifestation of task-specific dystonia.
Patient-Reported Outcomes in Left Ventricular Assist Device Therapy
Authors: Brouwers Corline , Denollet Johan , de Jonge Nicolaas , Caliskan Kadir , Kealy Jennifer , Pedersen Susanne S.
Published: September 2011

Background—

Technological advancements of left ventricular assist devices (LVAD) have created today's potential for extending the lives of patients with end-stage heart failure. Few studies have examined the effect of LVAD therapy on patient-reported outcomes (PROs), such as health status, quality of life, and anxiety/depression, despite poor PROs predicting mortality and rehospitalization in patients with heart failure. In this systematic review, we provide an overview of available evidence on the impact of LVAD therapy on PROs and discuss recommendations for clinical research and practice.

Methods and Results—

A systematic literature search identified 16 quantitative studies with a sample size ≥10 (mean±SD age=50.1±12.6 years) that examined the impact of LVAD therapy on PROs using a quantitative approach. Initial evidence suggests an improvement in health status, anxiety, and depression in the first few months after LVAD implantation. However, PRO scores of patients receiving LVAD therapy are still lower for physical, social, and emotional functioning compared with transplant recipients. These studies had several methodological shortcomings, including the use of relatively small sample sizes, and only a paucity of studies focused on anxiety and depression.

Conclusions—

There is a paucity of studies on the patient perspective of LVAD therapy. To advance the field of LVAD research and to optimize the care of an increasingly growing population of patients receiving LVAD therapy, more well-designed large-scale studies are needed to further elucidate the impact of LVAD therapy on PROs.
Transapical Aortic Valve Implantation
Authors: Kempfert Jörg , Rastan Ardawan , Holzhey David , Linke Axel , Schuler Gerhard , van Linden Arnaud , Blumenstein Johannes , Mohr Friedrich Wilhelm , Walther Thomas
Published: September 2011

Background—

Transapical aortic valve implantation has evolved to a reproducible therapeutic option for high-risk patients. The aim of the present study was to evaluate our learning experience over 4 years and to analyze outcome-related risk factors.

Methods and Results—

A total of 299 patients who received transapical aortic valve implantation between February 2006 and January 2010 with the Edwards SAPIEN transcatheter prosthesis were analyzed according to early experience (EE; patients 1 to 150) and recent experience (RE; patients 151 to 299). Patients consistently demonstrated high risk scores, and major perioperative parameters were comparable between the 2 groups. RE patients had a significantly higher logistic EuroSCORE (RE 33.2±17.2, EE 29.4±14;
P
=0.039) but a significantly lower STS (Society of Thoracic Surgeons) score (RE 11.4±7.5, EE 13.5±7.8;
P
=0.019). Use of contrast dye (EE 104±78 mL, RE 93±46 mL) and the need to perform a balloon redilation were significantly reduced in the RE group. Thirty-day mortality decreased from 11.3% to 6.0%, and 1-year mortality improved significantly from 30.7% (EE) to 21.5% in the RE patients (
P
=0.047). Multivariate logistic regression analysis revealed reduced vital capacity (<70%) and concomitant preoperative mitral regurgitation >1+ as the only independent predictors of 30-day mortality. Classic variables such as age, logistic EuroSCORE >30%, and STS score >15% failed to predict mortality.

Conclusions—

Recent results with transapical aortic valve implantation indicate a progressive improvement in outcomes despite an unchanged patient risk profile, which reflects a significant learning curve that includes a better understanding of optimal patient selection. Classic surgical risk factors fail to predict outcome, which indicates the need for new transapical aortic valve implantation–specific risk scores.
Double Knockdown of Prolyl Hydroxylase and Factor-Inhibiting Hypoxia-Inducible Factor With Nonviral Minicircle Gene Therapy Enhances Stem Cell Mobilization and Angiogenesis After Myocardial Infarction
Authors: Huang Mei , Nguyen Patricia , Jia Fangjun , Hu Shijun , Gong Yongquan , de Almeida Patricia E. , Wang Li , Nag Divya , Kay Mark A. , Giaccia Amato J. , Robbins Robert C. , Wu Joseph C.
Published: September 2011

Background—

Under normoxic conditions, hypoxia-inducible factor (HIF)-1α is rapidly degraded by 2 hydroxylases: prolyl hydroxylase (PHD) and factor-inhibiting HIF-1 (FIH). Because HIF-1α mediates the cardioprotective response to ischemic injury, its upregulation may be an effective therapeutic option for ischemic heart failure.

Methods and Results—

PHD and FIH were cloned from mouse embryonic stem cells. The best candidate short hairpin (sh) sequences for inhibiting PHD isoenzyme 2 and FIH were inserted into novel, nonviral, minicircle vectors. In vitro studies after cell transfection of mouse C2C12 myoblasts, HL-1 atrial myocytes, and c-kit
+
cardiac progenitor cells demonstrated higher expression of angiogenesis factors in the double-knockdown group compared with the single-knockdown and short hairpin scramble control groups. To confirm in vitro data, shRNA minicircle vectors were injected intramyocardially after left anterior descending coronary artery ligation in adult FVB mice (n=60). Functional studies using MRI, echocardiography, and pressure-volume loops showed greater improvement in cardiac function in the double-knockdown group. To assess mechanisms of this functional recovery, we performed a cell trafficking experiment, which demonstrated significantly greater recruitment of bone marrow cells to the ischemic myocardium in the double-knockdown group. Fluorescence-activated cell sorting showed significantly higher activation of endogenous c-kit
+
cardiac progenitor cells. Immunostaining showed increased neovascularization and decreased apoptosis in areas of injured myocardium. Finally, western blots and laser-capture microdissection analysis confirmed upregulation of HIF-1α protein and angiogenesis genes, respectively.

Conclusions—

We demonstrated that HIF-1α upregulation by double knockdown of PHD and FIH synergistically increases stem cell mobilization and myocardial angiogenesis, leading to improved cardiac function.
Circulation
Editors' Picks
Authors:   The Editors
Published: September 2011

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the most read manuscripts published on the topic of cardiovascular surgery and transplantation in 2009 and 2010.
Land Cover Change Effects on the Climate of the La Plata Basin
Authors: Lee Seung-Jae , Berbery Ernesto Hugo
Published: September 2011

Deforestation and replacement of natural pastures by agriculture have become a common practice in the La Plata River basin in South America. The changes in land cover imply changes in the biophysical properties of the land surface, with possible impacts on the basin’s hydroclimate. To help understand to what extent the climate could be affected, and through which processes, ensembles of seasonal simulations were prepared using the Weather Research and Forecasting Model for a control case and a scenario assuming an expansion of the agricultural activities to cover the entire basin. The La Plata River basin shows different climate responses to the land cover changes depending on the region. The northern part of the basin, where forests and savanna were replaced by crops, experiences an overall increase in albedo that leads to a reduction of sensible heat flux and near-surface temperature. A reduction of surface roughness length leads to stronger low-level winds that, in turn, favor a larger amount of moisture being advected out of the northern part of the basin. The result is a reduction of the vertically integrated moisture flux convergence (VIMFC) and, consequently, in precipitation. In the southern part of the basin, changes from grasslands to crops reduce the albedo and thus increase the near-surface temperature. The reduction in surface roughness length is not as large as in the northern sector, reducing the northerly moisture fluxes and resulting in a net increase of VIMFC and, thus, in precipitation. Notably, advective processes modify the downstream circulation and precipitation patterns over the South Atlantic Ocean.
Explaining the willingness of public professionals to implement new policies: a policy alienation framework
Authors: Tummers Lars
Published: September 2011

Nowadays, many public policies focus on economic values, such as efficiency and client choice. Public professionals often show resistance to implementing such policies. We analyse this problem using an interdisciplinary approach. From public administration, we draw on the policy alienation concept, which consists of five dimensions: strategic powerlessness, tactical powerlessness, operational powerlessness, societal meaninglessness and client meaninglessness. These are considered as factors that influence the willingness of professionals to implement policies (change willingness — a concept drawn from the change management literature). We test this model in a survey among 478 Dutch healthcare professionals implementing a new reimbursement policy. The first finding was that perceived autonomy (operational powerlessness) significantly influenced change willingness, whereas strategic and tactical powerlessness were not found to be significant. Second, both the meaninglessness dimensions proved highly significant. We conclude that clarifying the value of a policy is important in getting professionals to willingly implement a policy, whereas their participation on the strategic or tactical levels seems less of a motivational factor. These insights help in understanding why public professionals embrace or resist the implementation of particular policies.

Points for practitioners

Policymakers develop public policies which, nowadays, tend to focus strongly on economic values, such as increasing efficiency or offering citizens the opportunity to choose among suppliers of public services. Public professionals, who have to implement these policies, are often reluctant to do so. This study shows that the causes of this resistance are unlikely to be found in the lack of influence these professionals have in the shaping of the policy at the national or organizational level. Rather, professionals might resist implementing policies because they do not see them as meaningful for society, or for their own clients. Therefore, policymakers should focus on this perceived meaninglessness and adopt ways to counter this, for example by intensively communicating the value associated with a policy.
Employment policy confronted with new patterns of governance centred on coordination and performance
Authors: Jacob Steve , Genard Jean-Louis
Published: September 2011

At both the global and local levels, employment policy currently constitutes one of the major issues confronted by governments faced with economic crises and globalization. The success of these policies depends, in particular, on their ability to link together initiatives undertaken not only at different levels of power, but also within a single level between multiple actors that (more or less) have prerogatives in matters of employment policy. This domain of public policy constitutes a unique space in which to analyse the developments and circulation of principles promoted by advocates of two new patterns of governance: New Public Management and the Open Method of Coordination. On the basis of a qualitative analysis conducted with employment policy actors in the Brussels-Capital Region (BCR), this article studies the difficulties these actors come up against when faced with the implementation expectations of new managerial demands, as well as coordination demands that force an increasingly flexible economic landscape and an increasingly complex institutional landscape onto these actors. Enumerating the difficulties encountered, the article also updates the strategies put into place by the actors themselves to address the often severe diagnoses that are made of the situations to which they are subject. This article also constitutes a contribution to the clarification of both the favourable and undesirable conditions for the establishment of new forms of governance within public policy.

Points for practitioners

In most countries, employment policies figure among the highest priorities. When new initiatives in this sector need to be elaborated and implemented, practitioners attempt to balance a wide variety of opinions, focusing on the coherence of their decisions and actions. In the context of performance management, practitioners are also required to demonstrate the success of their public interventions. In Europe, these expectations are exacerbated by the requirements of the Open Method of Coordination and New Public Management. The appropriation of these two patterns of governance depends on a given practitioner’s receptivity regarding the perceived utility of these patterns to their particular work.
Analysis of Human Auricular Cartilage to Guide Tissue‐Engineered Nanofiber‐Based Chondrogenesis
Authors: Dahl John P. , Caballero Montserrat , Pappa Andrew K. , Madan Gitanjali , Shockley William W. , van Aalst John A.
Published: September 2011

Objective

Nanofiber‐supported, in vitro–generated cartilage may represent an optimal starting material for the development of a cartilage implant for use in microtia reconstruction. To do so, the authors aim to first characterize the molecular composition of endogenous auricular cartilage and determine if human umbilical cord mesenchymal stem cells (hUCMSCs) can be differentiated into cartilage in vitro.

Study Design

Prospective, controlled.

Setting

Academic research laboratory.

Subjects and Methods

Human ear cartilage from normal adults, pediatric patients with microtia, and pediatric patients with preauricular appendages (n = 2) was analyzed for collagens I, II, and X and elastin expression. In parallel, hUCMSCs were cultured on either polycaprolactone (PCL) or D, L‐lactide‐co‐glycolic acid (PLGA) nanofiber scaffolds for 21 days under chondrogenic conditions. Cells were harvested for histologic, biochemical, and quantitative polymerase chain reaction analysis. Control cells were grown under both chondrogenic and nonchondrogenic conditions in the absence of nanofiber scaffolds.

Results

Histological analysis of human ear cartilage revealed similar levels and distribution of collagens I and X and elastin. Collagen II was not highly expressed in the microtia samples. hUCMSC cultures stained positively for glycosaminosglycans (GAG) and sulfated proteoglycans. Compared to control cells, hUCMSCs grown on PLGA nanofiber scaffolds had a higher differentiation index (P ≤. 012) and higher levels of collagen X mRNA expression (P ≤. 006).

Conclusion

These data provide information regarding the composition of endogenous ear cartilage and suggest that hUCMSCs grown on PLGA nanofiber scaffolds may represent an optimal starting material for the development of a cartilage implant for use in microtia reconstruction.
Retrospective: Reflections on the OCMS International Programmes Project (1997–2007)
Authors: Farr Bernard C
Published: September 2011

This paper offers a descriptive and critical retrospective of an initiative of the Oxford Centre for Mission Studies (OCMS) to create a co-operative international network of partnering institutions under the aegis of The International Fellowship of Mission Theologians (INFEMIT). It focuses on the years 1997–2007.
Mariner, renegade and castaway: Chris Braithwaite, seamen’s organiser and Pan-Africanist
Authors: Høgsbjerg Christian
Published: September 2011

The author explores the political life in Britain of black Barbadian Chris Braithwaite (c.1885–1944), also known as ‘Chris Jones’, a hitherto overlooked, yet outstanding figure in the history of the twentieth-century Black and Red Atlantic. As leader of the Colonial Seamen’s Association and an important ‘class struggle Pan-Africanist’, he was the lynchpin of an anti-colonial maritime network in interwar London. Through his work in the Communist party in the early 1930s and then in the International African Friends of Ethiopia and the International African Service Bureau, led by George Padmore and C. L. R. James, Braithwaite’s talents as organiser, speaker and writer came to the fore.
Sketches for a Film Which Never Happened
Authors: Menon Bindu
Published: September 2011

Ramavarma Appan Thampuran’s unsuccessful attempt to make a film in Malayalam from his novel Bhootarayar (1929) has left behind sketches of scenes and characters by himself and an unknown local artist, now preserved at the Appan Thampuran Library of the Kerala Sahitya Academy. They illustrate Thampuran’s bid to depict an imagined past and compose an ethnohistory of communities, and are significant for the history of visual arts and cinema in the region. The sketches evoke studio and photo-graphic portraiture, visual typologies and the cinematic close-up, and seem to negotiate the complex exchange between linguistic narrative, cinematic spectacle, and imaginary histories.
Transaxillary Subpectoral Augmentation Mammaplasty: A Single Surgeon’s 20-Year Experience
Authors: Huang Georgeanna J , Wichmann Julian L , Mills Dan C
Published: September 2011

Background

Transaxillary subpectoral augmentation mammaplasty (TASPA) is not widely accepted due to perceived limitations in pocket access, visualization, control, and subsequent risk for postoperative complications. Current published data do little to substantiate or refute those claims.

Objective

A retrospective chart review of a single surgeon’s 20-year experience with the TASPA technique was undertaken to assess the incidence of total secondary procedures, implant-related revisions, and reoperations unrelated to the implant.

Methods

The senior author (DCM) performed 1776 primary TASPA procedures from January 1989 through December 2008. Of those, 94 patients did not meet inclusion criteria, leaving a total of 1682 records for analysis. Data reviewed included age, date of surgery, race, implant size and type, manufacturer, and reasons for reoperation.

Results

Average age was 32.7 ± 8.1 years (range, 16-62). Average implant size was 438.5 ± 51.5 cc (range, 270-630). Implants from Allergan/Inamed/McGhan (Irvine, CA), Dow-Corning (Midland, MI), Mentor (Santa Barbara, CA), and Surgitek (Racine, PA) were inserted (n = 2094 saline, n = 1270 silicone). Mean follow-up time was 37.9 ± 45.4 months (range, one month to 19.8 years). Excluding staged mastopexies and treatment for breast cancer, total secondary procedures were required in 225 patients (13.4%). Implant-related revisions included malposition (2.97%), size change (2.5%), and capsular contracture (1.9%). Perioperatively, no infections occurred, and two patients (0.12%) experienced hematoma. Most reoperations (62.8%) were performed through the axilla. Comparison to published data showed an equal or lower rate of capsular contracture, hematoma, and infection with the TASPA approach.

Conclusions

Given its advantages of an inconspicuous scar, decreased infection, and decreased capsular contracture, TASPA can be safely offered to patients as an option in breast augmentation.
'Too high an ideal for the work required'? Minnie James and the Intellectual Life of the Librarian
Authors: Sakr Mona
Published: September 2011

The relationship between the librarian and the intellectual is a complex one; it depends on time and place, and is mediated by the social status of both parties. Using the life and writings of Minnie Stewart Rhodes James (1865–1903), one of the first women to enter British librarianship, this article explores the extent to which the feminization of librarianship at the turn of the twentieth century was responsible for the de-intellectualization of the profession. It also offers a means of exploring the relationship between images of the woman, the intellectual, and the librarian, a relationship that was at the centre of both international debates and individuals' lives. In this article, James's earlier writings on women librarians and their intellectual contribution (or lack thereof) will be compared with the intellectual, social, and economic equality she later espoused. These ideals were influenced by her experiences of travel, her decision to settle in the USA, and the friendships she built with librarians around the world; they demonstrate the importance of national context and international influences when considering the role of gender in the construction of archetypes and images in librarianship.
Prudence and Controversy: The New York Public Library Response to Post-War Anti-Communist Pressures
Authors: Francoeur Stephen
Published: September 2011

As the New York Public Library entered the post-war era in the late 1940s, its operations fell under the zealous scrutiny of self-styled 'redhunters' intent upon rooting out library materials and staffers deemed un-American and politically subversive. The high point of attacks upon the New York Public Library came during the years 1947–54, a period that witnessed the Soviet atomic bomb, the Berlin airlift, and the Korean War. This article charts the narrow and carefully wrought trail blazed by the Library's leadership during that period. Through a reading of materials in the Library archives, we see how political pressures were perceived and handled by Library management and staff. We witness remarkable examples of brave defence of intellectual freedom alongside episodes of prudent equivocation. At the heart of the Library's situation stood the contradictions between the principled commitments of individual Library leaders and the practical political considerations underlying the Library's viability. As a general rule, the New York Public Library did not hesitate to acquire materials considered subversive by pressure groups, but the Library frequently struck a course that sought to avoid controversy when possible.
Host-derived adiponectin is tumor-suppressive and a novel therapeutic target for multiple myeloma and the associated bone disease
Authors: Fowler Jessica A. , Lwin Seint T. , Drake Matthew T. , Edwards James R. , Kyle Robert A. , Mundy Gregory R. , Edwards Claire M.
Published: September 2011

The contributions of the host microenvironment to the pathogenesis of multiple myeloma, including progression from the non-malignant disorder monoclonal gammopathy of undetermined significance, are poorly understood. In the present study, microarray analysis of a murine model requiring a unique host microenvironment for myeloma development identified decreased host-derived adiponectin compared with normal mice. In support, clinical analysis revealed decreased serum adiponectin concentrations in monoclonal gammopathy of undetermined significance patients who subsequently progressed to myeloma. We investigated the role of adiponectin in myeloma pathogenesis and as a treatment approach, using both mice deficient in adiponectin and pharmacologic enhancement of circulating adiponectin. Increased tumor burden and bone disease were observed in myeloma-bearing adiponectin-deficient mice, and adiponectin was found to induce myeloma cell apoptosis. The apolipoprotein peptide mimetic L-4F was used for pharmacologic enhancement of adiponectin. L-4F reduced tumor burden, increased survival of myeloma-bearing mice, and prevented myeloma bone disease. Collectively, our studies have identified a novel mechanism whereby decreased host-derived adiponectin promotes myeloma tumor growth and osteolysis. Furthermore, we have established the potential therapeutic benefit of increasing adiponectin for the treatment of myeloma and the associated bone disease.
4D in the deepwater Gulf of Mexico: Hoover, Madison, and Marshall fields
Authors: Helgerud Michael B. , Miller Alisa C. , Johnston David H. , Udoh Michael S. , Jardine Bill G. , Harris Chad , Aubuchon Neil
Published: September 2011

The use of time-lapse or 4D seismic technology is well established in the North Sea and West Africa where the application of 4D for reservoir production monitoring and surveillance has resulted in documented gains in recovery efficiency, increased reserves, and more efficient field operations. However, for several reasons, including challenging acquisition conditions, 4D technology has not been widely applied in the deepwater Gulf of Mexico. In late 2005 and early 2006, ExxonMobil acquired a deepwater Gulf of Mexico 4D survey covering the Hoover, Madison and Marshall fields in the Alaminos Canyon/East Breaks area (for simplicity, we will refer to this as the Hoover survey).