bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis ofKRASMutations of Exon 2 Codons 12 and 13 by SNaPshot Analysis in Comparison to Common DNA Sequencing
Authors: Zinsky Rica , Bölükbas Servet , Bartsch Holger , Schirren Joachim , Fisseler-Eckhoff Annette
Published: December 2010

Due to the call for fastKRASmutation status analysis for treatment of patients with monoclonal antibodies for metastatic colorectal cancer, sensitive, economic, and easily feasible methods are required. Under this aspect, the sensitivity and specificity of the SNaPshot analysis in comparison to the commonly used DNA sequencing was checked. We examinedKRASmutations in exon 2 codons 12 and 13 with DNA sequencing and SNaPshot analysis in 100 formalin-fixed paraffin-embedded tumor tissue samples of pancreatic carcinoma, colorectal carcinoma, and nonsmall cell lung cancer specimens of the primary tumor or metastases. 40% of these samples demonstrated mutatedKRASgenes using sequencing and SNaPshot-analysis; additional five samples (45/100) were identified only with the SNaPshot.KRASmutation detection is feasible with the reliable SNaPshot analysis method. The more frequent mutation detection by the SNaPshot analysis shows that this method has a high probability of accuracy in the detection ofKRASmutations compared to sequencing.
ADAM23, a Gene Related to LGI1, Is Not Linked to Autosomal Dominant Lateral Temporal Epilepsy
Authors: Rigon Laura , Vettori Andrea , Busolin Giorgia , Egeo Gabriella , Pulitano Patrizia , Santulli Lia , Pasini Elena , Striano Pasquale , la Neve Angela , Vianello Dri Valeria , Boniver Clementina , Gambardella Antonio , Banfi Paola , Binelli Simona , Di Bonaventura Carlo , Striano Salvatore , de Falco Fabrizio , Giallonardo Anna T. , Mecarelli Oriano , Michelucci Roberto , Nobile Carlo
Published: December 2010

Autosomal dominant lateral temporal epilepsy (ADTLE) is an inherited epileptic syndrome characterized by ictal auditory symptoms or aphasia, negative MRI findings, and relatively benign evolution. Mutations responsible for ADLTE have been found in the LGI1 gene. The functions of the Lgi1 protein apparently are mediated by interactions with members of the ADAM protein family: it binds the postsynaptic receptor ADAM22 to regulate glutamate-AMPA currents at excitatory synapses and also the ADAM23 receptor to promote neurite outgrowth in vitro and dendritic arborization in vivo. Because alteration of each of these neuronal mechanisms may underlie ADLTE, ADAM22 and ADAM23 are candidate genes for this syndrome. In a previous work, we excluded a major role of ADAM22 in the aetiology of ADLTE. Here, we performed linkage analysis between microsatellite markers within or flanking the ADAM23 gene and ADLTE in 13 Italian families. The results exclude ADAM23 as major causative gene for ADLTE.
Intrahepatic Cholestasis in Sickle Cell Disease: A Case Report
Authors: Brunetta Denise Menezes , Silva-Pinto Ana Cristina , Favarin de Macedo Maria do Carmo , Bassi Sarah Cristina , Piccolo Feliciano Joao Victor , Ribeiro Fernanda Borges , Prado Benedito de Pina Almeida , De Santis Gil Cunha , Angulo Ivan de Lucena , Covas Dimas Tadeu
Published: December 2010

Intrahepatic cholestasis (SCIC) is an uncommon but potentially fatal complication of sickle cell disease (SCD), with a high death rate, observed mainly in patients with homozygous sickle cell anemia. Herein, we describe a case of severe SCIC treated successfully with aggressive manual exchange transfusion (ET). The patient was admitted with enlarged liver and signs of hepatic failure, such as hyperbilirubinemia and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. We performed several sessions of ET in order to reduce the percentage of HbS to levels inferior to 30%, which was successfully accomplished. The patient had a complete recovery of hepatic function. This case has shown that ET is an effective treatment of SCIC and should be introduced early on the onset of this severe complication.
MYCN Sensitizes Human Neuroblastoma to Apoptosis by HIPK2 Activation through a DNA Damage Response
Authors: Petroni Marialaura , Veschi Veronica , Prodosmo Andrea , Rinaldo Cinzia , Massimi Isabella , Carbonari Maurizio , Dominici Carlo , McDowell Heather P. , Rinaldi Christian , Screpanti Isabella , Frati Luigi , Bartolazzi Armando , Gulino Alberto , Soddu Silvia , Giannini Giuseppe
Published: December 2010

MYCN amplification occurs in approximately 20% of human neuroblastomas and is associated with early tumor progression and poor outcome, despite intensive multimodal treatment. However, MYCN overexpression also sensitizes neuroblastoma cells to apoptosis. Thus, uncovering the molecular mechanisms linking MYCN to apoptosis might contribute to designing more efficient therapies for MYCN-amplified tumors. Here we show that MYCN-dependent sensitization to apoptosis requires activation of p53 and its phosphorylation at serine 46. The p53S46 kinase HIPK2 accumulates on MYCN expression, and its depletion by RNA interference impairs p53S46 phosphorylation and apoptosis. Remarkably, MYCN induces a DNA damage response that accounts for the inhibition of HIPK2 degradation through an ATM- and NBS1-dependent pathway. Prompted by the rare occurrence of p53 mutations and by the broad expression of HIPK2 in our human neuroblastoma series, we evaluated the effects of the p53-reactivating compound Nutlin-3 on this pathway. At variance from other tumor histotypes, in MYCN-amplified neuroblastoma, Nutlin-3 further induced HIPK2 accumulation, p53S46 phosphorylation, and apoptosis, and in combination with clastogenic agents purged virtually the entire cell population. Altogether, our data uncover a novel mechanism linking MYCN to apoptosis that can be triggered by the p53-reactivating compound Nutlin-3, supporting its use in the most difficult-to-treat subset of neuroblastoma. Mol Cancer Res; 9(1); 67–77 ©2010 AACR.
p53 Codon 72 Increased Biochemical Recurrence Risk after Radical Prostatectomy in a Southern Chinese Population
Authors: Xu Bin , Mi Yuan-Yuan , Min Zhi-Chao , Cheng Gong , Tong Na , Tao Jun , Li Peng-Chao , Wang Mei-Lin , Tang Jia-Lin , Zhang Zheng-Dong , Song Ning-Hong , Zhang Wei , Wu Hong-Fei , Feng Ning-Han , Hua Li-Xin
Published: December 2010

Introduction: Alterations in P53 and Murine Double Minute 2 (MDM2) genes appear to be important in the development of many human tumors. We investigated the potential prognostic roles of p53 codon 72 and MDM2 309 and 1797 polymorphisms in prostate cancer after radical prostatectomy. Patients and Methods: Fifty southern Chinese with prostate cancer undergoing radical prostatectomy were included in this study. All polymorphisms were detected by PCR-RFLP. Their prognosis on biochemical recurrence was assessed using Kaplan-Meier analysis and Cox regression model. Results:p53 codon 72 GG genotype was associated with increased biochemical recurrence compared with CG+CC genotypes and poorer PSA-free survival. It was also noted that GG genotype was an independent risk factor for biochemical recurrence after radical prostatectomy on multivariate analysis. No statistical difference was observed in MDM2 polymorphisms and prostate cancer prognosis. Conclusion: Our data revealed that p53 codon 72 GG genotype carriers more frequently show biochemical recurrence than CG+CC genotypes carriers.
Autonomic Correlates at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate
Authors: Negrao Bianca Lee , Bipath Priyesh , van der Westhuizen Deborah , Viljoen Margaretha
Published: December 2010

Objective: The aim of this study was to assess autonomic nervous system functioning in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of methylphenidate and focussed attention. Method: Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulants. On both occasions, autonomic nervous system functioning was tested at baseline and during focussed attention. Autonomic nervous system functioning of control subjects was also tested at baseline and during focussed attention. Autonomic nervous system activity was determined by means of heart rate variability (HRV) and skin conductivity analyses. Attention was evoked by means of the BioGraph Infiniti biofeedback apparatus. HRV was determined by time domain, frequency domain and Poincaré analysis of RR interval data. Skin conductivity was determined by the BioGraph Infiniti biofeedback apparatus. Results: The main findings of this study were (a) that stimulant-free children with ADHD showed a sympathetic underarousal and parasympathetic overarousal of the sympathovagal balance relative to control subjects; (b) methylphenidate shifted the autonomic balance of children with ADHD towards normal levels; however, a normal autonomic balance was not reached, and (c) stimulant-free children with ADHD exhibited a shift in the sympathovagal balance towards the sympathetic nervous system from baseline to focussed attention; however, methylphenidate appeared to abolish this shift. Conclusions: Stimulant-free children with ADHD have a parasympathetic dominance of the autonomic balance, relative to control subjects. Methylphenidate attempts to restore the normal autonomic balance in children with ADHD, but inhibits the normal autonomic nervous system response to a cognitive challenge. Clinical Applications: These results indicate that methylphenidate may have a suppressive effect on the normal stress response. Although this may be of benefit to those who interact with children who suffer from ADHD, the implications for the physiological and psychological well-being of the children themselves are debatable. Further research is needed. Limitations of the Study: Only 19 children with ADHD and 18 control subjects were tested. Further studies should include prior testing in order to exclude children with possible co-existing learning disabilities. Cognitive function and emotional responses of children with ADHD were not tested.
Are IgE Levels to Foods other than Rosaceae Predictive of Allergy in Lipid Transfer Protein-Hypersensitive Patients?
Authors: Asero R. , Arena A. , Cecchi L. , Conte M.E. , Crivellaro M. , Emiliani F. , Lodi Rizzini F. , Longo R. , Minale P. , Murzilli F. , Musarra A. , Nebiolo F. , Quercia O. , Ridolo E. , Savi E. , Senna G.E. , Villalta D.
Published: December 2010

Background: Lipid transfer protein (LTP), the most frequent cause of primary food allergy in Italy, is a cross-reacting plant pan-allergen. Markers able to predict whether a patient sensitized to a certain food but not yet clinically allergic will develop allergy would be extremely helpful. Objective: It was the aim of this study to investigate the relevance of IgE levels to some plant foods other than Rosaceae as predictors of either local or systemic allergic reaction in LTP-allergic subjects. Methods: One hundred (40 males, 60 females , mean age 29 years) peach-allergic patients monosensitized to LTP seen at 14 Italian centres in 2009 were studied. Walnut, hazelnut, peanut, tomato, rice and/or maize allergy was ascertained by interview and confirmed by positive skin prick test. IgE levels to these foods and to rPru p 3 were measured. Results: Higher levels of IgE to Pru p 3 were associated with a higher prevalence of allergy to hazelnut, peanut and walnut. For all study foods, except rice, median IgE levels in allergic subjects significantly exceeded those in tolerant subjects, though within single allergic groups, the differences between patients reporting systemic or local (oral) symptoms were not significant. Ninety-five percent cut-off IgE levels predictive of clinical allergy were established for study foods although the marked overlaps between allergic and tolerant subjects made them of limited usefulness. Conclusion: Specific IgE levels are only partially predictive of clinical allergy. The reasons why some individuals showing low specific IgE levels develop clinical allergy whereas others showing high IgE levels do not, despite similar exposure to the allergen, remain unclear.
Significant Association between IL-17F Promoter Region Polymorphism and Susceptibility to Asthma in a Korean Population
Authors: Jin Eun-Heui , Choi Eun-Young , Yang Ji Yeon , Chung Hun-Taeg , Yang Yun-Sik
Published: December 2010

Background: Individual differences in susceptibility to asthma would be expected because of common DNA variants of single nucleotide polymorphisms (SNPs) across populations. The pro-inflammatory cytokine IL-17F has homology with the IL-17 motif and induces the expression of other inflammatory cytokines in airway epithelial cells. This study aimed to identify IL-17F gene polymorphisms and to determine a possible association between these polymorphisms and susceptibility to asthma through a case-control study in a Korean population. Methods: We identified SNPs in the IL-17F gene by sequencing. Genotyping was conducted using the high-resolution melting (HRM) method on 424 asthma patients and 548 healthy controls. Results: The genotype and allele frequencies of rs1889570 SNP were significantly different between asthma patients and healthy controls (p = 0.001 and 0.002, respectively). The rs1889570 SNP genotype was also positively associated with the number of peripheral blood eosinophils in asthma patients (p = 0.03). The frequencies of haplotypes AA (p = 0.01), GG (p = 0.01) and AG (p = 0.006) were significantly different between asthma patients and healthy controls. Conclusions: In this study, we confirmed that the rs1889570 polymorphism of the IL-17F gene is associated with susceptibility to asthma in a Korean population.
Surgical Challenge in Patients Who Underwent Failed Hypospadias Repair: Is It Time to Change?
Authors: Perovic S. , Barbagli G. , Djinovic R. , Sansalone S. , Vallasciani S. , Lazzeri M.
Published: December 2010

Introduction: Our purpose was to evaluate patients who underwent failed hypospadias repair. Patients and Methods: We evaluated 4 different groups of patients who underwent failed hypospadias repair. Group 1: patients who underwent only urethral surgery; group 2: patients who underwent only corpora cavernosa surgery; group 3: patients who underwent urethral and corpora cavernosa surgery; group 4: patients who underwent complex reconstructive surgery. Success was defined as a functional urethra without fistula, with glandular meatus and acceptable esthetic appearance of the genitalia. Results: Out of 1,176 patients, group 1 included 301 patients (25.5%), group two 60 patients (5.2%), group three 166 patients (14.1%) and group four 649 patients (55.2%). The mean follow-up was 60.4 months. Out of 1,176 cases, 1,036 (88.1%) were considered successful and 140 (11.9%) failures. Conclusion: In the majority of patients (55.2%) with failed hypospadias repair, urethral reconstruction is associated with complex surgical procedures to fully resurface glands, penile shaft and genitalia.
Could Prostate Biopsies Be Avoided in Men Older than 75 Years with Raised PSA?
Authors: Nomikos Michael , Mariappan Paramananthan , Zachou Alexandra , McNeill Alan , Bollina Prasad R.
Published: December 2010

Objectives: Our purpose was to review current practice regarding the use of prostate biopsies in men older than 75 years with raised PSA by presenting the results of a retrospective audit and to identify these older men who really benefit from prostate biopsies. Methods: A high-volume tertiary center’s prospectively maintained prostate biopsy database of contemporary biopsies was reviewed. Men were stratified by age and PSA. Logistic regression analysis, Mantel-Haenszel and Fisher’s exact tests were used for statistical analysis. Results: Overall, 1,593 men underwent prostate biopsies between April 2004 and August 2006. Of these, 293 patients (18.4%) with a mean age of 82.62 years and mean PSA of 30.37 ng/ml were eligible for the study with an overall incidence of prostate cancer of 73.7%. Elderly men with PSA >20 ng/ml had a prostate cancer detection rate of 91%. They were more likely to have-high grade disease (OR = 5.4, 95% CI = 2.8–10.8, p < 0.0001) and receive hormone deprivation therapy (RR = 3.0, 95% CI = 2.1–4.3, p < 0.0001). Elderly men with PSA <20 ng/ml had a 3-fold risk of being placed on active monitoring. Almost 20% of them had 1 complication following biopsy, of whom 12 (4.1%) needed hospitalization. Conclusions: Given the high probability of detecting prostate cancer and receiving conservative treatment, prostate biopsies can be omitted in men >75 years with PSA >20 ng/ml. However, they are still useful in fit men >75 and <80 years with PSA <20 ng/ml who can be the potential candidates for treatment with curative intent.
Impact of Overactive Bladder Symptoms on Sexuality in Both Sexes
Authors: Heidler Stefan , Mert Can , Wehrberger Clemens , Temml Christian , Ponholzer Anton , Rauchenwald Michael , Madersbacher Stephan
Published: December 2010

Objectives: To define the epidemiological impact of the overactive bladder syndrome (OAB) on sexual life. We therefore analyzed this issue in a large cohort of individuals participating in a health screening project. Patients and Methods: A total of 2,365 men and women completed the Bristol Female Lower Urinary Tract Symptoms Questionnaire (BFLUTS). OAB was defined according to the International Continence Society (ICS). The impact of OAB on sexual life was assessed by a single question: ‘In general, how do your micturition problems affect your sexual life’. Results: A total of 1.199 men and 1.166 women with were analyzed. The overall prevalence of OAB was 13.9% (n = 329): 9.7% had OABdry and 4.2% OABwet. A total of 17.6% (n = 58) of individuals with OAB reported a negative impact of OAB on sexual life as compared to 4.7% of those without OAB (p < 0.001). One of 4 with OABwet reported a negative impact on sexual life (25%) as compared to 14.4% in those with OABdry (p < 0.005). Conclusion: Sexual dysfunction is frequently reported in individuals with OAB. Individuals with OABwet are experiencing a more profound impact on sexuality. Therefore, patients with OAB should be assessed regarding sexual dysfunction by the urologist.
Gangrenous Cystitis: Report of a Case and Review of the Literature
Authors: Hinev Alexander , Anakievski Deyan , Krasnaliev Ivan
Published: December 2010

Gangrenous cystitis is an extremely rare condition: only a total of 240 cases worldwide have been reported so far. Most of these cases have occurred in the preantibiotic era. After the advent and widespread use of antibiotics in clinical practice, only sporadic cases have been observed. We report a case of gangrenous cystitis in an 83-year-old woman who presented with symptoms of acute abdomen. The main causative factor was overdistension of the bladder due to urinary retention. The patient underwent total cystectomy and bilateral ureterocutaneostomy with a favorable outcome. The incidence, etiology, diagnosis, management and outcome of gangrenous cystitis are discussed.
Life-Threatening Complications Associated with the Tyrosine Kinase Inhibitor Sunitinib Malate
Authors: Lim Tae Joon , Lee Jee Han , Chang Sung-Goo , Lee Choong Hyun , Min Gyeong Eun , Yoo Koo Han , Jeon Seung Hyun
Published: December 2010

Adverse events associated with sunitinib, such as cardiac toxicities, renal damage, and hemostatic complications, are well known. The authors report 3 cases in which patients experienced severe life-threatening complications after commencing sunitinib treatment. One patient developed heart failure with dilation of the left ventricle and decrease in the ejection fraction after one cycle of sunitinib and required treatment with an angiotensin-converting enzyme inhibitor, loop diuretics, and dobutamine. Another patient developed coronary artery stenosis after one cycle of sunitinib and was managed through percutaneous coronary intervention. Although follow-on coronary angiography revealed normal findings after 6 further cycles of sunitinib, this patient eventually expired due to multi-organ failure. The third patient had chronic renal failure before sunitinib treatment and required hemodialysis due to acute-on-chronic renal failure after commencing sunitinib treatment.
Imaging in Bladder Cancer: Present Role and Future Perspectives
Authors: Totaro Angelo , Pinto Francesco , Brescia Antonio , Racioppi Marco , Cappa Emanuele , D’Agostino Daniele , Volpe Andrea , Sacco Emilio , Palermo Giuseppe , Valentini AnnaLia , Bassi PierFrancesco
Published: December 2010

Advances in imaging have an increasingly significant role in the diagnosis, staging and restaging of patients with bladder cancer. This paper reviews the current use of imaging in bladder neoplasms, comparing the different radiologic investigations, and discusses the potential applications of novel imaging techniques in the management of patients with bladder cancer.
Comparative Cytogenetic Study of Two Sister Species of Iberian Ground Voles, Microtus (Terricola) duodecimcostatus and M. (T.) lusitanicus (Rodentia, Cricetidae)
Authors: Gornung E. , Castiglia R. , Rovatsos M. , Marchal J.A. , Díaz de la Guardia-Quiles R. , Sanchez A.
Published: December 2010

The two Iberian species of pine voles, Microtus (Terricola) duodecimcostatus and M. (T.) lusitanicus of the subfamily Arvicolinae (Cricetidae, Rodentia), were compared after G- and C-banding and chromosomal mapping of ribosomal RNA genes (rDNA), telomeric repeats, and satellite DNA Msat-160. Notwithstanding their close relationship (one sister group in phylogenetic analyses) and sharing of the diploid and fundamental chromosome numbers, the 2 species show notable differences in the sex chromosome morphology, the number and distribution of rDNA sites, constitutive heterochromatin and satDNA patterns. The only telomeric repeats showed normal, all-telomeric, distribution in karyotypes of both species. The data are discussed with regard to interspecific and intrageneric variation of the analyzed characters and the chromosomal evolution in the genus Microtus.
Chromosomal Homologies among Vampire Bats Revealed by Chromosome Painting (Phyllostomidae, Chiroptera)
Authors: Sotero-Caio C.G. , Pieczarka J.C. , Nagamachi C.Y. , Gomes A.J.B. , Lira T.C. , O’Brien P.C.M. , Ferguson-Smith M.A. , Souza M.J. , Santos N.
Published: December 2010

Substantial effort has been made to elucidate karyotypic evolution of phyllostomid bats, mostly through comparisons of G-banding patterns. However, due to the limited number of G-bands in respective karyotypes and to the similarity of non-homologous bands, an accurate evolutionary history of chromosome segments remains questionable. This is the case for vampire bats (Desmodontinae). Despite several proposed homologies, banding data have not yet provided a detailed understanding of the chromosomal changes within vampire genera. We examined karyotype differentiation of the 3 species within this subfamily using whole chromosomal probes from Phyllostomus hastatus (Phyllostominae) and Carollia brevicauda (Carolliinae). Painting probes of P. hastatus respectively detected 22, 21 and 23 conserved segments in Diphylla ecaudata, Diaemus youngi, and Desmodus rotundus karyotypes, whereas 27, 27 and 28 were respectively detectedwith C. brevicauda paints. Based on the evolutionary relationships proposed by morphological and molecular data, we present probable chromosomal synapomorphies for vampire bats and propose chromosomes that were present in the common ancestor of the 5 genera analyzed. Karyotype comparisons allowed us to relate a number of conserved chromosomal segments among the 5 species, providing a broader database for understanding karyotype evolution in the family.
Is Prostate-Specific Antigen Surveillance Necessary in Men with Benign Prostate Pathology following Radical Cystoprostatectomy for Bladder Cancer?
Authors: Bivalacqua Trinity J. , Loeb Stacy , Pierorazio Phillip M. , Schoenberg Mark P. , Partin Alan W. , Guzzo Thomas J.
Published: December 2010

Background: Radical cystoprostatectomy (RCP) remains the gold standard for the treatment of muscle-invasive bladder cancer. There are limited data regarding the clinical impact and detection of PSA following complete prostatectomy or the need to monitor serum PSA in patients with benign prostate pathology at time of RCP. The purpose of our study was to analyze the postoperative PSA characteristics of men without prostate cancer who underwent a RCP for bladder cancer. Methods: The demographic, clinical and pathologic data were reviewed on 138 men who underwent RCP for bladder cancer from 1994 to 2008. Patients with known or incidentally discovered prostate cancer on final pathology were excluded from this study, and postoperative serum PSA values were reviewed in the remaining men. Results: The median age of the study population was 64 years (range 40–84). At a mean follow-up of 40.7 months, 137 (99.3%) of patients had an undetectable serum PSA. The one (0.7%) case in which serum PSA was not undetectable underwent an apex-sparing prostatectomy at the time of cystectomy. Conclusions: Serum PSA should remain undetectable for men with benign prostate pathology undergoing complete prostatectomy at the time of RCP. Elevated serum PSA following complete RCP in men with bladder cancer and pathologically confirmed benign prostate findings is rare. If the serum PSA is undetectable 3 months after RCP with benign prostate pathology, there is no need for continued PSA monitoring. These data support the notion that potential nonprostatic sources of PSA are clinically insignificant following complete removal of the prostate.
Temporal Trends and Associated Factors for Pre-Hospital and In-Hospital Delays of Stroke Patients over a 16-Year Period: The Athens Study
Authors: Papapanagiotou Panagiotis , Iacovidou Nicoletta , Spengos Konstantinos , Xanthos Theodoros , Zaganas Ioannis , Aggelina Afrodite , Alegakis Athanasios , Vemmos Konstantinos
Published: December 2010

Background: The management and outcome of acute ischemic stroke changed dramatically after the introduction of intravenous thrombolysis. However, relatively few patients have received thrombolytic treatment, mainly due to pre-hospital and/or in-hospital delays. Although the causes of these delays have been adequately studied, their change over a long period has not. Methods: All acute first-ever stroke patients (n = 2,746) presenting to our academic center from 1993 to 2008 were prospectively documented in a computerized stroke data bank. The time from symptoms onset to presentation at the emergency room and to acquisition of a brain CT was calculated. Time trends over this period as well as the factors affecting them were analyzed. Results: The final study cohort consisted of 2,326 acute stroke patients after excluding 302 patients with an unknown time of stroke onset and 118 who suffered a stroke during hospitalization for another illness. Over the 16-year period, the median time from stroke onset to presentation at the emergency room decreased significantly from 3.15 h (interquartile range 1.30–10.30) to 2.00 h (range 1.00–4.00) (p < 0.001). The median time from emergency room presentation to CT scan completion also decreased significantly (p < 0.001) from 12.3 h (range 4.1–29.8) to 1.0 h (range 0.31–2.77). As a result, the proportion of patients having a CT scan within 4 h of stroke onset increased significantly from 8.6% in 1993–1994 to 53.6% in 2007–2008 (p < 0.001). Thrombolytic treatment was applied in 4.15% of all ischemic stroke patients in the period from 2003 to 2008. Along with other significant factors, use of an emergency medical service was associated with a 57% greater chance of presenting within 3 h after symptoms onset. Conclusions: These results suggest a continued improvement in pre-hospital and in-hospital delays for stroke management. Public awareness and education regarding medical and paramedical services are necessary for the best early management of acute stroke patients.
Public Support for the Use of Newborn Screening Dried Blood Spots in Health Research
Authors: Duquette D. , Rafferty A.P. , Fussman C. , Gehring J. , Meyer S. , Bach J.
Published: December 2010

Objectives: The level of support among Michigan adults for the use of residual newborn screening dried blood spots (DBS) was investigated. Methods: We analyzed data from 4 questions on the 2008 Michigan Behavioral Risk Factor Surveillance System (n = 3,108). The questions asked about general support for the use of DBS for research and for research investigating childhood diseases, adult diseases and diseases related to environmental exposures. Results: The majority of adults (72.3%) favored the use of DBS for research intended to benefit the health of residents. With more question specificity, a higher proportion of adults (84.2%–86.8%) were found to favor the use of DBS for research, and a lower proportion had no opinion. The odds of favoring use were higher among those who were younger, female, white, healthy, or with at least a high school degree. Conclusions: This is the first population survey of adult attitudes regarding use of DBS for different types of health research, with results showing considerable public support. The findings are being used in community outreach efforts and highlight the need to investigate opposition in vulnerable populations.
Defining the Extent of Irreversible Brain Ischemia Using Perfusion Computed Tomography
Authors: Bivard Andrew , McElduff Patrick , Spratt Neil , Levi Christopher , Parsons Mark
Published: December 2010

Background: Perfusion computed tomography (PCT) shows promise in acute stroke assessment. However, the accuracy of CT perfusion thresholds in defining the acute infarct core remains uncertain. Method: Concurrent PCT and MRI-DWI performed 3–6 h after symptoms onset were assessed in 57 ischemic stroke patients. PCT was compared to DWI images to define the infarct core using a pixel-based receiver operating characteristic curve analysis to calculate the area under the curve (AUC) for thresholds from PCT maps that were coregistered with the DWI slice location. Results: A relative cerebral blood flow (CBF) of 45% of the contralateral hemisphere was found to be the most accurate threshold for describing the infarct core (AUC 0.788), and it was also by far the most frequent threshold with the highest AUC across patients. Conclusion: CBF thresholds on PCT define the acute infarct core more accurately than do other PCT thresholds, including a cerebral blood volume of 2 ml/100 g.
Neurocognitive Profiles of Children with Moyamoya Disease before and after Surgical Intervention
Authors: Lee Ji Yeoun , Phi Ji Hoon , Wang Kyu-Chang , Cho Byung-Kyu , Shin Min-Sup , Kim Seung-Ki
Published: December 2010

Background: Clinical research on moyamoya disease (MMD) has focused on symptomatic outcome such as transient ischemic attacks. Neurocognitive function in children critically affects social outcome and is closely related to quality of life. This study is the first to analyze the neurocognitive profiles of children with MMD before and after surgery. Methods: Sixty-five patients were selected out of 137 who underwent surgery for MMD between 2006 and 2008. The preoperative and postoperative neurocognitive function was tested using the Korean version of the Wechsler Intelligence Scale for Children-Revised (KEDI-WISC-R) and the Bender Gestalt Test (BGT). Pre- and postoperative profiles of patients with or without major infarctions were compared. Patients with borderzone infarctions were analyzed as well. Results: Preoperatively, patients had age-appropriate full-scale intelligence quotient (FSIQ) and verbal IQ (VIQ) scores, which were maintained after surgery. There was significant improvement in performance IQ (PIQ) (p = 0.01) and BGT scores postoperatively (p < 0.01). Among the subtests, Coding showed significant improvement postoperatively (p < 0.01). Preoperatively, patients with major infarctions had significantly lower FSIQ (p < 0.01), VIQ (p = 0.01) and PIQ (p < 0.01) scores compared with those without infarctions. The pre- and postoperative neurocognitive profiles of the patients with borderzone infarctions fell between those of patients with absolutely no infarctions and those of patients with major infarctions. Conclusions: Considering the natural history of MMD, which leads to a drastic decline in neurocognitive functions, the present findings indicate a role for early active surgery to save the intellectual abilities of children with MMD.
Accuracy of a Portable Multisensor Body Monitor for Predicting Resting Energy Expenditure in Older People: A Comparison with Indirect Calorimetry
Authors: Heiermann Stefanie , Khalaj Hedayati Kerstin , Müller Manfred J. , Dittmar Manuela
Published: December 2010

Background: Accurate and comfortable methods are needed to determine resting energy expenditure (REE) in older people who are characterized by a lowered metabolic rate. The portable SenseWear® armband (SWA) body monitor, worn on the right upper arm, can easily be used by this age group in an ambulatory manner. Objective: The purpose of this study was to evaluate the reliability and accuracy of the SWA armband in determining REE in healthy, normal-weight older people. Methods: Participants were 49 older, community-dwelling volunteers aged 60–87 years. Reliability was tested in all subjects. Accuracy was analyzed in 32 subjects by comparing REE estimated by SWA against REE measured by indirect calorimetry as a criterion method. Data were simultaneously and continuously recorded for 20 min in the morning. In the same subjects, REE determined by SWA from night recording was evaluated for accuracy against indirect calorimetry. The agreement between methods was assessed by the Bland-Altman procedure. Results: (1) REE measured by SWA was reliable when comparing 2 consecutive measurements (typical error: 1.9%). (2) REE calculated from morning recording (1,543 ± 181 kcal/24 h) was higher than REE from night recording (1,564 ± 192 kcal/24 h; p = 0.018). (3) Compared with REE by indirect calorimetry (1,377 ± 228 kcal/24 h) for accuracy, the SWA overestimated mean REE in the older people by 12 and 14%, respectively, for morning and night recording (each p < 0.001). Conclusions: The SWA provides a reliable estimate of REE in healthy older subjects and has the advantage of easy handling. The 20-min recording time, which was recommended by the manufacturer, can be applied. However, the SWA overestimates REE in this group, possibly due to age-related changes in skin conductance and thermoregulation, both being measured by sensors of the SWA armband. This requires improving the SWA by developing better fitting algorithms for predicting REE in older people.
Evolution of Atherosclerotic Carotid Plaque Morphology: Do Ulcerated Plaques Heal? A Serial Multidetector CT Angiography Study
Authors: van Gils M.J. , Homburg P.J. , Rozie S. , de Weert T.T. , Dippel D.W.J. , van der Lugt A.
Published: December 2010

Background: Atherosclerotic carotid plaque rupture may lead to thromboembolization, causing transient ischemic attack or ischemic stroke. Carotid plaque ulceration on angiography is associated with plaque rupture. Although healing of ruptured plaques has been described in coronary arteries, little is known about the natural development of plaque ulcerations in carotid arteries. We therefore explored the evolution of carotid plaque surface morphology with serial multidetector CT angiography (MDCTA). Methods: From a registry of patients with transient ischemic attack or minor ischemic stroke, we selected 83 patients who had undergone serial MDCTA of the carotid arteries. Arteries subjected to revascularization procedures between the two scans were excluded (n = 11). Plaque surface morphology was classified as smooth, irregular or ulcerated on both baseline and follow-up MDCTA. Progression (i.e. development of irregularities or ulceration) and regression (i.e. disappearance of irregularities or ulceration) in morphology were evaluated. Results: The mean time interval between the MDCTA scans was 21 ± 13 months. At baseline, 28 (18%) arteries were normal, 124 (80%) contained atherosclerotic plaque and 3 (2%) were occluded. Plaque surface morphology was smooth in 86 arteries (55%), irregular in 23 (15%) and ulcerated in 15 (10%). At follow-up, surface morphology was unchanged in 88% of arteries, had progressed in 8% and regressed in 4%. Most importantly, plaque morphology remained unchanged in most ulcerated plaques (10/15; 67%). One ulcerated plaque had progressed, whereas 4 had regressed. New ulcerations had developed in 2 nonulcerated plaques. Conclusion: MDCTA allows evaluation of temporal changes in atherosclerotic carotid plaque morphology. Plaque surface morphology remained unchanged in most arteries. Carotid ulcerations persist for a long time, and may remain a potential source of thromboembolism.
Protocol and Methodology of the Stroke in Young Fabry Patients (sifap1) Study: A Prospective Multicenter European Study of 5,024 Young Stroke Patients Aged 18–55 Years
Authors: Rolfs Arndt , Martus Peter , Heuschmann Peter U. , Grittner Ulrike , Holzhausen Martin , Tatlisumak Turgut , Böttcher Tobias , Fazekas Franz , Enzinger Christian , Ropele Stefan , Schmidt Reinhold , Riess Olaf , Norrving Bo ,   on behalf of the sifap1TMInvestigators
Published: December 2010

Background: Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients. Methods: We initiated the Stroke in Young Fabry Patients (sifap1) study as a multinational prospective European study of stroke patients aged 18–55 years and collected a broad range of clinical, laboratory, and radiological data using stringent standardized methods. All patients were tested for Fabry disease and blood was stored for future genetic testing. Results: We managed to enroll 5,024 eligible young stroke patients in 15 countries and 47 centers across Europe between April 2007 and January 2010. The median number of patients included per center was 98 with a range between 8 and 315. The average duration of patient recruitment per center was 22 months, ranging between 5 and 33 months. The database was closed in July 2010. This paper describes protocol and methodology of the sifap1 study. Conclusion: The sifap1 study included the largest series of young stroke patients so far and will allow for analyses on a large number of aspects of stroke in the young.
Social Structure and Group Dynamics of the Cao Vit Gibbon (Nomascus nasutus) in Bangliang, Jingxi, China
Authors: Fan Pengfei , Fei Hanlan , Xiang Zuofu , Zhang Wen , Ma Changyong , Huang Tao
Published: December 2010

The Cao Vit gibbon (Nomascus nasutus) was rediscovered in 2002 in Vietnam and then in 2006 in China. This is the only known population with about 110 individuals located along the China-Vietnam border. Little is known about it other than its population size and distribution. We describe the social structure and group dynamics of the Cao Vit gibbons in China based on 2 years of monitoring from 2007 to 2009. Four established study groups at this site consisted of 1 adult male, 2 adult females and 2–6 offspring. Two juveniles in 2 groups disappeared during the research. Four infants were born in 3 groups from November 2008 to February 2009. In 2 of the groups, both adult females had dependent infants. These observations suggest that Cao Vit gibbons live in polygynous groups, contrary to the usual monogamous group with only 1 adult female, but nevertheless similar to the social organization of both N. concolor and N. hainanus. We observed a coordinated dispersal of 1 adult male and 2 large juveniles, and the male formed a pair with a newly arrived female. Our observations support a growing awareness of variability in gibbon social organization.
A Direct Comparison of Scan and Focal Sampling Methods for Measuring Wild Chimpanzee Feeding Behaviour
Authors: Gilby Ian C. , Pokempner Amy A. , Wrangham Richard W.
Published: December 2010

Focal sampling is the most accurate method for measuring primate activity budgets but is sometimes impractical. An alternative is scan sampling, in which the behaviour of the group is recorded at regular intervals. The simplest technique is to record whether at least 1 animal is engaged in the behaviour of interest. By direct comparison with focal data collected simultaneously on the same population, we assess the validity of this simple group level sampling method for studying chimpanzee (Pan troglodytes schweinfurthii) feeding behaviour. In a 13-month study at Kanyawara, Kibale National Park, Uganda, group level scan sampling provided statistically similar measures of broad diet composition to those produced by focal data, despite considerable seasonal variation. Monthly means of the percentage of time spent consuming non-fig fruit calculated from group level scan sampling were highly correlated with those from focal sampling. This validates previous methodology used to identify periods of high energy availability. However, group level scans tended to overestimate the percentage of observation time spent feeding, particularly for adult males. We conclude that this method of group level scan sampling provides valuable data for characterizing broad diet choice in chimpanzees and other species, but may be of limited use for estimating individual feeding time.
Synteny Conservation of Chicken Macrochromosomes 1–10 in Different Avian Lineages Revealed by Cross-Species Chromosome Painting
Authors: Nanda I. , Benisch P. , Fetting D. , Haaf T. , Schmid M.
Published: December 2010

Cross-species chromosome painting can directly visualize syntenies between diverged karyotypes and, thus, increase our knowledge on avian genome evolution. DNA libraries of chicken (Gallus gallus, GGA) macrochromosomes 1 to 10 were hybridized to metaphase spreads of 9 different species from 3 different orders (Anseriformes, Gruiformes and Passeriformes). Depending on the analyzed species, GGA1–10 delineated 11 to 13 syntenic chromosome regions, indicating a high degree of synteny conservation. No exchange between the GGA macrochromosome complement and microchromosomes of the analyzed species was observed. GGA1 and GGA4 were distributed on 2 or 3 chromosomes each in some of the analyzed species, indicating rare evolutionary rearrangements between macrochromosomes. In all 6 analyzed species of Passeriformes, GGA1 was diverged on 2 macrochromosomes, representing a synapomorphic marker for this order. GGA4 was split on 2 chromosomes in most karyotypes, but syntenic to a single chromosome in blackcap (Passeriformes). GGA5/10 and also GGA8/9 associations on chromosomes were found to be important cytogenetic features of the Eurasian nuthatch (Passeriformes) karyotype. Fusion of GGA4 and GGA5 segments and of entire GGA6 and GGA7, respectively, was seen in the 2 analyzed species of Gruiformes. Consistent with the literature, our inter-species chromosome painting demonstrates remarkable conservation of macrochromosomal synteny over 100 million years of avian evolution. The low rate of rearrangements between macrochromosomes and the absence of detectable macrochromosome-microchromosome exchanges suggests a predominant role for rearrangements within the gene-dense microchromosome complement in karyotypic diversification.
Acute and Long-Term Efficacy and Safety of Sildenafil for the Treatment of Chronic Thromboembolic Pulmonary Hypertension in a Heart Transplant Recipient
Authors: Zacà Valerio , Padeletti Margherita , Pagliaro Antonio , Furiozzi Fabio , Mondillo Sergio , Favilli Roberto
Published: December 2010

We report on the successful treatment with sildenafil of a unique case of severe chronic thromboembolic pulmonary hypertension which developed as a late complication in a 71-year-old heart transplant recipient, with focus on the potential therapeutic challenges encountered in the management of such a peculiar association of clinical conditions.
Diagnostic Pitfall: Pigmented Lesion of the Nipple – Correlation between Dermoscopy, Reflectance Confocal Microscopy and Histopathology
Authors: Kolm I. , Kamarashev J. , Kerl K. , Mainetti C. , Giovanoli P. , French L.E. , Braun R.P.
Published: December 2010

We present an unusual case of a nevus of the nipple changing during pregnancy which caused a diagnostic pitfall. Nevi on the nipple and areola are infrequent, and diagnostic criteria for clinical, dermoscopy or reflectance confocal microscopy examination for nevi in this ‘special location’ are still missing. We comment on the literature on dermoscopic findings in mammary lesions and their management during pregnancy, as well as the challenging histopathology of nevi along the milk line. Finally, we focus on two main limitations of reflectance confocal microscopy: the misinterpretation of dendritic cells and the limitation of the imaging depth.
Low Aryl Hydrocarbon Receptor-Interacting Protein Expression Is a Better Marker of Invasiveness in Somatotropinomas than Ki-67 and p53
Authors: Kasuki Jomori de Pinho Leandro , Vieira Neto Leonardo , Armondi Wildemberg Luiz Eduardo , Gasparetto Emerson Leandro , Marcondes Jorge , de Almeida Nunes Bruno , Takiya Christina M. , Gadelha Mônica R.
Published: December 2010

Background: Some pituitary adenomas exhibit fast growth and invade surrounding structures. To date, there is no robust marker to predict invasiveness. Aim: To evaluate Ki-67, p53 and aryl hydrocarbon receptor-interacting protein (AIP) expression and compare these between invasive and noninvasive somatotropinomas and nonfunctioning pituitary adenomas (NFPAs). Methods: Protein expression was determined by immunohistochemistry. Tumors were classified according to percentage of immunolabeled nuclei for Ki-67 and p53. AIP immunopositivity was graded according to a score encompassing pattern and intensity. Invasiveness was defined according to radiological and surgical criteria. Results: Thirty-eight sporadic somatotropinomas were studied. Median Ki-67 labeling index in invasive and noninvasive tumors was 1.6 (range 0–20.6) and 0.26 (0–2.2), respectively (p = 0.01). With a 2.3% cut-off point obtained by ROC curve analysis, invasive adenomas were distinguished with 100% specificity, 39% sensitivity, and 63% accuracy. Low AIP expression was also correlated with tumor invasiveness (p = 0.001), with sensitivity, specificity and accuracy of 78, 80, and 79%, respectively. Expression of p53 was not different among tumors. Twenty-nine NFPAs were studied, with no significant difference between Ki-67, p53 and AIP expression in invasive and noninvasive tumors. High AIP expression was more frequent in NFPAs, with Ki-67 >3% (p = 0.051), especially when only gonadotrope cell adenomas (n = 25) were considered (p = 0.012). Conclusions: These data suggest, for the first time, that AIP is a better marker of invasiveness in somatotropinomas than Ki-67 and p53. In addition, low AIP expression is observed in invasive somatotropinomas, in contrast with high AIP expression in NFPAs (mainly gonadotrope cell tumors) with high proliferative indices.