bluuebunny/crossref_metadata_2025 huggingface dataset:
Ian Ellery McCarthy 1930 - 2005
Authors: Thomas Anthony W. , Afnan Iraj R. , Tandy Peter C.
Published: November 2008

Ian McCarthy was one of Australia's outstanding theoretical physicists. He was born in country South Australia and, after a PhD at the University of Adelaide, and periods of work in the UK and USA, he returned to South Australia where for several decades he led an outstanding research program at Flinders University. Ian's career had two major stages. In the first, he made major contributions to nuclear reaction theory, including very important insights into the physical consequences of the optical model and state-of-the-art calculations of proton knock-out from nuclei. In the second phase, he imported the concept of the knock-out reaction to atomic, molecular and solid state physics. Using the (e,2e) reaction, for which he and his colleagues developed the theoretical framework, his group made major contributions in these areas.
Non-DNA-binding platinum anticancer agents: Cytotoxic activities of platinum–phosphato complexes towards human ovarian cancer cells
Authors: Bose Rathindra N. , Maurmann Leila , Mishur Robert J. , Yasui Linda , Gupta Shefalika , Grayburn W. Scott , Hofstetter Heike , Salley Tara
Published: November 2008

DNA is believed to be the molecular target for the cytotoxic activities of platinum (Pt) anticancer drugs. We report here a class of platinum(II)- and platinum(IV)-pyrophosphato complexes that exhibit cytotoxicity comparable with and, in some cases, better than cisplatin in ovarian cell lines (A2780, A2780/C30, and CHO), yet they do not show any evidence of covalent binding to DNA. Moreover, some of these compounds are quite effective in cisplatin- and carboplatin-resistant cell line A2780/C30. The lack of DNA binding was demonstrated by the absence of a detectable Pt signal by atomic absorption spectroscopy using isolated DNA from human ovarian cells treated with a platinum(II)-pyrophosphato complex, (
trans
-1,2-cyclohexanediamine)(dihydrogen pyrophosphato) platinum(II), (pyrodach-2) and from NMR experiments using a variety of nucleotides including single- and double-stranded DNA. Furthermore, pyrodach-2 exhibited reduced cellular accumulations compared with cisplatin in cisplatin- and carboplatin-resistant human ovarian cells, yet the IC
50
value for the pyrophosphato complex was much less than that of cisplatin. Moreover, unlike cisplatin, pyrodach-2 treated cells overexpressed fas and fas-related transcription factors and some proapoptotic genes such as Bak and Bax. Data presented in this report collectively indicate that pyrodach-2 follows different cytotoxic mechanisms than does cisplatin. Unlike cisplatin, pyrodach-2 does not undergo aquation during 1 week and is quite soluble and stable in aqueous solutions. Results presented in this article represent a clear paradigm shift not only in expanding the molecular targets for Pt anticancer drugs but also in strategic development for more effective anticancer drugs.
Structural characterization of IrisFP, an optical highlighter undergoing multiple photo-induced transformations
Authors: Adam Virgile , Lelimousin Mickaël , Boehme Susan , Desfonds Guillaume , Nienhaus Karin , Field Martin J. , Wiedenmann Joerg , McSweeney Sean , Nienhaus G. Ulrich , Bourgeois Dominique
Published: November 2008

Photoactivatable fluorescent proteins (FPs) are powerful fluorescent highlighters in live cell imaging and offer perspectives for optical nanoscopy and the development of biophotonic devices. Two types of photoactivation are currently being distinguished, reversible photoswitching between fluorescent and nonfluorescent forms and irreversible photoconversion. Here, we have combined crystallography and (
in crystallo
) spectroscopy to characterize the Phe-173-Ser mutant of the tetrameric variant of EosFP, named IrisFP, which incorporates both types of phototransformations. In its green fluorescent state, IrisFP displays reversible photoswitching, which involves
cis–trans
isomerization of the chromophore. Like its parent protein EosFP, IrisFP also photoconverts irreversibly to a red-emitting state under violet light because of an extension of the conjugated π-electron system of the chromophore, accompanied by a cleavage of the polypeptide backbone. The red form of IrisFP exhibits a second reversible photoswitching process, which may also involve
cis–trans
isomerization of the chromophore. Therefore, IrisFP displays altogether 3 distinct photoactivation processes. The possibility to engineer and precisely control multiple phototransformations in photoactivatable FPs offers exciting perspectives for the extension of the fluorescent protein toolkit.
Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome
Authors: Krenz Maike , Gulick James , Osinska Hanna E. , Colbert Melissa C. , Molkentin Jeffery D. , Robbins Jeffrey
Published: November 2008

Noonan syndrome (NS) is the most common nonchromosomal genetic disorder associated with cardiovascular malformations. The most prominent cardiac defects in NS are pulmonary valve stenosis and hypertrophic cardiomyopathy. Gain-of-function mutations in the protein tyrosine phosphatase Shp2 have been identified in 50% of NS families. We created a NS mouse model with selective overexpression of mutant Shp2 (Q79R-Shp2) in the developing endocardial cushions. In our model, Cre recombinase driven by the Tie2 promoter irreversibly activates transgenic Q79R-Shp2 expression in the endothelial-derived cell lineage. Q79R-Shp2 expression resulted in embryonic lethality by embryonic day 14.5. Importantly, mutant embryos showed significantly enlarged endocardial cushions in the atrioventricular canal and in the outflow tract. In contrast, overexpression of wild-type Shp2 protein at comparable levels did not enhance endocardial cushion growth or alter the morphology of the mature adult valves. Expression of Q79R-Shp2 was accompanied by increased ERK1/2 activation in a subset of cells within the cushion mesenchyme, suggesting that hyperactivation of this signaling pathway may play a pathogenic role. To test this hypothesis in vivo, Q79R-Shp2-expressing mice were crossed with mice carrying either a homozygous ERK1 or a heterozygous ERK2 deletion. Deletion of ERK1 completely rescued the endocardial cushion phenotype, whereas ERK2 protein reduction did not affect endocardial cushion size. Constitutive hyperactivation of ERK1/2 signaling alone with a transgenic approach resulted in a phenocopy of the valvular phenotype. The data demonstrate both necessity and sufficiency of increased ERK activation downstream of Shp2 in mediating abnormal valve development in a NS mouse model.
Human Rad54 protein stimulates human Mus81–Eme1 endonuclease
Authors: Mazina Olga M. , Mazin Alexander V.
Published: November 2008

Rad54, a key protein of homologous recombination, physically interacts with a DNA structure-specific endonuclease, Mus81–Eme1. Genetic data indicate that Mus81–Eme1 and Rad54 might function together in the repair of damaged DNA. In vitro, Rad54 promotes branch migration of Holliday junctions, whereas the Mus81–Eme1 complex resolves DNA junctions by endonucleolytic cleavage. Here, we show that human Rad54 stimulates Mus81–Eme1 endonuclease activity on various Holliday junction-like intermediates. This stimulation is the product of specific interactions between the human Rad54 (hRad54) and Mus81 proteins, considering that
Saccharomyces cerevisiae
Rad54 protein does not stimulate human Mus81–Eme1 endonuclease activity. Stimulation of Mus81–Eme1 cleavage activity depends on formation of specific Rad54 complexes on DNA substrates occurring in the presence of ATP and, to a smaller extent, of other nucleotide cofactors. Thus, our results demonstrate a functional link between the branch migration activity of hRad54 and the structure-specific endonuclease activity of hMus81–Eme1, suggesting that the Rad54 and Mus81–Eme1 proteins may cooperate in the processing of Holliday junction-like intermediates during homologous recombination or DNA repair.
Initiation and elongation in fibrillation of ALS-linked superoxide dismutase
Authors: Chattopadhyay Madhuri , Durazo Armando , Sohn Se Hui , Strong Cynthia D. , Gralla Edith B. , Whitelegge Julian P. , Valentine Joan Selverstone
Published: November 2008

Familial amyotrophic lateral sclerosis (fALS) caused by mutations in copper–zinc superoxide dismutase (SOD1) is characterized by the presence of SOD1-rich inclusions in spinal cords. Similar inclusions observed in fALS transgenic mice have a fibrillar appearance suggestive of amyloid structure. Metal-free apo-SOD1 is a relatively stable protein and has been shown to form amyloid fibers in vitro only when it has been subjected to severely destabilizing conditions, such as low pH or reduction of its disulfide bonds. Here, by contrast, we show that a small amount of disulfide-reduced apo-SOD1 can rapidly initiate fibrillation of this exceptionally stable and highly structured protein under mild, physiologically accessible conditions, thus providing an unusual demonstration of a specific, physiologically relevant form of a protein acting as an initiating agent for the fibrillation of another form of the same protein. We also show that, once initiated, elongation can proceed via recruitment of either apo- or partially metallated disulfide-intact SOD1 and that the presence of copper, but not zinc, ions inhibits fibrillation. Our findings provide a rare glimpse into the specific changes in a protein that can lead to nucleation and into the ability of amyloid nuclei to recruit diverse forms of the same protein into fibrils.
Giant Stark effect in quantum dots at liquid/liquid interfaces: A new option for tunable optical filters
Authors: Flatté M. E. , Kornyshev A. A. , Urbakh M.
Published: November 2008

Control of the fundamental absorption edge of a quantum dot with an applied electric field has been limited by the breakdown fields of the solid-state material surrounding the dot. However, much larger fields can be applied at the interface of two immiscible electrolytic solutions (ITIES) in an electrochemical cell. These electric fields also localize the quantum dots at the ITIES. Our analysis shows that semiconductor nanocrystals localized at the ITIES should have electric-field-tunable optical properties across much of the visible spectrum. The transparency of the liquids in such cells indicates that this configuration would be well suited for electrically tunable optical filters with wide-angle acceptance.
Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome
Authors: Xue Yuan , Religa Piotr , Cao Renhai , Hansen Anker Jon , Lucchini Franco , Jones Bernt , Wu Yan , Zhu Zhenping , Pytowski Bronislaw , Liang Yuxiang , Zhong Weide , Vezzoni Paolo , Rozell Björn , Cao Yihai
Published: November 2008

The underlying mechanism by which anti-VEGF agents prolong cancer patient survival is poorly understood. We show that in a mouse tumor model, VEGF systemically impairs functions of multiple organs including those in the hematopoietic and endocrine systems, leading to early death. Anti-VEGF antibody, bevacizumab, and anti-VEGF receptor 2 (VEGFR-2), but not anti-VEGFR-1, reversed VEGF-induced cancer-associated systemic syndrome (CASS) and prevented death in tumor-bearing mice. Surprisingly, VEGFR2 blockage improved survival by rescuing mice from CASS without significantly compromising tumor growth, suggesting that “off-tumor” VEGF targets are more sensitive than the tumor vasculature to anti-VEGF drugs. Similarly, VEGF-induced CASS occurred in a spontaneous breast cancer mouse model overexpressing
neu
. Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs.
Transcriptome analysis and identification of regulators for long-term plasticity inAplysia kurodai
Authors: Lee Yong-Seok , Choi Sun-Lim , Kim Tae-Hyung , Lee Jin-A , Kim Hyong Kyu , Kim Hyoung , Jang Deok-Jin , Lee Jennifer J. , Lee Sunghoon , Sin Gwang Sik , Kim Chang-Bae , Suzuki Yutaka , Sugano Sumio , Kubo Tai , Moroz Leonid L. , Kandel Eric R. , Bhak Jong , Kaang Bong-Kiun
Published: November 2008

The marine molluskAplysiais a useful model organism for studying the cellular bases of behavior and plasticity. However, molecular studies ofAplysiahave been limited by the lack of genomic information. Recently, a large scale characterization of neuronal transcripts was performed inA. californica. Here, we report the analysis of a parallel set of neuronal transcripts from a closely related speciesA. kurodaifound in the northwestern Pacific. We collected 4,859 nonredundant sequences from the nervous system tissue ofA. kurodai. By performing microarray and real-time PCR analyses, we found that ApC/EBP, matrilin, antistasin, and eIF3e clones were significantly up-regulated and a BAT1 homologous clone was significantly down-regulated by 5-HT treatment. Among these, we further demonstrated that the Ap-eIF3e plays a key role in 5-HT-induced long-term facilitation (LTF) as a positive regulator.
Metagenomic analysis indicates that stressors induce production of herpes-like viruses in the coral
Porites compressa
Authors: Vega Thurber Rebecca L. , Barott Katie L. , Hall Dana , Liu Hong , Rodriguez-Mueller Beltran , Desnues Christelle , Edwards Robert A. , Haynes Matthew , Angly Florent E. , Wegley Linda , Rohwer Forest L.
Published: November 2008

During the last several decades corals have been in decline and at least one-third of all coral species are now threatened with extinction. Coral disease has been a major contributor to this threat, but little is known about the responsible pathogens. To date most research has focused on bacterial and fungal diseases; however, viruses may also be important for coral health. Using a combination of empirical viral metagenomics and real-time PCR, we show that
Porites compressa
corals contain a suite of eukaryotic viruses, many related to the Herpesviridae. This coral-associated viral consortium was found to shift in response to abiotic stressors. In particular, when exposed to reduced pH, elevated nutrients, and thermal stress, the abundance of herpes-like viral sequences rapidly increased in 2 separate experiments. Herpes-like viral sequences were rarely detected in apparently healthy corals, but were abundant in a majority of stressed samples. In addition, surveys of the
Nematostella
and
Hydra
genomic projects demonstrate that even distantly related Cnidarians contain numerous herpes-like viral genes, likely as a result of latent or endogenous viral infection. These data support the hypotheses that corals experience viral infections, which are exacerbated by stress, and that herpes-like viruses are common in Cnidarians.
Cdk5 is essential for adult hippocampal neurogenesis
Authors: Lagace Diane C. , Benavides David R. , Kansy Janice W. , Mapelli Marina , Greengard Paul , Bibb James A. , Eisch Amelia J.
Published: November 2008

The molecular factors regulating adult neurogenesis must be understood to harness the therapeutic potential of neuronal stem cells. Although cyclin-dependent kinase 5 (Cdk5) plays a critical role in embryonic corticogenesis, its function in adult neurogenesis is unknown. Here, we assessed the role of Cdk5 in the generation of dentate gyrus (DG) granule cell neurons in adult mice. Cre recombinase-mediated conditional knockout (KO) of Cdk5 from stem cells and their progeny in the DG subgranular zone (SGZ) prevented maturation of new neurons. In addition, selective KO of Cdk5 from mature neurons throughout the hippocampus reduced the number of immature neurons. Furthermore, Cdk5 gene deletion specifically from DG granule neurons via viral-mediated gene transfer also resulted in fewer immature neurons. In each case, the total number of proliferating cells was unaffected, indicating that Cdk5 is necessary for progression of adult-generated neurons to maturity. This role for Cdk5 in neurogenesis was activating-cofactor specific, as p35 KO but not p39 KO mice also had fewer immature neurons. Thus, Cdk5 has an essential role in the survival, but not proliferation, of adult-generated hippocampal neurons through both cell-intrinsic and cell-extrinsic mechanisms.
Decreased number of FoxP3+ regulatory T cells in preeclampsia
Authors: TOLDI GERGELY , ŠVEC PETER , VÁSÁRHELYI BARNA , MÉSZÁROS GERGO , RIGÓ JÁNOS , TULASSAY TIVADAR , TRESZL ANDRÁS
Published: November 2008

Systemic inflammation is characteristic for preeclampsia (PE). A hypothesis for immune dysregulation is that the function of regulatory T cells (CD4+FoxP3+, Tregs) inhibiting the activation of lymphocytes is impaired. We investigated the proportion of Tregs and their cellular network in preeclamptic women. Fifteen preeclamptic and 17 healthy pregnant women were enrolled in the 32nd gestational week (median age 29 (range 22–45) and 32 (range 26–38) years, respectively). PE was diagnosed according to international criteria at a median of 30 gestational weeks (range 21–31). Peripheral blood was taken and blood mononuclear cells were isolated. Flow cytometry was used to determine the proportion of regulatory (CD4+FoxP3+) T cells, lymphoid and myeloid dendritic cells, natural killer and natural killer T cells, naive and memory and activated CD4+ and CD8+cells. The proportion of Tregs and that of naive CD4+CD45RA+ cells was lower in preeclamptic than in control women (p = 0.025, p = 0.04, respectively). The proportion of other investigated cell types did not differ. Low Treg numbers may support the notion that PE shares similar features to autoimmune disorders. Low Treg numbers are not reflected in the proportion of activated lymphocytes, at least in this stage of pregnancy. This does not exclude, however, the functional alterations of these cell types.
Effect of availability of fetal ECG monitoring on operative deliveries
Authors: KALE ANITA , CHONG YAP‐SENG , BISWAS ARIJIT
Published: November 2008

Objective. The objective of our study was to test the hypothesis that the availability and selective use of STAN® in conjunction with cardiotocography for intrapartum monitoring, lowers the incidence of operative deliveries for fetal distress. Design. Observational study. Setting. Delivery suite of the National University Hospital, Singapore. Methods. The data regarding intrapartum cesarean sections and instrumental vaginal deliveries for presumed fetal distress and the condition of the neonate at birth (Apgar scores at one and five minutes and admission to neonatal intensive care unit (NICU) were collected over two consecutive three‐year periods. In the first triennium, only external cardiotocography was used for intrapartum fetal surveillance and in the second triennium STAN® monitoring was available for use in the delivery suite. Results. With the availability and selective use of STAN® monitoring, there was a significant decrease in the number of instrumental deliveries for fetal distress (from 66 out of 520 (0.9%) to 36 out of 474 (0.5%), p<0.025), the number of admissions to the NICU (from 418 (5.6%) to 311 (4.6%), p <0.01) and the number of neonates with Apgar score of seven or less at five minutes (from 192 (2.6%), p<0.001 to 113 (1.7%), p<0.001). There was no significant difference in the incidence of emergency cesarean sections for fetal distress during the two time periods. Conclusion. Intrapartum monitoring of term fetuses with cardiotocography combined with selective use of ST analysis leads to a significant reduction in the number of operative deliveries for suspected fetal distress with no adverse effect on neonatal outcome.
Design Issues and Application of Cable‐Based Parallel Manipulators for Rehabilitation Therapy
Authors: Ottaviano E.
Published: November 2008

In this study, cable‐based manipulators are proposed for application in rehabilitation therapies. Cable‐based manipulators show good features that are very useful when the system has to interact with humans. In particular, they can be used to aid motion or as monitoring/training systems in rehabilitation therapies. Modelling and simulation of both active and passive cable‐based parallel manipulators are presented for an application to help older people, patients or disabled people in the sit‐to‐stand transfer and as a monitoring/training system. Experimental results are presented by using built prototypes.
Complexity reduction in context-dependent DNA substitution models
Authors: Majoros William H. , Ohler Uwe
Published: November 2008

Motivation: The modeling of conservation patterns in genomic DNA has become increasingly popular for a number of bioinformatic applications. While several systems developed to date incorporate context-dependence in their substitution models, the impact on computational complexity and generalization ability of the resulting higher order models invites the question of whether simpler approaches to context modeling might permit appreciable reductions in model complexity and computational cost, without sacrificing prediction accuracy.

Results: We formulate several alternative methods for context modeling based on windowed Bayesian networks, and compare their effects on both accuracy and computational complexity for the task of discriminating functionally distinct segments in vertebrate DNA. Our results show that substantial reductions in the complexity of both the model and the associated inference algorithm can be achieved without reducing predictive accuracy.

Contact:  bmajoros@duke.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
CleaveLand: a pipeline for using degradome data to find cleaved small RNA targets
Authors: Addo-Quaye Charles , Miller Webb , Axtell Michael J.
Published: November 2008

Summary: MicroRNAs (miRNAs) are ∼20- to 22-nt long endogenous RNA sequences that play a critical role in the regulation of gene expression in eukaryotic genomes. Confident identification of miRNA targets is vital to understand their functions. Currently available computational algorithms for miRNA target prediction have diverse degrees of sensitivity and specificity and as a consequence each predicted target generally requires experimental confirmation. miRNAs and other small RNAs that direct endonucleolytic cleavage of target mRNAs produce diagnostic uncapped, polyadenylated mRNA fragments. Degradome sequencing [also known as PARE (parallel analysis of RNA ends) and GMUCT (genome-wide mapping of uncapped transcripts)] samples the 5′-ends of uncapped mRNAs and can be used to discover in vivo miRNA targets independent of computational predictions. Here, we describe a generalizable computational pipeline, CleaveLand, for the detection of cleaved miRNA targets from degradome data. CleaveLand takes as input degradome sequences, small RNAs and an mRNA database and outputs small RNA targets. CleaveLand can thus be applied to degradome data from any species provided a set of mRNA transcripts and a set of query miRNAs or other small RNAs are available.

Availability: The code and documentation for CleaveLand is freely available under a GNU license at http://www.bio.psu.edu/people/faculty/Axtell/AxtellLab/Software.html

Contact:  mja18@psu.edu
Elective Parotidectomy in the Management of Advanced Auricular Malignancies
Authors: Osborne Ryan F. , Shaw Travis , Zandifar Hootan , Kraus Dennis
Published: November 2008

Objective: The purpose of this study is to determine whether elective parotidectomy is necessary in patients with clinically and radiographically N0 parotid disease with isolated primary auricular nonmelanoma cutaneous malignancies. Auricular malignancies are typically managed by wedge resection or wide local excision. Although small lesions are easily managed by conservative excision, large bulky tumors, those with multifocal involvement, and recalcitrant lesions, often require more extensive resection including total auriculectomy, parotidectomy, and/or neck dissection.

Study Design: A 10‐year retrospective case review from four tertiary university medical centers from 1992 to 2002.

Methods: Information was retrospectively retrieved using a database of patients from the department of pathology. Seventy‐one charts were reviewed. Patients with a clinical history of advanced nonmelanoma auricular carcinoma undergoing elective parotidectomy and/or neck dissection with clinically and radiographically N0 nodal disease were evaluated for the presence of occult parotid metastasis. All patients underwent parotidectomy in conjunction with a total auriculectomy for surgical extirpation of their primary auricular carcinoma. Parotid specimens were evaluated for histopathologic evidence of metastatic neoplastic disease.

Results: Pathological examination showed no histological evidence of occult parotid metastasis in all 19 patients who underwent elective parotidectomy in the presence of clinically and radiographically N0 nodal disease of the parotid or cervical regions.

Conclusions: Parotidectomy may not be necessary in the surgical management of advanced auricularcarcinoma in the absence of clinically positive parotid disease or external auditory canal involvement.
Sexual Problems After Total or Partial Laryngectomy
Authors: Singer Susanne , Danker Helge , Dietz Andreas , Kienast Ulrike , Pabst Friedemann , Meister Eberhard F. , Oeken Jens , Thiele Alexander , Schwarz Reinhold
Published: November 2008

Objectives: To investigate sexual problems that can occur after laryngeal and hypopharyngeal cancer surgery and to specify possible influencing factors.

Study Design: Multi‐institutional cross‐sectional study.

Methods: Two hundred six patients were interviewed in person using the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Head and Neck Module (EORTC QLQ‐H&N35), the Hospital Anxiety and Depression Scale, and a structured interview assessing alcohol and tobacco consumption, sociodemographic data, and specific sexual problems. Type of surgery, tumor site, and tumor stage were documented according to the participants' medical records. Multivariate analysis of variance was used to assess the independent impact of each factor.

Results: More than half of the patients in our study reported having reduced libido and sexual enjoyment after treatment. Sixty percent considered it an important issue for their contentment with life. Sexual difficulties were found to be unrelated with gender, formal education, alcohol and tobacco consumption, type of surgery (partial vs. total laryngectomy), radiotherapy, and tumor site. Psychological distress (F = 46.27, P < .001) was seen to have a strong independent impact on the occurrence of sexual difficulties and stage of disease (F = 4.50, P < .05) and age (F = 4.79, P < .05), a moderate independent impact.

Conclusions: Reduced libido and sexual enjoyment is a common problem after laryngeal and hypopharyngeal cancer surgery. However, it is not caused by the oncological treatment but rather by the cancer itself. Depression is often associated with sexual problems. Both should be discussed in medical consultations with head and neck cancer patients when appropriate to provide adequate treatment.
Anatomy of the Middle‐Turn Cochleostomy
Authors: Isaacson Brandon , Roland Peter S. , Wright Charles G.
Published: November 2008

Objective: Middle‐turn cochleostomies are occasionally used for cochlear implant electrode placement in patients with labyrinthitis ossificans. This study evaluates the anatomic characteristics of the middle‐turn cochleostomy and its suitability for placement of implant electrodes.

Methods: Ten cadaveric human temporal bones were dissected using a facial recess approach. A middle‐turn cochleostomy was drilled 2 mm anterior to the oval window and just inferior to the cochleariform process. The preparations were then stained with osmium tetroxide and microdissections were performed. The location of the cochleostomy on the cochlear spiral and its path through the various cochlear compartments were evaluated in all 10 specimens. A Cochlear Corporation depth gauge was inserted in five of the specimens and insertion trauma, number of contact rings, and depth of insertion were recorded.

Results: Eight of the 10 cochleostomies were placed at approximately 360° on the cochlear spiral, near the transition between the basal and middle turns. In one case, the cochleostomy was found to enter the cochlear apex and in another it entered scala vestibuli of the proximal basal turn. The cochleostomy entered scala media in six bones and scala vestibuli in four specimens. A depth gauge was inserted in five specimens. The number of contacts placed within the cochlear lumen ranged from four to nine. There was evidence of insertional trauma to the lateral wall of the cochlear duct, basilar membrane, and Reissner's membrane, but no evidence of fractures to the osseous spiral lamina or modiolus.

Conclusion: This study demonstrates that electrodes inserted via a middle‐turn cochleostomy are likely to enter scala vestibuli and have access to the middle‐ and apical‐cochlear turns. It is also possible that the electrode could be directed into the descending portion of the basal turn depending on cochleostomy orientation. Middle‐turn cochleostomy seems to be a viable alternative for electrode placement when preservation of residual hearing is not a concern.
Proteomics Blood Testing to Distinguish Chronic Rhinosinusitis Subtypes
Authors: Das Subinoy , Maeso Patricia A. , Becker Adam M. , Prosser John D. , Adam Bao‐Ling , Kountakis Stilianos E.
Published: November 2008

Objectives: To evaluate the potential of surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF‐MS) proteomic profiling of serum samples to distinguish chronic rhinosinusitis subtypes.

Study Design: Translational study of serum samples from prospectively enrolled patients undergoing sinus surgery.

Methods: Patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis were prospectively enrolled in an ongoing, institutional review board approved proteomics study. SELDI‐TOF‐MS was performed on 42 serum samples in patients with chronic rhinosinusitis with nasal polyposis (15 patients diagnosed with allergic fungal rhinosinusitis, 10 patients with Samter's triad, and 17 with chronic rhinosinusitis with nasal polyposis). Classification tree analysis on protein spectra developed from peaks detected in the 0 to 100 kD range was performed to identify disease subtypes.

Results: SELDI‐TOF‐MS correctly identified patients with allergic fungal rhinosinusitis from serum samples with 84% sensitivity and 90% specificity, and correctly identified patients with Samter's triad with 88% sensitivity and 88% specificity in two subtype comparison groups. SELDI‐TOF‐MS correctly identified patients with allergic fungal rhinosinusitis with 76% sensitivity and 82% specificity, and correctly identified patients with Samter's triad with 80% sensitivity and 90% specificity in three subtype comparison groups.

Conclusion: The study provides molecular evidence that allergic fungal rhinosinusitis is a discrete subtype of chronic rhinosinusitis. SELDI‐TOF‐MS is a promising technology that could lead to the development of a rapid blood test, to identify severe chronic rhinosinusitis subtypes. Further investigation into the utility of this technology is warranted.
Treatment of Sinus Headache as Migraine: The Diagnostic Utility of Triptans
Authors: Kari Elina , DelGaudio John M.
Published: November 2008

Objective: To determine the response rate to triptans in alleviating “sinus headache” in patients with endoscopy‐ and computed tomography (CT)‐negative sinus examinations.

Study Design: Prospective clinical trial.

Methods: Patients who presented to a tertiary care center Otolaryngology Department with primary complaints of facial pain, pressure, or headache localized over the area of the sinuses, and a self‐ or physician‐diagnosis of “sinus headache” were enrolled. Patients underwent directed history, physical examination, rigid nasal endoscopy, a sinus CT scan, and completed a headache questionnaire. Those patients that had negative findings were treated empirically with triptans. Patients completed a headache diary for each headache, using a visual analogue scale to rate the headache before and after triptan use. Response was considered as significant improvement (greater than 50% reduction of pain), partial (25–50% reduction), and no response.

Results: Fifty‐four patients were enrolled. Thirty‐eight (69%) completed follow‐up, 63% were women. The mean age was 41 years (23–70). Thirty‐one patients (82%) had significant reduction of headache pain with triptan use. Thirty‐five patients (92%) had a significant reduction in headache pain in response to migraine‐directed therapy. Seventeen patients (31%) withdrew or failed to follow‐up, often reluctant to accept a diagnosis of migraine.

Conclusions: This study demonstrated that the demographics of patients with self‐described “sinus headaches” who did not have findings of sinusitis on endoscopy and CT scan closely reflected the demographics of patients afflicted with migraines. It also showed that 82% of these patients had a significant response to empiric treatment for sinus headaches with triptans. These findings support that “sinus headaches” may represent migraines, and response to triptans may aid in diagnosis.
Management of Spontaneous Cerebrospinal Fluid Otorrhea
Authors: Kutz Joe Walter , Husain Inna Athar , Isaacson Brandon , Roland Peter S.
Published: November 2008

Objectives/Hypothesis: To describe the surgical approaches and materials used to repair spontaneous cerebrospinal fluid (CSF) otorrhea of temporal bone origin.

Study Design: Retrospective case review at a tertiary academic medical center.

Methods: All patients presenting with spontaneous CSF otorrhea or rhinorrhea over a consecutive 8‐year period were included. Clinic charts and operative reports were reviewed to obtain the clinical presentation, examination findings, diagnostic test results, intraoperative findings, operative technique, and postoperative follow‐up. Surgical approach and materials used for repair were determined by the location of the defect(s) and surgeon preference.

Results: Seventeen patients underwent 19 operations for repair of spontaneous CSF otorrhea or rhinorrhea. The mean age was 61 years and the male to female ratio was 5:12. All female patients had a body mass index (BMI) greater than 30 mg/kg2. The most common presenting symptom was otorrhea after a myringotomy or placement of a tympanostomy tube. A middle fossa craniotomy was used in 17 approaches. The most common defect sites were located over the tegmen mastoideum and tegmen tympani. Multiple materials were used in most repairs including allogenic bone cement and autologous materials. One patient had persistent otorrhea after a transmastoid approach and required a middle fossa craniotomy to repair a tegmen mastoideum defect.

Conclusions: Spontaneous CSF otorrhea is uncommon and often not diagnosed until a myringotomy or tympanostomy tube is placed. The middle fossa craniotomy provides the best exposure for defects involving the middle fossa floor. Both alloplastic and autologous materials are highly successful in repairing the defect(s) responsible for CSF otorrhea. No infections of the alloplastic bone cement occurred in our series.
Malignancies of the Ear in Irradiated Patients of Nasopharyngeal Carcinoma
Authors: Lo Wu‐Chia , Ting Lai‐Lei , Ko Jenq‐Yuh , Lou Pei‐Jen , Yang Tsung‐Lin , Chang Yih‐Leong , Wang Cheng‐Ping
Published: November 2008

Objectives/Hypothesis: To report on the clinical profiles and treatment experiences of patients with second primary ear malignancy after treatment of nasopharyngeal carcinoma (NPC).

Study Design: Retrospective case series.

Methods: A retrospective review of the clinical outcomes and pathology of 11 irradiated NPC patients who subsequently had second primary malignancies of the ear at a single institution.

Results: Ten tumors were squamous cell carcinoma and one tumor was chondrosarcoma occurring within the radiation field of previous treatment for NPC. The interval between previous radiotherapy and diagnosis of ear malignancy was 3 to 27 years with a median time of 17 years. Six tumors were located in the external auditory canal, two in the middle ear cavity, two in the periauricular region and one in the mastoid cavity. Four patients underwent surgery, and the other seven patients underwent surgery plus adjuvant radiotherapy. The 3‐year disease‐free and overall survival rates were 30.3% and 20%, respectively.

Conclusions: Postirradiated malignancy of the ear is extremely rare, but is one of the causes of death for NPC long‐term survivors despite curative‐intended treatment with surgery plus adjuvant radiotherapy is instituted.
Regeneration of Aged Vocal Fold: First Human Case Treated With Fibroblast Growth Factor
Authors: Hirano Shigeru , Kishimoto Yo , Suehiro Atsushi , Kanemaru Shin‐ichi , Ito Juichi
Published: November 2008

Background/Objectives: Aged vocal folds are characterized by atrophy of the mucosa, which causes dysphonia and is difficult to treat. We have revealed a therapeutic potential of basic fibroblast growth factor (bFGF) for tissue regeneration of the aged vocal fold. We report here the first human case that has been treated with bFGF.

Study Design: Institutional review board approved clinical human trial.

Methods: A 63‐year‐old man with atrophied vocal folds was treated by local injection of 10 μg of bFGF into the left vocal fold under topical anesthesia. The effects of the injection were examined after 1 to 3 months by videostroboscopy, acoustic and aerodynamic measurements.

Results: The atrophy of the vocal fold was improved at 1 week after the injection and glottic gap disappeared. Aerodynamic and acoustic parameters also showed remarkable improvement. These positive effects were maintained up to 3 months.

Conclusion: The first case with aged vocal folds treated with bFGF administration is presented. The results are encouraging, suggesting therapeutic effects of bFGF for atrophied vocal folds in human.
Differential Diagnosis of Adductor Spasmodic Dysphonia and Muscle Tension Dysphonia Using Phonatory Break Analysis
Authors: Roy Nelson , Whitchurch Melissa , Merrill Ray M. , Houtz Daniel , Smith Marshall E.
Published: November 2008

Objectives: Muscle tension dysphonia (MTD) can masquerade as adductor spasmodic dysphonia (ADSD) leading to diagnostic confusion. Intraword phonatory breaks have been offered as the sine qua non of ADSD, however, little is known regarding the presence of phonatory breaks in MTD. This investigation assessed the diagnostic worth of acoustic analysis of phonatory breaks as a possible objective test to distinguish ADSD from MTD.

Study Design: Case‐control comparison.

Methods: Voice samples from patients with confirmed ADSD (n = 41) and MTD (n = 59) were analyzed acoustically to determine the presence, frequency, and duration of phonatory breaks—defined as complete interruption of phonation within a word. Estimates of sensitivity, specificity, positive and negative predictive value, and likelihood ratios were calculated to determine the precision and worth of phonatory break analysis as a clinical diagnostic test.

Results: 1) Individuals with ADSD showed a significantly higher number of phonatory breaks as compared with MTD. 2) All measures of diagnostic precision varied according to both duration and frequency of phonatory breaks, with separation of males and females leading to different diagnostic test performance results.

Conclusions: The results suggest that phonatory break analysis offers promise as an objective test to distinguish ADSD from MTD, with respectable diagnostic precision, especially among men. Automation of the acoustic analysis procedure should be explored.
Early Mortality Rate of Morbidly Obese Patients after Tracheotomy
Authors: Darrat Ilaaf , Yaremchuk Kathleen
Published: November 2008

Objectives: To 1) determine the early mortality rate (within 30 days) of morbidly obese patients after tracheotomy; 2) determine the difference between the mortality rate after tracheotomy of morbidly obese patients and patients who are not morbidly obese; and 3) determine the difference between the mortality rate after tracheotomy adjusted for case mix index (CMI) of morbidly obese patients and patients who are not morbidly obese.

Study Design: Retrospective cohort study of 278 patients who had undergone a tracheotomy by the otolaryngology head and neck surgery department from 2004 to 2006. The patients were subdivided into two groups: 1) body mass index (BMI) <35 (n = 229) and 2) BMI ≥35 (morbidly obese) (n = 49).

Methods: Charts reviewed for age, sex, weight, height, BMI, indication for tracheotomy, date of tracheotomy, type of tracheotomy, date of discharge, date of death, length of hospital stay, and CMI.

Results: There is a trend toward significance (P = .09) between the mortality rate after tracheotomy of morbidly obese patients (29%) and patients who are not morbidly obese (18%). There is less significance between the adjusted mortality rate based on CMI after tracheotomy when the patient population is divided into morbidly obese patients and patients who are not morbidly obese (P = .12).

Conclusion: The mortality rate after tracheotomy of morbidly obese patients is greater than patients who are not morbidly obese.
Revision Laryngeal Surgery for the Suboptimal Injection of Calcium Hydroxylapatite
Authors: Chheda Neil N. , Rosen Clark A. , Belafsky Peter C. , Simpson C Blake , Postma Gregory N.
Published: November 2008

Objective: The objective of this study was to describe the management of suboptimal injection of calcium hydroxylapatite during augmentation laryngoplasty.

Study Design: A retrospective review was conducted at four Voice and Swallowing centers to identify patients who had a suboptimal injection of calcium hydroxylapatite during augmentation laryngoplasty.

Results: Five patients (ages 19–75) were identified with an impaired voice secondary to a superficial injection of calcium hydroxylapatite or over‐medialization of the true vocal fold. All patients underwent revision surgery with all experiencing subjective and objective improvement.

Conclusion: Microflap excision can lead to successful return of vibratory function after a suboptimal injection of calcium hydroxylapatite. Complete control of the initial injection is paramount to avoiding this complication.
Avoiding Early Revision Rhytidectomy: A Biomechanical Comparison of Tissue Plication Suture Techniques
Authors: White Jeremy B. , Barraja Mathieu , Mengesha Tewodros , Bose Sumit , Ashktorab Samaneh , Bahn Ryan , Vallance Ryan , Lindsey William H.
Published: November 2008

Background: Manipulation and suspension of the superficial musculoaponeurotic system (SMAS) is performed by 74% of rhytidectomy surgeons. Multiple variations in suture techniques are employed in this task, but they have never been evaluated for differences in their ability to withstand stress.

Objective: To compare the biomechanical properties of two different suture techniques that are used in SMAS plications during rhytidectomy: a double‐layered running locking (DRL) stitch and multiple horizontal mattress stitches.

Methods: Fourteen horizontal mattress plications, in rows of six sutures, and comparable lengths of 16 DRL stitch plications of pig skin samples, were stressed using a tensometer with grip displacement increasing at a constant rate of 0.5 cm/Min. The required force to cause plication failure was recorded for each sample at three suture break points.

Results: There was no significant difference between the two groups in the force required to cause the initial suture failure. Unlike the horizontal mattress plication, an initial break seemed to cause minimal to no distortion of the DRL tissue plication. When results were normalized by the initial break forces to account for small variations in tissue properties, the force ratio required to cause a second suture break was significantly larger in the DRL group than in the horizontal mattress technique. This is evidenced by the average second to first break force ratios of 1.62 vs. 1.13 for the DRL and horizontal mattress stitches, respectively, with a P‐value of .60. The mean ratios of third to first break forces for the DRL and horizontal mattress groups were 2.08 and 0.91, respectively, with a P‐value of .08.

Conclusion: The DRL stitch requires more force than the horizontal mattress stitch to cause significant failure of tissue plication. This technique may enable plastic surgeons to avoid early revision rhytidectomy due to suture failure, and to create a long‐lasting, youthful cosmetic result.
Paecilomyces lilacinus peritonitis complicating peritoneal dialysis cured by oral voriconazole and terbinafine combination therapy
Authors: Chang Brian Pin-Hsuan , Sun Pei-Lun , Huang Fu-Yuan , Tsai Tsuen-Chiuan , Lin Chun-Chen , Lee Ming-Dar , Chen Yee-Chun , Sheu Jin-Cherng , Tsai Jeng-Daw
Published: November 2008

Fungal peritonitis (FP) is a serious complication in patients on continuous ambulatory peritoneal dialysis (CAPD). We report a case of CAPD-related FP caused by Paecilomyces lilacinus in a 15-year-old uraemic boy. The infection was successfully treated by combination therapy consisting of oral voriconazole and terbinafine, which has not been previously reported in the treatment of FP.
Synergy of gatifloxacin with cefoperazone and cefoperazone–sulbactam against resistant strains of Pseudomonas aeruginosa
Authors: Sivagurunathan N. , Krishnan S. , Rao J. Venkat , Nagappa Anantha Naik , Subrahmanyam V. M. , Vanathi B. Meenashi
Published: November 2008

Chequerboard and time–kill methods were used to compare the in vitro efficacies of the combinations gatifloxacin (GAT) with cefoperazone (CFP) and GAT with cefoperazone–sulbactam (CFP-SUL) against 58 clinical isolates of Pseudomonas aeruginosa. The combinations GAT+CFP and GAT+CFP-SUL were shown to be synergistic for 36.2 and 58.6 % of isolates tested, respectively, using the chequerboard method. Time–kill studies with 11 strains showed synergy in 54.5 % for the GAT+CFP combination and 72.7 % for the GAT+CFP-SUL combination. The agreement between these two methods was found to be 72–81 %. There was a significant difference in synergy between the two combinations tested (P=0.011).
Prevalence and dissemination of the Ser315Thr substitution within the KatG enzyme in isoniazid-resistant strains of Mycobacterium tuberculosis isolated in Uruguay
Authors: Varela Gustavo , González Sabina , Gadea Pilar , Coitinho Cecilia , Mota Inés , González Gladys , Goñi Fernando , Rivas Carlos , Schelotto Felipe
Published: November 2008

The aim of this study was to determine the prevalence of Ser315Thr substitution in isoniazid (INH)-resistant strains of Mycobacterium tuberculosis in Uruguay. The katG gene of 62 INH-resistant strains was analysed by an RFLP-PCR assay. PCR products were digested with MspI to detect Ser315Thr and Arg463Leu substitutions. A total of 16 of the 62 (26 %) INH-resistant strains analysed had a Ser315Thr substitution. Only one INH-resistant strain had an Arg463Leu substitution and two strains had a deletion in katG. Of the 16 strains with Ser315Thr, 15 showed different profiles using a double-repetitive-element PCR assay, demonstrating that there was no local dissemination of any particular strain. These findings are in agreement with published data from regions where the prevalence of tuberculosis (TB) is intermediate and may be due in part to the success of the local TB control programme.