bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening rhizobacteria for improving the growth, yield, and oil content of canola (Brassica napus L.)
Authors: Asghar H. N. , Zahir Z. A. , Arshad M.
Published: February 2004

One hundred rhizobacteria previously isolated from the rhizospheres of Brassica species were screened for their growth promoting activity in Brassica napus L. under gnotobiotic conditions. Results revealed that 58% of the rhizobacteria increased root length (up to 139%), 39% enhanced shoot length (up to 78%), and shoot weight (up to 72%) of Brassica napus L. Based upon growth promotion of B. napus seedlings under gnotobiotic conditions, 10 promising plant-growth-promoting rhizobacteria (PGPR) were selected and tested for their effectiveness in growth promotion, yield, and oil content of B. napus grown in pots. The pot trials revealed that inoculation with selected PGPR increased plant height, root length, number of branches per plant, stem diameter, number of pods per plant, 1000-grain weight, grain yield, and oil content over a range of 7–57% above the uninoculated control. These isolates were then assayed for their ability to produce auxins in vitro in the presence and absence of L-tryptophan. Regression analysis showed that in vitro auxin production by these bacteria was significantly related to the number of branches and oil content of B. napus. It is highly likely that improvement in growth and yield of the inoculated plants is due to an increase in the number of branches per plant, since there was a positive correlation of this growth parameter with the number of pods per plant, 1000-grain weight, grain yield, and seed oil content. Results indicated that simultaneous screening of rhizobacteria for growth promotion under gnotobiotic conditions and in vitro production of auxins could be a useful approach for selecting effective PGPR.
Lettuce big-vein disease: sources, patterns of spread, and losses
Authors: Latham L. J. , Jones R. A. C. , McKirdy S. J.
Published: February 2004

Most batches of lettuce seedlings taken over an 18-month period from a vegetable nursery were infested with lettuce big-vein disease (LBVD) with an up to 31% incidence. Using lettuce seedlings in bait tests, contamination was detected at the nursery in potting mix composted for different periods and in dirt from under the benches, and at the bark supplier's site in this ingredient of the potting mix and waste 'bark' from the ground. In a field experiment in which lettuce seedlings from the infested nursery were inoculated with infested roots or left uninoculated before transplanting into subplots on land with no history of lettuce planting, disease progress followed a sigmoid curve with the former but an almost straight line with the latter. However, significant clustering of symptomatic plants was found only in the subplot with the uninoculated plants. Leaf symptoms of LBVD were more severe in lettuces infested later, whereas symptoms in those infested earlier were obvious initially but then became milder. The disease impaired formation of hearts: the proportion of symptomatic plants that lacked hearts was 24–36% when leaf symptoms first appeared 5–7 weeks after transplanting, but 14–16% after 8–9 weeks. When leaf symptoms first appeared at 5–6 weeks, there was a fresh weight loss of 14–15% for heads (all plants) and 39% for hearts (excluding plants without hearts). When leaf symptoms first appeared 7 weeks after transplanting, there was no significant yield loss for heads and only a 14% loss for hearts. At 8–9 weeks, there were no significant yield losses for heads or hearts.
RAD and the RAD Study-Annotator: an approach to collection, organization and exchange of all relevant information for high-throughput gene expression studies
Authors: Manduchi E. , Grant G. R. , He H. , Liu J. , Mailman M. D. , Pizarro A. D. , Whetzel P. L. , Stoeckert C. J.
Published: February 2004

Motivation: Gene expression array technology has become increasingly widespread among researchers who recognize its numerous promises. At the same time, bench biologists and bioinformaticians have come to appreciate increasingly the importance of establishing a collaborative dialog from the onset of a study and of collecting and exchanging detailed information on the many experimental and computational procedures using a structured mechanism. This is crucial for adequate analyses of this kind of data.

Results: The RNA Abundance Database (RAD; http://www.cbil.upenn.edu/RAD) provides a comprehensive MIAME-supportive infrastructure for gene expression data management and makes extensive use of ontologies. Specific details on protocols, biomaterials, study designs, etc. are collected through a user-friendly suite of web annotation forms. Software has been developed to generate MAGE-ML documents to enable easy export of studies stored in RAD to any other database accepting data in this format (e.g. ArrayExpress). RAD is part of a more general Genomics Unified Schema (http://www.gusdb.org), which includes a richly annotated gene index (http://www.allgenes.org), thus providing a platform that integrates genomic and transcriptomic data from multiple organisms. This infrastructure enables a large variety of queries that incorporate visualization and analysis tools and have been tailored to serve the specific needs of projects focusing on particular organisms or biological systems.

Availability: The system is freely available. Information on how to obtain it and how to install it can be found at http://www.cbil.upenn.edu/RAD/RAD-installation.htm
Rapid and sensitive dot-matrix methods for genome analysis
Authors: Huang Yue , Zhang Ling
Published: February 2004

Motivation: Dot-matrix plots are widely used for similarity analysis of biological sequences. Many algorithms and computer software tools have been developed for this purpose. Though some of these tools have been reported to handle sequences of a few 100 kb, analysis of genome sequences with a length of >10 Mb on a microcomputer is still impractical due to long execution time and computer memory requirement.

Results: Two dot-matrix comparison methods have been developed for analysis of large sequences. The methods initially locate similarity regions between two sequences using a fast word search algorithm, followed with an explicit comparison on these regions. Since the initial screening removes most of random matches, the computing time is substantially reduced. The methods produce high quality dot-matrix plots with low background noise. Space requirements are linear, so the algorithms can be used for comparison of genome size sequences. Computing speed may be affected by highly repetitive sequence structures of eukaryote genomes. A dot-matrix plot of Yeast genome (12 Mb) with both strands was generated in 80 s with a 1 GHz personal computer.

Availability: The implementation of the described methods in C language is available at http://www.lynnon.com/dotplot/index.html
Mismatch string kernels for discriminative protein classification
Authors: Leslie Christina S. , Eskin Eleazar , Cohen Adiel , Weston Jason , Noble William Stafford
Published: February 2004

Motivation: Classification of proteins sequences into functional and structural families based on sequence homology is a central problem in computational biology. Discriminative supervised machine learning approaches provide good performance, but simplicity and computational efficiency of training and prediction are also important concerns.

Results: We introduce a class of string kernels, called mismatch kernels, for use with support vector machines (SVMs) in a discriminative approach to the problem of protein classification and remote homology detection. These kernels measure sequence similarity based on shared occurrences of fixed-length patterns in the data, allowing for mutations between patterns. Thus, the kernels provide a biologically well-motivated way to compare protein sequences without relying on family-based generative models such as hidden Markov models. We compute the kernels efficiently using a mismatch tree data structure, allowing us to calculate the contributions of all patterns occurring in the data in one pass while traversing the tree. When used with an SVM, the kernels enable fast prediction on test sequences. We report experiments on two benchmark SCOP datasets, where we show that the mismatch kernel used with an SVM classifier performs competitively with state-of-the-art methods for homology detection, particularly when very few training examples are available. Examination of the highest-weighted patterns learned by the SVM classifier recovers biologically important motifs in protein families and superfamilies.

Availability: SVM software is publicly available at http://microarray.cpmc.columbia.edu/gist. Mismatch kernel software is available upon request.
Analysis and prediction of DNA-binding proteins and their binding residues based on composition, sequence and structural information
Authors: Ahmad Shandar , Gromiha M. Michael , Sarai Akinori
Published: February 2004

Motivation: Though vitally important to cell function, the mechanism of protein–DNA binding has not yet been completely understood. We therefore analysed the relationship between DNA binding and protein sequence composition, solvent accessibility and secondary structure. Using non-redundant databases of transcription factors and protein–DNA complexes, neural network models were developed to utilize the information present in this relationship to predict DNA-binding proteins and their binding residues.

Results: Sequence composition was found to provide sufficient information to predict the probability of its binding to DNA with nearly 69% sensitivity at 64% accuracy for the considered proteins; sequence neighbourhood and solvent accessibility information were sufficient to make binding site predictions with 40% sensitivity at 79% accuracy. Detailed analysis of binding residues shows that some three- and five-residue segments frequently bind to DNA and that solvent accessibility plays a major role in binding. Although, binding behaviour was not associated with any particular secondary structure, there were interesting exceptions at the residue level. Over-representation of some residues in the binding sites was largely lost at the total sequence level, but a different kind of compositional preference was observed in DNA-binding proteins.

Availability: Online predictions of DNA-binding proteins and binding sites are available at http://www.netasa.org/dbs-pred/
Inverse modeling using multi-block PLS to determine the environmental conditions that provide optimal cellular function
Authors: Hwang Daehee , Stephanopoulos George , Chan Christina
Published: February 2004

Motivations: Tissue engineering constitutes an important field with its potential of addressing the current shortage in organ availability. To successfully develop tissue-engineered organs, it is crucial to understand how to maintain the cells under conditions that maximize their ability to perform their physiological roles, regardless of the environment, whether the cells are part of an extracorporeal system, such as the bioartificial liver assist device, or an implantable tissue-engineered device. Our goals are to (1) provide insight into how cells will behave when confronted with changes in its environment and (2) determine the optimal environmental factors to achieve a desired level of cellular function.

Results: Diverse sets of environmental factors were used to systematically perturb the metabolic behavior associated with pre-conditioning and plasma supplementation. To probe metabolic state of hepatocytes, metabolic flux analysis was used to obtain the metabolic profile. We applied a multi-block partial least square (MPLS) model to relate environmental factors and fluxes to levels of intracellular lipids and urea synthesis. The MPLS model identified: (1) the most influential environmental factors and (2) how the metabolic pathways are altered by these factors. Finally, we inverted the MPLS model to determine the concentrations and types of environmental factors required to obtain the most economical solution for achieving optimal levels of cellular function for practical situations.

Supplementary information: Appendices can be accessed at http://www.chems.msu.edu/fac.pub/chan/MPLS_App.pdf
Comparison of Li–Wong and loglinear mixed models for the statistical analysis of oligonucleotide arrays
Authors: Chu Tzu-Ming , Weir B.S. , Wolfinger Russell D.
Published: February 2004

Motivation: Li and Wong have described some useful statistical models for probe-level, oligonucleotide array data based on a multiplicative parametrization. In earlier work, we proposed similar analysis-of-variance-style mixed models fit on a log scale. With only subtle differences in the specification of their mean and stochastic error components, a question arises as to whether these models could lead to varying conclusions in practical application.

Results: In this paper, we provide an empirical comparison of the two models using a real data set, and find the models perform quite similarly across most genes, but with some interesting and important distinctions. We also present results from a simulation study designed to assess inferential properties of the models, and propose a modified test statistic for the Li–Wong model that provides an improvement in Type 1 error control. Advantages of both methods include the ability to directly assess and account for key sources of variability in the chip data and a means to automate statistical quality control.

Availability: The Li–Wong models are available in dChip: http://www.biostat.harvard.edu/complab/dchip/, and both methods will be commercially available in the forthcoming SAS Microarray Solution.

Supplementary information: Supplementary material is available at http://statgen.ncsu.edu/ggibson/Pubs.htm
Tailored gene array databases: applications in mechanistic toxicology
Authors: Karpinets Tatiana V. , Foy Brent D. , Frazier John M.
Published: February 2004

Motivation: The development of an annotated global database suitable for a wide range of investigations is a challenging and labor-intensive task. Thus, the development of databases tailored for specific applications remains necessary. For example, in the field of toxicology, no annotated gene array databases are now available that may assist in the correlation of changes in gene activity to cellular functions and processes associated with the toxic response.

Results: As an example of a tailored annotated database, an attempt was made to systematize available biological information on genes present on the Affymetrix Rat Toxicology U34 GeneChip, with a focus on how the gene products relate to liver cells and their response to chemical toxins. The information collected was imbedded in a local relational database to analyze data obtained in toxicological gene array experiments with hydrazine–exposed hepatocytes. The advantages and benefits of the tailored database in the biological interpretation of the results are demonstrated.

Availability: The database and gene expression data set are available at http://www.wright.edu/~tatiana.karpinets/
Reducing the variability in cDNA microarray image processing by Bayesian inference
Authors: Lawrence Neil D. , Milo Marta , Niranjan Mahesan , Rashbass Penny , Soullier Stephan
Published: February 2004

Motivation: Gene expression levels are obtained from microarray experiments through the extraction of pixel intensities from a scanned image of the slide. It is widely acknowledged that variabilities can occur in expression levels extracted from the same images by different users with the same software packages. These inconsistencies arise due to differences in the refinement of the placement of the microarray ‘grids’. We introduce a novel automated approach to the refinement of grid placements that is based upon the use of Bayesian inference for determining the size, shape and positioning of the microarray ‘spots’, capturing uncertainty that can be passed to downstream analysis.

Results: Our experiments demonstrate that variability between users can be significantly reduced using the approach. The automated nature of the approach also saves hours of researchers’ time normally spent in refining the grid placement.

Availability: A MATLAB implementation of the algorithm and tiff images of the slides used in our experiments, as well as the code necessary to recreate them are available for non-commercial use from http://www.dcs.shef.ac.uk/~neil/VIS
Fundamentals of massive automatic pairwise alignments of protein sequences: theoretical significance of Z-value statistics
Authors: Bastien Olivier , Aude Jean-Christophe , Roy Sylvaine , Maréchal Eric
Published: February 2004

Motivation:Different automatic methods of sequence alignments are routinely used as a starting point for homology searches and function inference. Confidence in an alignment probability is one of the major fundamentals of massive automatic genome-scale pairwise comparisons, for clustering of putative orthologs and paralogs, sequenced genome annotation or multiple-genomic tree constructions. Extreme value distribution based on the Karlin–Altschul model, usually advised for large-scale comparisons are not always valid, particularly in the case of comparisons of non-biased with nucleotide-biased genomes (such that of Plasmodium falciparum). Z-values estimates based on Monte Carlo technics, can be calculated experimentally for any alignment output, whatever the method used. Empirically, a Z-value higher than ∼8 is supposed reasonable to assess that an alignment score is significant, but this arbitrary figure was never theoretically justified.

Results: In this paper, we used the Bienaymé–Chebyshev inequality to demonstrate a theorem of the upper limit of an alignment score probability (or P-value). This theorem implies that a computed Z-value is a statistical test, a single-linkage clustering criterion and that 1/Z-value2 is an upper limit to the probability of an alignment score whatever the actual probability law is. Therefore, this study provides the missing theoretical link between a Z-value cut-off used for an automatic clustering of putative orthologs and/or paralogs, and the corresponding statistical risk in such genome-scale comparisons (using non-biased or biased genomes).
ChromoWheel: a new spin on eukaryotic chromosome visualization
Authors: Ekdahl Sven , Sonnhammer Erik L. L.
Published: February 2004

Summary: ChromoWheel is an Internet browser application for generating whole-genome illustrations. It can be used to depict chromosomes, genes and relations between chromosomal loci. The circular layout of chromosomes is advantageous for showing relationships between different chromosomes, as the connecting line never crosses over a chromosome. All graphical image components are in the vector-based format Scalable Vector Graphics, which are highly scaleable and admit user interaction. ChromoWheel can either be run with user-provided data in the generic SFS format, or as a browser front-end for precompiled genomic data.

Availability:  http://chromowheel.cgb.ki.se
Automated extraction of mutation data from the literature: application of MuteXt to G protein-coupled receptors and nuclear hormone receptors
Authors: Horn Florence , Lau Anthony L. , Cohen Fred E.
Published: February 2004

Motivation: The amount of genomic and proteomic data that is published daily in the scientific literature is outstripping the ability of experimental scientists to stay current. Reviews, the traditional medium for collating published observations, are also unable to keep pace. For some specific classes of information (e.g. sequences and protein structures), obligatory data deposition policies have helped. However, a great deal of other valuable information is spread throughout the literature hindering coherent access. We are involved in the Molecular Class-Specific Information System (MCSIS) project, a collaborative effort to design and automate the maintenance of protein family databases. The first two databases, the GPCRDB and NucleaRDB, are focused on G protein-coupled receptors (GPCRs) and nuclear hormone receptors (NRs), respectively. The main aim of the MCSIS project is to gather heterogeneous data from across a variety of electronic and literature sources in order to draw new inferences about the target protein families.

Results: We present a computational method that identifies and extracts mutation data from the scientific literature. We focused on the extraction of single point mutations for the GPCR and NR superfamilies. After validation by plausibility filters, the mutation data is integrated into the corresponding MCSIS where it is combined with structural and sequence information already stored in these databases. We extracted and validated 2736 true point mutations from 914 articles on GPCRs and 785 true point mutations from 1094 articles on NRs. The current version of our automated extraction algorithm identifies 49.3% of the GPCR point mutations with a specificity of 87.9%, and 64.5% of the NR point mutations with a specificity of 85.8%. MuteXt routinely analyzes 100 electronic articles in approximately 1 h.

Availability: Extracted results are available via the GPCRDB and NucleaRDB at http://www.gpcr.org/7tm/mutation/ and http://www.receptors.org/NR/mutation/, respectively. The algorithm is available upon request.
Extracting human protein interactions from MEDLINE using a full-sentence parser
Authors: Daraselia Nikolai , Yuryev Anton , Egorov Sergei , Novichkova Svetalana , Nikitin Alexander , Mazo Ilya
Published: March 2004

Motivation: The living cell is a complex machine that depends on the proper functioning of its numerous parts, including proteins. Understanding protein functions and how they modify and regulate each other is the next great challenge for life-sciences researchers. The collective knowledge about protein functions and pathways is scattered throughout numerous publications in scientific journals. Bringing the relevant information together becomes a bottleneck in a research and discovery process. The volume of such information grows exponentially, which renders manual curation impractical. As a viable alternative, automated literature processing tools could be employed to extract and organize biological data into a knowledge base, making it amenable to computational analysis and data mining.

Results: We present MedScan, a completely automated natural language processing-based information extraction system. We have used MedScan to extract 2976 interactions between human proteins from MEDLINE abstracts dated after 1988. The precision of the extracted information was found to be 91%. Comparison with the existing protein interaction databases BIND and DIP revealed that 96% of extracted information is novel. The recall rate of MedScan was found to be 21%. Additional experiments with MedScan suggest that MEDLINE is a unique source of diverse protein function information, which can be extracted in a completely automated way with a reasonably high precision. Further directions of the MedScan technology improvement are discussed.

Availability: MedScan is available for commercial licensing from Ariadne Genomics, Inc.
FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes
Authors: Al-Shahrour Fátima , Díaz-Uriarte Ramón , Dopazo Joaquín
Published: February 2004

Summary: We present a simple but powerful procedure to extract Gene Ontology (GO) terms that are significantly over- or under-represented in sets of genes within the context of a genome-scale experiment (DNA microarray, proteomics, etc.). Said procedure has been implemented as a web application, FatiGO, allowing for easy and interactive querying. FatiGO, which takes the multiple-testing nature of statistical contrast into account, currently includes GO associations for diverse organisms (human, mouse, fly, worm and yeast) and the TrEMBL/Swissprot GOAnnotations@EBI correspondences from the European Bioinformatics Institute.

Availability:  http://fatigo.bioinfo.cnio.es
CHOISS for selection of single nucleotide polymorphism markers on interval regularity
Authors: Lee Soohyun , Kang Changwon
Published: February 2004

Summary: We developed algorithms that find a set of single nucleotide polymorphism (SNP) markers based on interval regularity, given either the number of SNPs to choose (m) or the desired interval (I), subject to minimum variance or minimum sum of squared deviations from I. In both cases, the number of all possible sets increases exponentially with respect to the number of input SNPs (n), but our algorithms find the minima only with O(n2) calculations and comparisons by elimination of redundancy.

Availability: A Windows executable program CHOISS is freely available at http://biochem.kaist.ac.kr/choiss.htm

Supplementary information:  http://biochem.kaist.ac.kr/choiss.htm
AntiHunter: searching BLAST output for EST antisense transcripts
Authors: Lavorgna Giovanni , Sessa Luca , Guffanti Alessandro , Lassandro Lelio , Casari Giorgio
Published: February 2004

Summary: AntiHunter is a new web-based tool for the identification of expressed sequence tag (EST) antisense transcripts from BLAST output. In order to perform an analysis, user is required to input a genomic sequence plus an associated list of transcript names and coordinates of the genomic region (i.e. genome annotation). After masking the repeated regions (if any), program will perform a BLASTN search of the input sequence versus the selected EST database, reporting by Email the EST entries that reveal a putative antisense transcript with respect to the user supplied list.

Availability: AntiHunter is currently available through a web interface at http://bio.ifom-firc.it/ANTIHUNTER/.
me-PCR: a refined ultrafast algorithm for identifying sequence-defined genomic elements
Authors: Murphy Kevin , Raj Towfique , Winters R. Scott , White Peter S.
Published: February 2004

Summary: We have adapted the originally described electronic PCR (e-PCR) algorithm to perform string searches more accurately and much more rapidly than previously possible. Our implementation [multithreaded e-PCR (me-PCR)] runs sufficiently fast to allow even desktop machines to query quickly large genomes with very large genomic element sets. In addition, me-PCR is multithreaded, interprets all IUPAC nucleotide symbols, allows searches with elements specified by long sequences (such as SNPs), accepts ranges in the expected PCR size input field, requires substantially less memory for analysis of large sequences and corrects a number of minor flaws causing misreporting of hits in exceptional cases. Thus, me-PCR provides increased annotation capabilities for complex genomes to non-expert laboratories.

Availability: me-PCR has been compiled for Linux, Solaris, AIX, Windows and Macintosh platforms. Both source and executable code are freely available to the research community at http://genome.chop.edu/mePCR/
The PCR Suite
Authors: van Baren Marijke J. , Heutink Peter
Published: February 2004

Summary: The web application PCR Suite is an extension of the primer design program Primer3. It allows the design of primer sets encompassing single nucleotide polymorphisms, all exons of a single gene, all open reading frames in a list of cDNAs or the creation of overlapping PCR products.

Availability:  www.eur.nl/fgg/kgen/primer
FORTE: a profile–profile comparison tool for protein fold recognition
Authors: Tomii Kentaro , Akiyama Yutaka
Published: February 2004

Summary: We present FORTE, a profile–profile comparison tool for protein fold recognition. Users can submit a protein sequence to explore the possibilities of structural similarity existing in known structures. Results are reported via email in the form of pairwise alignments.

Availability: The server is available at http://www.cbrc.jp/forte/
GENIUS II: a high-throughput database system for linking ORFs in complete genomes to known protein three-dimensional structures
Authors: Yabuki Yukimitsu , Mukai Yuri , Swindells Mark B. , Suwa Makiko
Published: February 2004

Summary: GENIUS II is an automated database system in which open reading frames (ORFs) in complete genomes are assigned to known protein three-dimensional (3D) structures. The system uses the multiple intermediate sequence search method in which query and target sequences are linked by intermediate sequences gathered by PSI-BLAST search. By applying the system to 129 complete genomes, 43.8% on average of the ORFs in the genomes were assigned to known 3D structures and the results are available for free at GENIUS II web site.

Availability:  http://genius.cbrc.jp

Supplementary information:  http://genius.cbrc.jp/summary_linking.html
Dysregulation of Hypoxia Inducible Factor‐1α in Head and Neck Squamous Cell Carcinoma Cell Lines Correlates With Invasive Potential
Authors: Cohen Noam A. , Lai Stephen Y. , Ziober Amy F. , Ziober Barry L.
Published: February 2004

Objectives/Hypothesis Tumor hypoxia appears to be closely associated with tumor propagation, malignant progression, and resistance to radiotherapy. Hypoxia inducible factor‐1α (HIF‐1α) is a transcription factor that is upregulated under hypoxic conditions and activates hypoxic adaptation pathways which include neovascularization, erythropoiesis, and glycolysis. Hypoxia inducible factor‐1α is under tight regulation with undetectable levels of expression in normoxia and robust expression in hypoxia. Mutations that activate oncogenes or inactivate tumor suppressor genes increase the expression of HIF‐1α. Furthermore, it has been demonstrated that HIF‐1α is overexpressed in head and neck squamous cell carcinoma and that the degree of expression has predictive and prognostic significance for patients undergoing radiotherapy. The study investigated whether overexpression of HIF‐1α in head and neck squamous cell carcinoma results from a physiological response to local hypoxia or from oncogenic mutational progression.

Study Design Expression of HIF‐1α under normoxic and hypoxic conditions was evaluated in cell lines derived from head and neck squamous cell carcinoma. Cell lines that were used displayed varying degrees of in vitro invasiveness.

Methods Hypoxia inducible factor‐1α expression was detected by Western blot analysis. Cells were treated for 3 hours in 1% oxygen, then re‐exposed to normoxia for varying times before lysis and detection of HIF‐1α.

Results Under normoxic conditions, HIF‐1α expression was upregulated in invasive cells compared with noninvasive cells, and the degradation of HIF‐1α following a hypoxic stimulus was blunted in invasive cells as compared with noninvasive cells.

Conclusion The authors presented evidence that dysregulation of HIF‐1α may play a role in the malignant progression of head and neck squamous cell carcinoma. It is likely that dysregulated expression of the transcription factor HIF‐1α contributes to the invasive properties associated with hypoxia and advanced head and neck squamous cell carcinoma.
Utility of Image Guided Surgery in the Diagnosis of Pterygopalatine Fossa Lesions
Authors: Aronsohn Michael S. , Stringer Scott P. , Brown Heather M.
Published: February 2004

Objectives To describe the utility of image guided surgery in the diagnosis of pterygopalatine fossa lesions and to discuss the varied pathologic diagnoses from this area.

Study Design Case series presentation.

Methods Three cases of pterygopalatine fossa lesions were accessed and biopsied by way of a middle meatus antrostomy approach into the pterygopalatine fossa under image guidance for rapid localization.

Results The diagnoses of melanoma, squamous cell carcinoma, and schwannoma were obtained with minimal morbidity with image guidance. More extensive external approaches were avoided, and appropriate treatment was started without delay. The utility of the image guided approach will be discussed along with the varied pathologies encountered in the pterygopalatine fossa.

Conclusions 1) One must recognize the diverse, yet related, symptoms of patients presenting with pterygopalatine fossa lesions. Early recognition as well as skull‐base imaging is crucial. 2) Biopsy, in addition to imaging, is necessary for diagnosis and may be achieved with little morbidity and increased accuracy using the image guided surgery middle meatus antrostomy approach to the pterygopalatine fossa. 3) The origin of lesions that involve the pterygopalatine fossa may be difficult to identify. Involvement of the pterygopalatine fossa by malignancy may be by contiguous spread, by way of metastasis, or by perineural invasion.
Uvulopalatoplasty (UP2): A Modified Technique for Selected Patients
Authors: Friedman Michael , Ibrahim Hani , Lowenthal Sarah , Ramakrishnan Vidyasagar , Joseph Ninos J.
Published: February 2004

ObjectivesThe goal of uvulopalatopharyngoplasty (UP3) in the treatment of obstructive sleep apnea–hypopnea syndrome (OSAHS) is to reduce obstruction by eliminating redundant tissue in three areas: the soft palate, tonsils, and pharynx. However, some OSAHS patients may present with tonsil hypertrophy and elongated soft palate without redundant pharyngeal folds. We treated this group of patients with tonsil reduction using radiofrequency coblation combined with uvulopalatoplasty (UP2) using a palatal flap technique without pharyngoplasty. Morbidity and outcome was then compared with a group of patients who underwent classic UP3.

Study DesignA retrospective, nonrandomized study comparing morbidity and outcomes of the modified technique (UP2) with patients who underwent standard UP3.

MethodsPatients were all staged according to the previously described Friedman staging system. Those with redundant pharyngeal folds were treated with UP3 (n = 33), and those without redundant pharyngeal folds were treated with tonsil coblation and UP2 (n = 30). Charts of patients undergoing UP2 and UP3 between July 1, 2001 and July 1, 2002 were reviewed. Thirty‐three consecutive patients who underwent UP3 were selected for study as well as 30 consecutive patients who underwent UP2. Pre‐ and postoperative quality of life questionnaires and patient questionnaires focusing on diet, pain, and return to activity were reviewed to assess subjective morbidity and elimination of symptoms. Objective measurements include preoperative and postoperative (6–18 months) polysomnography (PSG).

ResultsSymptom elimination and objective PSG results were compared. There was no statistical difference in results between the UP3 group and the UP2 group. Morbidity, however, was significantly more prominent, and recovery was more prolonged, in the UP3 group. Patients undergoing UP2 had fewer pain days, less narcotic use, quicker return to solid diet, and less long‐term complaints of globus sensation.

ConclusionsUP2 with tonsil coblation offers some reduction in postoperative morbidity without affecting outcome for selected patients with OSAHS. Pain levels, however, are still very significant.
Incidence of Serious Complications After Uvulopalatopharyngoplasty
Authors: Kezirian Eric J. , Weaver Edward M. , Yueh Bevan , Deyo Richard A. , Khuri Shukri F. , Daley Jennifer , Henderson William
Published: February 2004

Objectives Uvulopalatopharyngoplasty (UPPP) is the most common surgical treatment for obstructive sleep apnea (OSA). Anatomic and physiologic abnormalities associated with OSA can make perioperative management difficult. Only single‐site case series provide current estimates of the incidence of perioperative complications, with a pooled crude serious complication rate of 3.5% and a crude mortality rate of 0.4%. The primary objective of this study was to calculate the incidence of perioperative morbidity and mortality in a large, multisite cohort of UPPP patients.

Study Design Prospective cohort study of adults undergoing inpatient UPPP with or without other concurrent procedures

Methods The serious complication and 30‐day mortality rates were calculated from the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program database of prospectively collected outcomes of all VA inpatient surgeries nationally 1991 to 2001. Serious complications were defined by 15 specific life‐threatening complications. Deaths were captured whether the patient was in the hospital or discharged.

Results Veteran patients (n = 3130) had a mean age of 50 years and were predominantly male (97%). The serious nonfatal complication rate was 1.5% (47/3,130) (95% confidence interval [CI] 1.1%, 1.9%). The 30‐day mortality rate was 0.2% (7/3130) (95% CI 0.1%, 0.4%). There was no significant effect of year of surgery or patient age on the risk of serious complication or death.

Conclusion The incidence of serious nonfatal complications and 30‐day mortality after UPPP are 1.5% and 0.2%, respectively, in a large cohort of UPPP patients at veteran hospitals.
Quantitative Analysis of Fungal DNA in Chronic Rhinosinusitis
Authors: Scheuller Michael C. , Murr Andrew H. , Goldberg Andrew N. , Mhatre Anand N. , Lalwani Anil K.
Published: February 2004

Objectives/Hypothesis Fungi have been recognized as important pathogens in sinusitis; however, they are equally present in patients with and without sinusitis. The authors postulated that the quantity of fungal DNA in the nose is determinant of disease, is greater in patients with chronic rhinosinusitis, and is directly correlated to their quality of life.

Study Design Prospective recruitment of patients with chronic rhinosinusitis.

Methods Objective quality of life data were collected using three validated questionnaires: the Sinonasal Outcomes Test (SNOT‐20), Medical Outcomes Short‐Form 36 Survey (SF‐36), and Guy Marks Asthma Questionnaire (GMAQ). Endoscopically guided middle meatus mucosal samples were collected from patients with chronic rhinosinusitis and normal control subjects. Fungal‐specific polymerase chain reaction was performed on each sample. Every fungal‐positive sample underwent fungal‐specific quantitative polymerase chain reaction analysis. Statistical analysis was used to correlate fungal DNA quantities with outcomes indices between groups.

Results Patients with chronic rhinosinusitis had a mean SNOT‐20 index of 32.0 as compared with a SNOT‐20 index of 17.3 (P < .01) in the normal control subjects. There were no statistical differences between the groups' indices for the SF‐36 or GMAQ outcomes questionnaires. Four of 19 (21.1%) patients with chronic rhinosinusitis and 7 of 19 (36.8%) normal control subjects had positive findings for fungal DNA using polymerase chain reaction. The median relative quantity of fungal DNA to human DNA for chronic rhinosinusitis and control samples was identical (0.13) using quantitative polymerase chain reaction.

Conclusion The quantity of fungal DNA in the middle meatus did not differ in patients with and without chronic rhinosinusitis and was not correlated with quality of life outcomes. Therefore, the quantity of fungi does not explain pathogenicity in patients with chronic rhinosinusitis. However, because of small sample size, the study must be replicated in a larger patient population.
Long‐Term Results of Armstrong Beveled Grommet Tympanostomy Tubes in Children
Authors: Lindstrom D. Richard , Reuben Brian , Jacobson Ken , Flanary Valerie A. , Kerschner Joseph E.
Published: February 2004

Objective Many different tympanostomy tubes have been developed with different sizes, shapes, compositions, and coatings. Despite the frequency of ventilation tube placement, very few large studies have examined the outcomes of patients receiving this procedure. An ideal tube would be easy to insert and would extrude at a predictable interval without complications. This study was performed to assess outcome measures and complication rates of the Armstrong beveled grommet tube.

Design A retrospective case series of patients who had Armstrong beveled grommet tympanostomy tubes placed over a 3 year period by two Children's Hospital of Wisconsin pediatric Otolaryngology staff.

Main Outcome Measures Patient age, diagnosis, operative findings, and time to tube extrusion were reviewed. Otorrhea, perforation, and cholesteatoma rates were also assessed.

Results Five hundred seven consecutive patients who had Armstrong tubes placed were reviewed. One thousand ninety‐six Armstrong tubes were placed in these patients. Follow‐up to extrusion rates were available for 756 tubes. The mean patient age at tube placement was 33.3 months, and the median age was 23 months. Mean and median times to extrusion were 16.5 and 15.5 months. One hundred sixty episodes of otorrhea were noted in 148 patients. Four patients had histories of cholesteatoma, none of which developed in conjunction with Armstrong tubes. Ten (1.32%) perforations that have not resolved over time were noted after Armstrong tube placement.

Conclusions Armstrong beveled grommet tympanostomy tubes have complication rates comparable with those reported for Armstrong or other short‐acting tubes in smaller series.
High‐Frequency Pulsed Electromagnetic Energy in Tinnitus Treatment
Authors: Ghossaini Soha N. , Spitzer Jaclyn B. , Mackins Cynthia C. , Zschommler Anne , Diamond Beverly E. , Wazen Jack J.
Published: February 2004

Objectives/Hypothesis Electromagnetic therapy has been used with reported success in multiple clinical settings, including the treatment of seizure disorders, brain edema, migraine headaches, revascularization of burn wounds, and diabetic ulcers. The purpose of the study was to investigate the effect of pulsed high‐frequency electromagnetic therapy on chronic tinnitus.

Study Design A randomized, prospective, double‐blind, placebo‐controlled pilot study was conducted to evaluate the effectiveness of high‐frequency pulsed electromagnetic energy using the Diapulse device in the treatment of chronic tinnitus. Thirty‐seven adult patients with chronic tinnitus of at least 6 months' duration were recruited and randomly assigned to either a treatment or a placebo group.

Methods Patients received 30‐minute treatments with the Diapulse device three times a week for 1 month. The unit was set to deliver electromagnetic energy at a frequency of 27.12 MHz at a repetition rate of 600 pulses per second. All subjects had pretreatment and post‐treatment audiological testing, including tinnitus frequency and intensity matching. They responded to a tinnitus rating questionnaire and the Tinnitus Handicap Inventory before and after treatment.

Results There was no significant change in the pretreatment and post‐treatment audiometric thresholds in either group. There were no significant differences between the pretreatment and post‐treatment Tinnitus Handicap Inventory scores or the tinnitus rating scores in either subject group (Student t test). No diagnosis‐specific differences were identified.

Conclusion High‐frequency pulsed electromagnetic energy (Diapulse) at the settings used in the study showed no role in the therapy of patients with chronic tinnitus.
Impact of Mastoidectomy on Simple Tympanic Membrane Perforation Repair
Authors: McGrew Benjamin M. , Jackson C. Gary , Glasscock Michael E.
Published: February 2004

Objectives/Hypothesis Mastoidectomy has long been identified as an effective method of treatment for chronic ear infection. The effect of mastoidectomy on patients without evidence of active infectious disease remains highly debated and unproven. The objective in the study was to examine the impact of mastoidectomy on the repair of uncomplicated tympanic membrane perforations.

Study Design Retrospective study of patients at tertiary referral center.

Methods Four hundred eighty‐four patients who underwent surgical repair of simple tympanic membrane perforations were identified and reviewed in a retrospective manner. Simple tympanic membrane perforations were defined as tympanic membrane perforations of any size and location without any of the following confounding variables: 1) active infection (active otorrhea, abnormal middle ear mucosa, or granulations tissue); 2) ossicular abnormalities (ossicular fixation, ossicular discontinuity, ossicular malformation, or ossicular absence); 3) cholesteatoma; or 4) prior attempt at tympanic membrane repair (prior tympanoplasty or mastoidectomy). Surgical outcome and clinical course were assessed to compare results of tympanic membrane perforation repair with and without canal wall up mastoidectomy.

Results Tympanic membrane repair was equally effective in both groups at 91%. Hearing results were comparable. Development of persistent ipsilateral otological disease requiring a subsequent ipsilateral procedure was approximately twice as common in the tympanoplasty group. In the tympanoplasty group, 14.1% of patients underwent subsequent ipsilateral otological procedures, and 6.1% of patients in the tympanoplasty with mastoidectomy intact canal wall group underwent subsequent ipsilateral procedures (P < .05). The most common subsequent ipsilateral procedures were tympanoplasty, tympanostomy tube placement, tympanoplasty with mastoidectomy canal wall up, and tympanoplasty with mastoidectomy canal wall down, in that order. After including untreated tympanic membrane perforations as subsequent procedures, the adjusted rate of subsequent procedures was 15.5% in the tympanoplasty group and 12.2% in the tympanoplasty with mastoidectomy group (P > .05).

Conclusion Mastoidectomy was not necessary for successful repair of simple tympanic membrane perforations. However, mastoidectomy impacted the clinical course in patients by reducing the number of patients requiring future procedures and by decreasing disease progression. This suggests that even in the absence of active evidence of infection, mastoidectomy improved the underlying disease process. Combining mastoidectomy with tympanoplasty during repair of simple perforations in patients with no active evidence of infection remains an appropriate option and may be valuable in reducing the need for future surgery.
Carbon Dioxide Laser Endoscopic Diverticulotomy Versus Open Diverticulectomy for Zenker's Diverticulum
Authors: Chang C. W. David , Burkey Brian B. , Netterville James L. , Courey Mark S. , Garrett C. Gaelyn , Bayles Stephen W.
Published: February 2004

Objectives/Hypothesis To compare open and CO2 laser–assisted endoscopic surgical management of Zenker's diverticulum.

Study Design A retrospective review of 49 consecutive surgically treated patients with Zenker's diverticulum was conducted.

Methods Patients' records were reviewed and analyzed for patient age and sex, size of diverticulum, incision time (time recorded from start of incision to surgical completion of case), length of hospital stay, complications, and follow‐up management. A postoperative questionnaire inquiring about swallow function was conducted by mail or telephone. Swallow function was assessed on a four‐point scale.

Results Various procedures performed included endoscopic CO2 laser–assisted diverticulotomy (n = 24) and open diverticulectomy with cricopharyngeal myotomy (n = 28). The average incision time of laser endoscopic cases (47 min) was significantly shorter (P < .001) than that of open diverticulectomy cases (170 min). Length of hospital stay did not significantly vary between the two groups. Five patients (21%) initially treated with laser endoscopic diverticulotomy demonstrated symptomatic persistent Zenker's diverticulum; three underwent repeat operation. No open cases required repeat operation. One endoscopic case was aborted secondary to esophageal injury from placement of the endoscope. Postoperative fever was seen in two (8%) endoscopic cases and four (14%) open approach cases. No major complications (recurrent laryngeal nerve paralysis, mediastinitis, or death) were encountered. More than 90% of respondents in each treatment group reported normal or near‐normal swallow function.

Conclusion Laser endoscopic management is a reasonable and safe method for surgical treatment of Zenker's diverticulum in comparison with the open technique. Employment of the endoscopic approach reduces operative time and the complexity of postoperative care. Practitioners should be aware that the endoscopic approach may result in a higher failure rate.