bluuebunny/crossref_metadata_2025 huggingface dataset:
Fludarabine increases oxaliplatin cytotoxicity in normal and chronic lymphocytic leukemia lymphocytes by suppressing interstrand DNA crosslink removal
Authors: Moufarij Mazin A. , Sampath Deepa , Keating Michael J. , Plunkett William
Published: September 2006

Oxaliplatin and fludarabine have different but potentially complementary mechanisms of action. Previous studies have shown that DNA repair is a major target for fludarabine. We postulate that potentiation of oxaliplatin toxicity by fludarabine may be due to the inhibition by fludarabine of the activity of the DNA excision repair pathways activated by oxaliplatin adducts. To test this, we investigated the cytotoxic interactions between the 2 drugs in normal and chronic lymphocytic leukemia (CLL) lymphocytes. In each population, the combination resulted in greater than additive killing. Analysis of oxaliplatin damage revealed that fludarabine enhanced accumulation of interstrand crosslinks (ICLs) in specific regions of the genome in both populations, but to a lesser extent in normal lymphocytes. The action of fludarabine on the removal of oxaliplatin ICLs was explored to investigate the mechanism by which oxaliplatin toxicity was increased by fludarabine. Lymphocytes from patients with CLL have a greater capacity for ICL unhooking compared with normal lymphocytes. In the presence of fludarabine the extent of repair was significantly reduced in both populations, more so in CLL. Our findings support a role of fludarabine-mediated DNA repair inhibition as a mechanism critical for the cytotoxic synergy of the 2 drugs.
An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study
Authors: Mallia Patrick , Message Simon D , Kebadze Tatiana , Parker Hayley L , Kon Onn M , Johnston Sebastian L
Published: September 2006

Background

Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists.

Methods

We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II). Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage.

Results

All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1. There were no severe exacerbations or other adverse events.

Conclusion

Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.
HIV-2 Protease resistance defined in yeast cells
Authors: M'Barek Najoua Ben , Audoly Gilles , Raoult Didier , Gluschankof Pablo
Published: September 2006

Background

Inhibitors of the HIV-1 Protease currently used in therapeutic protocols, have been found to inhibit, although at higher concentrations, the HIV-2 encoded enzyme homologue. Similar to observations in HIV-1 infected individuals, therapeutic failure has also been observed for some patients infected with HIV-2 as a consequence of the emergence of viral strains resistant to the anti-retroviral molecules. In order to be able to define the specific mutations in the Protease that confer loss of susceptibility to Protease Inhibitors, we set up an experimental model system based in the expression of the viral protein in yeast.

Results

Our results show that the HIV-2 Protease activity kills the yeast cell, and this process can be abolished by inhibiting the viral enzyme activity. Since this inhibition is dose dependent, IC50 values can be assessed for each anti-retroviral molecule tested. We then defined the susceptibility of HIV-2 Proteases to Protease Inhibitors by comparing the IC50 values of Proteases from 7 infected individuals to those of a sensitive wild type laboratory adapted strain.

Conclusion

This functional assay allowed us to show for the first time that the L90M substitution, present in a primary HIV-2 isolate, modifies the HIV-2 Protease susceptibility to Saquinavir but not Lopinavir. Developing a strategy based on the proposed yeast expressing system will contribute to define amino acid substitutions conferring HIV-2 Protease resistance.
Caveolin-1 interacts with the Gag precursor of murine leukaemia virus and modulates virus production
Authors: Yu Zheng , Beer Christiane , Koester Mario , Wirth Manfred
Published: September 2006

Background

Retroviral Gag determines virus assembly at the plasma membrane and the formation of virus-like particles in intracellular multivesicular bodies. Thereby, retroviruses exploit by interaction with cellular partners the cellular machineries for vesicular transport in various ways.

Results

The retroviral Gag precursor protein drives assembly of murine leukaemia viruses (MLV) at the plasma membrane (PM) and the formation of virus like particles in multivesicular bodies (MVBs). In our study we show that caveolin-1 (Cav-1), a multifunctional membrane-associated protein, co-localizes with Gag in a punctate pattern at the PM of infected NIH 3T3 cells. We provide evidence that Cav-1 interacts with the matrix protein (MA) of the Gag precursor. This interaction is mediated by a Cav-1 binding domain (CBD) within the N-terminus of MA. Interestingly, the CBD motif identified within MA is highly conserved among most other γ-retroviruses. Furthermore, Cav-1 is incorporated into MLV released from NIH 3T3 cells. Overexpression of a GFP fusion protein containing the putative CBD of the retroviral MA resulted in a considerable decrease in production of infectious retrovirus. Moreover, expression of a dominant-negative Cav-1 mutant affected retroviral titres significantly.

Conclusion

This study demonstrates that Cav-1 interacts with MLV Gag, co-localizes with Gag at the PM and affects the production of infectious virus. The results strongly suggest a role for Cav-1 in the process of virus assembly.
Prospective randomized study comparing the Teleflex Medical SaphLITE Retractor to the Ethicon CardioVations Clearglide Endoscopic System
Authors: Schultz Scot C , Stapleton Dennis , D'Ambra Paula , Loftis Cynthia , Wahrmann Christine , Ebra George
Published: September 2006

Background

Several minimally invasive saphenous vein harvesting techniques have been developed to reduce morbidities associated with coronary artery bypass grafting. This prospective, randomized study was designed to compare two commonly used minimally invasive saphenous vein harvesting techniques, the SaphLITE Retractor System (Teleflex Medical) and the Clearglide Endoscopic Vessel Harvesting System (Ethicon CardioVations, Inc.).

Methods

Between January 2003 and March 2004, a total of 200 patients scheduled for primary, nonemergent coronary artery bypass grafting, with or without concomitant procedures were randomized into two groups: SaphLITE (n = 100) and Clearglide (n = 100). Pre-, intra- and postoperative data was collected and subjected to statistical analysis. Randomization provided homogenous groups with respect to preoperative risk factors.

Results

Harvest location for the SaphLITE group was thigh (n = 40), lower leg (n = 5) and both lower leg and thigh (n = 55). The location of harvest for the Clearglide group was thigh (n = 3), lower leg (n = 16) and both lower leg and thigh (n = 81). The mean incision length was 3.6 cm (range, 2–6) in the SaphLITE group versus 2.1 cm (range, 1–4) in the Clearglide group (p < 0.05). The total incision length was 12.9 cm versus 8.9 (p < 0.05) in the SaphLITE and Clearglide groups. Conversion to the open technique occurred in 5 SaphLITE patients and 7 Clearglide patients. Intraoperative leg exploration for bleeding occurred in two of the Clearglide patients and none of the SaphLITE patients. Post-operative complications specifically related to minimally invasive harvesting technique, including a two-week post-discharge visit, were not statistically different between the groups.

Conclusion

The saphenous vein can be safely harvested utilizing the SaphLITE and Clearglide systems. While the Clearglide system allows for fewer incisions (number and length) and less harvest time, these benefits may be outweighed by the increased cost of the Clearglide system compared to the SaphLITE retractor.
Genomic features of Bordetella parapertussisclades with distinct host species specificity
Authors: Brinig Mary M , Register Karen B , Ackermann Mark R , Relman David A
Published: September 2006

Background

The respiratory pathogen Bordetella parapertussis is a valuable model in which to study the complex phenotype of host specificity because of its unique two-species host range. One subset of strains, including the sequenced representative, causes whooping cough in humans, while other strains infect only sheep. The disease process in sheep is not well understood, nor are the genetic and transcriptional differences that might provide the basis for host specificity among ovine and human strains.

Results

We found 40 previously unknown genomic regions in an ovine strain of B. parapertussis using subtractive hybridization, including unique lipopolysaccharide genes. A microarray survey of the gene contents of 71 human and ovine strains revealed further differences, with 47 regions of difference distinguishing the host-restricted subgroups. In addition, sheep and human strains displayed distinct whole-genome transcript abundance profiles. We developed an animal model in which sheep were inoculated with a sheep strain, human strain, or mixture of the two. We found that the ovine strain persisted in the nasal cavity for 12 to 14 days, while the human strain colonized at lower levels and was no longer detected by 7 days post-inoculation. The ovine strain induced less granulocyte infiltration of the nasal mucosa.

Conclusion

Several factors may play a role in determining host range of B. parapertussis. Human- and ovine-associated strains have differences in content and sequence of genes encoding proteins that mediate host-pathogen contact, such as lipopolysaccharide and fimbriae, as well as variation in regulation of toxins, type III secretion genes, and other virulence-associated genes.
Generalization of the Weibull distribution: the odd Weibull family
Authors: Cooray Kahadawala
Published: September 2006

A three-parameter generalization of the Weibull distribution is presented to deal with general situations in modeling survival process with various shapes in the hazard function. This generalized Weibull distribution will be referred to as the odd Weibull family, as it is derived by considering the distributions of the odds of the Weibull and inverse Weibull families. As a result, the odd Weibull family is not only useful for testing goodness-of-fit of the Weibull and inverse Weibull as submodels, but it is also convenient for modeling and fitting different data sets, especially in the presence of censoring. The model parameters for uncensored data are estimated in two different ways because of the fact that the inverse transformation of the odd Weibull family does not change its density function. Adequacy of the model for the given uncensored data is illustrated by using the plot of scaled fitted total time on test (TTT) transforms. Furthermore, simulation studies are conducted to measure the discrepancy between empirical and fitted TTT transforms by using a previously proposed test statistic. Three different examples are, respectively, providedbasedondatafromsurvival, reliabilityandenvironmentalsciencestoillustrateincreasing, bathtub and unimodal failure rates.
A Bayesian approach to inequality constrained linear mixed models: estimation and model selection
Authors: Kato Bernet S , Hoijtink Herbert
Published: September 2006

Constrained parameter problems arise in a wide variety of applications. This article deals with estimation and model selection in linear mixed models with inequality constraints on the parameters. It is shown that different theories can be translated into statistical models by putting constraints on the model parameters yielding a set of competing models. A new approach based on the principle of encompassing priors is proposed and used to compute Bayes factors and subsequently posterior model probabilities. Model selection is based on posterior model probabilities. The approach is illustrated using a longitudinal data set.
Using the Box-Cox t distribution in GAMLSS to model skewness and kurtosis
Authors: Rigby Robert A , Stasinopoulos D Mikis
Published: September 2006

The Box-Cox t (BCT) distribution is presented as a model for a dependent variable Y exhibiting both skewness and leptokurtosis. The distribution is defined by a power transformation Y v having a shifted and scaled (truncated) t distribution with degrees of freedom parameter τ. The distribution has four parameters and is denoted by BCT( μ, σ,ν, τ). The parameters μ, σ,ν and τ may be interpreted as relating to location (median), scale (centile-based coefficient of variation), skewness (power transformation to symmetry) and kurtosis (degrees of freedom), respectively. The generalized additive model for location, scale and shape (GAMLSS) is extended to allow each of the parameters of the distribution to be modelled as linear and /or non-linear parametric and/or smooth non-parametric functions of explanatory variables. A Fisher scoring algorithm is used to fit the model by maximizing a (penalized) likelihood. The first and expected second and cross derivatives of the likelihood with respect to μ, σ,ν and τ, required for the algorithm, are provided. The use of the BCT distribution is illustrated by two data applications.
Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors
Authors: Heinrich Michael C. , Corless Christopher L. , Blanke Charles D. , Demetri George D. , Joensuu Heikki , Roberts Peter J. , Eisenberg Burton L. , von Mehren Margaret , Fletcher Christopher D.M. , Sandau Katrin , McDougall Karen , Ou Wen-bin , Chen Chang-Jie , Fletcher Jonathan A.
Published: September 2006

Purpose

Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem.

Patients and Methods

One hundred forty-seven patients with advanced, unresectable GISTs were enrolled onto a randomized, phase II clinical study of imatinib. Specimens from pretreatment and/or imatinib-resistant tumors were analyzed to identify molecular correlates of imatinib resistance. Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity.

Results

Molecular studies were performed using specimens from 10 patients with primary and 33 patients with secondary resistance. Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs. Secondary kinase mutations were rare in GISTs with primary resistance but frequently found in GISTs with secondary resistance (10% v 67%; P = .002). Evidence for clonal evolution and/or polyclonal secondary kinase mutations was seen in three (18.8%) of 16 patients. Secondary kinase mutations were nonrandomly distributed and were associated with decreased imatinib sensitivity compared with typical KIT exon 11 mutations. Using RNAi technology, we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways.

Conclusion

Different molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs. These findings have implications for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs.
The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport
Authors: Rutherford Anna C. , Traer Colin , Wassmer Thomas , Pattni Krupa , Bujny Miriam V. , Carlton Jeremy G. , Stenmark Harald , Cullen Peter J.
Published: September 2006

The yeast gene fab1 and its mammalian orthologue Pip5k3 encode the phosphatidylinositol 3-phosphate [PtdIns(3)P] 5-kinases Fab1p and PIKfyve, respectively, enzymes that generates phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2]. A shared feature of fab1Δ yeast cells and mammalian cells overexpressing a kinase-dead PIKfyve mutant is the formation of a swollen vacuolar phenotype: a phenotype that is suggestive of a conserved function for these enzymes and their product, PtdIns(3,5)P2, in the regulation of endomembrane homeostasis. In the current study, fixed and live cell imaging has established that, when overexpressed at low levels in HeLa cells, PIKfyve is predominantly associated with dynamic tubular and vesicular elements of the early endosomal compartment. Moreover, through the use of small interfering RNA, it has been shown that suppression of PIKfyve induces the formation of swollen endosomal structures that maintain their early and late endosomal identity. Although internalisation, recycling and degradative sorting of receptors for epidermal growth factor and transferrin was unperturbed in PIKfyve suppressed cells, a clear defect in endosome to trans-Golgi-network (TGN) retrograde traffic was observed. These data argue that PIKfyve is predominantly associated with the early endosome, from where it regulates retrograde membrane trafficking to the TGN. It follows that the swollen endosomal phenotype observed in PIKfyve-suppressed cells results primarily from a reduction in retrograde membrane fission rather than a defect in multivesicular body biogenesis.
Neuronal polarity is regulated by glycogen synthase kinase-3 (GSK-3β) independently of Akt/PKB serine phosphorylation
Authors: Gärtner Annette , Huang Xu , Hall Alan
Published: September 2006

An essential step during the development of hippocampal neurons is the polarised outgrowth of a single axon. Recently, it has been suggested that inhibition of glycogen synthase kinase-3β (GSK-3β) via Akt/PKB-dependent phosphorylation of Ser9, specifically at the tip of the presumptive axon, is required for selective axonal outgrowth. We now report that, by using neurons from double knock-in mice in which Ser9 and Ser21 of the two GSK-3β isoforms have been replaced by Ala, polarity develops independently of phosphorylation at these sites. Nevertheless, global inhibition of GSK-3β disturbs polarity development by leading to the formation of multiple axon-like processes in both control and knock-in neurons. This unpolarised outgrowth is accompanied by the symmetric delivery of membrane components to all neurites. Finally, the adenomatous polyposis coli (APC) protein accumulates at the tip of one neurite before and during axon elongation, but global inhibition of GSK-3β leads to APC protein accumulation in all neurites. We conclude that GSK-3β inhibition promotes the development of neuronal polarity, but that this is not mediated by Akt/PKB-dependent phosphorylation.
Internal and external trauma to the larynx
Authors: Holinger Paul H. , Schild Joyce A. , Maurizi Dino G.
Published: September 2006

Trauma affects the larynx internally through vocal misuse, chemical and thermal burns, and intralaryngeal instrumentation; externally through physical violence, industrial accidents and automobile collisions. Occupational laryngeal trauma is that seen in the larynges of professional voice users such as singers, preachers, lawyers, school teachers, politicians, telephone operators, sales people, credit managers and auctioneers. Particularly common are the nodules on the vocal cords of housewives with several small children! In industry, voice changes and laryngeal pathology are common in voice abusers such as foremen, women assembly line workers, men working near a steam jack and engineers and firemen in cabs of diesel locomotives.1 Bridging these two categories of white collars and blue shirts are representatives in management‐labor relations who have additional reason to develop laryngeal trauma.
Sound evoked frequency‐following responses in the central auditory pathway
Authors: Marsh James T. , Worden Frederic G.
Published: September 2006

An acoustically evoked response is described which reproduces the frequency and waveform of the stimulus. This frequency following response (FFR.) is recordable from gross electrodes in the central auditory pathway.

The FFR. differs from an acoustic stimulus of graded onset, and the CM., in that it has a sharp onset and a latency appropriate to the locus from which it is recorded. It is less resistant to anoxia than CM., and disappears before CM. is seriously affected.

The frequency range of FFR. increases with stimulus intensity. At 80 db SPL., the range is approximately 500 Hz. to 5 KHz.

The waveform and amplitude of FFR. vary with stimulus frequency. Amplitude becomes smaller, and waveform becomes more variable.

The contrast to the auditory evoked potential, which can be recorded widely in the brain, FFR. is recordable only within, or close to, the auditory pathway. We have observed it only at and below the level of the inferior colliculus.

FFR. has implications for the neurophysiology of hearing which are different from those of the auditory evoked potential. Some of these are discussed.
Injury and repair of the recurrent laryngeal nerves in dogs.
Authors: Boles Roger , Fritzell Bjorn
Published: September 2006

Surgical repair of recurrent laryngeal nerve injuries has received renewed experimental attention in recent years.1,2,3 This work has been motivated by the considerable disability which vocal cord paralysis continues to cause, particularly regarding phonation, aspiration on swallowing, and difficulty in breathing. Interest in direct nerve repair has also evolved out of the frequent failure to achieve complete rehabilitation of the laryngeal functions with the usual surgical procedures of tracheostomy, arytenoidectomy and arytenopexy, and vocal fold injection and displacement techniques.
Wound healing.
Authors: Schiff Maurice
Published: September 2006

Wound healing is like a diamond with many facets. Newer techniques and methods are available to study some of the problems of wound healing. This is a highly complex subject with so many ramifications that only a few will be presented. Throughout the world, many laboratories are investigating the fundamental aspects of repair and regeneration. This starts at the cell level and terminates with the healed wound. In 1968, at a Centennial Symposium on Repair and Regeneration, at the University of California in San Francisco, there was assembled a group of pathologists, biochemists, bioengineers, enzymologists, and surgeons. All attempted to contribute something to the advancement of the new frontiers of study of wound healing. These proceedings will be published early in 1969. A study in wound repair requires consideration of the activity of the epithelium and the connective tissue beneath it. These two systems interact and inform each other of their status and the requirements of each other.
Cytotoxic reactions in the diagnosis of food allergy.
Authors: Bryan William T. K. , Bryan Marian P.
Published: September 2006

The diagnosis of food allergy remains one of the infrequently solved problems in medicine; furthermore, its importance is only occasionally recognized, and I emphasize the statement of Dr. William Kaufman in 195514 that no physician can estimate with any degree of accuracy how much ill health and human misery result from ailments caused by undiagnosed food allergy. From the large and varied sampling of patients who consulted him in his practice of internal medicine during the preceding 12 years, he could say with confidence that most practicing physicians see many patients almost daily who present themselves with a wide variety of complaints, which are caused by unrecognized food allergies.
Results of tympanoplasty and mastoidectomy at the massachusetts eye and ear infirmary
Authors: Lee Keatjin , Schuknecht Harold F.
Published: September 2006

The primary objectives of surgery for chronic suppurative disease of the ear are the elimination or arrest of disease and the preservation or improvement of auditory function. The concept is not new, for even the earliest otologists1 performed temporal bone surgery with the hope of preserving the sound transmitting mechanism of the middle ear. Before the availability of antibiotic drugs for the control of bacterial infection, it was not always prudent to compromise the removal of diseased tissues for the sake of preserving function. It was observed, however, that good thresholds of hearing sometimes occurred even though the ossicles and tympanic membrane were partly or completely destroyed by disease or surgery. These cases were the result of fortuitous patterns of healing in which the function of the ossicular system or the phase difference at the oval and round windows was preserved. Tympanoplasty tries to achieve these goals without compromising the desired end result of a safe, dry, and asymptomatic ear.
Tracheotomy in neonates
Authors: Gibson R. , Byrne J. E. T.
Published: September 2006

Fifty‐five tracheotomies have been performed on neonates. Forty suffered from respiratory distress syndrome and smaller groups had congenital defects and pneumonia. All tracheotomies were preceded by nasotracheal intubation for about 72 hours. Linear incision of the trachea from the second to fourth tracheal rings, insertion of lateral stay sutures and careful placement of the tube to allow aeration of both main bronchi have reduced complications. Eleven neonates developed pneumothorax as a result of high pressure ventilation; three had pneumonia, and one tracheotomy tube became temporarily” displaced. Fourteen of the neonates with respiratory distress syndrome recovered. Birth weight ranged from 1,200 G upward. Expert nursing is essential to ensure adequate humidification and suction.

Neonates are defined as babies aged less than 28 days. This definition applies whether or not the birth is premature. Tracheotomies on young children have been reported in the past: Pickard1 on premature babies; Holinger2 on those younger than 12 months; and Bridges3 on those aged less than five years. In all these papers, both operative and postoperative problems have been stressed. Complications have been emphasized by Oliver, et al.,4 who, in a series of 294 tracheotomies, found all their operative complications and 85 percent of their postoperative difficulties in small infants. It must be assumed that in the past postoperative care especially has been difficult in many centers. Recent years have brought the development of more dependable apparatus for humidification and ventilation, and this has been applied to respiratory tract care in a large variety of conditions which were previously fatal in this age group. The care of such infants and the sophisticated apparatus used in treating them requires adequate numbers of highly‐trained medical and nursing staff available night and day. Such well‐staffed and well‐equipped Intensive Care Units, specializing in the treatment of neonates, are now found in many large hospital complexes throughout the United Kingdom and North America.
Composite auricular graft in laryngeal reconstruction
Authors: Morgenstein Karl M.
Published: September 2006

When injury to the larynx and/or trachea results in significant loss of tissue, primary closure may predispose to stenosis. Reconstruction of the airway should include the addition of cartilage to maintain the lumen as well as a replacement for interior mucoperichondrium and exterior skin. The auricle provides an excellent source for a composite graft consisting of cartilage with its attached skin on one side and perichondrium on the other.

A case is presented in which a 2 cm. defect was successfully closed with such a composite graft.

The patient sustained a self‐inflicted wound which removed the lower portion of the thyroid cartilage in the midline, the anterior third of the cricoid cartilage and the anterior third of the first tracheal lumen. Several weeks later a composite graft was taken from the auricle, and a three‐layer closure was accomplished. After an initial period of cyanosis, the graft remained viable and survived in toto.

Long term follow‐up showed survival of the graft, normal laryngeal function and normal tracheal diameter.
A new prosthesis for stapes surgery
Authors: Draper W. L. , Herndon John W.
Published: September 2006

A new prosthesis for use in stapedial surgery has been described. This prosthesis, which can be made in the operating room in a very short time, at the time of surgery, is easy to construct, to place in position and is effective for regaining hearing. The materials used, the construction of the prosthesis and postoperative audiometric studies have been discussed.
Homograft transplants to the middle ear. A follow‐up report
Authors: Glasscock Michael E. , House William F. , Graham Malcolm
Published: September 2006

In April, 1967, we performed our first transplant of a homograft tympanic membrane in a case of chronic ear disease. This work was presented in a “Preliminary Report” in January, 1968. The purpose of this paper is to give our experience (almost five years) with this technique of tympanoplasty.

Our initial investigation was fraught with many difficulties. At the beginning of the project there were no clear cut legal priorities for obtaining and using cadaver material. No specific or generally accepted preservation solution was available, and the best method of storage was yet to be determined.

The aim of the series was to develop a method of grafting the drum in patients with chronic ear disease. In addition, it was our hope that by incorporating the intact ossicles as well we would be able to increase the hearing in those difficult cases in which all ossicular remnants had been destroyed.

While our original results were encouraging, the long term evaluation has been somewhat disappointing. The overall take rate for the drums has dropped to 65 percent. Hearing results are approximately the same as for any standard tympanoplasty procedure, no worse, but certainly no better.

Since the beginning of our series other investigators have begun to use the technique with considerable more success. Perkins has been able to raise the take rate to 90 percent (acceptable) by using a buffered Formalin solution. The passage of the Uniform Donor Act has made homograft tissues more available and opened the way for the new national ear bank programs.

While our experience has been disappointing, we feel we did help to stimulate interest in this procedure and that many of our failures have since been corrected by other investigators. We feel the future is good for homograft transplants to the middle ear and will continue to improve on our own techniques as well as those of others.
Current concepts of frontal sinus surgery: An appraisal of the osteoplastic flap‐fat obliteration operation
Authors: Sessions Roy B. , Alford Bobby R. , Stratton Cary , Ainsworth Jerry Z. , Roswell N. M. , Shill Otto
Published: September 2006

The osteoplastic flap‐fat obliteration operation has been utilized in a variety of clinical problems (osteomas, chronic infection, mucocele, extensive trauma) for the past eight years. The experience suggests that in carefully selected patients it is an effective operative procedure for the surgical control of these problems. Two failures, which were probably preventable, occurred in the 53 patients operated upon by this technique. Long term animal experiments and clinical experience support the merit of using fat as an obliterating material in the infected sinus. The only unfavorable long term result in otherwise successful patients has been the forehead embossment that has occurred over the frontal sinus osteoplastic flap area.
The present day spectrum of pediatric bronchoesophagology
Authors: Turtz Myles G. , Tucker Gabriel F.
Published: September 2006

We have presented an overview of the Jackson service at St. Christopher's Hospital for Children as a reflection of current pediatric bronchoesophagology in a pediatric center. As a model for study we have given our statistics for a 12‐month period; July 1, 1970, to June 30, 1971. During this period of time there were 906 procedures: 626 for airway problems and 280 for esophageal problems. Airway distress acute, chronic or recurrent, accounted for much of our airway endoscopy, although in the year reviewed not one case of croup required bronchoscopy. Caustic ingestion remained our major indication for pediatric esophagoscope. Endoscopic foreign body removed accounted for less than 6 percent of all procedures. Complications were minimal.

Although a considerable amount of the work was “traditional” pediatric bronchoesophagology, much of it was for diagnosis and treatment of problems encountered only rarely by our predecessors. Advances in pediatrics, neonatology, pediatric surgery and its subspecialties have created a large population of children formerly lost but now salvageable. A significant factor in this enhanced salvage rate is the assistance of the broncho‐esophagologist.
Cervical lymphadenopathy secondary to toxoplasmosis
Authors: Karlan Marc S. , Baker Daniel C.
Published: September 2006

Acquired lymphadenopathic toxoplasmosis is an insidious disease with protean manifestations. It usually follows a benign course. It is caused by a protozoan parasite, Isospora alias Toxoplasma. Infection is contracted by ingestion of raw encysted meat or ingestion of the oocyst found in cat litter. There is a large infected human population with a relatively high infection rate. The diagnosis is suggested by a nonspecific symptom complex, lymphadenopathy associated with a relative lymphocytosis, atypical lymphocytes, and a negative. heterophile antigen test. The microscopic findings of eosinophilic histiocytes further suggests toxoplasmosis. High serologic titers are considered most conclusive in diagnosing this usually self‐limited infection. Three cases in which biopsy was warranted are presented.
Facial paralysis in children. A review of 150 cases
Authors: Alberti P. W. , Biagioni E.
Published: September 2006

The in‐patient records at the Hospital for Sick Children were reviewed for the 10‐year period 1960 to 1970. All charts in which were coded a primary diagnosis of Bell's palsy, facial paralysis or paresis, or a secondary diagnosis of facial nerve functional disturbance were pulled and reviewed. As there was no out‐patient diagnostic index in that period, it proved impossible to identify the numbers or diagnosis of patients with the physical sign of those who were not admitted to the hospital.

There were 150 patients in whom a facial nerve disorder was recorded. The distribution and a broad etiological classification is shown in Table I. It will be seen that there were significantly more lower motor neurone than upper motor neurone lesions, although it is likely that many upper motor neurone facial pareses were not recorded because they formed but a small part of a more serious generalized neurological disorder.

The upper motor neurone pareses which were recorded had a variety of causes. The infections included meningitis and Guillain‐Barré syndrome. Three of the four infective cases made a complete recovery, as did all of the traumatic cases. In one of the hydrocephalic children the facial paresis diminished as the primary lesion responded to treatment. The presence of an upper motor neurone facial paresis is therefore not necessarily a sign of irreversible disease.

Trauma due to birth injury, accident or motor vehicle injury was the most common cause of lower motor neurone paresis. The birth injuries usually cleared spontaneously. Bell's palsy was the next most common cause of facial palsy. The sexes were equally affected and the age distributions even throughout childhood. Bell's palsy in children, as in adults, may not clear spontaneously, and should be treated with respect.

Facial palsy caused by acute inflammatory disease responds in most instances to antibiotic treatment, although simple mastoidectomy may be necessary. The outcome in this group is excellent. The remarkably few cases of facial palsy complicating chronic middle ear disease are a reflection of the changing pattern of disease.

Operative causes were surprisingly mainly due to parotid surgery, and the indication for surgery was always excision of parotid hemangioma. In a 10‐year period there were only two facial palsies attributable to temporal bone surgery.

There is a need for a detailed prospective study of all children with a facial paralysis and particularly the Bell's palsy group. Only in this way will accurate figures be obtained about the prognosis and thus allow appropriate regimens to be established.
Ultrastructure of the round window membrane
Authors: Bellucci Richard J. , Fisher Edward G. , Rhodin Johannes
Published: September 2006

The round window membrane presents the only non‐osseous wall of the labyrinth. Electron microscopic study of the round window membrane was undertaken in order to determine whether it could act as a route of transmission from the middle to the inner ear.

In the cat round window membrane three layers can be identified. The tympanic surface is composed of a single layer of flat cells resting on the basal lamina. Multiple desmosomes and tight cell junctions are present. The intermediate layer contains supporting elements collagen and elastic tissues. The labyrinthine layer is composed of a single layer of long squamous cells which lie end to end on the basal lamina.

The absence of intracellular organelles and microvilli, and the lack of basal lamina involutions into the epithelial cells preclude the presence of an active transport mechanism. The tight cell junctions also seem to present a barrier to free diffusion across the membrane.

The chemical agents which have been observed to pass from the middle ear into the inner ear may have done so by diffusion through the round window membrane after altering the cell junctions; however, a readily accessible route of transmission through the round window membrane does not appear to be present.
Acoustic neuroma: Primary arising in the vestibule
Authors: Wanamaker Harold H.
Published: September 2006

As more information on acoustic tumors is accumulated, it is apparent that the lesions may have several sites of origin. A case of an acoustic tumor arising primarily in the vestibule is presented. This case, which has been followed for seven years, supports the proposed theory that the tumor may develop from the nerves to either the saccule or the utricle.
Selective vestibular ablation in monkeys by laser irradiation
Authors: Wilpizeski Chester , Sataloff Joseph , Doyle Colin , Leonard James , Behrendt Thomas
Published: September 2006

Following bilateral simple mastoidectomy, eight adult squirrel monkeys were subjected to argon laser irradiation (output wavelength of 488 nanometers) of the horizontal or posterior semicircular canals. Penetration of the bony canal wall and damage to the membranous labyrinth was achieved if multiple or superimposed burns were made (one watt bursts with durations from 0.2 to 1 second). The major morphologic effect of the penetrating lesions was a mild to prolific growth of fibrous tissue restricted to the immediate site of irradiation. Endolymphatic ducts were blocked by collapse of one membranous wall against the other, by filling in of the lumen with fibrous growth of the duct walls or by constriction caused by overgrowth of surrounding fibrous tissue filling the perilymphatic space. Blocking of the duct, however, can not account fully for functional vestibular changes following irradiation, because some dysfunction occurred in the absence of any discernible structural abnormality. On the other hand, some function remained when ducts were completely occluded. Except for the control ear animal, all others exhibited slight to moderate ataxia and loss of acrobatic ability for several days after irradiation. No spontaneous nystagmus was detected in any monkey. All animals of our series, even those with no apparent morphological changes, were characterized by at least temporary reduction of caloric‐induced nystagmus, but only two showed complete absence of responses. All monkeys showed a change in the direction of caloric responses from horizontal to rotary or mixed, and vigor of the responses lessened considerably. Monkeys having penetrating lesions of the posterior canal exhibited subnormal postrotatory nystagmus when rotated in a forward direction with vertical canalsplaced in the horizontal plane. Two of the monkeys were trained to track their pure tone detection thresholds by means of an automated, single‐lever conditioned‐avoidance procedure. Bone conduction hearing was normal after irradiation except for a 16 db threshold shift at 2,000 Hz in one animal. On the basis of our experience with squirrel monkeys, there would appear to be no hazardous or life‐threatening side effects of laser surgery of otic structures when done in this manner. Serious consideration should be given by otologists to the experimental application of lasers for human microsurgical purposes.
Interpretation of electronystagmographic results
Authors: Eviatar Abraham
Published: September 2006

This preliminary communication presents 1,101 electronystagmographic results and correlates them with the final diagnosis. The aim of the study is to investigate the contribution made by electronystagmography to the final diagnosis.

The diagnostic conclusions were classified into four groups. Within the “Central” group were included all diseases of the central nervous system, acute, chronic or congenital, and also concussion and skull fractures. In the “Peripheral” group, only peripheral vestibular diseases were included. Patients who complained of dizziness and were diagnosed on a purely clinical basis, while all other examinations were within normal limits, were classified in the “Diagnosis Deferred” group. The “Normal” group included only patients free of true vertigo with their physical examination, hearing test and mastoid X‐ray, that were considered within normal limits.

Bithermal caloric irrigation was used for stimulation, and the speed of the slow component at culmination was the representative of the intensity of the nystagmic response.
Newer concepts of first branchial cleft defects
Authors: Work Walter P.
Published: September 2006

Duplication embryological anomalies of the first branchial cleft are reported. Six cases are presented which were treated since 1963.

A classification of these cases is suggested wherein there are Type I and Type II lesions.

Type I is of ectodermal origin and is considered a duplication of the membranous external auditory canal. Initial infection and subsequent infection often necessitate repeated incision and drainage. Only one of the five cases of Type I did not show infection. Characteristically, these lesions occur medial to the concha and frequently extend to the postauricular crease. They pass anterior and deep to the ear lobe, superior to the facial nerve, parallel to normal external auditory canal and finally end in a cul‐de‐sac on a bony plate at the level of the mesotympanum. Microscopically, these lesions are cystic, have a squamous epithelium lining, form keratin and may or may not show accessory skin structures. Surgical excision is the treatment of choice. The surgery must be performed during remission from infection and consists mainly of parotid gland and facial nerve dissections. After the lesion is excised, the normal membranous external auditory canal is incised lengthwise, and an iodoform pack is placed in the area of the excised anomaly and brought out externally through the recently incised membranous external auditory canal and the meatus. During the first few days postoperatively, the pack is gradually removed and the bed of the wound repacked if necessary. Such a technique enhances wound healing.

Type II are duplication anomalies of the membranous external auditory canal and pinna; they contain skin (ectoderm )and cartilage (mesoderm). These anomalies likewise are usually diagnosed after infection has taken place and after incision and drainage of an abscess at a point below the angle of the mandible. The upward extension of this lesion passes over the angle or horizontal ramus of the mandible. It continues upward passing either lateral or medial to the facial nerve and in rare instances may split its main trunk. It may end inferior to the membranous external auditory canal or form a sinus in that location. The middle ear is normal. Only one case with such anomaly is reported here, but in 1963, Work and Proctor reported five of six cases as Type II anomalies. Wide surgical excision is curative. The facial nerve must be preserved intact.

Types I and II anomalies are not associated with pretragal cysts or sinuses.