bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis
Authors: Delhommeau François , Dupont Sabrina , Tonetti Carole , Massé Aline , Godin Isabelle , Couedic Jean-Pierre Le , Debili Najet , Saulnier Patrick , Casadevall Nicole , Vainchenker William , Giraudier Stéphane
Published: September 2006

The JAK2 V617F mutation has recently been described as an essential oncogenic event associated with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocythemia. This mutation has been detected in all myeloid lineages but has not yet been detected in lymphoid cells. This raises the question whether this molecular event occurs in a true lymphomyeloid progenitor cell. In this work, we studied the presence of the mutation in peripheral blood cells and sorted B, T, and natural killer (NK) cells from PV and IMF. We detected the JAK2 V617F mutation in B and NK cells in approximately half the patients with IMF and a minority of those with PV. Moreover, in a few cases patients with IMF had mutated peripheral T cells. The mutation (homozygous or heterozygous) could be subsequently detected in B/NK/myeloid progenitors from PV and IMF, with a much higher frequency in clones derived from IMF. Using the fetal thymus organ culture (FTOC) assay, the mutation was also detected in all T-cell fractions derived from IMF and PV CD34+ cells. These results demonstrate that myeloproliferative disorders take their origin in a true myeloid/lymphoid progenitor cell but that their phenotype is related to a downstream selective proliferative advantage of the myeloid lineages.
RDMAS: a web server for RNA deleterious mutation analysis
Authors: Shu Wenjie , Bo Xiaochen , Liu Rujia , Zhao Dongsheng , Zheng Zhiqiang , Wang Shengqi
Published: September 2006

Background

The diverse functions of ncRNAs critically depend on their structures. Mutations in ncRNAs disrupting the structures of functional sites are expected to be deleterious. RNA deleterious mutations have attracted wide attentions because some of them in cells result in serious disease, and some others in microbes influence their fitness.

Results

The RDMAS web server we describe here is an online tool for evaluating structural deleteriousness of single nucleotide mutation in RNA genes. Several structure comparison methods have been integrated; sub-optimal structures predicted can be optionally involved to mitigate the uncertainty of secondary structure prediction. With a user-friendly interface, the web application is easy to use. Intuitive illustrations are provided along with the original computational results to facilitate quick analysis.

Conclusion

RDMAS can be used to explore the structure alterations which cause mutations pathogenic, and to predict deleterious mutations which may help to determine the functionally critical regions. RDMAS is freely accessed via http://biosrv1.bmi.ac.cn/rdmas.
Indications that "codon boundaries" are physico-chemically defined and that protein-folding information is contained in the redundant exon bases
Authors: Biro Jan Charles
Published: September 2006

Background

All the information necessary for protein folding is supposed to be present in the amino acid sequence. It is still not possible to provide specific ab initio structure predictions by bioinformatical methods. It is suspected that additional folding information is present in protein coding nucleic acid sequences, but this is not represented by the known genetic code.

Results

Nucleic acid subsequences comprising the 1st and/or 3rd codon residues in mRNAs express significantly higher free folding energy (FFE) than the subsequence containing only the 2nd residues (p < 0.0001, n = 81). This periodic FFE difference is not present in introns. It is therefore a specific physico-chemical characteristic of coding sequences and might contribute to unambiguous definition of codon boundaries during translation. The FFEs of the 1st and 3rd residues are additive, which suggests that these residues contain a significant number of complementary bases and that may contribute to selection for local RNA secondary structures in coding regions. This periodic, codon-related structure-formation of mRNAs indicates a connection between the structures of exons and the corresponding (translated) proteins. The folding energy dot plots of RNAs and the residue contact maps of the coded proteins are indeed similar. Residue contact statistics using 81 different protein structures confirmed that amino acids that are coded by partially reverse and complementary codons (Watson-Crick (WC) base pairs at the 1st and 3rd codon positions and translated in reverse orientation) are preferentially co-located in protein structures.

Conclusion

Exons are distinguished from introns, and codon boundaries are physico-chemically defined, by periodically distributed FFE differences between codon positions. There is a selection for local RNA secondary structures in coding regions and this nucleic acid structure resembles the folding profiles of the coded proteins. The preferentially (specifically) interacting amino acids are coded by partially complementary codons, which strongly supports the connection between mRNA and the corresponding protein structures and indicates that there is protein folding information in nucleic acids that is not present in the genetic code. This might suggest an additional explanation of codon redundancy.
Green fluorescent protein as a reporter of prion protein folding
Authors: Vasiljevic Snezana , Ren Junyuan , Yao YongXiu , Dalton Kevin , Adamson Catherine S , Jones Ian M
Published: September 2006

Background

The amino terminal half of the cellular prion protein PrPc is implicated in both the binding of copper ions and the conformational changes that lead to disease but has no defined structure. However, as some structure is likely to exist we have investigated the use of an established protein refolding technology, fusion to green fluorescence protein (GFP), as a method to examine the refolding of the amino terminal domain of mouse prion protein.

Results

Fusion proteins of PrPc and GFP were expressed at high level in E.coli and could be purified to near homogeneity as insoluble inclusion bodies. Following denaturation, proteins were diluted into a refolding buffer whereupon GFP fluorescence recovered with time. Using several truncations of PrPc the rate of refolding was shown to depend on the prion sequence expressed. In a variation of the format, direct observation in E.coli, mutations introduced randomly in the PrPc protein sequence that affected folding could be selected directly by recovery of GFP fluorescence.

Conclusion

Use of GFP as a measure of refolding of PrPc fusion proteins in vitro and in vivo proved informative. Refolding in vitro suggested a local structure within the amino terminal domain while direct selection via fluorescence showed that as little as one amino acid change could significantly alter folding. These assay formats, not previously used to study PrP folding, may be generally useful for investigating PrPc structure and PrPc-ligand interaction.
Refuting phylogenetic relationships
Authors: Bucknam James , Boucher Yan , Bapteste Eric
Published: September 2006

Background

Phylogenetic methods are philosophically grounded, and so can be philosophically biased in ways that limit explanatory power. This constitutes an important methodologic dimension not often taken into account. Here we address this dimension in the context of concatenation approaches to phylogeny.

Results

We discuss some of the limits of a methodology restricted to verificationism, the philosophy on which gene concatenation practices generally rely. As an alternative, we describe a software which identifies and focuses on impossible or refuted relationships, through a simple analysis of bootstrap bipartitions, followed by multivariate statistical analyses. We show how refuting phylogenetic relationships could in principle facilitate systematics. We also apply our method to the study of two complex phylogenies: the phylogeny of the archaea and the phylogeny of the core of genes shared by all life forms. While many groups are rejected, our results left open a possible proximity ofN. equitansand the Methanopyrales, of the Archaea and the Cyanobacteria, and as well the possible grouping of the Methanobacteriales/Methanoccocales and Thermosplasmatales, of the Spirochaetes and the Actinobacteria and of the Proteobacteria and firmicutes.

Conclusion

It is sometimes easier (and preferable) to decide which species do not group together than which ones do. When possible topologies are limited, identifying local relationships that are rejected may be a useful alternative to classical concatenation approaches aiming to find a globally resolved tree on the basis of weak phylogenetic markers.

Reviewers

This article was reviewed by Mark Ragan, Eugene V Koonin and J Peter Gogarten.
Substance abuse prevention infrastructure: a survey-based study of the organizational structure and function of the D.A.R.E. program
Authors: Merrill Jeffrey C , Pinsky Ilana , Killeya-Jones Ley A , Sloboda Zili , Dilascio Tracey
Published: September 2006

Background

The only national drug abuse prevention delivery system that supports the rapid diffusion of new prevention strategies and includes uniform training and credentialing of instructors who are monitored for quality implementation of prevention programming is the Drug Abuse Resistance Education network (D.A.R.E.) linking community law enforcement to schools. Analysis of the organizational structure and function of D.A.R.E. provides an understanding of the essential parameters of this successful delivery system that can be used in the development of other types of national infrastructures for community-based prevention services. Information regarding organizational structure and function around funding issues, training, quality control and community relationships was gathered through telephone surveys with 50 state D.A.R.E. coordinators (including two major cities), focus groups with local D.A.R.E. officers and mentors, and interviews with national D.A.R.E. office staff.

Results

The surveys helped identify several strengths inherent in the D.A.R.E. program necessary for building a prevention infrastructure, including a well-defined organizational focus (D.A.R.E. America), uniform training and means for rapid dissemination (through its organized training structure), continuing education mechanisms (through the state and national conference and website), mechanisms for program monitoring and fidelity of implementation (formal and informal), branding and, for several states, predictable and consistent financing. Weaknesses of the program as currently structured include unstable funding and the failure to incorporate components for the continual upgrading of curricula reflecting research evidence and "principles of prevention".

Conclusion

The D.A.R.E. organization and service delivery network provides a framework for the rapid dissemination of evidence-based prevention strategies. The major strength of D.A.R.E. is its natural affiliation to local law enforcement agencies through state coordinators. Through these affiliations, it has been possible for D.A.R.E. to become established nationally within a few years and internationally within a decade. Understanding how this structure developed and currently functions provides insights into how other such delivery systems could be developed.
Modelling repeated ordinal reports from multiple informants
Authors: Plewis Ian , Vitaro Frank , Tremblay Richard
Published: September 2006

Cross-informant associations tend to be low for reports of children’s behaviours at one point in time. The paper extends the literature on multiple informants using data from a well-known longitudinal study of Quebec, Canada, boys to show how to estimate associations between repeated teachers′ and self-reports of aggressive behaviour. These associations, for both level and change, are derived from multilevel models for repeated measures of variables best treated as ordered categories. The ordering is represented by sets of continuation ratios, change by linear and quadratic functions of age, and the multivariate models are estimated using penalized quasi-likelihood. The analyses also incorporate a risk variable: socio-economic status (SES). The correlations between estimates of the growth parameters for the two sets of reports tend to be rather small and smaller than the cross-informant associations for levels. SES is associated with levels of aggression, more so for teacher reports than for self-reports, but not with the decline in aggression with age.
Correlations Between O6-Methylguanine DNA Methyltransferase Promoter Methylation Status, 1p and 19q Deletions, and Response to Temozolomide in Anaplastic and Recurrent Oligodendroglioma: A Prospective GICNO Study
Authors: Brandes Alba A. , Tosoni Alicia , Cavallo Giovanna , Reni Michele , Franceschi Enrico , Bonaldi Laura , Bertorelle Roberta , Gardiman Marina , Ghimenton Claudio , Iuzzolino Paolo , Pession Annalisa , Blatt Valeria , Ermani Mario
Published: September 2006

Purpose

To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting.

Patients and Methods

From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction.

Results

The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09).

Conclusion

TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.
Acute In Vivo Regulation of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity by Insulin and Intralipid Infusions in Humans
Authors: Wake Deborah J. , Homer Natalie Z. M. , Andrew Ruth , Walker Brian R.
Published: September 2006

Context: Extraadrenal regeneration of cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) is increased after a mixed meal. It is unknown which tissue is responsible and whether this reflects the complex transcriptional control of 11HSD1 or posttranscriptional control exerted by supply of reduced nicotinamide adenine dinucleotide phosphate from hexose-6-phosphate dehydrogenase.

Objective: The objective of this study was to test whether hyperinsulinemia and/or increased serum free fatty acids increase whole-body and intraadipose 11HSD1, and whether adipose 11HSD1 switches from dehydrogenase to reductase activity.

Methods: In nine healthy men, we measured whole-body cortisol regeneration (by iv infusion of 9,11,12,12-[2H]4-cortisol) and intra-adipose interconversion of cortisol and cortisone (by sc microdialysis infusion of [3H]4-cortisol and [3H]2-cortisone in separate cannulae) during: 1) a hyperinsulinemic euglycemic clamp; 2) iv lipid infusion (Intralipid 20% fat emulsion); and 3) saline infusion, each for 3.5 h.

Results: Hyperinsulinemia increased rate of appearance of 9,12,12-[2H]3-cortisol (19.3 ± 0.8 vs. 16.7 ± 1.1 nmol/min with saline, P < 0.001), indicating increased whole-body 11HSD1. Within adipose, the predominant reaction was reductase conversion of cortisone to cortisol (after 3.5 h of saline infusion, reaching 11.0 ± 2.7% per hour reductase vs. 5.2 ± 1.3 dehydrogenase, P < 0.02); insulin increased reductase (reaching 15.8 ± 3.0, P < 0.05) and tended to increase dehydrogenase activity. Intralipid infusion had no effects on whole-body deuterated cortisol metabolism, but increased both dehydrogenase and reductase (reaching 16.7 ± 1.8, P < 0.01) activities in adipose.

Conclusions: Hyperinsulinemia and increased free fatty acids induce acute increases in 11HSD1 activity in adipose tissue that are not attributable to a switch from dehydrogenase to reductase. Hyperinsulinemia also increases systemic cortisol regeneration. These effects may enhance intracellular cortisol concentrations after a meal.
Heat Shock Treatment of Tumor Lysate-Pulsed Dendritic Cells Enhances Their Capacity to Elicit Antitumor T Cell Responses against Medullary Thyroid Carcinoma
Authors: Bachleitner-Hofmann Thomas , Strohschneider Michaela , Krieger Peter , Sachet Monika , Dubsky Peter , Hayden Hubert , Schoppmann Sebastian F. , Pfragner Roswitha , Gnant Michael , Friedl Josef , Stift Anton
Published: September 2006

Background: In vitro and in vivo studies have shown that dendritic cells (DCs) can stimulate antitumor T cell responses against medullary thyroid carcinoma (MTC). However, despite promising results in selected cases, the clinical efficacy of DC immunotherapy in patients with MTC has been limited. Recently, it has been demonstrated in mice that heat shock enhances the capacity of bone-marrow-derived DCs to stimulate antigen-specific T cells. The aim of our investigations was to evaluate whether heat shock also increases the capacity of human monocyte-derived DCs to stimulate antitumor T cell responses against MTC tumor cells.

Methods: DCs from six patients with metastatic MTC were pulsed with tumor lysate derived from allogeneic MTC tumor cells and were heat shocked for 12 h at 40 C or kept at 37 C. Thereafter, the DCs were matured and cocultured with T cells. Finally, the cytotoxic activity of T cells against MTC tumor cells was measured in vitro.

Results: In all patient samples, cytotoxic T cell responses against MTC tumor cells could be induced. Notably, heat-shocked DCs were more potent stimulators of cytotoxic T cell responses than control DCs, with T cells stimulated with heat-shocked DCs displaying a significantly increased cytotoxic activity against MTC tumor cells as compared with T cells stimulated with control DCs. In none of the experiments was a cytotoxic T cell response against unrelated pancreatic tumor cells (PANC-1) observed, using both control and heat-shocked DCs.

Conclusions: Our study shows that heat-shocking DCs may be a valuable strategy to increase the immunostimulatory capacity of DCs used for immunotherapy of MTC.
Trypanosome IFT mutants provide insight into the motor location for mobility of the flagella connector and flagellar membrane formation
Authors: Davidge Jacqueline A. , Chambers Emma , Dickinson Harriet A. , Towers Katie , Ginger Michael L. , McKean Paul G. , Gull Keith
Published: September 2006

The flagella connector (FC) of procyclic trypanosomes is a mobile, transmembrane junction important in providing cytotactic morphogenetic information to the daughter cell. Quantitative analyses of FC positioning along the old flagellum, involving direct observations and use of the MPM2 anti-phosphoprotein monoclonal reveals a `stop point' is reached on the old flagellum which correlates well with the initiation of basal body migration and kinetoplast segregation. This demonstrates further complexities of the FC and its movement in morphogenetic events in trypanosomes than have hitherto been described. We used intraflagellar transport RNAi mutants to ablate the formation of a new flagellum. Intriguingly the FC could still move, indicating that a motor function beyond the new flagellum is sufficient to move it. When such a FC moves, it drags a sleeve of new flagellar membrane out of the flagellar pocket. This axoneme-less flagellar membrane maintains appropriate developmental relationships to the cell body including following the correct helical path and being connected to the internal cytoskeleton by macula adherens junctions. Movement of the FC in the apparent absence of intraflagellar transport raises the possibility of a new form of motility within a eukaryotic flagellum.
The classification of respiratory viruses and their clinical manifestations.
Authors: Snow James B.
Published: September 2006

The continuing discovery of new viruses and the rapid accumulation of new information on the biologic, biochemical and physical properties of animal viruses have necessitated a reclassification of viruses.
Cryosurgery in chronic rhinitis
Authors: Ozenberger James M.
Published: September 2006

Cryotherapy, a tool of dermatologists for many years, has received increasing attention among otolaryngologists since being “reintroduced” as a surgical technique by Cooper in 1961.1 Miller2 and others have studied extensively its value in treatment of tumors of the head and neck. In non‐neoplastic diseases, freezing has been used by House3 and others for Ménière's syndrome, and by Hill4,5 for tonsils, nasal polyps, and for epistaxis. The response of tissues to freezing have been summarized by Hanckel.6
Basal cell nevus syndrome: A case report with associated carcinoma of the maxilla
Authors: Shapiro Myron J.
Published: September 2006

Basal cell nevus syndrome is a rare hereditary multiple‐system progressive disorder which was first reported as such by Binkley and Johnson in 1951.1 Since then, retrospectively and de novo, over 150 cases have been reported. Reviews2,3,4 have tried to define the clinical features which constitute the syndrome, but so many anomalies have been described that for the sake of clarity, I have eliminated all but the more salient features.
The bifid uvula
Authors: Taylor G. Dekle
Published: September 2006

Seemingly minor anatomical variants may herald more serious and complicated anatomical or physiological abnormalities. A white forelock is present in 20 percent of cases with Waardenburg's syndrome. Blue sclera suggests the diagnosis of otosclerosis or osteogenesis imperfecta. A subtle variation of the ear lobe may suggest a congenital defect of the ossicular chain in the patient with conductive deafness and normal appearing tympanic membranes. I believe the bifid uvula to be a sentinel, manifesting a disturbance of the normal embryological development of the palate and related structures. Otologic sequelae and velo‐pharyngeal incompetency seen with the more familiar cleft palate may also occur in patients with a bifid uvula. An increased awareness for this seemingly benign variant may aid the otolaryngologist in his quest for ways to prevent conductive deafness and the adverse anatomical changes accompanying tubal inefficiency.
Nasopharyngeal malignancies in children
Authors: Straka John A. , Bluestone Charles D.
Published: September 2006

Nasopharyngeal malignancies are thought to be uncommon in children. A review of the literature reveals 166 documented cases of nasopharyngeal malignancy in childhood. This appears to be a deceptively small number due to a lack of specificity in the reporting of oral and pharyngeal neoplasms. This report adds six more cases, making a total of 172.

Children with this disease are more likely to present with neurological signs and symptoms than adults. Neurological involvement carries a poor prognosis.

Patients with nasopharyngeal malignancy are often misdiagnosed and subjected to needless surgical procedures. The fact that the early symptoms of nasopharyngeal malignancy are common in childhood from benign causes and the false security that a malignancy in this area is rare in childhood, undoubtedly contribute to the diagnostic delay.
Increased cerebrospinal fluid pressure following unilateral radical neck dissection
Authors: Tobin Howard A.
Published: September 2006

A case of prolonged increased cerebrospinal fluid pressure, accompanied by papilledema is described in a patient who underwent unilateral radical neck dissection for low‐grade mucoepidermoid tumor of the submaxillary gland. A superior sagittal sinogram revealed a normal sinus and venous system on the opposite side. The patient ultimately recovered completely with no specific therapy. Only two other cases of visual disturbance following unilateral neck dissection have been reported. The similarity to otitic hydrocephalus is apparent, although this patient had a normal spinal fluid cell count and chemistries in contra distinction to the increased protein and lymphocytes seen in otitic hydrocepha lis. The etiology of this patient's CSF hypertension could not be determined, and although no specific therapy was necessary, various forms of therapy were discussed.
Otologic surgery in patients with one hearing ear only
Authors: Chandler J. R. , Freeman Joseph
Published: September 2006

On occasions, the otologist is confronted with the possibility of performing surgery on the ear of a patient with useless or no hearing in the opposite ear. Because any surgical procedure on a patient's ear may result in further loss of hearing or even total deafness in the operated ear, an ill‐advised operative procedure in such a patient may result in a catastrophe. Up to 2 percent of patients undergoing surgery for otosclerosis develop further severe sensori‐neural hearing losses in the operated ear. Idiopathic sudden deafness in patients following stapedectomy can occur for causes unrelated to surgery. Further loss of hearing can also occur after simple myringoplasty and tympanoplasty. Such a possibility must be considered and to a great degree should influence the otologist's decision as to whether or not surgery is indicated, and if so, what is the surgical procedure of choice?

A deaf patient can be compared to a blind patient only superficially, and not at all when it comes to any consideration of surgery upon the remaining organ of hearing and vision. Consider the patient with total blindness in one eye who cannot be helped with glasses. Should blindness of any degree affect the remaining eye, an operative procedure which can restore vision may be the only recourse. On the other hand, should the patient with only one hearing ear lose some hearing acuity in that ear, it may always be corrected or helped by the use of amplification. Therein lies the great difference. Total deafness cannot be helped by a hearing aid, and such a catastrophe cannot be risked when any other choice is available. This must be the guiding principle of all otologic surgeons in such instances.
Acute mastoiditis following pseudomonas maltophilia infection: Case report
Authors: Harlowe H. D.
Published: September 2006

Acute mastoiditis is now an uncommon finding. The early use of the various antibiotics has made surgical mastoiditis a rarity. A comparatively new pathogen “Pseudomonas maltophilia” was the causative organism in this case.

Pseudomonas maltophilia responds only to Garamycin and Polymixin B. Unless one of these two antibiotics is used in its treatment, it will continue to cause a severe infection.
Enlarging the ear canal in intact canal wall tympanoplasty
Authors: Shea John J.
Published: September 2006

In chronic otitis media, the external meatus and ear canal are often small and tortuous. Gill reported that a third of_250_ears with. congenital atresia had chronic otitis media, often unsuspected. Bellucci has emphasized the role of the Eustachian tube in determining the extent of chronic otitis media, so it follows that the small and tortuous ear canal are part of the congenital defects in this disease.

Farrior and Caparosa have previously mentioned enlarging the ear canal in intact canal wall tympanoplasty.

The usual post‐aural incision is made and the soft tissue of the canal dissected forward off the bone. A first vertical incision is made through the canal wall skin near the annulus, a second through the concha, and the two are connected by a longitudinal incision. The flaps are shifted apart to enlarge the canal, and an elipse of conchal cartilage is excised. The intact tympanoplasty is completed in the usual fashion, and the defect in the drum and canal is closed with a large tongue‐shaped piece of fascia which is brought out over the concha through the second incision. The canal is packed with strips of silk and cotton balls for two weeks.

The result is a meatal opening and canal with a trumpet shape and adequate size.
Relapsing polychondritis
Authors: Swain Ronnie E. , Stroud Malcolm H.
Published: September 2006

To date only 55 cases of relapsing polychondritis have been reported in the English literature. The present information concerning the history, clinical and laboratory findings, diagnosis, prognosis, and treatment is reviewed. Two unusual cases of this disease which exemplify the extreme variability of the symptomatology among these patients are presented. While asleep one patient developed a classical “saddle nose” deformity which spontaneously improved within three days. The other patient's disease manifested predominately non‐cartilaginous symptoms and emphasizes the possibility of an auto‐immune or allergic mechanism affecting a molecular target common to both cartilaginous and non‐cartilaginous structures.
Mycosis of the maxillary sinuses
Authors: Iwamoto Hikonojo , Katsura Masumi , Fujimaki Tatsub
Published: September 2006

Fungus infection of the maxillary sinus has been considered a rare disorder; recently, however, such cases have been reported in increasing number.

The authors have recently observed five cases of mycosis of the paranasal sinuses. Three of these cases showed the clinical symptoms and signs of swelling and pain in the cheek area and epistaxis and aroused suspicion of maxillary cancer. Of the remaining two cases one was misdiagnosed as maxillary cancer with pulmonary metastasis and radiation therapy without preliminary tissue diagnosis given because of the poor general condition of the patient. On improvement of the patient's condition exploratory maxillotomy and mucosal biopsy revealed mycotic invasion; in the other, chronic bacterial maxillary sinusitis was suspected, but exploratory sin‐usostomy showed mycosis.

The authors emphasize an apparent increasing frequency of mycosis of the paranasal sinuses and the fact that the symptoms and signs of mycotic invasion may duplicate those of early malignancy of this area.
Juvenile nasopharyngeal angiofibroma
Authors: Wilson W. R. , Miller D. , Lee K. J. , Yules R. B.
Published: September 2006

This paper contains a review of the gross pathology and histopathology of juvenile nasopharyngeal angiofibroma and a review of the theories of origin of this tumor. The relative merits of hormone therapy, carotid arteriography, external and interstitial radiation therapy, cryosurgery, and various surgical approaches are discussed.

A plan for the management of these tumors has been developed:

1. Estrogen therapy is begun one month pre‐operatively, if it is to be used.

2. The patient sees a prosthodontist so that he may have a temporary plastic plate made which will fit onto the teeth in such a manner that it will hold a transpalatal flap in place following surgery, without disturbing the suture line.

3. Arteriography is scheduled only if there is evidence of intracranial extension or an extensive recurrence.

4. Radon seeds, usually 10 in number and 1 me in size, are ordered for the day of surgery.

5. Liquid nitrogen is made ready for use with a closed cryo‐probe system.

6. The expected blood loss and the possible use of planned hypotensive anesthesia are discussed with the anesthesiologist. An adequate supply of blood is to be available in the operating room at the start of the resection of tumor.

7. A plan is made for a transpalatal or transantral approach, or both, or occasionally for a lateral rhinotomy approach. Rarely has a transmandibular pterygoid approach been found necessary.

The combined transpalatal‐transantral approach is described in detail. Two. cases are presented.
Premalignant changes in the vocal cord
Authors: Robbett William F.
Published: September 2006

The subject of premalignant changes in the vocal cords encompasses a very extensive scope; therefore, only two aspects are discussed in this presentation.

The two most common clinically identifiable entities that progress to invasive carcinoma are examined, namely, keratosis and carcinoma in situ.

The treatment of keratosis and carcinoma in situ is probably the most provocative subject in laryngeal disease. There is a great difference of opinion as to the action or inaction to be taken when these conditions are identified in the larynx.

Keratosis may appear in two forms: delineated keratosis and diffuse keratosis. They_have distinct‐Glinical appearances and have a different potential for malignant progression.

The treatment of carcinoma in situ is a very controversial subject. The value and advisability of treating this disease with irradiation is questioned.

The use of microlaryngeal surgery has been a valuable aid in the identification and delineation of both of these diseases of the vocal cords.

The second part of this presentation discusses the role of the submucosa in intraepithelial and early invasive carcinoma of the vocal cord.

Some interesting investigative studies have been performed in the study of the role of the stroma in epidermal carcinogenesis. These observations suggest the possibility of stromal elements being of pathogenic importance in the origin of epithelial tumors.

The very rapid reappearance of carcinoma_ in situ in the regenerated epithelium of the vpcal cord after complete mucosal removal is suggestive of some extra‐epithelial stimulus. Both vocal cords being exposed to the same extrinsic irritants, carcinoma in situ will frequently appear only in the regenerated epithelium of the vocal cord that first evidenced the disease. Multicentric foci of carcinoma is mentioned but not discussed in the presentation.
An immunological concept for bell's palsy — Experimental study
Authors: Mcgovern Francis H. , Konigsmark Bruce W. , Sydnor J. Brantley
Published: September 2006

Bell's palsy is considered by many authorities to be an ischemic paralysis. The mechanism is thought to be a primary vasoconstriction of the vasa nervorum supplying the facial nerve within the fallopian canal and a secondary ischemia induced by the bony canal. The factor precipitating the vasospasm is the proclivity of certain individuals toward segmental arteriolar spasm.

In our work.on experimental ischemic facial paralysis, another explanation for the etiology of Bell's palsy presented itself. We observed that dogs sensitized to horse serum showed a greater paralytic response and more marked histopathologic changes after the intrafallopian injection of saline than non‐sensitized dogs. Subsequent investigations using a more potent antigen seemed to strengthen the idea that the experimental paralysis we have accomplished in these dogs is the result of an immunologic or hypersensitivity reaction.

In these experiments using adequate control dogs, the animals were sensitized with intravenous horse serum and with a Freund's. adjuvant — horse serum mixture. The presence of horse serum antibodies was demonstrated in the serum of three dogs. The fallopian canal was injected with a combination of solutions: saline solution, Ringer's solution, distilled water, horse serum and the dog's serum. At the end of two weeks, the degree of paralysis was recorded, the nerve was removed and was sent for histopathologic examination.

The significant degree of paralysis and the major histopathologic changes were seen in the sensitized dogs injected with saline or Ringer's solution or horse serum.

The mechanism of the paralysis is postulated to be an initial antigenantibody reaction with a complement fixation, a degranulation of mast cells producing vasoactive components, an increased capillary permeability, edema, vasospastic phenomenia, and subsequent trophic changes in the nerve. In addition, the edematous neuropathy is severely affected by the compression of the nerve by the bony canal wall.

We suggest that these events observed experimentally may be related to the changes seen in Bell's palsy, and Bell's palsy is caused by a localized immunologic or hypersensitivity reaction.
Symposium on prophylaxis and treatment of middle ear effusions.: I. The morphological basis for understanding middle ear effusions.: An electron microscopic, cytochemical, and autoradiographic investigation
Authors: Lim David J. , Viall John , Birck Herbert , St. Pierre Ronald
Published: September 2006

An attempt was made to elucidate the cytological nature of the defense mechanisms of the normal middle ear with special emphasis on the secretory system.

Autoradiography was performed with the use of isotope‐labeled glucose in order to determine the rate of glucose uptake by middle ear cells, particularly by secretory cells. Mucus‐secreting glands in the guinea pig eustachian tube incorporated a large amount of glucose, while the demilune cells (serous) incorporated only a moderate amount. Some simple squamous epithelium of the bulla also took up a large amount of glucose. Since the mucous blanket of the bulla was labeled after only one hour, it is speculated that these flat cells are of the secretory type.

A cytochemical demonstration of the enzyme acid phosphatase was done in order to determine the localization of this lysosomal enzyme in the middle ear cells. A strong reaction was consistently noted in the cytoplasm of both light (mucous) and dark (serous) secretory cells. This reaction appears to take place on the outer surface of the secretory granules, but, occasionally, it takes place inside the granules. The strongest reaction was noted in the lysosomal bodies. A weak reaction was frequently noted in the nuclear chromatin of the secretory cells.

An immunofluorescent study demonstrated the presence of immunoglobulin‐producing cells in the eustachian tube and in the guinea pig middle ear mucosa. Fluorescein‐labeled cells (round cells) were numerous, particularly in the eustachian tube near the glands.

It can be suggested from the foregoing that the middle ear is provided with mucociliary, enzymatic, and immunological (secretory and serum) defense systems.

The pathological characteristics of human serous otitis were also reviewed. Evidence was shown of an increase in the number of secretory and ciliated cells, of free macrophages, and of the round cells of the submucosal connective tissue. Evidence of the free escape of transudate through intercellular spaces of the epithelial cells and capillary wall damage in the submucosal layer was also noted in pure serous effusion cases. These changes are identical to those that take place in inflammatory reactions. The middle ear effusion, therefore, can be looked upon as the result of enhanced middle ear defense mechanisms occurring in different phases.
Symposium on meniere's disease.: I. Meniere's disease: Results of a two and one‐half‐year study of etiology, natural history and results of treatment
Authors: Pulec Jack L.
Published: September 2006

The results of a two and one‐half year study of 120 patients with Ménière's disease has revealed multiple but specific etiology for 36 percent of the patients: 1. allergy, 14 percent; 2. congenital or acquired syphilis, seven percent; 3. adrenal pituitary insufficiency, six percent; 4. myxedema, three percent; 5. stenosis of the internal auditory canal, three percent; and 6. trauma, acoustic or physical, three percent.

Emotional or psychiatric factors are not involved in etiology of this disease. The vestibular and cochlear aqueduct on both temporal bones of patients with Ménière's disease could not be visualized in a significantly greater number than a normal control group suggesting an anatomic predisposition to the development of Ménière's disease. Preliminary immunologic viral investigation suggests the possibility of viral etiology in the remaining group considered idiopathic. Medical treatment with vasodilators is effective in many cases. The endolymphatic subarachnoid shunt operation was the treatment of choice for patients unresponsive to medical treatment and it is effective in controlling symptoms in 62 percent of cases. It is hoped that this study will encourage other investigators to criticize and help intensify our efforts to solve the questions remaining about Ménière's disease.
Symposium on meniere's disease.: Ii. Metabolic aspects of meniere's disease
Authors: Powers W. Hugh
Published: September 2006

Metabolic dysfunction is one of many factors mentioned as a primary or contributing cause of Ménière's disease. This evaluation consists of three parts: thyroid studies, five‐hour glucose tolerance test, and adrenal and pituitary tests.

Ninety‐eight patients with Ménière's disease are evaluated with an FTA absorption test, neuro‐otologic, allergic, and metabolic studies. The results of the metabolic evaluation are reviewed.

Thyroid function is evaluated with the thyroxine (T4) free index test and the serum‐bound thyroxine (T4) test of Murphy‐Pattee. Although 27 percent had low normal or hypothyroid findings, it was of clinical significance in only 17 percent of the patients.

The five‐hour glucose tolerance test was used to diagnose hyperglycemia and hypoglycemia.

Thirty percent of the 70 patients evaluated had an abnormal five‐hour glucose tolerance test. The 19 patients (28 percent) with a hypoglycemic curve were almost equally divided among a flat glucose tolerance curve, a reactive hypoglycemia curve, and chemical or latent diabetic curve. A manifest diabetic curve was present in two patients. Hypoglycemia was not a primary factor in Ménière's disease but was an important contributing cause in 12 patients that responded to a combination of dietary, allergic or endocrine therapy.

The symptoms of Ménière's disease often become manifest during periods of stress. The adrenal pituitary axis plays a vital role in man's reaction to stress. For this reason, hypoadrenal function was suggested as an etiology in some patients with Ménière's disease.

In this study two tests were used to measure adreno‐cortical reserve: ACTH plasma cortisol stimulation test and insulin stimulation test.

Sixty of the 98 patients were evaluated with the ACTH plasma cortisol stimulation test, and one‐third had a lowered adrenocortical reserve. Further endocrine studies are being performed to determine the presence of a specific endocrine problem.

After evaluation of 98 patients with Ménière's disease, we concluded the following:

1. The five‐hour glucose tolerance test is helpful in identifying hypoglycemia, which may be a contributing factor in Ménière's disease.

2. Non‐myxedematous hypothyroidism may play an important role in some patients with Ménière's disease.

3. Further endocrine studies will be necessary to determine the significance of the lowered adrenocortical reserve as shown by the ACTH plasma cortisol stimulation test.
Otological problems of the alaskan native population.
Authors: Weymuller Ernest A. , Reed David G.
Published: September 2006

The Alaskan Otological Fellowship of the New York Eye and Ear Infirmary operates at the Alaskan Native Health Facility in Mt. Edgecumbe, Sitka, Alaska. It is a division of the Health Education and Welfare Program. The Fellowship is now in its fourth year.

The area we service is approximately 35,000 square miles. All villages and schools in the area have been screened for otological care and for possible hearing aids.

The incidence of otitis media and its complications is 13 percent in the Eskimo and 9.1 percent in the Indian. These percentages are those reported in the Southwest Native. There is no ready explanation of the preponderance of otologic disease in this group.

In the first three years, 360 procedures were performed on 310 chronically diseased ears. Following is a breakdown of these procedures:

Myringoplastys 165

Simple Mastoidectomies 25

Simple Mastoidectomy with Myringoplasty 66

Mastoidectomy with Type III Tympanoplasty 17

Modified Radical Mastoidectomy 26

Radical Mastoidectomies 36

Miscellaneous Procedures 25

It is the opinion of the authors that the choice of procedure is much more limited in this group than in an urban community. It must be remembered that aftercare and follow‐up is more difficult in these areas.

It has been our policy to use conservative procedures. Elimination of the disease is the first consideration, and conservation of hearing is secondary. A dry ear is of the utmost importance, and for this reason, modified radical and classical radical mastoidectomies are more frequently performed. Types IV and V tympanoplastys are not considered feasible.
Dacron prosthesis in frontal sinus surgery.
Authors: Barton Richard Thomas
Published: September 2006

This is a report of 34 cases of chronic frontal sinusitis in which a modified Lynch external frontal sinusotomy was performed successfully, using a Dacron Woven Arterial Graft (Bard) to maintain a naso‐frontal communication. In none of the patients was it necessary to remove the prosthesis later. The patients have been generally symptom‐free for periods up to 17 years after the surgery.

It is proposed that whereas the Goodale osteoplastic obliterative operation is the procedure of choice in the presence of relatively low‐grade infection, it is less satisfactory in patients with uncontrolled infection; also, in those instances of pan‐sinusitis, wherein the ethmoid labyrinth is infected or involved by a mucocele, this technique is preferred rather than combining an osteoplastic frontal operation with a transantral ethmoidectomy as has been recommended.

From the patient's point of view, the postoperative complaints registered with this Dacron tube technique are occasionally bothersome crusting, odor, and discharge. These symptoms have been easily relieved by short courses of antibiotic therapy.