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Dicistroviruses are single-stranded RNA viruses in the family Dicistroviridae . The viruses have mainly been detected in arthropods and are the cause of several devastating diseases in many of these species such as honeybees. Increasingly, dicistroviruses have also been detected in both mammalian and avian species in faeces, blood and liver, but with unconfirmed pathology. Here, we report a novel dicistrovirus detected in the intestinal content of a captive red squirrel with enteritis along with the disease history, pathology and genomic characterisation of the virus. Virus particle morphology resembled those of picornaviruses with a diameter of 28-32 nm but failed to be detected using a mammalian/avian pan viral microarray. Next-generation sequencing confirmed a dicistrovirus having a typical dicistrovirus genome organization, but with the polyprotein 1 being shorter by about 100 amino acids, compared to that of other dicistroviruses. Phylogenetic analysis of ORF1 and ORF2 sequences clustered the virus with two yet unassigned dicistroviruses detected in Gorilla gorilla and a freshwater arthropod and likely to be designated to a new genus. Our data further highlights the ever-growing diversity of dicistroviruses, but the clinical significance of the virus in mammalian species and particularly red squirrels has yet to be established.

Cryptococcosis is widely reported in North America and Australia but considered rare in the UK. Disease is mainly caused by Cryptococcus neoformans and Cryptococcus gattii and affects animals and humans. Cases of cryptococcosis have been described in non-human primates, including a few in the Callitrichidae family. Six captive callitrichids from five zoological facilities in the UK were diagnosed with cryptococcosis on post-mortem examination over a 13-year period. Histological examination revealed intralesional yeast bodies consistent with Cryptococcus spp in lung, brain, lymph nodes, larynx, salivary gland and ears. C. neoformans was confirmed in two cases by culture and by culture and polymerase chain reaction (28S rRNA gene), respectively. This case series is the first report of Cryptococcus spp in captive callitrichids in the UK and reinforces the need to include this fungal disease in the differential diagnosis of sick callitrichids in zoo settings., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Leukoencephalomyelopathy (LEM) is suggested to be an age-related degenerative condition in geriatric Eastern quolls ( Dasyurus viverrinus ), manifesting in animals greater than 3.5 yr of age. This case series describes four LEM cases from two zoologic collections; three in nongeriatric animals, with one only 1 yr of age, and details advanced diagnostic investigation, including magnetic resonance imaging, cerebrospinal fluid analysis, and electrodiagnostic studies, not previously reported in Eastern quolls. Animals presented clinically with forelimb proprioceptive deficits and hindlimb and lumbar muscle hypotrophy, which were not noted in previous reports, in addition to hindlimb ataxia. Blindness and emaciation, which have been reported previously, were not seen. Disease progression was variable, and time from first clinical signs to euthanasia ranged from 46 days to over 2 yr. Histopathologic findings in the central nervous system were typical of those in previous LEM cases; concomitant polyneuropathy was observed in two quolls. Our findings suggest that age-related degeneration may not be the only cause of LEM in Eastern quolls. Because all quolls were related, a familial component cannot be excluded. LEM should be further investigated for its potential impact on future captive breeding programs, and our findings suggest that daily quality-of-life assessment should guide euthanasia of affected animals.

This study investigates the occurrence of erythematous lip lesions in a captive sun bear population in Cambodia, including the progression of cheilitis to squamous cell carcinoma, and the presence of Ursid gammaherpesvirus 1. Visual assessment conducted in 2015 and 2016 recorded the prevalence and severity of lesions. Opportunistic sampling for disease testing was conducted on a subset of 39 sun bears, with histopathological examination of lip and tongue biopsies and PCR testing of oral swabs and tissue biopsies collected during health examinations. Lip lesions were similarly prevalent in 2015 (66.0%) and 2016 (68.3%). Degradation of lip lesion severity was seen between 2015 and 2016, and the odds of having lip lesions, having more severe lip lesions, and having lip lesion degradation over time, all increased with age. Cheilitis was found in all lip lesion biopsies, with histological confirmation of squamous cell carcinoma in 64.5% of cases. Single biopsies frequently showed progression from dysplasia to neoplasia. Eighteen of 31 sun bears (58.1%) had at least one sample positive for Ursid gammaherpesvirus 1. The virus was detected in sun bears with and without lip lesions, however due to case selection being strongly biased towards those showing lip lesions it was not possible to test for association between Ursid gammaherpesvirus 1 and lip squamous cell carcinoma. Given gammaherpesviruses can play a role in cancer development under certain conditions in other species, we believe further investigation into Ursid gammaherpesvirus 1 as one of a number of possible co-factors in the progression of lip lesions to squamous cell carcinoma is warranted. This study highlights the progressively neoplastic nature of this lip lesion syndrome in sun bears which has consequences for captive and re-release management. Similarly, the detection of Ursid gammaherpesvirus 1 should be considered in pre-release risk analyses, at least until data is available on the prevalence of the virus in wild sun bears., Competing Interests: The authors have declared that no competing interests exist.

Fifty-eight frozen postmortem lung and air sac samples were collected from penguins housed at 21 zoological collections throughout the United Kingdom, from 2007 to 2018. Aspergillus fumigatus , a significant respiratory pathogen of penguins in captivity, was isolated from 15 of the 22 penguins with gross lesions. Of the penguins with gross lesions of aspergillosis at postmortem examination, the pathogen was cultured from 63.6% (15 of 22) of frozen samples. Aspergillus fumigatus was cultured from 2.7% (1 of 36) of tissues collected from penguins without gross lesions at postmortem. Additionally, of 18 fresh samples that cultured A. fumigatus at the time of postmortem, 15 samples (83%) yielded isolates that were successfully cultured from frozen tissue. Minimum inhibitory concentration (MIC) data demonstrated that all isolates were susceptible to terbinafine and voriconazole, and all were resistant to itraconazole, using published MIC cutoff values. Comparison isolates from fresh tissues had identical antimicrobial susceptibility to isolates from the same tissues after being frozen. This study demonstrates that A. fumigatus can be isolated from frozen respiratory tissues of penguins, even after freezing for more than 10 yr.

Syngnathidae (seahorses, pipefish and seadragons) are charismatic species commonly kept in commercial aquaria, but published literature on syngnathid diseases is limited and immunohistochemical techniques not routinely employed. A retrospective review of 2,541 syngnathid submissions received between March 2003 and October 2016 identified 18 neoplasms including germ cell tumours, exocrine pancreatic and intestinal carcinomas, chromatophoromas, and single cases of lymphoma, thyroid and renal carcinoma, swim bladder and pituitary adenoma. Big-bellied seahorses accounted for 19% of submissions, but 50% of neoplasms were diagnosed in this species. This study includes the first reported cases of germ cell tumours, chromatophoroma, thyroid carcinoma and pituitary adenoma in Syngnathidae and the first reports of neoplasia in pipefish species. Out of nine commercial antibodies trialled for immunohistochemical characterization of neoplastic tissue, only pan-cytokeratin proved cross-reactive. Electron microscopy was performed in four cases. Tumours should be considered as differential diagnosis in cases with buoyancy issues, debilitated or emaciated animals, and may predispose to secondary infections. This study highlights the value of histopathological disease surveillance for commercial aquarium settings., (© 2020 John Wiley & Sons Ltd.)

Background: Neoplasia has historically been regarded as an unusual occurrence in reptiles. The aim of the present study was to evaluate the prevalence of neoplasms in routine diagnostic samples submitted to a specialist exotic animal laboratory., Methods: Over a 10-year period, 690 lizard samples were submitted for histopathological or cytopathological examination by Royal College of Veterinary Surgeons specialists in Veterinary Pathology (Zoo and Wildlife). Records were reviewed retrospectively and non-neoplastic diagnoses excluded from further analysis., Results: 158 neoplasms were diagnosed in 149 lizards, with 22.9% of submissions resulting in a diagnosis of neoplasia. The skin was the most commonly affected organ, and squamous cell carcinomas were the most common neoplasms identified (17.7% of all neoplastic diagnoses).Bearded dragons and panther chameleons had a statistically significant higher proportion of neoplasia diagnosis than the lizard population as a whole, and geckos had a statistically significantly lower proportion.Several neoplasms identified in this study have not been previously reported in lizards, including a testicular Sertoli cell tumour, testicular granulosa cell tumour, splenic haemangiosarcoma, gastric adenocarcinoma and basal cell carcinoma., Conclusion: The results suggest that the prevalence of neoplasia in captive lizards may be higher than previously reported, and that there is variation in prevalence between different lizard species and families. It is unclear whether these differences relate to genetic or management factors., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

: Today, efficient delivery of sorafenib to hepatocellular carcinoma remains a challenge for current drug formulation strategies. Incorporating the lipophilic molecule into biocompatible and biodegradable theranostic nanocarriers has great potential for improving the efficacy and safety of cancer therapy. In the present study, three different technologies for the encapsulation of sorafenib into poly(d,l-lactide- co -glycolide) and polyethylene glycol-poly(d,l-lactide- co -glycolide) copolymers were compared. The particles ranged in size between 220 and 240 nm, with encapsulation efficiencies from 76.1 ± 1.7% to 69.1 ± 10.1%. A remarkable maximum drug load of approximately 9.0% was achieved. Finally, a gadolinium complex was covalently attached to the nanoparticle surface, transforming the nanospheres into theranostic devices, allowing their localization using magnetic resonance imaging. The manufacture of sorafenib-loaded nanoparticles alongside the functionalization of the particle surface with gadolinium complexes resulted in a highly efficacious nanodelivery system which exhibited a strong magnetic resonance imaging signal, optimal stability features, and a sustained release profile., Competing Interests: The authors declare no conflicts of interest.

Tapeworms of the genus Echinococcus reside in the small intestine of a number of carnivorous species, predominantly canids. In enzootic areas, hydatidosis caused by taeniid metacestodes can present a significant problem in accidental intermediate hosts, including humans. Whereas the United Kingdom is currently considered free of Echinococcus multilocularis, Echinococcus granulosus sensu stricto (s.s.) and Echinococcus equinus are endemic in the UK and have been reported in a variety of captive mammals. The presentation of echinoccocosis in non-human primates widely parallels disease in humans, and public health concerns are related to the four genera, E. granulosus, E. multilocularis, Echinococcus vogeli and Echinococcus oligarthrus. In contrast, sporadic outbreaks and individual hydatid disease cases in non-human primates have been associated with several Echinococcus and Taenia species. Here we describe three fatal cases of cystic echinococcosis in two captive ring-tailed lemurs (Lemur catta) and one captive red-ruffed lemur (Varecia variegata rubra) and provide molecular tapeworm characterisation. To the best of the authors' knowledge, this includes the first report of Echinococcus ortleppi in a UK born ring-tailed lemur and provides the first in depth case reports of echinococcosis due to E. equinus in UK born ring-tailed and red ruffed lemurs with detailed clinical and pathological findings. The cestode life cycle and implications for zoo collections are discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Bilateral phacoclastic uveitis caused by lenticular infection with Encephalitozoon cuniculi is described in a snow leopard. The diagnosis was made on histopathological and immunohistological examination of both eyes submitted after postmortem examination. There was a positive antibody titer for E. cuniculi (1:320). Polymerase chain reaction (PCR) and sequence analysis of formalin-fixed, paraffin-embedded ocular tissue detected the DNA of E. cuniculi, strain III. No other systemic lesions attributable to the E. cuniculi infection were identified., (© 2014 American College of Veterinary Ophthalmologists.)

Infections of Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus (EEHV) can cause a rapid, highly lethal, hemorrhagic disease, which primarily affects juvenile animals up to the age of four years. So far, the majority of deaths have been attributed to infections with genotype EEHV1 or, more rarely, EEHV3 and EEHV4. Here, we report the pathological characteristics of the first fatality linked to EEHV5 infection, and describe the complete viral DNA sequence. Gross post-mortem and histological findings were indistinguishable from lethal cases previously attributed to other EEHV genotypes, and the presence of characteristic herpesviral inclusions in capillary endothelial cells at several sites was consistent with the diagnosis of acute EEHV infection. Molecular analysis confirmed the presence of EEHV5 DNA and was followed by sequencing of the viral genome directly from post-mortem material. The genome is 180,800 bp in size and contains 120 predicted protein-coding genes, five of which are fragmented and presumably nonfunctional. The seven families of paralogous genes recognized in EEHV1 are also represented in EEHV5. The overall degree of divergence (37%) between the EEHV5 and EEHV1 genomes, and phylogenetic analysis of eight conserved genes, support the proposed classification of EEHV5 into a new species (Elephantid herpesvirus 5).

Unlabelled: PAX5, a transcription factor pivotal for B-cell commitment and maintenance, is one of the most frequent targets of somatic mutations in B-cell precursor acute lymphoblastic leukemia. A number of PAX5 rearrangements result in the expression of in-frame fusion genes encoding chimeric proteins, which at the N-terminus consistently retain the PAX5 DNA-binding paired domain fused to the C-terminal domains of a markedly heterogeneous group of fusion partners. PAX5 fusion proteins are thought to function as aberrant transcription factors, which antagonize wild-type PAX5 activity. To gain mechanistic insight into the role of PAX5 fusion proteins in leukemogenesis, the biochemical and functional properties of uncharacterized fusions: PAX5-DACH1, PAX5-DACH2, PAX5-ETV6, PAX5-HIPK1, and PAX5-POM121 were ascertained. Independent of the subcellular distribution of the wild-type partner proteins, ectopic expression of all PAX5 fusion proteins showed a predominant nuclear localization, and by chromatin immunoprecipitation all of the chimeric proteins exhibited binding to endogenous PAX5 target sequences. Furthermore, consistent with the presence of potential oligomerization motifs provided by the partner proteins, the self-interaction capability of several fusion proteins was confirmed. Remarkably, a subset of the PAX5 fusion proteins conferred CD79A promoter activity; however, in contrast with wild-type PAX5, the fusion proteins were unable to induce Cd79a transcription in a murine plasmacytoma cell line. These data show that leukemia-associated PAX5 fusion proteins share some dominating characteristics such as nuclear localization and DNA binding but also show distinctive features., Implications: This comparative study of multiple PAX5 fusion proteins demonstrates both common and unique properties, which likely dictate their function and impact on leukemia development., (Mol Cancer Res; 12(4); 595-606. ©2014 AACR.)

Any two individuals differ from each other by an average of 3 million single-nucleotide polymorphisms. Some polymorphisms have a functional impact on cofactor-using enzymes and therefore represent points of possible therapeutic intervention through elevated-cofactor remediation. Because most known disease-causing mutations affect protein stability, we evaluated how the in vivo impact caused by single amino acid substitutions in a prototypical enzyme of this type compared with physical characteristics of the variant enzymes in vitro. We focused on cystathionine β-synthase (CBS) because of its clinical relevance in homocysteine metabolism and because some variants of the enzyme are clinically responsive to increased levels of its B6 cofactor. Single amino-acid substitutions throughout the CBS protein caused reduced function in vivo, and a subset of these altered sensitivity to limiting B6-cofactor. Some of these B6-sensitive substitutions also had altered sensitivity to limiting heme, another CBS cofactor. Limiting heme resulted in reduced incorporation of heme into these variants, and subsequently increased protease sensitivity of the enzyme in vitro. We hypothesize that these alleles caused a modest, yet significant, destabilization of the native state of the protein, and that the functional impact of the amino acid substitutions caused by these alleles can be influenced by cofactor(s) even when the affected amino acid is distant from the cofactor binding site.

PAX5 rearrangements resulting in the expression of fusion transcripts account for 2-3% of childhood B-cell precursor acute lymphoblastic leukemia. Most PAX5 fusions are rare and many of them have only been described in a couple of, or even only in single, cases. We have identified the third case with a PAX5-AUTS2 fusion, which results from unbalanced t(7;9)(q11.2;p13.2) rearrangements. Our findings substantiate that PAX5-AUTS2 is a recurrent fusion gene in pediatric B-cell precursor acute lymphoblastic leukemia, and we summarize the clinical characteristics of such patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cystathionine-β-synthase (CBS) deficiency is a human genetic disease causing homocystinuria, thrombosis, mental retardation, and a suite of other devastating manifestations. Early detection coupled with dietary modification greatly reduces pathology, but the response to treatment differs with the allele of CBS. A better understanding of the relationship between allelic variants and protein function will improve both diagnosis and treatment. To this end, we tested the function of 84 CBS alleles previously sequenced from patients with homocystinuria by ortholog replacement in Saccharomyces cerevisiae. Within this clinically associated set, 15% of variant alleles were indistinguishable from the predominant CBS allele in function, suggesting enzymatic activity was retained. An additional 37% of the alleles were partially functional or could be rescued by cofactor supplementation in the growth medium. This large class included alleles rescued by elevated levels of the cofactor vitamin B6, but also alleles rescued by elevated heme, a second CBS cofactor. Measurement of the metabolite levels in CBS-substituted yeast grown with different B6 levels using LC-MS revealed changes in metabolism that propagated beyond the substrate and product of CBS. Production of the critical antioxidant glutathione through the CBS pathway was greatly decreased when CBS function was restricted through genetic, cofactor, or substrate restriction, a metabolic consequence with implications for treatment.

Galpha subunits act to regulate vegetative growth, conidiation, and the mycoparasitic response in Trichoderma atroviride. To extend our knowledge on G protein signalling, we analysed G protein-coupled receptors (GPCRs). As the genome sequence of T. atroviride is not publicly available yet, we carried out an in silico exploration of the genome database of the close relative T. reesei. Twenty genes encoding putative GPCRs distributed over eight classes and additional 35 proteins similar to the Magnaporthe grisea PTH11 receptor were identified. Subsequently, four T. atroviride GPCR-encoding genes were isolated and affiliated to the cAMP receptor-like family by phylogenetic and topological analyses. All four genes showed lowest expression on glycerol and highest mRNA levels upon carbon starvation. Transcription of gpr3 and gpr4 responded to exogenously added cAMP and the shift from liquid to solid media. gpr3 mRNA levels also responded to the presence of fungal hyphae or cellulose membranes. Further characterisation of mutants bearing a gpr1-silencing construct revealed that Gpr1 is essential for vegetative growth, conidiation and conidial germination. Four genes encoding the first GPCRs described in Trichoderma were isolated and their expression characterized. At least one of these GPCRs is important for several cellular processes, supporting the fundamental role of G protein signalling in this fungus.

The accurate description of a microbial community is an important first step in understanding the roles of its components in ecosystem function. A method for surveying microbial communities termed serial analysis of rRNA genes (SARD) is described here. Through a series of molecular cloning steps, short DNA sequence tags are recovered from the fifth variable (V5) region of the prokaryotic 16S rRNA genes from microbial communities. These tags are ligated to form concatemers comprised of 20 to 40 tags which are cloned and identified by DNA sequencing. Four agricultural soil samples were profiled with SARD to assess the method's utility. A total of 37,008 SARD tags comprising 3,127 unique sequences were identified. A comparison of duplicate profiles from one soil genomic DNA preparation revealed that the method was highly reproducible. The large numbers of singleton tags, together with nonparametric richness estimates, indicated that a significant amount of sequence tag diversity remained undetected with this level of sampling. The abundance classes of the observed tags were scale-free and conformed to a power law distribution. Numerically, the majority of the total tags observed belonged to abundance classes that were each present at less than 1% of the community. Over 99% of the unique tags individually made up less than 1% of the community. Therefore, from either a numerical or diversity standpoint, taxa with low abundance comprised a significant proportion of the microbial communities examined and could potentially make a large contribution to ecosystem function. SARD may provide a means to explore the ecological roles of these rare members of microbial communities in qualitative and quantitative terms.

Background: Superimposed high-frequency jet ventilation (SHFJV), which does not require any tracheal tubes or catheters, was developed specifically for use in laryngotracheal surgery. SHFJV uses two jet streams with different frequencies simultaneously and is applied in the supraglottic space using a jet laryngoscope and jet ventilator., Methods: Between 1990 and 2004, SHFJV was studied in 1515 consecutive patients (including 158 children requiring laryngotracheal surgery) prospectively. Ventilation was performed with an air/oxygen mixture and anaesthesia was administered i.v., Results: Adequate oxygenation and ventilation was achieved in 1512 patients. Arterial blood gas analyses (BGA) were performed between 1990 and 1994; thereafter BGA was only performed in patients with high-grade stenosis of the larynx/trachea or high-risk patients [n=623, mean Pa(O(2)) 133.8 (39.4) mm Hg and mean Pa(CO(2)) 42.3 (10.1) mm Hg]. There were no significant changes in Pa(O(2)) or Pa(CO(2)) during the entire period of SHFJV. No complications secondary to the ventilation technique were observed; in particular, no barotrauma occurred. Three patients required tracheal intubation. SHFJV was also successfully used for laser surgery (n=312). It proved to be a safe mode of ventilation without any complications such as airway fire, major haemorrhage, or aspiration of debris., Conclusion: SHFJV is an advanced ventilation mode playing a pivotal role in the (open) ventilatory support/ventilation of patients with laryngotracheal stenosis. It is particularly indicated in cases of severe stenosis and offers optimal conditions for laryngotracheal surgery, including laser surgery and stent implantation techniques.

Aim: Videofluoroscopic assessment of the spectrum and incidence of swallowing complications after state-of-the-art laryngeal cancer surgery., Materials and Methods: We retrospectively studied videofluoroscopic examinations of 120 patients (94 men, 26 women; mean age, 58 years) with suspected complications after laryngeal resection (partial laryngectomy, 65; total laryngectomy, 55). Swallowing function (i.e., oral bolus control, laryngeal elevation and closure, presence of pharyngeal residue, aspiration) and structural abnormalities such as strictures, fistulas and tumour recurrence were assessed by videofluoroscopy., Results: Abnormalities were found in 110 patients, including strictures in nine, fistulas in six and mass lesions in 13 patients. Aspiration was found in 63 patients overall (partial laryngectomy, 61/65; total laryngectomy, 2/55), occurring before swallowing in five, during swallowing in 34, after swallowing in nine and at more than one phase in 15 patients. Pharyngeal paresis was detected in three and pharyngeal weakness in 19 patients. Pharyngo-oesophageal sphincter dysfunction was observed in 10 cases., Conclusion: Aspiration is a very common complication after partial laryngeal resection. It is mainly caused by incomplete laryngeal closure, sphincter dysfunction or pharyngeal pooling. Videofluoroscopy is the only radiological technique able to identify both disordered swallowing function and structural changes after laryngeal resection. Detection of these complications is crucial for appropriate further therapy.Kreuzer, S. H. (2000). Clinical Radiology55, 775-781., (Copyright 2000 The Royal College of Radiologists.)

The aim of the present study was to evaluate the short term effect of cochlear implantation on the fundamental frequency and the articulation of 13 patients. This investigation objectives for the first time the changes of fundamental frequency and articulation in cochlear implant patients. All postlingual deaf patients were provided with a Combi 40+ cochlear implant. Voice recording was performed pre- and three months post-implantation. The voice data was analyzed using the "X-Tool" software. The results show that 38% of the patients had a significant (p < 0.05) decrease of F0 mean three months after implantation. A postoperative decrease of F0 towards the normal range was observed generally in all patients. Spectographs pre- and post-implantation showed that the articulation improved already 3 months after partial restoration of auditory feedback. A large variability of F0 was noticed among the deaf subjects, but no correlation to the duration of deafness could be established.

Objective: The aim of this study was to evaluate whether specific patterns of swallowing dysfunction occur in symptomatic patients after long-term intubation., Subjects and Methods: Twenty-one patients (16 men, five women; mean age, 66 years) who presented with clinical signs of aspiration after long-term intubation (mean duration, 24.6 days) underwent videofluoroscopy. They were analyzed for functional abnormalities of the tongue, soft palate, epiglottis, hyoid and larynx, pharynx, and the upper esophageal sphincter. We assessed the presence or absence of aspiration, the type of aspiration (pre-, intra-, and postdeglutitive), and a spectrum of other swallowing abnormalities., Results: There were 18 patients (86%) with radiologically proven aspiration. In another patient only laryngeal penetration occurred. There were 11 combinations of pre-, intra-, and postdeglutitive aspiration. Predeglutitive aspiration was predominant and present in 52% of our patients. We found functional abnormalities of the tongue in 48%, of the soft palate in 10%, of the epiglottis in 48%, of the pharynx in 71%, and of the upper esophageal sphincter in 24%., Conclusion: Patients who are symptomatic after undergoing long-term intubation do not develop a specific type or pattern of swallowing dysfunction or aspiration, but show a large variety of aspiration types and associated swallowing disorders. Nevertheless, videofluoroscopy has the ability to reveal complex deglutition disorders and to aid precise planning of individualized functional swallowing therapy.

Objective: This study evaluated the clinical significance of cervical osteophytes impinging on the pharynx in patients with dysphagia and the importance of concurrent disorders that may affect swallowing function., Materials and Methods: On videofluoroscopy, anterior cervical osteophytes were found in 55 (32 men, 23 women; mean age, 69 years) of 3318 patients with dysphagia (1.7%). Coexisting diseases that affected swallowing function were found in 28 patients (stroke, n = 7; thyroidectomy, n = 7; tongue base or laryngeal cancer surgery, n = 5; other diseases, n = 9). Swallowing function was assessed with videofluoroscopy evaluating epiglottic tilting, laryngeal closure, impression of the hypopharynx, pharyngeal residue, and aspiration., Results: With advancing age, the probability of aspiration (odds ratio, 1.07; p < 0.05) and of enlarging osteophytes (odds ratio, 1.26; p < 0.01) increased; the probability was higher for osteophytes at more than one vertebrae (odds ratio, 8.00; p < 0.01) and for concurrent diseases (odds ratio, 8.02; p < 0.01). Aspiration was found in 75% of patients with osteophytes larger than 10 mm and in 34% with osteophytes smaller than or equal to 10 mm. In 88% of patients with small osteophytes who aspirated, other diseases affected swallowing function., Conclusion: Aspiration is common in patients with dysphagia and cervical osteophytes larger than 10 mm. Aspiration is rare in patients with osteophytes smaller than or equal to 10 mm unless these patients suffer from other disorders that may affect swallowing.

Therapeutic choice in laryngeal carcinoma is influenced by the nature of the tumor and a variety of factors involving the patient and physician. Small (T1) and exophytic (T1, T2) tumors are suitable for radiotherapy. Limited lesions (T1, T2) can be cured by functional endoscopic resection techniques or external partial laryngectomies. Extensive tumors (large T2; T3) are treated by total laryngectomy or by primary irradiation, especially in the case of a good response to induction chemotherapy. When radiation treatment fails, surgery succeeds in more than half of the cases. Tumors infiltrating or transgressing the laryngeal framework (T4) can only be cured by total laryngectomy followed by radiotherapy. Subtotal or circular ablation of the adjacent pharynx or esophagectomy needs repair with visceral or myocutaneous grafts. Lymphatics are preferentially treated with the same modality as used in the primary disease. Inconspicuous lymphatics should be treated electively in most cases, with the exception of early glottic cancer.

In past decades, the surgical techniques for treating laryngeal carcinoma have been vastly improved. For circumscribed tumors, voice-conserving resections are possible and for extensive neoplasms, radical laryngectomy, sometimes combined with chemoradiation, has been developed. Postoperative complications regarding swallowing function are not uncommon. Radiologic examinations, especially pharyngography and videofluoroscopy, are most often used to evaluate patients with complications after laryngeal surgery. An optimized videofluoroscopic technique for evaluation of complications is described. The radiologic appearance of early and late complications, such as fistulas, hematomas, aspiration, strictures, dysfunction of the pharyngoesophageal sphincter, tumor recurrence, and metachronous tumors is demonstrated.

Although health problems in musicians have been previously reported; not much is known about noise-induced hearing loss due to choir singing. However, there are data to show that peak levels of more than 110 dB SPL are produced in choir singing, and major parts of sound energy can be found below 1 kHz and even 500 Hz but not below 100 Hz. To find out about possible hearing loss due to professional choir singing, we measured the hearing threshold level of 62 choir singers in a large opera choir. Most publications about noise-induced hearing loss report that the high-frequency region is impaired most. However, in our study the low frequency region was affected most, when compared with normative data (especially ISO 7029). Control groups of women and men with normal auditory function did not show pure-tone hearing thresholds different from ISO 7029. The permanent threshold shifts at 250 Hz and above are most likely noise induced with choir singing as noise source. However, hearing losses at 125 Hz and possibly partial at 250 Hz are caused by some other effect. An (unproven) hypothesis is that singing might lead to increased endolymph pressure, and thus might cause hearing loss especially in the low-frequency region. Whether more choirs show similar hearing impairment and whether singing raises cerebrospinal fluid pressure will be the subject of further investigations.

Thirty-two head and neck surgical patients with prolonged moderate to severe aspiration were assessed with videoendoscopic and videofluoroscopic swallowing studies to reveal all components of dysphagia and aspiration. All patients received functional swallowing therapy, and 75% of the patients regained full oral intake diet. The duration of non-oral feeding varied widely. The outcome of swallowing rehabilitation (success or failure, duration of non-oral feeding) was statistically correlated with preoperative tumour stage, patients' age, therapy onset, severity of aspiration and the results of the videofluoroscopic measurements of oral and pharyngeal transit time, pharyngeal delay time, duration of laryngeal closure and cricopharyngeal opening, hyoid and laryngeal elevation, presence or absence of a stenosis at the pharyngoesophageal segment. The following factors proved to be statistically significant for the prognostic estimate of swallowing rehabilitation: preoperative tumour stage, therapy onset, and severity of aspiration. For postoperative swallow recovery, an early therapy onset after thorough diagnostics with videoendoscopic and videofluoroscopic swallowing studies is recommended. Videofluoroscopic measurements will yield some prognostic estimate of oropharyngeal dysphagia and aspiration. Videoendoscopy, by it's availability and immediacy, proved to be useful for monitoring the course of rehabilitation.

The value of flexible videoendoscopy as a biofeedback tool in conservative swallowing rehabilitation of patients suffering from aspiration after head and neck surgery was examined. For this purpose, the outcomes of conventional swallowing therapy and of swallowing therapy with support of videoendoscopic biofeedback were compared. In the first 40 days of swallowing therapy, videoendoscopic biofeedback significantly increased the chance of therapeutic success, shortening the period of functional rehabilitation in comparison to conventional swallowing therapy. Limitations of this visual biofeedback procedure are poor cognitive skills of the patient, rejection of the procedure by the patient and local factors that make the positioning of the endoscope difficult.

Hydroxymethylglutaryl-CoA reductase (HMG-R) is a key enzyme in the mevalonate pathway, from which thousands of molecules are derived including cholesterol and prenyl moieties. The regulation of HMG-R is complex and includes feedback control, cross-regulation by independent bio-chemical processes and contra-regulation of separate isozymes. From studies in yeast, these separate modes of regulation can be considered in an integrated fashion.

Lymph node tuberculosis is the most frequent tuberculous manifestation in the otorhinolaryngological area. In 13 patients with histologically verified tuberculous lymphadenitis cervical sonographic examinations revealed characteristic findings. The sonographic features typical for this disease were multiple, enlarged, conglomerating roundish and oval lymph nodes. These lymph nodes were hypoechoic, exhibited dorsal sound amplification and had sharp margins. With caseation, however, there were blurred borders. In cold abscesses an inhomogeneous texture with inhomogeneous shadows was found. Differential diagnosis included non-specific abscess-forming lymphadenitis, lymph node metastases and malignant lymphoma. A tentative diagnosis of cervical lymph node tuberculosis may be made due to the polymorphous sonographic pattern if history and clinical findings are taken into account. A proper histological and microbiological work-up is still essential for confirmation of the sonographic diagnosis.

The symptom tinnitus may be due to a number of causes. Pathological processes within the sense-organ "ear" as well as non-otologic diseases may result in tinnitus. Therefore a thorough ENT diagnosis is necessary. The evaluation of the patient includes the history, ENT-status examination, audiological and vestibular findings, imaging investigations and, if necessary, examinations by other specialists. The therapy of tinnitus is difficult. If possible, the therapy should be causally orientated. Mostly, this is only the case with tinnitus caused by diseases of the external and middle ear. The therapeutic aim is the compensation of tinnitus. The most common type of tinnitus is of cochlear-synaptic origin. According to results of inner ear research new possibilities of pharmacologically influencing the cochlear synapse have been found. By intravenous application of the specific Quisqualate antagonist glutamic acid diethyl ester (GDEE) 77.2% of our patients with cochlear synaptic tinnitus noted a tinnitus reduction.

Serine acetyltransferase (SAT) from Escherichia coli is subject to feedback inhibition by L-cysteine. A mutant was isolated which excretes L-cysteine because of a lesion in cysE, the structural gene for SAT, rendering the enzyme less feedback sensitive. To analyse the structural basis for this mutation the cysE genes both from wild-type E. coli and the mutant strain were cloned and their nucleotide sequences determined. The cysE gene contained an open reading frame consisting of 819 bp, equivalent to a protein of 273 amino acids. The mutant gene showed a single base change in position 767 resulting in a methionine to isoleucine substitution. A causal connection between this SAT sequence alteration, feedback insensitivity and L-cysteine excretion was demonstrated. The SAT from the wild-type strain was purified. It was composed of a single polypeptide chain migrating in SDS gels according to an Mr of 34,000. As in Salmonella typhimurium, the enzyme was associated in a bifunctional complex with O-acetylserine (thiol)-lyase.