Therese Ovesen

Positron emission tomography of cortical centers of tinnitus

Tinnitus is associated with a wide variety of disorders in the auditory system. Whether generated peripherally or centrally, tinnitus is believed to be associated with activity in specific cortical regions. The present study tested the hypothesis that these cortical centers subserve the generation, perception and processing of the tinnitus stimulus and that these processes are suppressed by lidocaine and masking. Positron emission tomography was used to map the tinnitus-specific central activity. By subtracting positron emission tomography images of regional cerebral blood flow distribution obtained during suppression of the tinnitus from positron emission tomography images obtained during the habitual tinnitus sensation, we were able to identify brain areas concerned with the cerebral representation of tinnitus. Increased neuronal activity caused by tinnitus occurred predominantly in the right hemisphere with significant foci in the middle frontal and middle temporal gyri, in addition to lateral and mesial posterior sites. The results are consistent with the hypothesis that the sensation of tinnitus is associated with activity in cortical regions functionally linked to subserve attention, emotion and memory. For the first time, the functional anatomy of conditions with and without the habitual tinnitus sensation was obtained and compared in the same subjects.

Fusobacterium necrophorum: most prevalent pathogen in peritonsillar abscess in Denmark.

BACKGROUND Group A streptococci are commonly regarded as the most prevalent cause of acute bacterial tonsillitis and peritonsillar abscess (PTA). However, the majority of PTA aspirates also contain strains of anaerobes, and accumulating evidence indicates that Fusobacterium necrophorum (FN) could be involved in acute tonsillitis. The purpose of the present study was to describe the epidemiology and bacteriology of PTA in Denmark, with particular emphasis on correlations between microbiological, clinical, and laboratory data. METHODS A retrospective study on all patients with PTA admitted to the ear, nose, and throat department at Aarhus University Hospitals from January 2001 through December 2006 was conducted. RESULTS In total, 847 patients were included in the study. The mean annual incidence of PTA was 41 cases/100,000 population. FN was the most frequently detected bacteria (in 23% of cultures), followed by group A streptococci (in 17%) and groups C and G streptococci (counted together, in 5%). Of the 191 FN isolates detected, 155 (81%) grew as pure culture. Patients infected with FN were significantly younger than patients infected with other strains of bacteria (P < .001). Patients with FN exhibited significantly higher neutrophil counts (P < .001) and C-reactive protein values (P = .01) than did patients infected with other bacteria. CONCLUSIONS To our knowledge, this study is the first report of FN being the most prevalent pathogen in PTA patients. The significantly higher neutrophil counts and C-reactive protein values strongly indicate the pathogenic importance of FN in PTA. The widespread reliance on rapid streptococcal antigen test in general practice to appoint patients for antibiotics and the highest PTA incidence ever reported raise concern that highly virulent bacteria may be left initially untreated.

Acute mastoidectomy in a Danish county from 1977 to 1996 with focus on the bacteriology

To evaluate if the nature of acute mastoiditis (AM) treated surgically has changed during the last 20 years (1977-1996), the data from patients undergoing acute mastoidectomy were examined retrospectively. Cases with cholesteatomas and intracranial complications were excluded, while 79 patients (48% male) with a median age of 16 months were included. There was a history of infectious middle ear disease in 37% and the mean duration from onset of symptoms to admission was 9 days. The well-being was affected in 46 and 82% had fever. Purulent middle ear effusion was recognized in 92%. A subperiosteal abscess in 66% of the ears peroperatively. Specimens yielded growth of pathogens in 58%, predominantly gram positive bacteria, fully or partially sensitive to penicillin. Antimicrobial treatment before admittance masked or reduced more symptoms significantly. The patients from the last 10-year-period had less frequently acute otitis media in their history, shorter duration of hospitalization, and more frequently haemolytic Streptococcus group A. Conclusively, AM affects especially infants without previous middle ear disease. The clinical picture has become more subtle in time, probably due to antibiotics, and concomitantly the bacteriological pattern has changed.

The interplay between HPV and host immunity in head and neck squamous cell carcinoma.

Persistent infection with human papillomavirus (HPV) type 16 is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal squamous cell carcinoma (OPSCC). The oropharyngeal epithelium differs from the mucosal epithelium at other commonly HPV16‐infected sites (i.e., cervix and anogenital region) in that it is juxtaposed with the underlying lymphatic tissue, serving a key immunologic function in the surveillance of inhaled and ingested pathogens. Therefore, the natural history of infection and immune response to HPV at this site may differ from that at other anatomic locations. This review summarizes the literature concerning the adaptive immune response against HPV in the context of HNSCC, with a focus on the T‐cell response. Recent studies have shown that a broad repertoire of tumor‐infiltrating HPV‐specific T‐cells are found in nearly all patients with HPV‐positive tumors. A systemic response is found in only a proportion of these. Furthermore, the local response is more frequent in OPSCC patients than in cervical cancer patients and HPV‐negative OPSCC patients. Despite this, tumor persistence may be facilitated by abnormalities in antigen processing, a skewed T‐helper cell response, and an increased local prevalence of T‐regulatory cells. Nonetheless, the immunologic profile of HPV‐positive vs. HPV‐negative HNSCC is associated with a significantly better outcome, and the HPV‐specific immune response is suggested to play a role in the significantly better response to therapy of HPV‐positive patients. Immunoprofiling may prove a valuable prognostic tool, and immunotherapy trials targeting HPV are underway, providing hope for decreasing treatment‐related toxicity.

Stimulus-dependent central processing of auditory stimuli: A PET study

Positron emission tomography (PET) was used to investigate the neural systems involved in the central processing of different auditory stimuli. Noise, pure tone and pure-tone pulses, music and speech were presented monaurally. O-15-water PET scans were obtained in relation to these stimulations presented to five normal hearing and healthy subjects. All stimuli were related to a basic scan in silence. Processing of simple auditory stimuli, such as pure tones and noise, predominantly activate the left transverse temporal gyrus (Brodmann area [BA] 41), whereas sounds with discontinued acoustic patterns, such as pure-tone pulse trains, activated parts of the auditory association area in the superior temporal gyri (BA 42) in both hemispheres. Moreover, sounds with complex spectral, intensity, and temporal structures (words, speech, music) activated spatially even more extensive associative auditory areas in both hemispheres (BA 21, 22). PET has revealed a remarkable potential to investigate early central auditory processing, and has provided evidence of the coexistence of functionally linked, but individually active parallel and serial auditory networks.

Post-operative problems and complications in 313 consecutive cochlear implantations

OBJECTIVE To describe problems and complications associated with cochlear implantation, and their management, in a Danish patient population comprising both paediatric and adult patients. DESIGN Retrospective chart review. SETTING Tertiary referral centre. SUBJECTS Three hundred and thirteen consecutive cochlear implantations were studied. The median age of the study population was 10 years. Sixty per cent of patients were children and 40 per cent were adult; 52 per cent were female and 48 per cent were male. INTERVENTION Two hundred and ninety-four patients received a Cochlear Nucleus implant. The remaining 19 received an Advanced Bionics implant. MAIN OUTCOME MEASURE Presence of problems and complications after cochlear implantation. RESULTS Post-operative complications were found in 15.7 per cent of patients. The majority of these complications (11.2 per cent) were minor; 4.5 per cent were major. The major complications included one patient with meningitis, one patient with multiple antibiotic resistant Staphylococcus aureus infection of a radical cavity, and one diabetic patient who developed a severe skin infection and whose implant became exposed. CONCLUSION Cochlear implantation is a safe procedure within the studied setting. However, it is essential that careful attention be paid to surgical planning and technique, and it is important that healthcare staff and patients be aware of the possible problems and complications.

Cubilin and Megalin Co-Localize in the Neonatal Inner Ear

Cubilin and megalin are multifunctional endocytotic receptors expressed in many absorptive epithelia. The receptors have separate functions but may act in concert in several tissues including the small intestine, the visceral yolk sac and the renal proximal tubule to perform significant physiological functions essential to homeostasis in the extracellular fluid compartments. Because of the importance of fluid homeostasis in the inner ear, we investigated the expression of cubilin and megalin in this structure. Furthermore, we examined the binding properties of 6 different aminoglycosides (AGs) to cubilin and compared the results to data obtained for megalin, which is a well-known receptor for AGs and other polybasic substances, including several ototoxic drugs. In the cochlea, immunohistochemical labelling for cubilin showed expression corresponding to the apical surface of the strial marginal cells, to epithelial cells at the spiral prominence and to epithelial cells of Reissner’s membrane facing the cochlear duct. In the vestibular apparatus, positive labelling was found in dark cells of the utricle and those flanking the crista ampullaris of the semicircular canals. Exactly the same tissue distribution was found for megalin. These findings support the prevailing view that cubilin and megalin constitute a dual-receptor complex facilitating the function of each other. The physiological role of this receptor complex in the inner ear remains unknown, although several established ligands for both cubilin and megalin are present in the inner ear fluids. Receptor-ligand interaction analysis showed that all 6 AGs bind to both receptors and with approximately the same affinity. The results demonstrate a novel role for cubilin as a drug receptor for AGs and possibly other ototoxic substances.

Significant pathogens in peritonsillar abscesses

Peritonsillar abscesses (PTA) are polymicrobial infections, with a diverse aerobic and anaerobic flora. The aim of the present study is to compare bacteriologic culture results from patients with PTA to those from patients undergoing elective tonsillectomy (clinically non-infected tonsils), to better elucidate the pathogenic significance of various isolates. A prospective study was conducted on 36 PTA patients undergoing acute tonsillectomy and on 80 electively tonsillectomised patients. Fusobacterium necrophorum (FN) and Streptococcus group A (GAS) were isolated significantly more frequently from the tonsillar cores of PTA patients, from both the abscessed (p = 0.001 and p = 0.046, respectively) and non-abscessed sides (p < 0.001 and p = 0.046, respectively), than from the tonsillar cores of electively tonsillectomised patients. Our findings indicate that FN and GAS are the prominent pathogens in PTA. In patients with PTA, the incidence of FN and GAS isolated from the abscessed tonsil was the same as from the non-abscessed contralateral side, and the growth was comparable by a semi-quantitative approach. Our findings suggest that FN is also of pathogenic importance in acute tonsillitis, and that FN growth is not a subsequent phenomenon once an abscess has formed. Our findings further suggest that other factors influence the development of PTA.

Necrotizing fasciitis of the head and neck

Necrotizing fasciitis of the head and neck is a rapidly progressing and life‐threatening condition. The purpose of this study was to describe the patients with a focus on clinical presentation, microbiology, treatment, and prognosis.

Balloon Eustachian Tuboplasty A Systematic Review

Objective A systematic review and meta-analysis of the evidence on balloon Eustachian tuboplasty (BET) as a treatment modality for Eustachian tube dysfunction (ETD). We followed the PRISMA guideline and registered with PROSPERO No. CRD42014009461. Data Sources We searched 12 databases including PubMed and Embase from January 1, 2010, to April 7, 2014, for studies of BET. Endpoints: change in symptoms, middle ear pathology, eardrum status, Eustachian tube function tests, hearing, adverse events, complications, and health-related quality of life. Review Methods Study quality was assessed using the modified Delphi technique quality appraisal tool for case series studies. Risk of bias was assessed using the Cochrane Collaboration’s tool for assessing risk of bias. Results Nine case series studies with 443 patients (642 tubes) were included. Population size n = 4 (7 tubes) to n = 210 (320 tubes). All studies were of poor quality and featured a high risk of bias. We found reduction of patient symptoms in ETD questionnaire (P < .001), postoperative normalization of the tympanic membrane, conversion of type B or type C into type A tympanograms, reduced mucosal inflammation, increased number of positive Valsalva test and Swallowing tests, improvement in Eustachian tube score, reduction in Sino-Nasal Outcome Test (SNOT)-22 score (P = .001), and increased quality of life (P = .001). No serious adverse events were found. Conclusion The evidence of BET is poor and biased. No firm conclusions can be made to identify patients who will benefit from the procedure or to accurately predict surgical results. Randomized controlled trials or case-control trials are needed.