Inter-observer variability between radiologists reporting on cerebellopontine angle tumours on magnetic resonance imaging.

BACKGROUND: Studies demonstrate the significance of intra- and inter-observer variability when measuring cerebellopontine angle tumours on magnetic resonance imaging, with measured differences as high as 2 mm. OBJECTIVE: To determine intra- and inter-observer measurement variability of cerebellopontine angle tumours in a specialised institution. METHODS: The magnetic resonance imaging maximal diameter of 12 randomly selected cerebellopontine angle tumours were independently measured by 4 neuroradiologists at a tertiary referral centre using a standard definition for maximal tumour diameter. Average deviation and intraclass correlation were subsequently calculated. RESULTS: Inter-observer difference averaged 0.33 ± 0.04 mm (range, 0.0-0.8 mm). Intra-observer measurements were more consistent than inter-observer measurements, with differences averaging 0.17 mm (95 per cent confidence interval = 0.27-0.06, p = 0.002). Inter-observer reliability was 0.99 (95 per cent confidence interval = 0.97-0.99), suggesting high reliability between the readings. CONCLUSION: The use of a standard definition for maximal tumour volume provided high reliability amongst radiologists' readings. To avoid oversizing tumours, it is recommended that conservative monitoring be conducted by the same institution with thin slice magnetic resonance imaging scans.

Association between menthol-flavoured cigarette smoking and flavoured little cigar and cigarillo use among African-American, Hispanic, and white young and middle-aged adult smokers.

OBJECTIVES: Flavour additives in cigarettes and little cigars and cigarillos (LCCs), which influence smokers' risk perceptions, may reinforce dual flavoured tobacco use. We examined the association among mentholated cigarette use, risk perceptions for flavour additives in LCCs and flavoured LCC smoking behaviour. METHODS: Data from a national probability sample of 964 young and middle-aged adult current cigarette smokers were analysed. Multinomial logistic regression models examined the relationship among mentholated cigarette smoking, risk perceptions and current flavoured LCC use for the analytic sample and gender and race/ethnicity. RESULTS: Daily menthol cigarette smokers, compared to occasional, non-menthol smokers, had increased odds of flavoured LCC smoking (OR=1.75, 95% CI 1.02 to 2.98). This relationship was found for males, blacks/African-Americans and Hispanics/Latinos (p<0.05). Positive perceptions of menthol-flavoured additives in LCCs was associated with increased odds of flavoured LCC use among the analytic sample, males and blacks/African-Americans (p<0.05). Positive perceptions for clove-flavoured, spice-flavoured and alcohol-flavoured additives were also associated with flavoured LCC use among the analytic sample (p<0.05). CONCLUSIONS: Use of menthol-flavoured cigarettes and positive perceptions about menthol-flavoured and other flavour additives in LCCs may contribute to dual use with flavoured LCCs among adult cigarette smokers, specifically those from vulnerable populations.

Open and endovascular repair of aneurysms affecting the distal extracranial internal carotid artery: case series.

OBJECTIVE: Three cases of internal carotid artery aneurysm affecting the distal cervical segment were retrospectively reviewed. METHODS: Two patients underwent open surgical repair requiring petrous segment exposure for bypass of the affected segment using a Fisch type A lateral skull base approach. The third patient underwent endovascular stenting. RESULTS: There were no cerebrovascular complications post-operatively. Both open repair patients experienced temporary lower cranial nerve palsies. One required facial nerve grafting. All patients had patent grafts at follow up. The stent graft patient had a small endoleak at six months. CONCLUSION: Endovascular and open approaches both have advantages and disadvantages. Treatment needs to be tailored to the lesion and the patient. An open surgical approach is difficult but well established. Endovascular treatment of these lesions is a relatively recent technique, and new cases need to be continually reported with a view to attaining long-term data.

Role of cyclins D1 and D3 in vestibular schwannoma.

BACKGROUND: Vestibular schwannomas in younger patients have been observed to be larger in size and grow more quickly. OBJECTIVE: This study aimed to evaluate the expression of three important cell cycle proteins, cyclin D1, cyclin D3 and Ki-67, in vestibular schwannoma patients separated into two age groups: ≤ 40 years or > 40 years. METHOD: Immunohistochemical detection of cyclin D1, cyclin D3 and Ki-67 was undertaken in 180 surgically resected vestibular schwannomas. RESULTS: The proliferation index of vestibular schwannomas was statistically higher in the ≤ 40 years age group compared to that in the > 40 years age group (mean of 4.52 vs 3.27, respectively; p = 0.01). Overexpression of cyclin D1 and cyclin D3 was found in 68 per cent and 44 per cent of tumours, respectively. CONCLUSION: There was an increased Ki-67 proliferation index in the younger age group that appears to correlate with clinical behaviour. Vestibular schwannomas in both age groups show increased expression of cyclin D1 and cyclin D3.

Management of cochlear implant device extrusion: case series and literature review.

INTRODUCTION AND AIMS: Cochlear implants have enabled an improved quality of life for many patients with deafness. Implant extrusion and skin flap necrosis are the most common complications associated with implant use. We report our management of patients presenting with complications as a result of cochlear implant insertion. The goal of surgery was to achieve a stable, healed wound for use as a cochlear device implantation site. METHODS AND RESULTS: We describe a series of patients presenting with skin flap necrosis and/or extrusion of their cochlear implant. The reconstructive options employed are discussed. CONCLUSION: Surgeons should be aware of the reconstructive options available in such circumstances, and should choose appropriate management depending on the clinical situation, in order to optimise the functional result for the patient.

Cochlear implantation after selective vestibular nerve section.

INTRODUCTION: Vestibular nerve section is a highly effective procedure for the control of vertigo in patients with Ménière's disease. However, hearing loss is a possible complication. If hearing loss occurs after vestibular nerve section, magnetic resonance imaging should make it possible to establish the presence or absence of an intact cochlear nerve. METHOD: Case report and review of the world literature concerning cochlear implantation after vestibular nerve section. CASE REPORT: We present a patient who developed subtotal hearing loss after vestibular nerve section. Magnetic resonance imaging was used to verify the presence of an intact cochlear nerve, enabling successful cochlear implantation. CONCLUSION: To our knowledge, this is the first reported case of cochlear implantation carried out after selective vestibular nerve section. Given recent advances in cochlear implantation, this case indicates that it is essential to make every effort to spare the cochlear nerve if vestibular nerve section is required. If hearing loss occurs after vestibular nerve section, magnetic resonance imaging should be undertaken to establish whether the cochlear nerve is intact.

Preliminary validation of a novel high-resolution melt-based typing method based on the multilocus sequence typing scheme of Streptococcus pyogenes.

The major limitation of current typing methods for Streptococcus pyogenes, such as emm sequence typing and T typing, is that these are based on regions subject to considerable selective pressure. Multilocus sequence typing (MLST) is a better indicator of the genetic backbone of a strain but is not widely used due to high costs. The objective of this study was to develop a robust and cost-effective alternative to S. pyogenes MLST. A 10-member single nucleotide polymorphism (SNP) set that provides a Simpson's Index of Diversity (D) of 0.99 with respect to the S. pyogenes MLST database was derived. A typing format involving high-resolution melting (HRM) analysis of small fragments nucleated by each of the resolution-optimized SNPs was developed. The fragments were 59-119 bp in size and, based on differences in G+C content, were predicted to generate three to six resolvable HRM curves. The combination of curves across each of the 10 fragments can be used to generate a melt type (MelT) for each sequence type (ST). The 525 STs currently in the S. pyogenes MLST database are predicted to resolve into 298 distinct MelTs and the method is calculated to provide a D of 0.996 against the MLST database. The MelTs are concordant with the S. pyogenes population structure. To validate the method we examined clinical isolates of S. pyogenes of 70 STs. Curves were generated as predicted by G+C content discriminating the 70 STs into 65 distinct MelTs.

A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model.

BACKGROUND AND PURPOSE: The aim of this study was to assess the potential of an antagonist selective for the lysophosphatidic acid receptor, LPA(1), in treating lung fibrosis We evaluated the in vitro and in vivo pharmacological properties of the high affinity, selective, oral LPA(1)-antagonist (4'-{4-[(R)-1-(2-chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-biphenyl-4-yl)-acetic acid (AM966). EXPERIMENTAL APPROACH: The potency and selectivity of AM966 for LPA(1) receptors was determined in vitro by calcium flux and cell chemotaxis assays using recombinant and native cell cultures. The in vivo efficacy of AM966 to reduce tissue injury, vascular leakage, inflammation and fibrosis was assessed at several time points in the mouse bleomycin model. KEY RESULTS: AM966 was a potent antagonist of LPA(1) receptors, with selectivity for this receptor over the other LPA receptors. In vitro, AM966 inhibited LPA-stimulated intracellular calcium release (IC(50)= 17 nM) from Chinese hamster ovary cells stably expressing human LPA(1) receptors and inhibited LPA-induced chemotaxis (IC(50)= 181 nM) of human IMR-90 lung fibroblasts expressing LPA(1) receptors. AM966 demonstrated a good pharmacokinetic profile following oral dosing in mice. In the mouse, AM966 reduced lung injury, vascular leakage, inflammation and fibrosis at multiple time points following intratracheal bleomycin instillation. AM966 also decreased lactate dehydrogenase activity and tissue inhibitor of metalloproteinase-1, transforming growth factor beta1, hyaluronan and matrix metalloproteinase-7, in bronchoalveolar lavage fluid. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that AM966 is a potent, selective, orally bioavailable LPA(1) receptor antagonist that may be beneficial in treating lung injury and fibrosis, as well as other diseases that are characterized by pathological inflammation, oedema and fibrosis.

Latent superior canal dehiscence syndrome unmasked by stapedotomy for otosclerosis.

OBJECTIVE: This report describes a novel case in which superior canal dehiscence syndrome was unmasked by successful stapes surgery for otosclerosis. METHODS: Case report and literature review regarding superior canal dehiscence syndrome. INTRODUCTION: Superior canal dehiscence syndrome is a rare but well described condition in which audiovestibular symptoms are caused by noise or straining. A dehiscence of the superior semicircular canal in the floor of the middle cranial fossa is responsible, and acts as a 'third window' into the inner ear. CASE HISTORY: A patient with confirmed otosclerosis underwent second-side stapedotomy, with good audiometric outcomes. Unfortunately, surgery was complicated by immediate post-operative vertigo and persistent auditory symptoms. A diagnosis of superior canal dehiscence syndrome was eventually made, on the basis of low threshold vestibular evoked myogenic potentials and characteristic computed tomography findings. Superior canal resurfacing resulted in complete resolution of symptoms. DISCUSSION: The otosclerotic focus in the oval window prevented the development of symptoms from this patient's superior canal dehiscence syndrome. Surgical stapedotomy created a third window and resulted in immediate post-operative imbalance and auditory symptoms. CONCLUSION: The diagnosis of superior canal dehiscence syndrome should be considered in patients with persistent audiovestibular symptoms after stapes surgery. High resolution computed tomography of the temporal bone and vestibular evoked myogenic potential testing, if available, are the investigations of choice in confirming the diagnosis.

Spontaneous intracranial hypotension presenting to the ENT surgeon: case report.

OBJECTIVE: To highlight a case of spontaneous intracranial hypotension presenting to the ENT surgeon. METHOD: We present a case report and a review of the literature concerning spontaneous intracranial hypotension. RESULTS: Spontaneous intracranial hypotension is a rare diagnosis, particularly to the ENT surgeon. We report a patient with tinnitus, hearing loss and headache, symptoms suggestive of an ENT diagnosis such as Ménière's disease or vestibular schwannoma. However, magnetic resonance imaging revealed the characteristic findings of spontaneous intracranial hypotension. The patient's symptoms resolved, except for a mild residual tinnitus, with conservative management alone. CONCLUSION: This case highlights the importance of considering spontaneous intracranial hypotension as a differential diagnosis of certain ENT symptoms.

Facial schwannoma: results of a large case series and review.

OBJECTIVES AND HYPOTHESIS: To report a series of 53 cases of facial schwannoma, to review the current literature, addressing contentious issues, and to present a management algorithm. STUDY DESIGN: Retrospective case review combined with review of current literature. MATERIALS AND METHODS: A review of the case notes of 53 patients with intracranial and intratemporal facial schwannoma, from two tertiary referral centres, was undertaken. This represents the largest series of facial schwannomas with clinical correlations in the literature. Data relating to epidemiological, clinical and management details were tabulated and compared with other large series. A review of the current literature was performed, and a management algorithm presented. RESULTS: There were 23 (43 per cent) female and 30 (57 per cent) male patients. Patients' ages at presentation ranged from five to 84 years, with a mean of 49 years. Twenty-five (47 per cent) of the tumours were present on the left side and 28 (53 per cent) on the right side. Hearing loss was the most common presenting symptom, being present in 31/53 (58 per cent) patients, followed by facial weakness in 27/53 (51 per cent). Two patients (4 per cent) were completely asymptomatic, and their facial neuromas were diagnosed incidentally. The schwannoma extended along more than one segment of the facial nerve in 39 patients (74 per cent), with the mean number of segments involved being 2.5. A conservative approach of clinical observation was undertaken in 20 patients (38 per cent). Thirty-three patients (62 per cent) underwent surgery, with a total of 36 procedures. The translabyrinthine approach was most common, being utilised in 17 of the 36 procedures. Two patients underwent revision surgery for residual or recurrent disease on three occasions. There was total removal of tumour in 21 cases; the remainder had subtotal or no removal with drainage or decompression of the tumours. Twenty-one nerve reconstructions were performed, and 18 facial rehabilitation procedures were performed on 14 patients. DISCUSSION: The results of this case series are similar to those of other reported series. The diagnosis of facial schwannoma is now generally made pre-operatively, due to improved imaging techniques and heightened awareness. Clinical assessment of facial function and imaging form the mainstays of surveillance for these tumours. These tumours are managed via clinical observation or surgical intervention; the latter can range from simple procedures (such as drainage of cystic components) to aggressive tumour removal and facial nerve reconstruction. Facial rehabilitation procedures may also be applied. The timing of intervention is contentious; surgical intervention is indicated when facial function deteriorates to a House-Brackmann grade IV level. CONCLUSION: Facial schwannomas are rare lesions, and reported series are generally small. Due to the complex management issues involved, these tumours are best managed in a tertiary referral setting. Observation is preferred until facial function deteriorates to a House-Brackmann grade III level, at which time surgery is considered. When facial function deteriorates to House-Brackmann grade IV, surgical intervention is indicated. We advocate surgical management based on the treatment algorithm described.

The dynamic nature of group A streptococcal epidemiology in tropical communities with high rates of rheumatic heart disease.

Prospective surveillance was conducted in three remote Aboriginal communities with high rates of rheumatic heart disease in order to investigate the epidemiology of group A beta-haemolytic streptococci (GAS). At each household visit, participants were asked about sore throat. Swabs were taken from all throats and any skin sores. GAS isolates were emm sequence and pattern-typed using standard laboratory methods. There were 531 household visits; 43 different emm types and subtypes (emmST) were recovered. Four epidemiological patterns were observed. Multiple emmST were present in the population at any one time and household acquisition rates were high. Household acquisition was most commonly via 5- to 9-year-olds. Following acquisition, there was a 1 in 5 chance of secondary detection in the household. Throat detection of emmST was brief, usually <2 months. The epidemiology of GAS in these remote Aboriginal communities is a highly dynamic process characterized by emmST diversity and turnover.

Molecular typing of Streptococcus pyogenes from remote Aboriginal communities where rheumatic fever is common and pyoderma is the predominant streptococcal infection.

Aboriginal Australians in remote communities have high rates of rheumatic heart disease (RHD); yet pharyngitis is reportedly rare whilst pyoderma is common. Some strains of group A streptococci (GAS) have preference for the throat and others for the skin depending on M protein type. A study in three remote communities provided 350 GAS isolates for emm sequence typing, 244 were also emm pattern typed. There was 100% correlation between emm sequence and pattern type. Patterns D and E (non-throat tropic) made up 71% of throat and 87% of skin isolates although patterns A-C (throat tropic) were more common in the throat than the skin (RR 2.3, 95% CI 1.4-3.8) whilst the opposite was found for pattern D (RR 2.2, 95% CI 1.7-3.0). Pattern E favoured the throat (RR 1.4, 95% CI 1.1-1.8). Where environmental factors predispose to skin infection, emm pattern types D and E prevail, whatever the recovery site.

Reduction meatoplasty with a post-auricular island flap.

The importance of an adequate meatoplasty is often emphasised in mastoid surgery. However, bigger is not always better, as an excessively widened external meatus can be cosmetically unacceptable, provide little extra benefit for cleaning, be an obstacle to the good fitting of hearing aids and expose the mastoid cavity to exaggerated caloric effect. The problems created by an overly large meatus can occasionally be difficult to manage, prompting consideration of reduction of the meatus. We describe the use of a pedicled, post-auricular skin flap to achieve reduction of an excessively large meatus.

Locating the scala media in the fixed human temporal bone for therapeutic access: a preliminary study.

OBJECTIVE: To investigate the location of the scala media in relation to the round window niche in human temporal bones. DESIGN: Ten human temporal bones were investigated by radical mastoidectomy and promontory drill-out. SETTING: Temporal bone laboratory. OUTCOME MEASURES: The distance from the scala media to the anterior edge of the round window niche, measured by Fisch's stapedectomy measuring cylinders. RESULTS: The scala media was identified at the transection point of a vertical line 1.6 to 2.2 mm (mean=1.8 mm; standard deviation=0.2) anterior to the anterior edge of the round window niche and a horizontal line 0.2 mm inferior to the lower border of the oval window. CONCLUSION: This report demonstrates the point of entry into the scala media via the promontory in fixed temporal bone models, which may provide a site of entry for stem cells and gene therapy insertion.

Complications of keratosis obturans.

Three patients with extensive keratosis obturans were treated during a 12-month period. One presented with an idiopathic sensorineural hearing loss and was found to have keratosis obturans in the contralateral, asymptomatic ear. The disease process had resulted in a horizontal semicircular canal fistula in what was now, effectively, the only hearing ear. The second patient had an extensive dehiscence of the tegmen tympani. The third presented with a facial palsy. An automastoidectomy cavity was present, with circumferential skeletonization of the descending facial nerve over a length of 1.5 cm and dehiscence of the temporomandibular joint and jugular bulb. All three patients were successfully treated by surgical formalization of their automastoidectomy cavities. They appeared to represent cases of keratosis obturans rather than external auditory canal cholesteatoma, on the basis of previously published reports.These complications and patterns of bone erosion have not previously been described in keratosis obturans. The third patient is believed to have the most extensive case of keratosis obturans yet described.

Facial nerve outcome in non-vestibular schwannoma tumour surgery.

PROBLEMS/OBJECTIVES: Tumour size, intra-operative electrophysiologic thresholds and postoperative facial nerve function have been demonstrated to be important predictors of ultimate facial nerve function after vestibular schwannoma surgery. In general little attention has been given to the prediction of outcome of facial nerve function in non-vestibular schwannoma tumour surgery of the cerebellopontine angle (CPA). METHODOLOGY: A prospective study was performed to assess the predictive value of patient, tumour histology and electrophysiologic factors in the estimation of ultimate facial nerve outcome after this form of surgery. RESULTS: Sixteen patients satisfied the requirements of the study. Poor long-term facial nerve outcome was associated with abnormal pre-operative facial nerve function, facial nerve schwannomas, premeatal meningiomas and electrophysiologic stimulation thresholds of greater than 0.1 mA. CONCLUSIONS: It is concluded that tumour histology and pre-operative facial nerve function are additional factors that must be considered in the prediction of facial nerve function after non-vestibular schwannoma surgery of the CPA.

Two distinct genotypes of prtF2, encoding a fibronectin binding protein, and evolution of the gene family in Streptococcus pyogenes.

The group A Streptococcus (GAS) is an important pathogen that is responsible for a wide range of human diseases. Fibronectin binding proteins (FBPs) play an important role in promoting GAS adherence and invasion of host cells. The prtF2 gene encodes an FBP and is present in approximately 60% of GAS strains. In the present study we examined 51 prtF2-positive GAS strains isolated from the Northern Territory of Australia, and here we describe two genotypes of prtF2 which are mutually exclusive. The two genotypes have been identified previously as pfbp and fbaB. We show that these genotypes map to the same chromosomal location within the highly recombinatorial fibronectin-collagen-T antigen (FCT) locus, indicating that they arose from a common ancestor, and in this study these genotypes were designated the pfbp type and the fbaB type. Phylogenetic analysis of seven pfbp types, 14 fbaB types, and 11 prtF2-negative GAS strains by pulsed-field gel electrophoresis (PFGE) produced 32 distinct PFGE patterns. Interpretation of evolution based on the PFGE dendrogram by parsimony suggested that the pfbp type had a recent origin compared to the fbaB type. A comparison of multiple DNA sequences of the pfbp and fbaB types revealed a mosaic pattern for the amino-terminal region of the pfbp types. The fbaB type is generally conserved at the amino terminus but varies in the number of fibronectin binding repeats in the carboxy terminus. Our data also suggest that there is a possible association of the pfbp genotype with sof (84.2%), while the fbaB genotype was found in a majority of the GAS strains negative for sof (90.6%), indicating that these two prtF2 subtypes may be under different selective pressures.