Effect of intratympanic steroid administration on sensorineural hearing loss associated with acute otitis media.

OBJECTIVE: To evaluate a small cohort of patients who presented with symptoms and signs consistent with acute infective sensorineural hearing loss who were treated with intratympanic steroids. METHOD: Seven patients received a 7-day course of oral antibiotics and oral prednisolone followed by 3 intratympanic injections of methylprednisolone and 1 week of topical dexamethasone drops. RESULTS: Hearing improved in 57 per cent of patients (four out of seven). The mean improvement in this group was 24 dB (range, 10-52 dB). The magnitude of the sensorineural hearing loss at presentation was less in those who responded to intratympanic steroid therapy than in non-responders (mean pure tone average of 30 dB versus 65 dB pre-intratympanic steroids, and 14 dB versus 83 dB post-intratympanic steroids, respectively). CONCLUSION: The results of our study suggest that intratympanic steroids provide a valuable contribution to the treatment of acute infective sensorineural hearing loss and may provide additional benefit by virtue of a concentrated local steroid effect in patients who do not respond to antibiotics.

Simultaneous cochlear implantation and labyrinthectomy for advanced Ménière's disease.

BACKGROUND: Patients with Ménière's disease can develop unaidable sensorineural hearing loss. Cochlear implantation has recently been utilised in this group with favourable results. A more challenging group are those with intractable vertigo, and they have traditionally posed a significant management dilemma. CASE REPORT: Two female patients with unaidable hearing and recurrent incapacitating vertigo attacks despite conservative management underwent simultaneous labyrinthectomy and cochlear implantation. There was complete resolution of vertigo in both patients. Speech perception in quiet conditions and the ability to hear in background noise improved considerably. CONCLUSION: Surgical labyrinthectomy is effective for the elimination of vertigo in Ménière's disease patients. The major disadvantage in the past was loss of residual hearing. Cochlear implantation is now an option in these patients. The benefits of simultaneous labyrinthectomy with cochlear implantation include the prevention of implantation of a fibrosed or ossified cochlea, a decrease in the duration of deafness, and a single operative procedure.

Samter's triad with aural involvement: a novel approach to management.

BACKGROUND: Samter's triad is a well described condition manifesting as chronic rhinosinusitis with nasal polyposis, asthma and aspirin intolerance in a non-atopic individual. The underlying mechanism is still to be fully elucidated. However, aural disease has not been widely reported in these patients. In the few reported cases, most patients underwent major surgery with varying degrees of success. CASE REPORT: We report two Samter's triad patients with aural involvement. Both were successfully managed by conservative treatment, thus avoiding the need for major surgery. It appears that more Samter's triad patients may have aural disease than previously thought. CONCLUSION: We report good outcomes with conservative treatment, which is relevant because aural disease tends to reoccur in these patients.

A prospective, single-blind, randomised, crossover study comparing three nasal hygiene systems and corresponding patient preference for such devices.

OBJECTIVE: To assess subjective preference using three nasal hygiene systems: Stérimar Original(®), Emcur(®) and Sinus Rinse™. DESIGN: We used a prospective, single-blind, randomised, crossover study to compare three nasal hygiene systems: Stérimar Original, Emcur and Sinus Rinse. SUBJECTS: Eighteen adult volunteers were recruited and were asked to rate their experience over three days using three well-established nasal hygiene systems. A standard visual analogue scale was used to assess five criteria: (1) simplicity of instructions; (2) ease of use; (3) comfort; (4) perceived nasal clearance (effectiveness) and (5) single best overall system. RESULTS: Stérimar Original was found to have the easiest instructions to understand compared to the other two systems. There was no significant difference between Stérimar Original and Sinus Rinse with regards to ease of use but they were both significantly easier to use than Emcur (p < 0.05). There was no statistically significant difference between the three systems when comparing the last three criteria. There was no alteration in preference when the cost of each treatment was disclosed to the subjects, and no significant side effects were reported. CONCLUSION: The instructions accompanying Stérimar Original appeared to be the easiest to understand, while Stérimar Original and Sinus Rinse were easier to use than Emcur.

Infliximab for autoimmune inner ear disease: case report and literature review.

OBJECTIVES: This study aimed (1) to report the long-term effects of infliximab, a murine monoclonal antibody directed against tumour necrosis factor-α, on autoimmune inner ear disease, and (2) to discuss dilemmas surrounding the long-term management of autoimmune inner ear disease. CASE REPORT: A 49-year-old man presented with sudden-onset, left-sided, sensorineural hearing loss, tinnitus and vertigo. He was prescribed oral prednisolone, with benefit. Over several subsequent months, he experienced frequent relapses and progressive deterioration of high-frequency hearing bilaterally. Multiple agents failed to stabilise his condition. Following infliximab treatment, there was a documented and sustained improvement in his hearing and tinnitus. He stopped the treatment after 46 weeks, with rapid relapse of his condition. His hearing recovered quickly again after recommencing infliximab. CONCLUSION: The benefits of prolonged infliximab use and potential side effects must be balanced against allowing the disease to take its course, with progressive deafness. Randomised controlled trials are required to assess infliximab's optimal duration of use, long-term efficacy and safety in the treatment of autoimmune inner ear disease.

The fate of granulosa cells following premature oocyte loss and the development of ovarian cancers.

This review examines the importance of the epithelial origin of granulosa cells and their possible contribution to the development of ovarian cancers in three animal models. We hypothesise that undifferentiated granulosa cells, devoid of their germ cell regulator, retain their embryonic plasticity and may give rise to ovarian cancers of epithelial origin. Dazl-KO and FancD2-KO mice and BMP15-KO sheep are animal models in which germ cells or oocytes are lost at specific stages of follicular formation or growth, leaving behind clusters of residual, but healthy somatic cells. A common feature in Dazl- and Fancd2-KO animals following germ cell/oocyte loss is the presence of sex cords and intraovarian epithelial ducts or tubules. In Dazl-KO mice, cord/tubule-like structures, OSE invaginations and clusters of steroidogenic cells became increasingly prominent with age, but these abnormal structures remained benign. In Fancd2-KO mice, the formation of sex-cords and intraovarian tubules lead to the formation of tumours with multiple phenotypes including luteomas, papillary cysts and malignant carcinomas (e.g. adenocarcinomas). In BMP15-KO sheep, oocytes die as follicles start to grow, leaving 'nodules' containing granulosa cells with a capacity to respond to follicle stimulating hormone and synthesize inhibin. Thereafter, these nodules coalesced and a range of benign solid or semi-solid tumour phenotypes developed. We conclude that premature loss of oocytes, but not granulosa cells, leads to tumour formation with multiple phenotypes. Moreover, the severity of tumour development is linked to both the specificity of the mutation and the timing of oocyte loss relative to that of follicular formation.

Radiological airway changes following bipolar radiofrequency volumetric tissue reduction.

OBJECTIVE: To characterise the appearance of lesions of the tongue base and soft palate induced by bipolar radiofrequency volumetric tissue reduction, using magnetic resonance imaging up to six weeks post-procedure. METHODS: Five men with sleep-disordered breathing were treated with one session of bipolar radiofrequency volumetric tissue reduction to a number of sites, including the tongue base and soft palate. Magnetic resonance imaging was performed pre-operatively and one week and six weeks after surgery. RESULTS: Lesions were visible from day one. T1 (spine lattice relaxation Time)-weighted images demonstrated areas of central hyperintensity, reflecting haemorrhagic, coagulative necrosis, surrounded by hypointensity, representing oedema; corresponding short tau inversion recovery (STIR) sequences showed central hypointensity with surrounding high signal. The lesions expanded up to day three and then gradually diminished, but were still evident at week six on short tau inversion recovery images. CONCLUSION: The characterisation of lesions induced by bipolar radiofrequency volumetric tissue reduction enables us to elucidate the pathophysiology of this procedure, to optimise treatment benefits and clinical outcomes, and to explain patient symptoms.

Prospective, comparative, cohort study comparing the rhinogram, Sino-Nasal Outcome Test-20 and Heath-Related Quality of Life questionnaire.

BACKGROUND: Many outcome measures exist for rhinosinusitis. However, few are used in the clinical setting due to their long completion times. OBJECTIVE: To assess the validity, reliability and responsiveness of the rhinogram, compared with two validated rhinosinusitis outcome measures: the Sino-Nasal Outcome Test-20 and the Heath-Related Quality of Life questionnaire. METHODS: Fifty-one patients were entered into a prospective, comparative, cohort study using all three outcome measures one week pre-operatively and three months post-operatively. Outcome scores were then correlated using non-parametric Spearman's rank correlation and chi-square testing for the diagnostic criteria of all three outcome measures. RESULTS: Statistically significant correlations were found between all three outcome measures for all symptom scores, individually as well as combined (p < 0.01 for all calculations). Comparison of the diagnostic accuracy of the rhinogram, compared with the Sino-Nasal Outcome Test-20 and the Heath-Related Quality of Life questionnaire, showed statistical significance (p < 0.05; chi-square test). CONCLUSION: The rhinogram is a reliable, valid and responsive rhinosinusitis outcome measure which can assist patient diagnosis and management in the clinical setting. Due to its quick completion time, this outcome measure could be used in rhinology out-patient clinics.

Parotid duct ligation for treatment of drooling in children with neurological impairment.

OBJECTIVE: Multiple surgical procedures have been advocated for the management of problematic drooling in neurologically impaired children. Parotid duct ligation is a quick and simple operation conducted via an intra-oral approach and usually performed simultaneously with other procedures. In this study, we aimed to evaluate the effectiveness of parotid duct ligation as a discrete procedure. METHODS: All children who underwent bilateral parotid duct ligation as the solitary operative intervention at that time, between February 2003 and September 2006, were included in the study. RESULTS: Ten children were studied. Surgery was successful in 80 per cent of cases. One patient (10 per cent) had a post-operative wound infection. CONCLUSIONS: Bilateral parotid duct ligation is an effective yet conservative operation for drooling in neurologically impaired children. It requires minimal surgical dissection and has a low morbidity rate. It should be considered as a potential first-line procedure in children who aspirate, and as a further surgical option in anterior droolers or those who continue to drool unacceptably following prior surgical intervention.

Following anterior resection for rectal cancer, defunctioning ileostomy closure may be significantly delayed by adjuvant chemotherapy: a retrospective study.

OBJECTIVE: A temporary loop ileostomy is often created to minimize the impact of peritoneal sepsis from an anastomotic dehiscence following colo-anal or low colorectal anastomosis. These stomas are not without complications. Clinicians tend to advise patients that their loop ileostomy will be reversed within 6-12 weeks of formation. However, factors such as adjuvant chemotherapy may affect the timing of closure. The aim of this study was to review the time between formation and closure of loop ileostomies following total mesorectal excision in patients with rectal cancer. METHOD: A retrospective study of 50 patients with loop ileostomies to defunction total mesorectal excisions for rectal cancer, between April 2002 and July 2005. RESULTS: Of the 50 patients with defunctioning loop ileostomies, 24 received adjuvant chemo-radiotherapy, and 26 did not. There was a 28% morbidity. The overall median time from formation to closure was 142 days (35-575). Median time from formation to closure in those with adjuvant therapy was 197 days (35-575) and in those with no adjuvant therapy was 133 days (75-395). This was a significant delay (P = 0.049). Sixteen stomas were not closed to date. CONCLUSION: Time between formation and closure of loop ileostomy following anterior resection of rectum is significantly delayed by adjuvant chemotherapy. Because of their high morbidity, defunctioning ileostomies should be closed as early as medically possible, especially if adjuvant chemotherapy is planned.

Sperm morphology in stallions: ultrastructure as a functional and diagnostic tool.

Conventional light microscopic evaluation of a seminal ejaculate does not fully avail potential indicators of functional impairment in spermatozoal organelles. The technique of critical quantitative evaluation of morphologic features of individual structural components of spermatozoa at a light microscopic level in conjunction with critical qualitative evaluation of spermatozoal organelles at an ultrastructural level, as described in this article, is a valuable clinical tool. Compared with a battery of sperm function assays used in human andrology clinics, this relatively less expensive and simple technique is an efficient functional and diagnostic tool.

An unusual case of segmental clavicle fracture.

Fracture of the clavicle is a common traumatic injury and comprises 4% of all fractures in adults. Amongst these, midshaft injuries account for the majority and medial fractures are uncommon. Whilst segmental fractures have been reported in the literature, concurrent lateral and medial injuries are very rare. These injuries are, therefore, susceptible to being missed, due to failure to look for a second injury after the initial diagnosis, and difficult X-ray interpretation around the area of the medial clavicle. The nature of segmental fractures can pose a difficult management problem for numerous reasons, and initial operative fixation is usually indicated. Early diagnosis is therefore imperative, and as such, clinical examination is essential even if an obvious mid or lateral shaft fracture is seen on X-ray. This unusual case of combined lateral and medial fractures was initially missed and the presentation and management is discussed.

Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

Origins of follicular cells and ontogeny of steroidogenesis in ovine fetal ovaries.

Using fetal sheep as the experimental model, we have elucidated some of the key events that culminate in the formation of primordial follicles. A special effort was made to determine the source of the somatic cells that ultimately become granulosa cells of primordial follicles. Between gestational days 38-100: (1) light and electron microscopy was used to characterize changes in ovarian histoarchitecture; (2) incorporation of BrdU was used to identify populations of proliferating cells within fetal ovaries before, during and after, follicular formation; and (3) in situ hybridisation was used to determine the cell-specific and temporal patterns of expression of mRNAs encoding for selected steroidogenic enzymes. At day 38 somatic (pregranulosa) cells were in contact with oogonia and easily distinguished from endothelial and mesenchymal cells. Between days 38 and 45, pregranulosa cell-oogonia complexes progressively coalesced to form 'tube-like' structures referred to as ovigerous cords. These cords consisted of pregranulosa cells and oogonia arranged such that pregranulosa cells formed the outer wall of the cords. Ovigerous cords were avascular, enveloped in a prominent basal lamina, open-ended where they interfaced with the ovarian surface epithelium, and formed a separate compartment whereby oogonia/oocytes were segregated from the surrounding stroma and vasculature until the time of follicular formation. The structural integrity of ovigerous cords was maintained through day 75, at which time primordial follicles (type 1 and type 1a) first emerged from the cords at the interface of the cortex and medulla. On the basis of the sequential structural changes that occurred during the differentiation and development of fetal ovaries and location of proliferating cells identified by the incorporation of BrdU, we conclude that the majority of the granulosa cells in primordial follicles are derived from mesothelial cells originating from the ovarian surface epithelium. In addition, from the cell-specific distribution and temporal pattern of expression of mRNAs for key steroidogenic enzymes we hypothesize that steroid hormones may play a pivotal paracrine/autocrine role in the formation and/or function of ovigerous cords as well as the development of the ovarian vascular network.

Formation of ovarian follicles during fetal development in sheep.

The origin of follicle (i.e., pregranulosa) cells that become the somatic component of primordial follicles is obscure. In addition, information regarding the structural changes that accompany the concomitant regression of ovigerous cords and the appearance of primordial follicles is lacking. In the present study, ovine ovaries collected at frequent time intervals between Day 38 and Day 100 of fetal life were examined by light and electron microscopy. To gain new information regarding the origin of follicular cells, incorporation of 5-bromo-2'-deoxyuridine was used to identify proliferating cells at selected stages of development. Based on the location and identity of proliferating cells, apoptotic cells, and sequential changes in histoarchitecture, we hypothesize 1) that most (i.e., >95%) of the granulosal cells in newly formed primordial follicles originate from the ovarian surface epithelium; 2) that the sequential events leading to follicle formation take place entirely within ovigerous cords, with the first follicles forming at the interface of the cortex and medulla; and 3) that the loss (i.e., >75%) of germ cells, but not of somatic cells, within the ovigerous cords is a means by which each surviving oocyte gains additional pregranulosal cells before follicle formation. Conceptual models detailing the chronology of developmental events involved in the formation of primordial follicles in sheep are discussed.

Quantification of polynuclear aromatic hydrocarbons in transformer oils by enzyme immunoassay.

Many polynuclear aromatic hydrocarbons (PAHs) are either known or suspected carcinogens and are a common constituent of mineral oils. Due to the large number of possible PAH structures, standard quantification methods fail since they either lack specificity or are too complex, requiring individual fractionation, identification, and quantification. A rapid, low-cost, novel analytical screening method, incorporating a silica-based solid-phase extraction (SPE) method linked to co-solvent dilution and quantification of total and carcinogenic PAH levels by immunoassay, is reported here. The method yielded high extraction efficiencies and minimal matrix effects. This novel approach yielded total and carcinogenic PAH levels x 5.7 and x 126, respectively, lower than that recorded by the industry-recognised BS2000 Pt. 346 (IP346) method which estimates the polyaromatic carbon (PAC) content of oils by gravimetry. The method is expected to be of benefit where an indication of PAH levels in oils is important for purchasing, management or disposal purposes and also for risk assessment and for appropriate labelling of oils in line with current legislation.

Prospects for reducing and refining the use of dogs in the regulatory toxicity testing of pharmaceuticals.

A workshop was held to critically discuss the need for a nonrodent species and the role of the dog in regulatory toxicity testing of pharmaceuticals; to discuss opportunities to reduce and refine the use of dogs in preclinical toxicology; and to identify a number of specific recommendations which could be feasibly achieved to move the process forward. To facilitate a preliminary evaluation of the contribution of dog studies to the risk assessment process, anonymised, unpublished data were provided from fully evaluated, repeat-dose toxicity studies in the rat and dog. Results of the International Life Sciences Institute (ILSI) Human Toxicity Project were also presented and discussed. Analysis of the data demonstrated that the dog can provide additional toxicity information, which, in some cases, was shown to be predictive for humans. Discussions indicated that there is potential for achieving a reduction in dog use and several possible approaches were identified. To further the progress of this initiative, there is a need to collate the results of pharmacology, toxicology, and clinical studies to address some of the proposed approaches. One of the outcomes of the workshop will be the establishment of a steering group to co-ordinate data collation for further analysis.