The challenge of performing mastoidectomy using the operating microscope with coronavirus disease 2019 personal protective equipment (PPE).

OBJECTIVE: Mastoidectomy is considered an aerosol-generating procedure. This study examined the effect of wearing personal protective equipment on the view achieved using the operating microscope. METHODS: ENT surgeons assessed the area of a calibrated target visible through an operating microscope whilst wearing a range of personal protective equipment, with prescription glasses when required. The distance between the surgeon's eye and the microscope was measured in each personal protective equipment condition. RESULTS: Eleven surgeons participated. The distance from the eye to the microscope inversely correlated with the diameter and area visible (p < 0.001). The median area visible while wearing the filtering facepiece code 3 mask and full-face visor was 4 per cent (range, 4-16 per cent). CONCLUSION: The full-face visor is incompatible with the operating microscope. Solutions offering adequate eye protection for aerosol-generating procedures that require the microscope, including mastoidectomy, are urgently needed. Low-profile safety goggles should have a working distance of less than 20 mm and be compatible with prescription lenses.

Dizziness, driving, and the Driver and Vehicle Licensing Agency: audit of advice given to patients, and design of a patient information leaflet.

BACKGROUND: Evidence from the literature shows that clinicians' knowledge of rules and legislation surrounding driving can often be poor. A closed-loop audit was conducted to gauge the level of driving advice given to patients with dizziness. METHODS: The clinical notes of 100 patients referred to the vertigo clinic at a tertiary referral centre were retrospectively searched for evidence of driving advice. Education sessions were undertaken and a patient information leaflet was developed before a second cycle of the audit. RESULTS AND CONCLUSION: The proportion of patients having documented evidence of receiving driving advice increased from 6.3 per cent to 10.4 per cent. It is therefore clear that, despite this improvement, a significant proportion of patients' notes did not contain documentation about driving. This is likely because of many reasons, including individual interpretation by clinicians. This paper provides a reminder of the rules, and discusses their interpretation and implementation in an increasingly medicolegal environment.

Supplementation of Merino ewes with vitamin E plus selenium increases α-tocopherol and selenium concentrations in plasma of the lamb but does not improve their immune function.

Vitamin E and selenium have been reported to improve immune function across a range of species. Ewes lambing on poor-quality dry pasture in autumn in Western Australia are at risk of being deficient in vitamin E and selenium at lambing thus predisposing their lambs to deficiencies and increasing the risk of infection and disease. This study tested the hypotheses that (i) supplementation of autumn-lambing ewes with vitamin E plus selenium in late gestation will increase the concentrations of vitamin E and selenium in plasma in the ewe and lamb and (ii) that the increased concentrations of vitamin E and selenium in plasma in the lambs will improve their innate and adaptive immune responses and thus survival. Pregnant Merino ewes were divided into a control group (n=58) which received no supplementation or a group supplemented with vitamin E plus selenium (n=55). On days 111, 125 and 140 of pregnancy ewes in the vitamin E plus selenium group were given 4 g all-rac-α-tocopherol acetate orally. On day 111 the ewes were also given 60 mg of selenium as barium selenate by subcutaneous injection. The concentrations of α-tocopherol and selenium were measured in ewes and/or lambs from day 111 of pregnancy to 14 weeks of age±10 days (weaning). Immune function of the lamb was assessed by analysing the numbers and phagocytic capacities of monocytes and polymorphonuclear leucocytes and plasma IgG and anti-tetanus toxoid antibody concentrations between birth and 14 weeks of age±10 days. Maternal supplementation with vitamin E plus selenium increased the concentration of α-tocopherol in plasma (1.13 v. 0.67 mg/l; P<0.001) and selenium in whole blood (0.12 v. 0.07 mg/l; P<0.01) of the ewes at lambing compared with controls. Supplementation also increased the concentration of α-tocopherol (0.14 v. 0.08 mg/l; P<0.001) and selenium (0.08 v. 0.05 mg/l; P<0.01) in lambs at birth compared with controls. There was no significant effect of supplementation on immune function or survival in the lambs.

Results of a prospective surgical audit of bilateral paediatric cochlear implantation in the UK.

BACKGROUND: Following the approval of bilateral paediatric cochlear implantation in 2009, the prospective multi-centre UK National Paediatric Cochlear Implant Audit was established to collect a large dataset of paediatric implantations. The aim of the surgical part of the audit, reported here, was to collect data on surgical practice, outcomes and complications. METHODS: Data from 14 surgical centres was collected prospectively, including simultaneous and sequential bilateral as well as unilateral implantations. Data collected included age at implantation, aetiology of deafness, implant type, duration of surgery, the use of electrophysiological testing, and the use of pre- and post-operative imaging. Details of major and immediate minor complications were also recorded. RESULTS: 1397 CI procedures in 961 CI recipients were included; 436 bilateral simultaneous, 394 bilateral sequential, 131 unilateral. The overall major complication rate was 1.6% (0.9% excluding device failure) and was similar following bilateral CI compared to sequential and unilateral CI. CONCLUSION: This prospective multi-centre audit provides evidence that bilateral paediatric CI is a safe procedure in the UK, thus endorsing its role as a major therapeutic intervention in childhood deafness.

Primary endoscopic repair of intermediate laryngeal clefts.

INTRODUCTION: Traditionally, small laryngeal clefts may be closed endoscopically, while larger clefts necessitate an open anterior approach. We report the presentation, evaluation and outcome following endoscopic surgical repair of a series of laryngeal clefts. METHOD: Retrospective study of children treated in a tertiary referral centre between 2003 and 2008. The presenting symptoms, patient demographics, cleft type, surgical outcome and complications were evaluated. RESULTS: Seven children underwent primary endoscopic repair of their laryngeal clefts (four Benjamin-Inglis type III clefts and three type II clefts). Presenting symptoms included stridor, cough and cyanosis with feeds, swallowing problems, weak cry, and recurrent lower respiratory tract infection. Treatment was ultimately successful in six of the seven children; treatment was ongoing for the remaining child, who underwent subsequent revision surgery via an open approach. Two children went on to require a second endoscopic repair, and two underwent an open repair of a residual defect. One child required a tracheostomy for failed extubation in the post-operative period. CONCLUSION: Endoscopic repair is a safe, useful technique in the management of laryngeal clefts. Laryngeal clefts must be excluded in a child presenting with persistent aerodigestive tract symptoms, as described here.

12 minute consultation: a patient with nasal crusting.

BACKGROUND: Nasal crusting is frequently encountered by the otorhinolaryngologist and often requires no specific treatment. It is, however, important to carry out a full history and examination, followed by appropriate investigations, in order to detect the small number of cases in which crusting is caused by systemic or malignant disease. METHODS: This review was based on a literature search last performed on 30th July 2009. The MEDLINE, EMBASE and Cochrane databases were searched using the subject headings (nasal crusting OR crusts) and in combination with diagnosis, therapy and surgery. Similar searches were performed for relevant diseases, e.g. Wegener's granulomatosis, sarcoidosis. Results were limited to English language articles including clinical trials, meta-analyses, systematic reviews and review articles. Relevant references from selected articles were reviewed. RESULTS: Knowledge of the causes of nasal crusting will help to target the history, examination and investigation of patients with this condition. Screening tests for systemic conditions can be useful but most have limited sensitivity and must be interpreted cautiously. Nasal septal biopsy is indicated when there is a suspicion of malignancy, or to support a suspected diagnosis of vasculitis. The treatment offered depends upon the cause of crusting and the severity of symptoms. CONCLUSION: A careful and thorough history and examination, and targeted investigation, of the patient with nasal crusting will ensure correct diagnosis and treatment of patients with this common condition.

Endovascular management of the carotid blowout syndrome.

Bleeding from the carotid artery or its branches ('carotid blowout') is a well recognized complication following treatment or recurrence of head and neck cancer. The traditional surgical treatment for carotid blowout is often technically difficult and is associated with an unacceptably high morbidity and mortality. The majority of such patients are currently treated conservatively with end of life supportive measures. We report the case of a young patient with recurrent supraglottic carcinoma complicated by carotid blowout on two separate occasions over a five month period, which was successfully treated endovascularly under local anaesthetic, without neurological sequelae. With the continuing development of interventional radiology, endovascular techniques are now emerging as a viable, low morbidity treatment option in selected patients.

Coimmunisation with type I IFN genes enhances protective immunity against cytomegalovirus and myocarditis in gB DNA-vaccinated mice.

Viral DNA vaccines encoding the glycoprotein B (gB) of cytomegalovirus provide partial protective immunity upon challenge with infectious virus. Although it is known that type I IFN can stimulate the adaptive immune response, their direct use in vaccines has been limited. Here we show that coimmunisation of type I IFN and gB CMV DNA constructs enhances protective immunity in mice. In vivo expression of IFN transgenes ranged from 1.2 to 2.0 x 10(4) IU/g tibialis anterior muscle. Viral titre in major target organs and the severity of acute CMV-induced myocarditis was reduced preferentially with either IFN-alpha 9 or IFN-beta, but not with IFN-alpha 6, coimmunisation. However, all IFN subtypes investigated markedly reduced chronic myocarditis in gB-vaccinated mice. The early antiviral IgG1 and IgG2a titres were enhanced with IFN-beta coimmunisation. TNF and IL-10 was increased in response to MCMV infection in mice coimmunised with IFN subtypes and viral gB DNA. Indeed T cells from IFN-inoculated mice reduced myocarditis upon in vivo transfer. These results suggest that select type I IFNs may act as a natural adjuvant for the immune response against CMV infection. Type I IFN DNA coimmunisation may provide increased efficacy for viral vaccines and subsequently modulate post-viral chronic inflammatory disorders.

DNA postreplication repair and mutagenesis in Saccharomyces cerevisiae.

DNA postreplication repair (PRR) is defined as an activity to convert DNA damage-induced single-stranded gaps into large molecular weight DNA without actually removing the replication-blocking lesions. In bacteria such as Escherichia coli, this activity requires RecA and the RecA-mediated SOS response and is accomplished by recombination and mutagenic translesion DNA synthesis. Eukaryotic cells appear to share similar DNA damage tolerance pathways; however, some enzymes required for PRR in eukaryotes are rather different from those of prokaryotes. In the yeast Saccharomyces cerevisiae, PRR is centrally controlled by RAD6 and RAD18, whose products form a stable complex with single-stranded DNA-binding, ATPase and ubiquitin-conjugating activities. PRR can be further divided into translesion DNA synthesis and error-free modes, the exact molecular events of which are largely unknown. This error-free PRR is analogous to DNA damage-avoidance as defined in mammalian cells, which relies on recombination processes. Two possible mechanisms by which recombination participate in PRR to resolve the stalled replication folk are discussed. Recombination and PRR are also genetically regulated by a DNA helicase and are coupled to the cell-cycle. The PRR processes appear to be highly conserved within eukaryotes, from yeast to human.

The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two error-free postreplication repair pathways.

The RAD6 postreplication repair and mutagenesis pathway is the only major radiation repair pathway yet to be extensively characterized. It has been previously speculated that the RAD6 pathway consists of two parallel subpathways, one error free and another error prone (mutagenic). Here we show that the RAD6 group genes can be exclusively divided into three rather than two independent subpathways represented by the RAD5, POL30, and REV3 genes; the REV3 pathway is largely mutagenic, whereas the RAD5 and the POL30 pathways are deemed error free. Mutants carrying characteristic mutations in each of the three subpathways are phenotypically indistinguishable from a single mutant such as rad18, which is defective in the entire RAD6 postreplication repair/tolerance pathway. Furthermore, the rad18 mutation is epistatic to all single or combined mutations in any of the above three subpathways. Our data also suggest that MMS2 and UBC13 play a key role in coordinating the response of the error-free subpathways; Mms2 and Ubc13 form a complex required for a novel polyubiquitin chain assembly, which probably serves as a signal transducer to promote both RAD5 and POL30 error-free postreplication repair pathways. The model established by this study will facilitate further research into the molecular mechanisms of postreplication repair and translesion DNA synthesis. In view of the high degree of sequence conservation of the RAD6 pathway genes among all eukaryotes, the model presented in this study may also apply to mammalian cells and predicts links to human diseases.

Non-auditory stimulation in adult cochlear implant users.

This is a retrospective case review of all 163 adults to have received multichannel cochlear implants on the Manchester University/Manchester Royal Infirmary programme between 1988 and 1998. The aims were to investigate the incidence of unwanted non-auditory effects of electrical stimulation (NAS) of the cochlea, and to try to identify any factors that seemed to be related to these effects. The effectiveness of programming strategies in eliminating unwanted effects was also studied. Most of the devices were Nucleus CI 22M or CI 24M. The remainder were Med-el Combi 40 or Combi 40+. NAS occurred in 23.9% of implantees. There were 20 cases of facial nerve stimulation (12.3%), 18 cases of pain in the ear or throat (11.0%) and one case of vestibulospinal spinal stimulation (0.6%). Two aetiologies were significantly associated with NAS. Otosclerosis tended to be associated with facial nerve stimulation and skull base fracture was associated with pain. Pain was associated with electrodes stimulated in the base turn of the cochlea and facial nerve stimulation tended to occur with more distally situated electrodes, close to labyrinthine segment of the nerve. There was no association with one particular make of device. The T and C levels for the rogue electrodes were in the normal range. It is concluded that the unwanted effects result from shorting of current through areas of low electrical resistance in the temporal bone. A number of different strategies were employed to prevent the effect, including alteration of current levels, removal of electrodes from the map and changing the stimulation mode, and this was successfully achieved in all cases. There was no difference between the performance of patients who had had NAS and those who had not, as assessed on open-set BKB sentence scores.

Genetic interactions between error-prone and error-free postreplication repair pathways in Saccharomyces cerevisiae.

Evidence obtained from recent studies supports the existence of an error-free postreplication repair (PRR) and a mutagenesis pathway within the Saccharomyces cerevisiae RAD6 DNA repair group. The MMS2 gene is the only known yeast gene involved in error-free PRR that, when mutated, significantly increases the spontaneous mutation rate. In this study, the mutational spectrum of the mms2 mutator was determined and compared to the wild type strain. In addition, mutagenenic effects and genetic interactions of the mms2 mutator and rev3 anti-mutator were examined with respect to forward mutations, frameshift reversions as well as amber and ochre suppressions. It was concluded from these results that the mms2 mutator phenotype is largely dependent on the functional REV3 gene. The synergistic effects of mms2 and rev3 mutations towards killing by a variety of DNA-damaging agents ruled out the possibility that MMS2 simply acts to suppress REV3 activity and favored the hypothesis that MMS2 and REV3 form two alternative subpathways within the RAD6 DNA repair pathway. Taken together, we propose that two pathways represented by MMS2 and REV3 deal with a similar range of endogenous and environmental DNA damage but with different biological consequences, namely, error-free repair and mutagenesis, respectively.

Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor-derived human cell lines.

Acquisition of the immortal phenotype by tumor cells represents an essential and potentially rate-limiting step in tumorigenesis. To identify changes in gene expression that are associated with the early stages of cell immortalization, we compared genetically matched pairs of pre-immortal and immortal human cell clones by mRNA differential display. Two transcripts, denoted CIR1 and CIR2, were identified which were up-regulated in immortal cells. Sequence analysis revealed CIR1 to be identical to the recently cloned CROC1/UEV-1 gene, whereas CIR2 corresponds to an as yet uncharacterized 1.2 kb mRNA. A 5-6-fold elevation in CIR1/CROC1 expression and a 2-3-fold elevation in CIR2 expression were observed in SV40-transformed human embryonic kidney cells immediately following proliferative crisis, suggesting a potential role for these genes in immortalization. Expression of CIR1/CROC1 was found to be elevated also in a variety of immortal human tumor-derived cell lines, as compared to their normal tissue counterparts. These results are compatible with induction of CIR1/CROC1 being an early event in the acquisition of immortality and with a role for this gene in the immortal phenotype of tumor cells.