Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis.

BACKGROUND: Myeloid (m) and plasmacytoid (p) dendritic cells (DCs) regulate immune responses to allergens, whereas it remains unclear whether abnormal DC function characterizes patients with airway allergy and whether putative dysfunction exists only in target organs. To evaluate DC function from patients with allergic rhinitis (AR), we assessed nasal, cutaneous as well as blood DCs after in vivo and in vitro allergen challenge, respectively. METHODS: DCs were immunostained in nasal and skin tissues, and cytokine expression was assessed by dual immunofluorescence. Cytokine production and regulation of cocultured peripheral CD4+ T cells were assayed by ELISA. RESULTS: In AR patients, local allergen challenge resulted in increases in pDC and mDC numbers at 8 h in the nasal mucosa and at 8-48 h in the skin. Defects in IL-10 and IFN-α were observed in both organs from AR. Blood mDCs from AR exhibited reduced IL-10 and IL-12 expression. The capacity of activated pDCs from AR to produce IFN-α and to trigger IL-10 by allogeneic CD4(+) T cells was diminished, whereas mDCs from these patients supported Th2- and Th17-cell differentiation. CONCLUSION: In allergic rhinitis, DCs are altered not only locally but also in the systemic circulation. mDCs and pDCs increased in airway and skin tissues exposed to the allergen and displayed reduced production of IL-10 and 'type 1 signals' (IL-12, IFN-α) both locally and in blood. Functional studies showed that this results in preferential Th2/Th17-cell polarization and impaired generation by blood DCs of IL-10+ T cells, linking systemic DC dysfunction and biased T-cell responses.

Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (NP) and allergic rhinitis (AR) is characterized by local Th2 inflammation and up-regulation of IgE; however, IgE in NP is 'polyclonal' and allergen specific, whereas IgE in AR is 'oligoclonal' and allergen specific. Germinal center (GC) reactions occur in AR, while only the formation of GC-like structures in NP is described. The aim of this study was to investigate the involvement of local IgE production, class switch recombination, and receptor revision in NP. METHODS: We compared the levels of local IgE, germline gene transcripts, and mature Ig mRNA expression, recombination activating gene (RAG1 and RAG2), key markers of Th2 inflammation, and GC reactions in NP tissue vs AR and control tissue. Nasal mucosa was immunostained for the co-expression of RAG1 and RAG2 in B cells, plasma cells, and T cells, using dual or triple immunofluorescence (IF). RESULTS: In NP, local IgE level and key markers of local class switching are increased compared with AR and normal controls (NC). In NP, switch circle transcripts reveal ongoing local class switch recombination to IgE. Up to 30% of B cells, plasma cells, and T cells in nasal polyps re-express both RAG1 and RAG2, required for receptor revision. RAG1 and RAG2 mRNA concentrations are increased in NP and correlated with the magnitude of inflammation and the presence of S. aureus enterotoxin (superantigen)-specific IgE in the nasal polyp mucosa. CONCLUSION: Our results provide the first evidence of local receptor revision and class switching to IgE, and B-cell differentiation into IgE-secreting plasma cells in NP.

Reduced T-bet in addition to enhanced STAT6 and GATA3 expressing T cells contribute to human allergen-induced late responses.

BACKGROUND: T-bet and GATA-3 are transcriptional factors involved in Th1 and Th2 cell differentiation, although their concomitant roles at protein levels in target organs during human allergic disease have not been assessed. OBJECTIVES: We investigated the expression of T-bet and GATA-3 in nasal and cutaneous models of Th2 (grass-pollen allergen) and a cutaneous model of Th1 (PPD) responses in man. METHODS: Nasal biopsies were obtained at 8 h and skin biopsies at 8 and 48 h after allergen and PPD challenges, respectively, from 10 allergic rhinitics and 6 non-atopic controls. T cells were assessed using immunofluorescence microscopy. RESULTS: There were increases in CD3(+)STAT6(+)cells (P = 0.01 for nose and skin) and CD3(+)GATA3(+)cells (P = 0.03 for skin) in response to allergen compared with diluent in allergics. When compared with non-atopics after allergen challenge the difference between the two groups was also significant for CD3(+)STAT6(+) (P = 0.001 and 0.03) and for CD3(+)GATA3(+)cells (P = 0.04 and 0.001) for nose and skin respectively. Following PPD challenge CD3(+)STAT4(+)cells and CD3(+)T-bet(+)cells increased in both groups compared with diluent (P = 0.02 and 0.03 for both TFs), whereas only CD3(+)T-bet(+) cells were significantly greater in non-atopics compared with allergics (P = 0.04). The ratio of GATA3(+):T-bet(+) T cells in allergen-induced responses was significantly greater in the allergics (P = 0.008 and 0.01 nose and skin respectively), whereas the ratio of T-bet:GATA3(+)T cells was significantly higher in the non-atopics during PPD-induced responses (P = 0.003). CONCLUSIONS AND CLINICAL RELEVANCE: Dysregulation of Th1 transcription may contribute to heightened expression of STAT6 and GATA3 leading to exaggerated Th2-driven manifestations of allergic disease.

Outcomes from penetrating ballistic cervical injury.

AIMS: Ballistic cervical injury has become a significant source of both morbidity and mortality for the deployed UK soldier. The aim of this paper was to document a case series of ballistic cervical wounds to describe the pattern of these injuries and relate them to outcome. METHODS: The records of all UK service personnel sustaining wounds to the neck in Iraq or Afghanistan between 01 August 2004 and 01 January 2008 were analysed following identification by the Joint Theatre Trauma Registry. Blunt or thermal injuries were excluded. RESULTS: The records of 75/76 service personnel sustaining penetrating cervical injury during this period were available for analysis. 56/75 (75%) were due to explosive fragmentation and the remainder due to gunshot wounds (GSW). 33/75 (44%) of soldiers sustained vascular injury, 32/75 (43%) injury to the spine or spinal cord, 29/75 (39%) injury to the larynx or trachea and 11/75 (15%) injury to the pharynx or oesophagus. 14/75 (19%) patients in this series underwent surgery in a hospital facility for treatment of potentially life threatening cervical injuries, with a survival rate after surgery of 12/14 (86%). The overall mortality from this series of battlefield penetrating neck injury was 63%. CONCLUSIONS: Penetrating cervical ballistic injury is a significant source of injury to deployed UK service personnel, predominantly due to neurovascular damage. Neck collars if worn would likely prevent many of the injuries in this case series but such protection is uncomfortable and may interfere with common military tasks. Newer methods of protecting the neck should be investigated that will be acceptable to the deployed UK soldier.

Self assessment questions in ear, nose & throat surgery.

Ear, nose and throat conditions make up a large amount of a Medical Officer's clinical workload. The examples given here illustrate some principles that should be employed when dealing with such problems.

CC chemokine receptor 4 (CCR4) in human allergen-induced late nasal responses.

BACKGROUND: CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4-mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 - ligand interaction may abrogate allergen-induced inflammation. METHODS: Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T-lymphocytes, CCR4(+)CD3(+) and CXCR3(+)CD3(+) cells and examined by in situ hybridization for CCR4, IL-4 and IFN-gamma mRNA(+) cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4(+)CD4(+) cells assessed for actin polymerization in response to the CCR4 ligand macrophage-derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested. RESULTS: Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3(+) T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4(+)CD3(+) protein-positive cells relative to CXCR3(+)CD3(+) cells; CCR4 mRNA+ cells were increased and IL-4 increased to a greater extent than IFN-gamma. CCR4(+)CD4(+) T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist. CONCLUSION: Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses. Blocking CCR4-ligand interaction may provide a novel therapeutic approach in allergic disease.

Prevalence of back and neck pain amongst ENT consultants: national survey.

Back and neck pain is an established occupational disease for many professions. No previous studies have shown the association of back and neck pain with ENT surgery. Our objective was to determine the prevalence of neck and back pain in ENT consultants in the United Kingdom and which sub-specialties were most at risk. A national survey from 325 ENT consultants in the UK revealed that 72 per cent had either back pain or neck pain or even both. Of those with pain 53 per cent attributed their symptoms directly to ENT surgery. Highest figures were received from otologists, related to microscope work and prolonged sitting. The importance of these findings has demonstrated the lack of awareness and adequate training to prevent long-term disability in ENT surgeons.

Monoclonal antibodies raised to human cells--specificity for pig leukocytes.

A total of 27 monoclonal antibodies raised to human targets were included in the present Pig CD workshop. 14 of these had been tested in previous workshops and had been reported as cross-reactive, a further 13 had been reported as cross-reactive during the Human Leukocyte Differentiation Antigens Workshop VI (HLDA VI) and/or by the donor (a commercial company submitting these mAb for validation by the workshop community). Of the 27 antibodies, three antibodies with previously reported reactivity for pig cells were eliminated from the workshop following preliminary tests due to lack of reactivity. Nine antibodies, although initially positive, gave inconsistent results during the course of the workshop. We found consistent reactivity for 15 antibodies. However, the cellular distribution of the target molecules on pig and human cells was shown to be different for three of these antibodies. These findings have important implications for the usefulness of these antibodies as research tools in the pig.

Patient benefit from functional and cosmetic rhinoplasty.

The Glasgow Benefit Inventory, a validated post-interventional questionnaire, was used to determine patient benefit from septorhinoplasty according to indication (function, cosmesis or a combination) in 87 patients. We showed a very significant patient benefit from this procedure and have demonstrated that the benefit is greatest when cosmesis is an indication (P = 0.05).

Does vestibular habituation still have a place in the treatment of benign paroxysmal positional vertigo?

Particle repositioning procedures such as the Epley manoeuvre have become popular in the management of benign paroxysmal positional vertigo (BPPV) at the expense of more traditional therapies such as vestibular habituation. We prospectively analysed the response of consecutive patients presenting with BPPV to treatment with vestibular habituation exercises using a symptom score sheet before and after treatment. This same patient group was then followed up, on average three years, eight months after discharge, to determine their long-term response to treatment. The results of the study demonstrated an excellent short-term response rate to treatment but a high level of recurrence after discharge. Most patients who experienced further symptoms following discharge were however self-reliant and were able to return to their habituation exercises without the need for further medical input. The aim in the management of these patients must be to provide long-term self reliance as well as short-term cure and it may be that this has not yet been well demonstrated with the Epley manoeuvre. It must also be remembered that particle repositioning manoeuvres cannot be used in all patients for example those who suffer with cervical or thoracic spine pathology and that some will fail to respond at all. We believe that vestibular habituation retains a useful role in the treatment of BPPV.

A national survey of disinfection techniques for flexible nasendoscopes in UK ENT out-patient departments.

Flexible fibre-optic nasendoscopes have become a ubiquitous ENT out-patient tool for the inspection of the nasopharynx, larynx and hypopharynx. Disinfection of the instrument between patient use is important to prevent potential spread of infection but the methods used vary considerably. We designed a questionnaire which was piloted and then sent to 115 UK ENT out-patient departments to establish current UK practice. Most units (67 per cent) use a chemical soak system but the type of chemical disinfectant, the method of delivery and the duration of soak varied considerably. A few hospitals use a disposable plastic sheath system and others simply wipe the instrument with an alcohol swab in between patient use. The protocols for disinfection after high risk patients e.g. human immunodeficiency virus (HIV), hepatitis B varied from hospital to hospital. The results demonstrate a lack of standard practice that is wasteful of financial resources and may expose patients to unnecessary risk. There is a need for an authoritative ENT body to publish national guidelines as may be found in other specialties and other countries.

Day case rhinoplasty.

Rhinoplasty is considered by many to be an inpatient surgical procedure. This may be because the operation is thought to be traumatic with a risk of epistaxis and periorbital haematoma. Since 1992 rhinoplasty surgery at St George's hospital has been routinely performed on a planned day case basis. The hospital records of 97 patients were examined of which 17 patients (18%) underwent planned admission and 12 (12%) unplanned admission. No patients were re-admitted to hospital after discharge. With the advances in day case surgical practice within the UK we consider that the practice of day case rhinoplasty is likely to have its place. Such surgery should ideally be performed in a dedicated day case unit and provision for admission overnight should be available.

Partial resection of the middle turbinate at functional endoscopic sinus surgery.

The middle turbinate is often carefully preserved at Functional Endoscopic Sinus Surgery (FESS). However there is no clear understanding of its importance and its presence may prevent good access to the middle meatus to the detriment of the surgical result. In addition its bulk may cause symptoms of nasal obstruction and prevent paranasal sinus drainage. Adhesions and stenosis have been reported at the middle meatus following its preservation. We undertook a prospective study of 50 consecutive patients all of whom underwent resection of the anterior half of the middle turbinate at the time of Functional Endoscopic Sinus Surgery. The patients were asked to complete a symptom score sheet before and ten weeks after surgery. The parameters considered were nasal obstruction, nasal congestion, discharge, facial pain and headache. Non parametric analysis of the results indicated a significant improvement in all patient symptom scores and no postoperative complications were noted. We conclude that partial resection of the middle turbinate is a useful modification of accepted endoscopic sinus surgery techniques.

Surgical emphysema and pneumomediastinum in a child following minor blunt injury to the neck.

Largyngotracheal and pharyngoesophageal tears following minor blunt trauma to the neck are uncommon. A child with such an injury is reported and the modes of diagnosis and management are discussed. Patients may initially present with minimal signs and symptoms, but their condition may deteriorate rapidly or insidiously. In the absence of respiratory compromise, conservative management is appropriate, but all patients with significant blunt neck trauma should undergo early direct laryngoscopy under a general anaesthetic.

Establishing a new ENT-head and neck clinic.

We report our experience of the first fourteen months of a new head and neck surgical clinic established at a district general hospital. The structure of the clinic together with analysis of the patient case mix and referral patterns are considered. The perceived benefits include rapid patient access to specialist management, the development of subspecialty skills and excellent training opportunities for trainee registrars.

Rhabdomyosarcoma arising in teratoma of the testis.

Rhabdomyosarcoma arising in teratoma of the testis is an exceptionally rare occurrence. The rhabdomyosarcomatous element infers a less favourable prognosis and standard treatment regimes well recognised for the treatment of teratoma of the testis may not be effective.

Intrapetrous carotid artery aneurysm presenting as epistaxis and otalgia.

Aneurysm of the intrapetrous carotid artery is an extremely rare and potentially serious occurrence that presents diagnostic and therapeutic difficulties. Such aneurysms may follow trauma, atherosclerosis, mastoid surgery or most commonly can represent a developmental abnormality. We present the case of an 18-year-old female with a short history of recurrent left-sided otalgia and epistaxis who underwent successful endovascular balloon entrapment of a left intrapetrous carotid aneurysm.

Long-term sequelae of Palmar-Plantar erythrodysaesthesia syndrome secondary to 5-fluorouracil therapy.

Palmar-Plantar erythrodyasesthesia syndrome has been reported as a temporary complication of 5-fluorouracil therapy consisting of a debilitating erythema and tenderness of the skin of hands and feet. The syndrome has previously been observed to respond rapidly to either temporary cessation of chemotherapy or pyridoxine with little residual disability. We report a case which was characterized by persistent morbidity necessitating prolonged discontinuation of treatment.