The role of barium swallow in the management of the globus pharyngeus.

Globus pharyngeus is a common benign condition with controversial management. Patients with globus pharyngeus are usually investigated to exclude the possibility of upper aerodiagestive malignancies. There is a great debate about the role of barium swallow in the management of this condition. Review of 1,145 barium swallow repourts of patients presented with globus pharyngeus between 1999 and 2004 has failed to diagnose any patient with pharyngeal or oesophageal cancer. We conclude that barium swallow should not be requested systematically as part of management of globus pharyngeus patients. This approach will reduce the cost and radiation effect of unnecessary investigations.

Prospective randomised single-blind controlled trial of glacial acetic acid versus glacial acetic acid, neomycin sulphate and dexamethasone spray in otitis externa and infected mastoid cavities.

OBJECTIVES: The literature reports the merits of antibacterial, antibiotic and steroid agents in treating otological infections but no controlled clinical trial has directly compared 2% glacial acetic acid (EarCalm; Stafford-Miller Ltd, Brentford, UK) against 2% glacial acetic acid, 0.1% dexamethasone and 3250 U/ml of neomycin sulphate (Otomize; Stafford-Miller Ltd) in the treatment of otitis externa and infected mastoid cavities. DESIGN: Prospective, single-blind randomised controlled trial. SETTING: Outpatients, Derby Royal Infirmary, Derby, UK. PATIENTS: Emergency and GP referrals with acute otitis externa (n = 53) and infected mastoid cavities (n = 56). MAIN OUTCOME MEASURES: Otoscopy was performed at initial randomisation and then at 2 and 4 weeks, the ear assessed for active and inactive disease. RESULTS: Patients with active otitis externa, 71% (15/21) resolved with glacial acetic acid, dexamethasone and of neomycin sulphate after 2 weeks, increasing to 86% (18/21) after 4 weeks treatment. Patients on glacial acetic acid had only 38% (12/32) resolution after 4 weeks (P < 0.0005). Two per cent glacial acetic acid, dexamethasone and neomycin sulphate resolved only 30% (8/27) of infected mastoid cavities compared to only 10% (3/29) on glacial acetic acid (P < 0.07). A further 2 weeks treatment this increased to 67%, (18/27) with glacial acetic acid, dexamethasone and neomycin sulphate and 48% (14/29) with glacial acetic acid. These results are not statistically significant. CONCLUSION: Glacial acetic acid, dexamethasone and neomycin sulphate is significantly more effective in treating otitis externa when compared with glacial acetic acid. This effect failed to be significant in the infected mastoid cavities group. We therefore recommend that in conjunction with aural toilet, antibiotic/steroid combination is more effective than an antibacterial agent for otitis externa. Larger numbers of infected mastoid cavities are required to be studied.

Principles of septal correction.

The operation of septoplasty is often given to junior surgeons to perform and dismissed as a simple procedure. This can lead to unsatisfactory results with unnecessary morbidity for the patient and disillusionment for the surgeon. Trainee surgeons feel that the operation of septoplasty is poorly taught. Some common problems encountered during septal surgery are described and a variety of surgical solutions are offered.

Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load.

Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

Constitutive and stimulated expression of ICAM-1 protein on pulmonary endothelial cells in vivo.

The expression of intercellular adhesion molecule-1 (ICAM-1) on pulmonary endothelial cells after stimulus and subsequent binding of neutrophils is a first step leading to lung injury. A similar process may dictate the binding of tumor cells to the pulmonary endothelium during metastasis. We report the development of a new technique that allowed us to monitor the location and relative expression of ICAM-1 levels on the luminal surface of the pulmonary microvasculature in vivo. This technique uses intravital microscopy together with a two-step labeling procedure involving fluorescent microspheres. Constitutive expression of ICAM-1 was not detectable to a significant level by our model, but expression was observed after upregulation by the systemic administration of TNF alpha. Sprague-Dawley rats were injected with 0-5.0 micrograms/kg TNF alpha and ICAM-1 expression was monitored through 24 hr. ICAM-1 expression was related to both the dose of TNF alpha administered and the time elapsed between injection of TNF alpha and observation. Injection of 5 micrograms/kg TNF alpha caused upregulation of ICAM-1 protein expression from 0.30 +/- 2.76 binding events/175,000 microns2 to 62.6 +/- 5.48 through 4 hr observation, after which levels returned to near baseline within 24 hr. The delay required for maximal expression is likely related to the time required for the cell to respond to the stimulus and generate ICAM-1 protein. Reductions in the relative numbers of ICAM-1 protein expressed between 4 and 24 hr in vivo are likely a result of protein turnover after the initial stimulus.

Bepridil protects sickle cells against the adverse rheological effects of cyclical deoxygenation.

Calcium influx into sickle cells, with consequential activation of the Ca2(+)-activated K+ efflux (Gardos) channel, is a potential cause of cellular dehydration and loss of deformability. Bepridil, a recently described inhibitor of the Gardos channel, was found at pharmacological concentration (1 mumol/l) to inhibit significantly (P less than 0.01) the loss of deformability when sickle cells were subjected to cycles of oxygenation-deoxygenation for 15 h at 37 degrees C. Bepridil also inhibited significantly (P less than 0.005) the formation of irreversibly sickled cells. Drugs that preserve the K+ and therefore water content of erythrocytes are of potential value for hydrotherapy of sickle cell disease.