The 5-lipoxygenase-activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma.

BACKGROUND: GSK2190915, a potent 5-lipoxygenase-activating protein inhibitor, prevents the synthesis of leukotrienes and 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). OBJECTIVE: To assess the effect of GSK2190915 on the allergen-induced asthmatic responses. METHODS: Nineteen eligible male subjects with mild asthma were enrolled in and completed this four-centre, double-blind, two-way crossover study (ClinicalTrials.gov NCT00748306). Subjects took GSK2190915 100 mg and placebo orally once daily for 5 days in randomized order. On Day 1 and 4 they had a methacholine challenge, on Day 3 they had an inhaled allergen challenge, and on Days 4 and 6 they had sputum induction. RESULTS: GSK2190915 attenuated the early (0-2 h) and late (4-10 h) asthmatic responses to inhaled allergen compared with placebo. There was a statistically significant attenuation of the early asthmatic response (EAR) by GSK2190915; treatment difference of GSK2190915 vs. placebo for the minimum FEV(1) EAR was 0.408 L (0.205, 0.611). There was a statistically significant attenuation of the late asthmatic response (LAR) by GSK2190915; the treatment difference of GSK2190915 vs. placebo for the minimum FEV(1) LAR was 0.229 L (0.041, 0.417). There was a statistically significant attenuation of allergen-induced sputum eosinophil count on Day 4 following GSK2190915: mean treatment difference (95% CI) between GSK2190915 and placebo was -9.95% (-18.15%, -1.77%). Compared with placebo, GSK2190915 100 mg reduced median sputum LTB(4) by > 90% on Days 4 and 6. There was no effect on methacholine PC(20) post allergen. GSK2190915 was generally well tolerated. CONCLUSION AND CLINICAL RELEVANCE: GSK2190915 shows potential as a treatment for patients with asthma.

Surgery for snoring: are partners satisfied in the long run?

Patients seek surgery for snoring, essentially for the sake of their partners. Few studies have looked into the long-term results from this angle. We herein report the findings of a study of partner satisfaction, following laser-assisted uvulopalatoplasty (LAUP) and uvulopalatopharyngoplasty (UVPP). This was a questionnaire-based survey, with a minimum follow-up of 1 year. A total of 91 procedures (LAUP = 50 and UVPP = 41) were evaluated. Response rate was 65.93%. Both groups were matched for age, gender and duration of the follow-up. Residual snoring was even more frequently following LAUP than it was following UVPP (Mann-Whitney U = 244, P = 0.012). After UVPP, partners were less likely to have trouble falling asleep (Mann-Whitney U = 255, P = 0.041). There was a highly significant reduction in the disturbance of sleep and need to wake up after both types of surgery (McNemar test, chi2 = 25.037, P < 0.001). Both groups reported improvements in quality of life. We propose a grading system to record partner satisfaction. The long-term results show that surgery for snoring is justified in the National Health Service (NHS) in the new millennium.

Comparison of compliance between topical aural medications.

Patients receiving Gentisone HC, Sofradex and Otomize for chronic suppurative otitis media and otitis externa were investigated for compliance of medication. Drops were accurately weighed before and after use so that both the amount used and the expected amount patients should have used could be calculated. The amount used differed statistically from the amount expected for Sofradex (P = 0.0008) but not for Gentisone HC (P = 0.1049) or Otomize (P = 0.7553) when analysed by a Mann-Whitney U-test. There was a trend to overdose with both Sofradex & Gentisone HC. The reason for the differences, we believe, is due to a combination of both differing delivery systems and drop viscosities. Manufacturers need to improve delivery systems so that patients can deliver a reproducible volume of medication each time with ease.

Bilateral aneurysms of the extracranial internal carotid artery presenting as vocal fold palsy.

Bilateral extracranial internal carotid aneurysms are very rare, though well documented. We report a case of bilateral extracranial internal carotid aneurysms presenting with vocal fold paralysis, which we believe to be the first.

The relationship of nasal septal deformity and palatal symmetry in neonates.

Results are reported of a study to evaluate possible associations between nasal septal deformity and palatal symmetry in neonates. Five hundred babies, born consecutively, were examined within three days of birth. Prenatal and delivery data were recorded for each baby and the nose was examined to determine airway patency and possible septal deformity. When a deviation of the septum was discovered an alginate impression of the palate was taken along with photographs of the nostrils. A matched control was then selected for each study group baby and similar records were obtained. Only 14 cases of septal deformity were found, an incidence of 2.8 per cent. No evidence of palatal asymmetry was found. The theory that moulding pressures during delivery may be a major cause of nasal septal deformity was not supported.

The mechanism of healing of tympanic membrane perforations. A two-dimensional histological study in guinea pigs.

The healing of small perforations, made in 60 tympanic membranes (30 guinea pigs) with either a thermal myringotome or a needle was observed over a 10-day period using an operating microscope. Thirty-six of these were sectioned either parallel with the handle of the malleus, or at right angles to it, and the closing perforations studied by light microscopy. The epidermis closed the perforations first, in the direction of surface migration. This process began within 48 hours and was complete within 9 days. A fibrous reaction occurred, starting at 3 days, and this was seen on the side of the perforation adjacent to the malleus or bony tympanic annulus. There was no response visible in the middle ear mucosa. The conclusion of this study is that the epidermis is the first layer to close a perforation because of its migratory function, and the direction of closure is the direction of migration. Healing of the fibrous layer occurs secondarily, and the site of the response in this layer is related to the vascular distribution in the tympanic membrane.

Laryngeal foreign bodies.

This paper presents our experience with four cases of impacted laryngeal foreign bodies. A review of the literature reveals that the condition is rare, but far more dramatic and life threatening than bronchial foreign bodies. The history may not indicate the diagnosis, especially in the ethnic minority races where there is a language barrier. Suspicion of the diagnosis by the casualty officer and the immediate attendance of an experienced otolaryngologist may be life saving. Radiological examination is not necessary where the diagnosis is obvious. If the diagnosis is in doubt it must be remembered that many foreign bodies are not radio-opaque. The patient must be accompanied at all times by an otolaryngologist until the foreign body is removed.

Treatment of auricular haematoma by silicone rubber splints.

A modification of existing techniques for the treatment of auricular haematoma is described. This method employs incision, drainage and the application of silicone rubber splints (Silastic). Existing methods of treatment are reviewed and discussed. A retrospective review of 16 cases using this technique showed a satisfactory cosmetic result in all cases.

Thermal myringotomy versus grommets in the management of secretory otitis media.

This paper presents the findings of a study of thermal myringotomy compared with the insertion of a grommet, in 30 children with secretory otitis media. The procedure was found to be easy to perform and free from complications. It provided ventilation of the middle ear for up to 8 weeks. However, there was a recurrence of the middle ear effusion in 40% of the thermal myringotomy ears. On the other hand, grommets were very effective in eliminating effusion over a 6 month period. I was unable to identify any parameter that will predict which patients will remain free of effusion after ventilation with a thermal myringotomy.

Pseudomonas vaccination in chronic ear disease.

This paper presents the results of a pilot study of vaccination in thirteen patients with chronically infected mastoid cavities or central perforations of the tympanic membrane. In each patient Pseudomonas aeruginosa was repeatedly cultured from the ear and a long list of medical and surgical treatments had been tried, without success, to control the infection. The clinical, bacteriological and immunological responses were monitored over a six-month period. The results are extremely encouraging. Eight patients' ears became dry for the first time in many years. However, three months after vaccination three ears had become reinfected. All of the patients except one had a good immunological response to vaccination, with many-fold increases in the total serum immunoglobulin G, A and M levels.

Neonatal septal deviations.

In a review of 1000 consecutive neonates of all races, nasal septal deformity was identified in 29, an incident of 2.9%; significantly fewer cases were found in negroid babies (0.1 greater than P greater than 0.05). Ten cases (35%) underwent manipulation of the deviated septum. Six-monthly review revealed that symptoms associated with the septal deformity are rare. In 7 (44%) of the 16 cases not manipulated, the septum straightened spontaneously during the first few months of life. The appearance of the deviation is not of a dislocation of the caudal edge of the cartilage but a smooth concavity. In vitro compression of the neonatal nasal cavity reproduced this C-shaped deformity, but only temporarily. Histological serial sections of 6 postmortem nasal cavities showed that the high laminae of the vomer prevent any caudal dislocation of the septal cartilage.

Post-laryngectomy pharyngo-cutaneous fistulae.

A personal series of 66 total laryngectomy cases is presented with special reference to post-operative fistula formation. The incidence of fistulae was 7.4 per cent. We could not verify previous reports that any specific factors were significantly related to fistula formation and we feel that operative technique and the post-operative drainage of any fluid collection under the flaps, are the most important ways of reducing the complication of a fistula to a minimum.

Metastatic tumours in the maxillary sinus. A report of two cases and a review of the literature.

We present two further cases of metastasis in the antrum. A review of the literature reveals renal carcinoma as the commonest primary tumour. When an adenocarcinoma of the antrum is diagnosed, an intravenous pyelogram should be performed to exclude a renal primary. This investigation, if negative, should be repeated during follow-up. The possibility of a bronchial tumour should be investigated in patients with an anaplastic tumour in the antrum.

Prolongation of the cochlear microphonic in man. Cochlear microphonic ringing.

During routine extra-tympanic electrocochleographic (ECochG) recording we have observed that in many cases more cycles are seen in the cochlear microphonic (CM) recording than are present in the acoustic stimulus. We have termed this phenomenon CM 'ringing'. Ringing is present in 69% of our normal subjects and in 43% of patients with deafness of different aetiologies. In the cochlear and Ménière subgroups those cases showing ringing have a significantly larger CM amplitude (p less than 0.001 and p less than 0.01 respectively). The possible origin of this phenomenon is discussed.

Normal function of extra-adrenal chromaffin tissues in the young rabbit and guinea-pig.

An attempt has been made to determine the relative functional activities of adrenal and extra-adrenal chromaffin tissue during the neonatal phase and up to 1 week of age using young rabbits and guinea-pigs whose main extra-adrenal abdominal para-aortic chromaffin bodies are respectively non-innervated and innervated. Amine synthesis and storage were followed by assay and autoradiography after a single intraperitoneal injection of L-[2,5,6-3H]DOPA and the findings correlated with amine content as assessed by high performance liquid chromatography and by volume of tissue. The results indicate that in the guinea-pig, in spite of differences in proportions of adrenaline and noradrenaline in the adrenal gland and para-aortic body (PAB), the loss of labelled catecholamines from the innervated PAB closely follows that from the adrenal medulla, suggesting that both participate in normal sympathoadrenal activity. By comparison, in the rabbit the PAB shows only a minimal decreased labelled amine during the first week of life during which period the amine content and concentration of the PAB doubles: the functional significance of this non-innervated extra-adrenal chromaffin tissue, which persists throughout life, has still to be determined.