Effect of azithromycin on acid reflux, hiatus hernia and proximal acid pocket in the postprandial period.

BACKGROUND: The risk for acidic reflux is mainly determined by the position of the gastric acid pocket. It was hypothesised that compounds affecting proximal stomach tone might reduce gastro-oesophageal reflux by changing the acid pocket position. OBJECTIVE: To study the effect of azithromycin (Azi) on acid pocket position and acid exposure in patients with gastro-oesophageal reflux disease (GORD). METHODS: Nineteen patients with GORD were included, of whom seven had a large hiatal hernia (≥3 cm) (L-HH) and 12 had a small or no hiatal hernia (S-HH). Patients were randomised to Azi 250 mg/day or placebo during 3 days in a crossover manner. On each study day, reflux episodes were detected using concurrent high-resolution manometry and pH-impedance monitoring after a standardised meal. The acid pocket was visualised using scintigraphy, and its position was determined relative to the diaphragm. RESULTS: Azi reduced the number of acid reflux events (placebo 8.0±2.2 vs Azi 5.6±1.8, p<0.01) and postprandial acid exposure (placebo 10.5±3.8% vs Azi 5.9±2.5%, p<0.05) in all patients without affecting the total number of reflux episodes. Acid reflux occurred mainly when the acid pocket was located above, or at the level of, the diaphragm, rather than below the diaphragm. Treatment with Azi reduced hiatal hernia size and resulted in a more distal position of the acid pocket compared with placebo (below the diaphragm 39% vs 29%, p=0.03). Azi reduced the rate of acid reflux episodes in patients with S-HH (38% to 17%) to a greater extent than in patients with L-HH (69% to 62%, p=0.04). CONCLUSION: Azi reduces acid reflux episodes and oesophageal acid exposure. This effect was associated with a smaller hiatal hernia size and a more distal position of the acid pocket, further indicating the importance of the acid pocket in the pathogenesis of GORD. CLINICAL TRIAL REGISTRATION: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1970 NTR1970.

A discussion of airway and respiratory complications along with general considerations in obese patients.

Obesity is defined as the degree of excess weight associated with adverse health consequences. Within Great Britain, it is reported that a quarter of men and women are obese; these rates have trebled over the past 20 years. In 2001, it was estimated that obesity cost the National Health Service at least half a billion pounds, with a further two billion pounds lost on lower productivity and lost output. Obesity poses a significant risk factor for diseases, such as coronary heart disease, diabetes mellitus and certain forms of cancer, amongst others. Obese individuals pose significant problems to the clinician because of airway and respiratory complications. Sleep apnoea, obesity-hypoventilation syndrome, pulmonary atelectasis are associated with obesity and tracheostomy insertion is made all the more difficult in these patients. This article aims to discuss some of these issues relevant to the clinician and examine present strategies for dealing with them.

Pathophysiology and management of gastroesophageal reflux disease.

Gastroesophageal reflux is a physiological phenomenon but becomes pathological if troublesome symptoms and/or complications occur. Gastroesophageal reflux disease (GERD) has different phenotypes ranging from non-erosive reflux disease (NERD), through reflux esophagitis and Barrett's esophagus, and can present with either typical symptoms such as regurgitation and heartburn, or extra-esophageal symptoms such as cough and laryngitis. In the diagnosis of GERD endoscopy, empirical PPI test, and pH impedance testing all have their own position. Although proton pump inhibitors (PPIs) are very effective in the treatment of esophagitis, a significant proportion of patients have persistent symptoms even during high dosing of PPIs. Therefore, insight into the multifactorial pathophysiology of GERD is needed to develop new anti-reflux therapies. The predominant mechanism underlying reflux is the transient lower esophageal sphincter relaxation (TLESR). Hiatal hernia, impaired esophageal clearance and reduced lower esophageal sphincter pressure play a significant role in patients with moderate to severe reflux disease. Refluxate containing acid, pepsin and bile can cause epithelial injury when epithelial barrier of the esophagus fails to defend. In the majority of patients there is histopathological evidence of epithelial injury, even with NERD where there are more dilated intercellular spaces. The perception of heartburn can be enhanced due to visceral hypersensitivity, leading to more and more severe symptoms. Anti-reflux surgery is as effective as PPI therapy, but has higher morbidity and results decline in the long term. Therefore, new pharmacological, endoscopic and surgical interventions are being developed for these patients.

Reproducibility of meal-induced transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease.

AIM: To calculate the number of subjects required in trials investigating drugs reducing the number of transient lower oesophageal sphincter relaxations (TLOSRs), the inter- and intra-individual variability of TLOSRs were determined, using meal ingestion as a trigger of TLOSRs and reflux. METHODS: A total of 23 gastro-oesophageal reflux disease (GORD) patients with no to grade B oesophagitis and a hiatal hernia < or =3 cm underwent oesophageal manometry and pHmetry 1 h before and 3 h after ingestion of a solid meal on two separate days approximately 4 weeks apart. Reflux episodes and the underlying mechanisms and the number of TLOSRs were evaluated. RESULTS: The number of TLOSRs, reflux episodes and % time with pH < 4 after meal ingestion did not differ significantly between the two sessions. The intra-individual variation of TLOSRs in the 3 h postprandial period (24.4) was smaller compared with the inter-individual variation (47.5). Transient lower oesophageal sphincter relaxations were the predominant cause of reflux accounting for 61 +/- 7 and 70 +/- 5% of the reflux episodes in visits 1 and 2, respectively. CONCLUSIONS: These data for the first time provide information on the variability of TLOSRs and reflux evoked by meal ingestion, which is of crucial importance for the design and power calculations of future clinical studies evaluating the efficacy of new drugs targeting TLOSRs.

Transient lower oesophageal sphincter relaxations--a pharmacological target for gastro-oesophageal reflux disease?

The oesophago-gastric junction functions as an anti-reflux barrier preventing increased exposure of the oesophageal mucosa to gastric contents. Failure of this anti-reflux barrier results in gastro-oesophageal reflux disease, and may lead to complications such as oesophagitis, Barrett's oesophagus and eventually oesophageal carcinoma. Recent studies have suggested that transient lower oesophageal sphincter relaxation is the main mechanism underlying gastro-oesophageal reflux. It involves a prolonged relaxation of the lower oesophageal sphincter, mediated by a vago-vagal neural pathway, synapsing in the brainstem. Several drugs, such as atropine, baclofen and loxiglumide, have been shown to reduce the rate of transient lower oesophageal sphincter relaxations and concomitantly the number of reflux episodes. These findings illustrate that transient lower oesophageal sphincter relaxations may represent a potential new target for the pharmacological treatment of gastro-oesophageal reflux disease. It is possible that the reduction in the number of transient lower oesophageal sphincter relaxations may also contribute to the beneficial effect of fundoplication and new endoscopic anti-reflux procedures. It should be emphasized, however, that other factors, such as low lower oesophageal sphincter pressure, the presence of a hiatal hernia and impaired oesophageal peristalsis, are also of great importance. Therefore, whether the targeting of transient lower oesophageal sphincter relaxations is the 'golden bullet' in anti-reflux therapy remains to be proven, as evidence of an effective control of gastro-oesophageal reflux in reflux patients is still lacking.

Activation of an adrenergic and vagally-mediated NANC pathway in surgery-induced fundic relaxation in the rat.

The aim of this study was to pharmacologically characterize and investigate the possible contribution of adrenergic and nonadrenergic noncholinergic (NANC) pathways involved in the relaxation of the rat gastric fundus following abdominal surgery. Using an intragastric balloon, the effect of skin incision (SI), laparotomy (LT) and manipulation of the small intestine followed by caecal resection (M + R) on fundic pressure was evaluated. SI resulted in a brief relaxation of the gastric fundus abolished by guanethidine and blocked by hexamethonium and the combination of phentolamine, propranolol and atropine (PPA). LT induced a longer lasting relaxation which was abolished by guanethidine and hexamethonium. It was blocked by PPA and the combination of ganglionectomy and vagotomy, but unaffected by atropine, vagotomy or ganglionectomy. M + R induced a long-lasting relaxation which was only partly blocked by guanethidine or PPA, illustrating an inhibitory NANC component. Vagotomy combined with guanethidine completely abolished the relaxation following M + R, whereas it was significantly blocked by hexamethonium and the combination of ganglionectomy with vagotomy. These results indicate that SI, LT and M + R induce inhibition of fundic motility via an adrenergic mechanism. During M + R, an additional vagally mediated inhibitory NANC pathway is activated. Finally, we suggest that LT and M + R inhibit the gastric fundus via both a splanchnic and a vagal reflex pathway.

Nasal pH and saccharin clearance are unrelated in the physiologically normal nose.

A group of 56 asymptomatic non-smoking men was prospectively recruited to study the relationship between nasal mucosal pH and saccharin clearance rate. No significant relationship was found between the two variables (Pearson correlation coefficient = -.105, p = 0.44). This finding suggests that in vivo mucociliary flow rates are resistant to change within the pH range of the physiologically normal nose.

Conchal flap meatoplasty.

A meatoplasty technique is described which has proved successful in the treatment of chronic otitis externa. The procedure opens the superficial meatus by eliminating the sharp rim at the junction of the conchal bowl and the posterior canal wall cartilage; thinning the skin and increasing the circumference of the external auditory orifice.

Autosuture GIA gun: a new application in the treatment of hypopharyngeal diverticula.

A new surgical technique for the treatment of moderate to large hypopharyngeal diverticula is described. The procedure is particularly useful in debilitated patients in that it is quick and guarantees closure of the party wall between the pouch and upper oesophagus.

Distribution of topical antibiotic preparations in mastoid cavities.

Topical antibiotic preparations are widely prescribed in the treatment of infected mastoid cavities with no knowledge of the distribution of the preparation within the cavity. This study ascertains the distribution of drop and spray preparations within mastoid cavities and suggests methods of delivery to maximize coverage.

Right vocal fold paralysis as a result of central venous catheterization.

Invasive peri- and post-operative monitoring is being increasingly utilized, and a corresponding increase of concomitant complications are becoming apparent. Two cases of complete right vocal fold paralysis are reported as a possible complication of right central venous catheterization. The underlying aetiology of this complication is presumed to be either direct trauma at the time of introduction of the central venous catheter, or by thrombosis and fibrosis around the recurrent laryngeal or vagus nerve. It is suggested that multiple attempts at cannulation and leaving the central line in situ for long periods increases the risk of this complication. When the integrity of the left recurrent laryngeal nerve or vagus is jeopardized or must be sacrificed during surgery, it is suggested that ipsilateral central lines are inserted to minimize the risk of bilateral vocal fold paralysis. Cases of vocal fold paralysis secondary to central line insertion should be followed expectantly and surgical intervention only be considered after 12 months review.

Pharyngo-oesophageal fistula following iatrogenic perforation of a pharyngeal pouch.

A unique, previously undescribed case of iatrogenic perforation of a pharyngeal pouch which resulted in pharyngo-oesophageal fistulation is described. The correct management of such complications is discussed.

The management of benign thyroid goitre causing tracheo-oesophageal embarrassment.

The case of a massive benign thyroid goitre extending from the arch of aorta to the nasopharynx presenting with acute aerodigestive obstruction is reported. The management of the case is discussed and also a review of the relevant literature.

Improvement in hand-held CO2 laser safety.

A modification of the CO2 laser hand-piece is presented which utilizes a simple finger controlled mechanical shutter. This instrument safeguards against accidental direction of the laser beam.

Latent mastoiditis: no room for complacency.

The administration of antibiotics in otitis media alters the natural course of the disease process. If the antibiotics used are inappropriate, or if dosage or duration of treatment is inadequate, an imminent intracranial complication may be masked. A case of latent mastoiditis presenting with Pott's puffy tumour is described.

Oncocytic papillary cystadenomatosis of the larynx.

Symptomatic oncocytic disease of the larynx is rare. Review of the world literature reveals that isolated, symptomatic cases of oncocytoma of the larynx have been previously reported to involve discrete sites usually the laryngeal ventricles and vestibular folds. A unique case of multifocal cystic oncocytic hyperplasia necessitating laryngectomy is reported. CT scan of the larynx suggested destruction of the cartilage. Malignant histological features were not present. This report raises the question whether previously described cases of oncocytoma of the larynx also had diffuse involvement. If oncocytosis is a diffuse process then it is suggested that patients should be kept under review for recurring lesions.

Long-term ventilation of the middle ear using a tympanotomy technique.

The technique of long-term middle ear ventilation using a tympanotomy technique is presented. This has proved successful in the management of persistent middle ear effusion despite numerous previous short- and intermediate-term tympanic membrane ventilation tubes. The technique is particularly appropriate in the presence of severe tympanosclerosis as a result of previous tympanostomy tubes, posterior tympanic membrane collapse and adhesion, and atelectasis.

Post-irradiation liposarcoma of the temporal bone.

The first reported case of liposarcoma of the temporal bone is presented. Its association with previous irradiation for benign parotid disease is discussed.

Primary sinonasal amyloidosis.

Primary amyloidosis localized to the sinonasal tract is extremely rare with only 20 reported cases in the English literature. We describe a further case and review the literature.

Laryngeal gout.

A review of the literature reveals only 12 reported cases of laryngeal gout. We describe three further cases of laryngeal gout, the largest series ever published. The first case is previously undescribed acute gouty cricoarytenoiditis resulting in acute airway embarrassment requiring tracheotomy, and then we describe two cases of chronic tophaceous involvement of the thyroid lamina with computed tomography (CT) images of this process. The paucity of literature on this subject may not only be due to rarity but also lack of clinical awareness. Gouty involvement of the larynx must be considered in any patient with a history of gout who presents with hoarseness, odynophagia, dysphagia, stridor or neck lump. Acute airway compromise may require tracheotomy, whereas chronic airway problems may necessitate endoscopic tophi removal, lateralization procedures or even permanent tracheostomy.