Objectives To characterize opiate effects on motor function of the oesophagus in patients presenting with dysphagia. Methods Retrospective review of 15 patients with dysphagia referred for oesophageal manometry while on chronic opiates. Manometry was completed during opiate use and in three cases, after opiates were discontinued. Results All patients demonstrated motility abnormalities. Incomplete lower oesophageal sphincter (LES) relaxation (11.5 ± 1.6mmHg) was seen in most cases. Ten patients demonstrated non-peristaltic contractions in ≥ 3 out of 10 swallows. Additional abnormalities included high amplitude contractions; triple peaked contractions; and increased velocity. The average resting lower oesophageal sphincter (LESP) met criteria for hypertensive LES in 3 patients. These features were suggestive of spasm or achalasia. Repeat manometry off opiates was performed in 3 cases. LES relaxation was noted to be complete upon repeat manometry in these cases. There was also improved peristalsis and normal velocity. Conclusions A range of manometric abnormalities were seen in patients with dysphagia in the setting of opiate use: impaired LES relaxation, high amplitude/velocity, and simultaneous oesophageal waves. These data suggest the oesophagus is susceptible to the effects of opiates and care must be taken before ascribing dysphagia to a primary oesophageal motility disorder in patients taking opiates.

Normal gastrointestinal (GI) motility is required to mix digestive enzymes and food and to move content along the GI tract. Underlying the complex motor patterns of the gut are electrical events that reflect ion flux across cell membranes. Smooth muscle electrical activity is directly influenced by GI interstitial cells of Cajal, whose rhythmic oscillations in membrane potential in part determine the excitability of GI smooth muscle and its response to neuronal input. Coordinated activity of the ion channels responsible for the conductances that underlie ion flux in both smooth muscle and interstitial cells is a requisite for normal motility. These conductances are regulated by many factors, including mechanical stress. Recent studies have revealed mechanosensitivity at the level of the ion channels, and the mechanosensor within the channel has been identified in many cases. This has led to better comprehension of the role of mechanosensitive conductances in normal physiology and will undoubtedly lead to understanding of the consequences of disturbances in these conductances.

The etiology and pathogenesis of primary achalasia are unknown. Postulated mechanisms include autoimmune, viral-immune, and central neurodegenerative. The aim of this study was to investigate the serum profile of neural autoantibodies in patients with primary achalasia. Coded sera from 70 patients with primary achalasia and 161 healthy control subjects, matched in sex, age and smoking habits, were screened for antibodies targeting neuronal, glial and muscle autoantigens. No specific myenteric neuronal antibody was identified. However, the overall prevalence of neural autoantibodies in patients with primary achalasia was significantly higher than in healthy control subjects (25.7% vs 4.4%, p < 0.0001). Most noteworthy was the 21.4% frequency of glutamic acid decarboxylase-65 (GAD65) antibody in patients with achalasia (versus 2.5 % in control subjects), in the absence of diabetes or companion antibodies predictive of type 1 diabetes. This profile of autoantibodies suggests an autoimmune basis for a subset of primary achalasia.

Achalasia is a disorder of esophageal motility that has been well documented for over 300 years. Despite this, the initiating factor or factors and the underlying mechanisms leading to the characteristic features of achalasia, the absence of distal esophageal peristalsis and abnormal lower esophageal sphincter relaxation, are still not well understood. Recent work has shed light on changes in neurotransmission and cell signaling in the lower esophagus and lower esophageal sphincter that lead to achalasia. A number of recent reviews have thoroughly discussed diagnostic and therapeutic modalities and the reader is referred to these for in-depth review of these topics. The focus of this review will be on our current understanding of the physiology of esophageal peristalsis and lower esophageal sphincter function as it relates to achalasia and on available evidence for etiology and proposed pathophysiologic mechanisms.

A 27-year-old man with poorly controlled type 1 diabetes mellitus (average hemoglobin A1c of 15%) presented with a 1-week history of progressive pressure-like right upper abdominal discomfort associated with early satiety and nausea. On physical exam, he had firm hepatomegaly extending into the right pelvis. Laboratory testing revealed an aspartate aminotransferase ϭ 6720 U/L (normal, 8-43 U/L), alanine aminotransferase level ϭ 2549 U/L (normal, 7-45 U/L), alkaline phosphatase ϭ 529 U/L (normal, 41-108 U/L), total bilirubin ϭ 1.7 mg/dL (normal 0.1-1.0 mg/dL), with direct bilirubin ϭ 1.5 mg/dL (normal 0.0-0.3 mg/dL) and a normal international normalized ratio. A computed tomography (CT) scan of the abdomen showed massive hepatomegaly of increased density as compared to the spleen (Fig. 1). Infectious and autoimmune causes of liver disease were excluded by laboratory testing. A liver biopsy was obtained and revealed preserved parenchymal architecture and enlarged pale hepatocytes (Fig. 2) with abundant cytoplasmic glycogen deposits demonstrated by periodic acid-Schiff stain (Fig. 3) and diastase digestion removing the glycogen resulting in "ghost cells" (Fig. 4). These histologic findings are characteristic of glycogenic hepatopathy.The combination of a history of poorly controlled diabetes mellitus, acute liver injury indicated by marked elevation in aminotransferases, and the characteristic histologic changes on liver biopsy are diagnostic of glycogenic hepatopathy. 1 It was first described as part of