Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Achalasia presenting as an acute airway obstruction is a rarely reported phenomenon. The pathophysiology of this dramatic complication of achalasia remains an enigma. Our patient with achalasia presented with an acute airway compromise necessitating emergent endotracheal intubation. We review the available literature on this interesting yet rare complication of achalasia. We also add some information to help elucidate the possible pathophysiologic mechanism of this emergency, proposing that specific upper esophageal sphincter manometry may indicate abnormality of the "belch reflex."
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PMID:Acute airway obstruction in achalasia. Possible role of defective belch reflex. 267 85

Achalasia is an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.
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PMID:The nature of the myenteric infiltrate in achalasia: an immunohistochemical analysis. 1093 57

Background and aims Chronic visceral pain is common both in patients with identifiable organic disease and also in those without any structural, biochemical or immunological abnormality such as in the functional gastrointestinal disorders (FGIDs). We aim to provide a contemporaneous summary of pathways involved in visceral nociception and how a variety of mechanisms may influence an individual's experience of visceral pain. Methods In this narrative review, we have brought together evidence through a detailed search of Medline in addition to using our experience and exposure to recent research developments from ourselves and other research groups. Results FGIDs are a heterogeneous group of disorders whose aetiology largely remains an enigma. The germane hypothesis for the genesis and maintenance of chronic visceral pain in FGIDs is the concept of visceral hypersensitivity. A number of peripheral and central mechanisms have been proposed to account for this epiphenomenon. In the periphery, inflammatory mediators activate and sensitize nociceptive afferent nerves by reducing their transduction thresholds and by inducing the expression and recruitment of hitherto silent nociceptors culminating in an increase in pain sensitivity at the site of injury known as primary hyperalgesia. Centrally, secondary hyperalgesia, defined as an increase in pain sensitivity in anatomically distinct sites, occurs at the level of the spinal dorsal horn. Moreover, the stress responsive physiological systems, genetic and psychological factors may modulate the experience of visceral pain. We also address some novel aetiological concepts in FGIDs, namely the gastrointestinal microbiota, connective tissue abnormalities and the gastrointestinal neuromuscular disorders. Firstly, the gastrointestinal microbiota is a diverse and dynamic ecosystem, that safeguards the host from external pathogens, aids in the metabolism of polysaccharides and lipids, modulates intestinal motility, in addition to modulating visceral perception. Secondly, connective tissue disorders, which traditionally have been considered to be confined largely to the musculoskeletal system, have an increasing evidence base demonstrating the presence of visceral manifestations. Since the sensorimotor apparatus of the GI tract is embedded within connective tissue it should not be surprising that such disorder may result in visceral pain and abnormal gut motility. Thirdly, gastrointestinal neuromuscular diseases refer to a heterogeneous group of disorders in which symptoms arise from impaired GI motor activity often manifesting as abnormal transit with or without radiological evidence of transient or persistent dilation of the viscera. Although a number of these are readily recognizable, such as achalasia or Hirschsprung's disease, the cause in a number of patients is not. An international working group has recently addressed this "gap", providing a comprehensive morphologically based diagnostic criteria. Conclusions/implications Although marked advances have been made in understanding the mechanisms that contribute to the development and maintenance of visceral pain, many interventions have failed to produce tangible improvement in patient outcomes. In the last part of this review we highlight an emerging approach that has allowed the definition and delineation of temporally stable visceral pain clusters, which may improve participant homogeneity in future studies, potentially facilitate stratification of treatment in FGID and lead to improvements in diagnostic criteria and outcomes.
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PMID:Mechanisms of visceral pain in health and functional gastrointestinal disorders. 2991 80