Nausea and vomiting can be induced by a wide variety of stimuli such as pregnancy, space travel, raised intracranial pressure, radiation and cytotoxic drugs. The mechanisms by which all these diverse stimuli culminate in a final common act is unknown. From studies in the 1950s a model of the emetic reflex emerged consisting of a chemoreceptor trigger zone in the area postrema and a vomiting centre in the brain stem. This concept has been reviewed and revised in the light of recent studies. Many discussions of emesis involve detailed descriptions of the gastrointestinal events associated with the act of vomiting only-nausea and retching receiving little attention. Here we have tried to give a broader view by considering the neurophysiology of such events and have included nausea and retching, phenomena that are usually inseparable from vomiting. The possible biological function of these events is also discussed. The involvement of visceral systems (such as the heart, airways and gut) is included, and particular attention is paid to vagal mechanisms underlying the changes in gut motor activity. Emesis has long been thought to be organized by a 'vomiting centre'; the possibility that this vomiting centre could be the parvocellular reticular formation is reviewed, as is the concept that the 'centre' is larger than an anatomically defined single group of cells. The mechanism of action of two clinically relevant emetic stimuli--radiation and cytotoxic drugs-is considered in detail. Recent studies of the antiemetic properties of novel 5-HT-3 receptor antagonists against radiation and cytotoxic drug-induced vomiting are discussed; these studies suggest that important advances will be made in the treatment of emesis induced by these and other related agents.

In most mammals (except ruminants) activity in the gastrointestinal (GI) tract depends upon the condition or state of the animal, namely, fasted or fed. The fasted state is characterized by a caudally migrating, cycling motor complex, showing periods of intense contractile and secretory activity alternating with periods of quiescence. Although the mechanisms involved in the transition from the fasted to the fed state are not fully understood it seems likely that both states utilize intrinsically located neural control mechanisms and common neuronal pathways to the effector tissues. We have commented on the reported properties of the myenteric neurones and their projections to the muscle layers. The data suggests that there are both cholinergic and non-cholinergic excitatory motor neurones supplying the muscle layers. In the guinea-pig, at least, the projections of the neurones to the circular muscle layer run for relatively short distances in oral-aboral axis of the gut. The non-cholinergic excitatory transmitter substance may be Substance P or a similar tachykinin. Other excitatory nerves may well be present. There are at least two mechanisms used by non-cholinergic non-adrenergic inhibitory nerves supplying the muscle layers. In the guinea-pig ileum, there are at least two distinct projections of inhibitory motor neurones; both have aborally directed projections. The first of these is relatively short and the other long (greater than 10 mm). Individual myenteric neurones appear to contain unique and perhaps identifying groups of peptides. The functional role of many of these peptides, either within the myenteric plexus or their projections to the muscle layers, remains to be elucidated. The projections of the neurones of the submucous plexus run primarily to the mucosa. Both cholinergic and non-cholinergic secretomotor neurones appear to be present. The activation of local neural reflexes, which results in secretomotor activity, may involve submucous sensory neurones containing acetylcholine and Substance P together with cholinergic interneurones. Projections from the myenteric to the submucous plexus are likely to be involved in the coordination of intestinal movement and secretomotor activity. A simplified schematic diagram of some of the neuronal circuitry of the submucous plexus has been developed and includes the findings from immunocytochemical and electrophysiological studies.

In the United States, 1500 people die yearly of ingested foreign bodies of the upper gastrointestinal tract. The flexible esophagogastroduodenoscope has had a major impact on the treatment of these foreign bodies. The following discussion includes the management of coins, meat impaction, sharp and pointed objects, button batteries, and cocaine packets; and it reflects both a personal experience and a review of the literature. The uses of the rigid and the flexible endoscopes, the Foley catheter, glucagon, papain, and gas-forming agents are presented. The cost-effectiveness impact of the flexible endoscope is also detailed, and morbidity and mortality rates for foreign body management are included.

1. The spinal sympathetic outflow that innervates the gastrointestinal tract, including its blood vessels, has an impressive representation quantitatively, yet little is known about the functions of this system and its peripheral or central organization. Electrical stimulation or section of the splanchnic nerves have variable effects on the GI tract and does not, therefore, lead to a deeper understanding of the system. 2. The targets of the sympathetic supply of the GI tract are blood vessels, nonvascular (sphincteric) smooth musculature, myenteric neurones, submucous neurones and gut associated lymphoid tissues. The corresponding functions associated with these targets are regulation of blood flow (particularly through the mucosa) and resistance to flow, of motility, of secretion and absorption and of immune responses. Little is known about the effects of the sympathetic nervous system on the latter function. 3. The sympathetic postganglionic neurones are (at least in the guinea-pig) neurochemically characterized with respect to the targets. Neurones projecting to blood vessels contain neuropeptide Y in addition to noradrenaline, while neurones projecting to the submucous plexus contain somatostatin. No neuropeptide has been detected to date in neurones projecting to the myenteric plexus. 4. Transmission through guinea-pig prevertebral ganglia in vitro have been studied electrophysiologically. The following functions have been demonstrated: (a) transmission and distribution of preganglionic impulse activity to the targets in a relay-like fashion; (b) mediation of peripheral intestinointestinal reflexes between different sections of the GI tract; (c) integration of activity from the spinal cord and from various peripheral sources. The first function may apply particularly to the sympathetic pathway innervating blood vessels. Whether the second function occurs in vivo is questionable. The third function is the most important one for pathways involved in the regulation of motility and probably secretion and absorption. 5. Only limited information is available on preganglionic neurones projecting to prevertebral ganglia. Neurones regulating blood vessels are probably located in the intermediolateral cell column, and non-vascular visceral preganglionic neurones are situated medial to this cell column in the intermediate zone of the spinal cord. Vascular (vasoconstrictor) neurones exhibit a reflex pattern which is largely dependent on the brain stem. Spinal cord transection rostral to the sympathetic outflow causes an immediate abolition of basal and reflex activity in these neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

The only non-general sensation that can be evoked from the gastrointestinal (GI) tract is that of pain ranging from mild discomfort to intense pain. However, in certain regions of the gut, such as the rectum and gastro-oesophagus, the feeling of pain can be preceded by non-painful sensations of distension at lower stimulus intensities. GI pain is often dull, aching, ill-defined and badly localized. In some cases, GI pain is projected to areas of the body away from the originating viscus ('referred' pain). These properties indicate that the representation of internal organs within the central nervous system is very imprecise. Behavioural, neurophysiological and clinical evidence shows that most forms of GI pain are mediated by activity in visceral afferent fibres running in sympathetic nerves and that the afferent innervation of the gut mediated by parasympathetic nerves is not primarily concerned with the signalling and transmission of GI pain. As for the encoding mechanism of the peripheral sensory receptor in the gut, there is evidence for the existence of specific visceral nociceptors in some locations (e.g. the biliary system) and for the existence of non-specific 'intensity' type receptors in other locations (e.g. the colon). In any case, the actual number of nociceptive afferent fibres in the gut is very small and this explains why large areas of the GI tract appear to be insensitive or require considerable stimulation before giving rise to painful sensations. The few nociceptive afferents contained in sympathetic nerves can excite many second order neurones in the spinal cord which in turn generate extensive divergence within the spinal cord and brain stem, sometimes involving long supraspinal loops. Such a divergent input can activate many different systems, motor and autonomic as well as sensory, and thus trigger the general reactions that are characteristic of visceral nociception: a diffuse and ill-localized pain sometimes referred to somatic areas, and autonomic and somatic reflexes that result in prolonged motor activity.

Opioid peptides and opioid receptors are distributed along the gastrointestinal (GI) tract, indicating endogenous opiates released peripherally may modulate GI motor and secretory functions. Animal studies have revealed that the effects of opiates on gut motility depend on the nature of the subclasses of receptor involved, the species and the part of bowel. Most opiates that have a selective or predominant mu agonist activity inhibit gastric motility and delay gastric emptying by acting centrally; delta and kappa agonist are inactive when injected systemically. The effect of opiates in delaying intestinal transit observed in man, rat and other species is related to an inhibition (rat) or a stimulation (dog and man) of intestinal contractions as premature phase III-like sequences. The constipating effects of morphine probably result mainly from its action on colonic motility. Morphine stimulates colonic motility in humans by action on both central and peripheral sites. This increase in colonic motility and the delay in colonic transit is associated with a reinforcement of tonic contractions and reduced propulsive waves. Opioid peptides have been shown to participate in the colonic motor response to eating in man and animals. Both delta and mu receptors are involved in the stimulatory effects of opiates on colonic motility, while kappa receptors inhibit colonic contractions, mainly by acting centrally. The effects of opiates on gastric acid secretion are still controversial but it has been well demonstrated that opiates act centrally to reduce pancreatic secretion in rats. Opiates also inhibit intestinal secretions via an action on the enteric nervous system as well as in the CNS. All these results reinforce the hypothesis that opioid peptides have a major physiological role in the control of gut motility and secretions, and these actions explain most of the pharmacological effects of opiate substances on the digestive tract.

In this review, we compared the outcome of 25 studies of experimentally induced pancreatitis in animals with 13 studies of human acute pancreatitis in which the same therapeutic agents were used (aprotinin, glucagon, 5-fluorouracil, somatostatin, peritoneal lavage). Whereas 81% of the animal studies had a positive outcome (improvement in survival), only 7.7% of the human studies showed a positive outcome on survival. Most animal studies suffered from a protocol in which treatment was not significantly delayed after induction of acute pancreatitis. Of the 12 human studies that showed no effect of treatment on survival, none had sufficient statistical power (1 - beta error) for the investigators to have confidence in the negative outcomes. This was due to the fact that the studies had too few patients or that the event rates in the untreated populations were too low. Only five of the human studies reported the complication rates of acute pancreatitis in patients who did not die of their disease. Treatment (by any agent) did not improve the complication rate in these studies, but only one of the five reports had sufficient statistical power for the investigators to have confidence in these negative results. Large multicenter studies with sufficient numbers of patients with severe pancreatitis (high mortality and complication rates) are needed to evaluate new therapies in this disease.

Angina-like chest pain of non-cardiac origin is a major diagnostic and therapeutic problem. The oesophagus is frequently suspected to be the cause of the chest pain in these patients. However, a positive statement for the oesophageal origin of the pain can only be made when during manometry or pH-monitoring the familiar pain attack appears to be accompanied by reflux, severe motor disorders or a combination of both. Due to the intermittent nature of the pain this is only rarely the case during short-listing conventional examinations. Provocation tests have been used to induce the familiar chest pain. The Bernstein acid perfusion test and the edrophonium test yield the best results. Prolonged (24-hour) ambulatory recording of intra-oesophageal pressure and pH to increase the chances of recording chest pain concomitantly with an episode of reflux and/or motor disorders appears to be the most sensitive and also the most physiological test. It is the only test that provides reliable information on the underlying mechanism of the pain, especially in patients with the syndrome of irritable oesophagus, thus contributing in establishing the appropriate therapy for these patients.

The scope of therapeutic endoscopy, especially in the context of oesophageal dilatation, has greatly expanded in recent years. In this chapter we have described the currently used wire-guided systems and their dilatation technique. This technique can be used with most dilatation instrumentation now on the market. Perforation, the major risk of dilatation, is now rare (0.22% out of 909 dilatations with Savary-Gilliard bougies). Finally, we have presented the results of our own comparative studies for the Eder-Puestow, Savary Gilliard and Biomed systems and those of other authors for systems with which we have had no experience. In our opinion Savary-Gilliard bougies are the best, not only because of their greater flexibility and progressivity but also because of the improved safety tip of the guide wire.

The pathogenesis of GORD depends on a mix of factors which vary amongst individual patients. The central issue in the pathogenesis of gastro-oesophageal reflux is understanding of the mechanisms that lead to reflux, since the effects of all other factors depend on this event. Consequently, new information and views about the mechanisms of gastro-oesophageal reflux have been presented in detail. This information suggests that defective lower oesophageal sphincter motility is the most important abnormality that underlies pathological gastro-oesophageal reflux. Two major forms of LOS dysfunction have been identified as responsible for pathological gastro-oesophageal reflux in the horizontal position: (1) an excessively frequent rate of occurrence of transient LOS relaxations; and (2) defective basal LOS tone. Both of these dysfunctions appear to arise from abnormal neural control of the LOS, probably by the central nervous system. The effect of these LOS dysfunctions on gastro-oesophageal competence is probably significantly influenced by non-sphincteric factors, the most important of these apparently being hiatus hernia. Though there is currently poor understanding about the ways in which hiatus hernia impairs gastro-oesophageal competence, measurement techniques have now advanced sufficiently to allow significant accrual of knowledge in this field. Once reflux has occurred, the efficiency of oesophageal acid clearance plays a major role in determining the impact of reflux on the oesophageal mucosa. Recent studies have shown that oesophageal acid clearance depends on both effective volume clearance and neutralization by saliva of residual acid in the oesophageal lumen. The efficiency of oesophageal volume clearance of both stimulated and real reflux has not been studied formally in GORD patients, but the high incidence of peristaltic dysfunction in reflux disease suggests that volume clearance will be defective in some patients. The limited information available about salivation in GORD patients suggests that salivary secretion is no different from that of age-matched controls, but that there is an age-dependent loss of the salivary response to oesophageal acidification. This impairment of salivary response may produce an age-dependent decline of the efficiency of oesophageal acid clearance. Unusually aggressive refluxate and impaired mucosal resistance to injury have been proposed as significant variables which contribute to pathogenesis of reflux disease. The evidence for these factors is circumstantial and scanty. Their importance has probably been overestimated.(ABSTRACT TRUNCATED AT 400 WORDS)