C. Scarpignato

Reflux related symptoms in patients with normal oesophageal exposure to acid.

Several studies, using pH monitoring with event markers, have identified patients with normal oesophageal exposure to acid despite an apparent relation between symptoms and reflux episodes. In this series of 771 consecutive patients referred for 24 hour oesophageal pH monitoring, a probability calculation was used to evaluate the relation between symptoms and reflux episodes. Oesophageal exposure to acid was normal in 462 of 771 recordings (59.9%); despite this, 70.8% (327 of 462) of these patients used at least once the event marker. In 96 patients (12.5% of total patients) with normal oesophageal exposure to acid, there was a statistically significant association between symptoms and reflux episodes. The symptom cluster of such patients was similar to that usually seen in patients with gastro-oesophageal reflux disease, but symptoms like belching, bloating, and nausea were common thus overlapping with the symptom pattern of functional dyspepsia. In these patients both the duration and the minimum pH of reflux episodes (either symptom related or asymptomatic) were significantly shorter and higher, respectively, when compared with those of patients with gastro-oesophageal reflux disease. These results are consistent with the idea that oesophageal hypersensitivity to acid is the underlying pathophysiological feature of this syndrome.

Specific adaptation of gastric emptying to diets with differing protein content in the rat: is endogenous cholecystokinin implicated?

Background—Recent studies indicate that gastric emptying may be influenced by patterns of previous nutrient intake. Endogenous cholecystokinin (CCK), whose synthesis and release can be affected by dietary intake, has a major role in the regulation of gastric emptying. Aims—To evaluate the influence of diets with differing protein content on gastric emptying of differing liquid test meals and plasma CCK levels in the rat and to check whether the inhibitory effect of exogenous CCK on gastric emptying is modified after long term intake of diets with differing protein content. Methods—Rats were fed for three weeks with high protein, medium protein (regular), or low protein diet. On day 22 gastric emptying of a peptone meal was studied. In addition, basal and postprandial CCK levels after the different dietary regimens were measured by bioassay. The time course of dietary adaptation was studied and its specificity assessed through the use of different (peptone, glucose, and methylcellulose) test meals. The effect of exogenous CCK-8 on gastric emptying was studied at the end of the adaptation period (three weeks). Results—Feeding the animals with a high protein diet for three weeks resulted in a significant (p<0.05) acceleration (by 21.2 (8.2)%) of gastric emptying while feeding with a low protein diet was followed by a significant (p<0.05) delay (by 24.0 (6.2)%) in the emptying rate. When the time course of the effect of dietary adaptation on gastric emptying was studied, it appeared that at least two weeks are required for dietary protein to be effective. The regulatory effect of dietary protein on gastric emptying proved to be dependent on meal composition. Only the emptying rate of a protein containing meal (40% peptone) was significantly modified by previous dietary intake. No significant (p>0.05) changes were observed with glucose and methylcellulose meals whose emptying rates were similar in rats receiving a high protein or low protein diet. A peptone meal strongly and significantly (p<0.05) increased plasma CCK levels in rats fed a medium protein (regular) diet. Results were similar in rats receiving a low protein diet (p<0.05) but not in rats on a high protein diet (p>0.05). As a consequence, postprandial plasma levels of CCK in rats fed with a medium or low protein diet were significantly (p<0.05) higher than those in rats receiving a high protein diet. In rats on high and low protein diets, dose response curves to CCK-8 were virtually identical, suggesting that dietary protein intake has no influence on the effect of exogenous CCK. Conclusions—These results clearly show that gastric emptying of a protein containing meal can be modified by previous dietary protein intake. This effect, which is time dependent and meal specific, may be related to changes in endogenous CCK release which will affect emptying rate. While the exact mechanisms underlying this adaptive response need to be studied and clarified further, these results emphasise the importance of dietary history in the evaluation and interpretation of gastric emptying data.

Different affinity states of CCK1 receptors on pancreatic acini and gastric smooth muscle in the rat

It has recently been shown that--after chronic cholecystokinin (CCK) treatment--an adaptation of pancreatic secretory but not gastric motor function does occur. Recent studies indicate that the CCK(1)-receptor exists in two (i.e. high and low) affinity states, which could be distinguished by the CCK-analogue JMV-180. CCK occupancy of high and low affinity sites is thought to be related to the initiation of different intracellular events and consequent biological responses. Affinity states of CCK(1)-receptors on pancreas and gastrointestinal (GI) smooth muscle could be different and this can offer an explanation for the different effects of CCK on pancreatic and gastric growth. We therefore studied the affinity states of CCK(1)-receptors on isolated rat pancreatic acini and gastric smooth muscle preparations. When acini were incubated with increasing concentrations of CCK-8, a biphasic (i.e. stimulation followed by inhibition) effect on amylase release was observed. JMV-180 caused only stimulation of enzyme release and combined JMV-180 and CCK stimulation (at submaximal doses) resulted in an additive secretory response. CCK-8 induced contractions of pyloric, antral and fundic muscle in a concentration-dependent manner. The response was monophasic, reaching a plateau. JMV-180 had only a very weak effect on these preparations. On the contrary, it inhibited CCK-induced contractions in a competitive manner, the concentration-response curve to CCK being shifted to the right by the CCK analogue. Our data suggest that the affinity states of CCK(1)-receptors on rat pancreatic and gastric tissue are different. On pancreatic acini CCK(1)-receptors exist in both high- and low-affinity states whose occupation is followed by the sequence of intracellular events leading to growth. In contrast, occupation of low affinity receptors (the only ones present in the GI smooth muscle) does not lead to cell proliferation. This difference therefore explains the different adaptive response of the pancreas and the stomach to chronic CCK administration. Furthermore, different affinity states of CCK(1)-receptors may mediate different functions of the digestive tract.

Therapeutic Strategy in Gastro-oesophageal Reflux Disease

Gastro-oesophageal reflux disease (GORD) encompasses a wide spectrum of disorders in which gastric refluxate causes symptoms and/or damage to the oesophageal mucosa (Fig. 1). It is a very common disorder, epidemiological surveys in Europe and USA having shown that 5%–15% of the general population suffer from frequent heartburn or regurgitation [1, 2]. Most subjects, however, have mild, intermittent symptoms. They do not seek medical help or are managed by primary care physicians. At the other end of the spectrum of the disease are patients with long-standing recurrent disease, persistent symptoms, severe esophagitis lesions and complications such as strictures, bleeding, columnar-lined (Barrett’s) esophagus or extra-esophageal complications (e.g. asthma, acid laryngitis or non-cardiac chest pain).

Die Behandlung der gastroösophagealen Refluxkrankheit

Der Terminus „gastroosophageale Refluxkrankheit“ umfast ein weites Spektrum von Krankheiten, bei denen Reflux aus dem Magen Symptome und/oder eine Schadigung der Osophagusschleimhaut hervorruft (Abb. 1). Es handelt sich um eine weit verbreitete Erkrankung; epidemiologische Studien in Europa und den USA [1, 2] haben gezeigt, das 5–15% der Gesamtbevolkerung regelmasig an Sodbrennen oder Erbrechen leiden. Haufig bestehen allerdings nur milde intermittierende Symptome. Die Betroffenen suchen keine medizinische Hilfe oder werden im Rahmen der Primarversorgung betreut. Am anderen Ende des Krankheitsspektrums finden sich Patienten mit langandauerndem, immer wiederkehrenden Reflux, standigen Symptomen, schweren Lasionen im Rahmen einer Osophagitis und Komplikationen wie Strikturen, Blutungen, BarrettOsophagus oder uber die Speiserohre hinausgehenden Komplikationen (z.B. Asthma, saureinduzierter Laryngitis oder nicht-kardialen Brustschmerzen).