Detection of duodenal fluid in the oesophagus with a sodium ion selective electrode.

The assessment of duodeno-oesophageal reflux is difficult as, until recently, no technique has been readily available for continuous ambulatory monitoring. A sodium ion selective electrode placed in the stomach has been previously shown to detect duodenogastric reflux by using sodium as a marker. This relies on the difference in sodium concentration between gastric (5-60 mmol/L) and duodenal, biliary and pancreatic (150 mmol/L) fluids. In this pilot study to assess the efficacy of the electrode in the distal oesophagus, eight subjects without symptomatic gastro-oesophageal reflux and eight subjects with known duodenogastric reflux were studied. Thirty millilitre volumes of varying sodium solutions (40, 80, 100 and 140 mmol/L) were swallowed to assess the response of the electrode to sodium ions. In both groups, this revealed a constant and reproducible rise in response with increasing concentration (P < 0.0001). The stomachs of subjects with duodenogastric reflux were aspirated via a nasogastric tube to obtain 12 different samples of gastric fluid. This was assayed for sodium and bile acid concentration. The fluid was then reinfused as a 30 mL bolus into the oesophagus through a tube to simulate oesophageal reflux. A rise equivalent to 40-72 mmol/L Na+ was recorded by the electrode in response to samples that contained 58-81 mmol/L Na+ and 0.4-16 mmol/L bile acids, recorded by quantitative analysis, and a response of up to 20 mmol/L Na+ was recorded by the electrode to sodium concentrations < 49 mmol/L and bile acid concentrations of 0.005-0.6 mmol/L. The response was appropriate to the assayed bile acid concentration in all but one sample. The sodium ion selective electrode responds to bile containing fluids introduced into the oesophagus. Further investigation is warranted to determine its ability to measure duodeno-oesophageal reflux continuously.

Identifying oesophageal contents using electrical impedance tomography.

Investigations have been carried out using the Sheffield mark II real-time EIT system, to look at changes in conductivity associated with swallowing. A ring of 16 electrodes was placed around the neck of 10 subjects, who then performed swallows with four liquids of different conductivities, ranging from water (sigma = 0.03 mS cm-1) to salty soup (sigma = 35.8 mS cm-1). Results showed that the conductive and non-conductive liquids could be distinguished. Bolus transit times were calculated from region of interest curves, and the average transit time for the 10 subjects was found to be 320 +/- 100 ms.

Applied potential tomography in the measurement of gastric emptying in infants.

The aim of this study was to investigate the feasibility of using applied potential tomography (APT), a noninvasive and nonradioactive method, to measure the rate of gastric emptying in preterm babies and infants < 3 months old. APT, a form of electrical impedance tomography, creates tomographic images of tissue resistivity to a small electrical current and has been used to study gastric emptying in adults. The rate of gastric emptying of 53 preterm infants and 29 term infants was measured. The test feed was either milk (formula milk or expressed breast milk) or Dioralyte (a commercial rehydration solution). When a nasogastric tube was present, the results obtained by APT were validated by comparing the volume of feed estimated to be present with the volume that could be aspirated. All infants completed the investigation without any problems. APT demonstrated a slower rate of emptying of milk feeds than Dioralyte and showed that milk and Dioralyte feeds in preterm babies emptied at a similar rate to feeds in term infants. In validation studies, gastric emptying has been observed in 44 of 47 studies, and this finding was confirmed by aspiration of the nasogastric tube. Applied potential tomography is a safe, noninvasive method for measuring gastric emptying in small infants.

Transport of gastric contents.

A planar array of electrodes has been used to provide a longitudinal section of the stomach. Impedance changes at the gastric frequency of 0.05 Hz can be detected. The changes are mainly located around the periphery of the stomach image, suggesting that they are the result of movement of the stomach wall. The generation of a vector histogram of wall movement gives a non-invasive method which appears to quantify the peristaltic waves which produce transport in the stomach.

Measurement of gastric emptying in infants with pyloric stenosis using applied potential tomography.

Gastric emptying in a group of 49 vomiting infants with infantile hypertrophic pyloric stenosis (IHPS) was investigated using applied potential tomography. Fourteen asymptomatic infants were also studied as a control group. A Dioralyte test feed (25 ml/kg/feed) was used for all the studies. The infants with IHPS were investigated before and at two, four, and seven days after an operation; the other infants were investigated once. The results show that the infants with IHPS have no or little gastric emptying before the operation and gradually return to normal emptying by the seventh day after the operation. A significant difference in gastric emptying was noted between the control infants and the infants with IHPS before and at two and four days after the operation. The applied potential tomography method is suitable for studying gastric emptying in infants, with no morbidity nor complications. It also allows multiple studies to be performed without upset or discomfort.

Electrical impedance tomography: prospects for non-invasive control of deep hyperthermia treatments.

Electrical Impedance Tomography (EIT) is assessed as a means of monitoring deep hyperthermia treatments in both phantom and in vivo studies. EIT measurements during heating of an inhomogeneous leg phantom show good correlation with internal temperatures measured with invasive probes. Measurements whilst altering the temperature of the stomach contents in volunteers demonstrate the capability of EIT for imaging temperature change at depth in the torso. Significant problems remain to be overcome before EIT can be used in the clinic; however, the technique may be an important additional control factor as a complement to invasive monitoring.

Experimental assessment of electrical impedance imaging for hyperthermia monitoring.

Two experimental studies are presented that attempt to assess the use of electrical impedance tomography (EIT) to map thermal changes deep in the body. The first was a joint study between our group in Sheffield and the Daniel den Hoed Cancer Center in Rotterdam, funded by the COMAC-BME Hyperthermia project. Phantom and in vivo experiments were conducted with a deep heating ring-capacitive hyperthermia device; the results highlighted some of the inherent problems (electromagnetic interference, nonuniform sensitivity) that remain to be solved for this application. The second experimental study involved heating the stomachs of volunteers by pumping known quantities of liquid (a salt/glucose solution, conductivity 5 mS) at controlled temperatures (25, 37 and 47 degrees C) in and out of the stomach via a nasogastric tube. Results indicated that the level of thermal change induced by these liquids could be reproducibly measured by impedance imaging. Both studies were a further step in assessing the capabilities of EIT for noninvasive monitoring of deep body hyperthermia. The results are encouraging and indicate the value of continued development of EIT for non-invasive thermometry.

Applied potential tomography. Noninvasive method for measuring gastric emptying of a solid test meal.

Applied potential tomography (APT) is a new noninvasive, nonradioactive method of measuring gastric emptying, which generates profiles of emptying of liquids that are similar to those obtained simultaneously by scintigraphy and dye dilution. This study validates the ability of APT to measure emptying of a solid beefburger test meal from the stomach by comparing the results obtained with those obtained simultaneously by scintigraphy. When acid secretion was inhibited, there was a significant correlation between the two methods for the time taken for half the meal to empty from the stomach and the amount of meal emptied at different time intervals. Furthermore, the profiles of gastric emptying obtained by APT resembled those obtained by scintigraphy in most studies. If acid secretion was not inhibited, there was no correlation between values obtained by the two methods.

Influence of acid-pepsin secretion on gastric emptying of solids in humans: studies with cimetidine.

The commonly accepted model for gastric emptying suggests that the 'antral mill' is responsible for the triturition and subsequent emptying of solid food from the stomach. Little is known about the contribution to solid emptying made by other digestive mechanisms such as acid-pepsin secretion. We have investigated the effect of inhibiting gastic secretion on the rate at which a solid test meal emptied from the stomach. Using a radiolabelled beefburger, we performed paired gammacamera studies on consecutive days in 10 fasted, healthy volunteers to compare gastric emptying of the test meal with and without oral cimetidine (400 mg 1 hour before the test, 800 mg at the start of the meal). Inhibition of acid-pepsin secretion by cimetidine was associated with an appreciable delay in the rate of emptying of the burger from the stomach (T50 cimetidine 187 (16) min (mean (SEM); T50 no cimetidine 146 (15) min; p less than 0.01, paired t test). This delay was related to a change in the slope of the emptying profile and was not associated with a prolonged lag phase. These results may be explained by the relative achlorhydria and reduced pepsin activity induced by cimetidine impairing the breakdown of solid food into particles small enough to leave the stomach.

Effect of incorporating fat into a liquid test meal on the relation between intragastric distribution and gastric emptying in human volunteers.

The relation between gastric emptying and the intragastric distribution of 300 ml radiolabelled beef consommé with and without 60 g margarine was investigated by performing randomised, paired gammacamera studies in seven healthy male volunteers (aged 20-22 years). The low calorie bland meal emptied rapidly from both the proximal and distal stomach after a short lag period (4-6 min), during which 24-50% of the liquid passed into the distal stomach. Addition of margarine to the liquid test meal increased the lag period (median 32 min, range 7-60 min; p less than 0.01) and decreased the slope of emptying (T1/2 lag period 88 min, 49-146 min v 15 min, 10-57 min; p less than 0.01). During the lag period there was an initial filling of the distal stomach, similar to that with the bland liquid, followed by a redistribution of between 19% and 61% (median 46%) of the distal stomach contents back into the proximal stomach. At the onset of emptying, the distal stomach filled (median 30%, range 16-34%) and during this time the proximal stomach emptied twice as fast as the whole stomach (p less than 0.05). Thereafter, the distal stomach capacity remained relatively constant while both the proximal and whole stomach emptied at similar rates. This study shows that the delay in gastric emptying of a liquid that has a high fat content is due in part to a redistribution of distal stomach contents back into the proximal stomach.

Evaluation of applied potential tomography as a new non-invasive gastric secretion test.

Applied potential tomography (APT) is a new, non-invasive technique that can yield sequential images of changes in the resistivity of gastric contents. Studies were performed to investigate the application of APT to measure gastric acid secretion. Experiments in 20 normal volunteers showed that changes in gastric resistivity were closely correlated with changes in the volume (r = 0.80), the acidity (r = 0.83) and the total conductivity of gastric contents (r = 0.87). Studies in 13 patients referred for a pentagastrin test showed that changes in gastric resistivity before pentagastrin were closely correlated with basal acid output measured on a separate occasion (r = 0.85, p less than 0.001), while changes in gastric resistivity after pentagastrin were correlated with maximal acid output (r = 0.58, p less than 0.05). Ingestion of alcohol by six normal subjects decreased gastric resistivity markedly, probably due to alcohol induced gastric acid secretion as it was prevented by cimetidine. Applied potential tomography is a safe non-invasive method of measuring gastric acid secretion. The equipment is simple to use, and the test is comfortable and acceptable to patients.

Comparison of applied potential tomography and impedance epigastrography as methods of measuring gastric emptying.

Two new non-invasive methods of measuring gastric emptying, impedance epigastrography (IE) and applied potential tomography (APT) have been compared. Measurements in vitro showed that there is a good correlation between the square of the radius of a glass rod placed in the centre of a tank and values obtained by IE or APT. However, if the rod is moved anteriorly in the tank IE values increase markedly, whereas APT values are unchanged. Both APT and IE can be used to follow gastric emptying of liquid meals; however, the results obtained using APT are more reproducible and have a better correlation with those obtained simultaneously by scintigraphy. Neither method was able accurately to follow gastric emptying unless gastric acid secretion was inhibited by cimetidine.

Relative contribution of bile and pancreatic juice duodenogastric reflux in gastric ulcer disease and cholelithiasis.

Bile acid concentrations, phospholipase A2 activity and pH in the stomach were measured in the fasting state and for 2 h after a fat-containing test meal in patients with an active gastric ulcer (GU), in patients with gallstones before and after cholecystectomy and in normal subjects. Fasting and peak postprandial bile acid concentrations in the stomach were low in all normal controls. Although high concentrations were found in many patients with GU (P less than 0.01), similar concentrations were found in many patients with radiologically non-functioning gallbladders containing gallstones (NFG) (P less than 0.01) and also after cholecystectomy (AC) (P less than 0.01). Fasting intragastric phospholipase A2 activities were similar, and very high in GU and NFG patients compared with control subjects (P less than 0.01). High values were not found after cholecystectomy. There was no difference in pH profile or in postprandial phospholipase A2 between patient groups. Since patients with cholelithiasis or after cholecystectomy are not known to have an increased incidence of gastric ulceration, the significance of duodenogastric reflux in the aetiology of gastric ulcers must be questioned. If reflux does produce ulcers in GU patients then factors in addition to bile acid are probably involved. However, neither patterns of phospholipase A2 reflux nor pH profiles can explain the absence of gastric ulceration in those patients with gallstones who reflux large quantities of bile acid.

Applied potential tomography. A new noninvasive technique for measuring gastric emptying.

Applied potential tomography is a new, noninvasive technique that yields sequential images of the resistivity of gastric contents after subjects have ingested a liquid or semisolid meal. This study validates the technique as a means of measuring gastric emptying. Experiments in vitro showed an excellent correlation between measurements of resistivity and either the square of the radius of a glass rod or the volume of water in a spherical balloon when both were placed in an oval tank containing saline. Altering the lateral position of the rod in the tank did not alter the values obtained. Images of abdominal resistivity were also directly correlated with the volume of air in a gastric balloon. Profiles of gastric emptying of liquid meals obtained using applied potential tomography were very similar to those obtained using scintigraphy or dye dilution techniques, provided that acid secretion was inhibited by cimetidine. Profiles of emptying of a mashed potato meal using applied potential tomography were also very similar to those obtained by scintigraphy. Measurements of the emptying of a liquid meal from the stomach were reproducible if acid secretion was inhibited by cimetidine. Thus, applied potential tomography is an accurate and reproducible method of measuring gastric emptying of liquids and particulate food. It is inexpensive, well tolerated, easy to use, and ideally suited for multiple studies in patients, even those who are pregnant.

Applied potential tomography: a new non-invasive technique for assessing gastric function.

Applied potential tomography is a new, non-invasive technique that yields sequential images of the resistivity of gastric contents after subjects have ingested a liquid or semi-solid meal. This study validates the technique as a means of measuring gastric emptying. Experiments in vitro showed an excellent correlation between measurements of resistivity and either the square of the radius of a glass rod or the volume of water in a spherical balloon when both were placed in an oval tank containing saline. Altering the lateral position of the rod in the tank did not alter the values obtained. Images of abdominal resistivity were also directly correlated with the volume of air in a gastric balloon. Profiles of gastric emptying of liquid meals obtained using APT were very similar to those obtained using scintigraphy or dye dilution techniques provided that acid secretion was inhibited by cimetidine. Profiles of emptying of a mashed potato meal using APT were also very similar to those obtained by scintigraphy. Measurements of the emptying of a liquid meal from the stomach were reproducible if acid secretion was inhibited by cimetidine. Thus, APT is an accurate and reproducible method of measuring gastric emptying of liquids and particulate food. It is inexpensive, well tolerated, easy to use and ideally suited for multiple studies in patients, even those who are pregnant. A preliminary study is also presented that assesses the technique as a means of measuring gastric acid secretion. Comparison of resistivity changes with measured acid secretion following the injection of pentagastrin shows good correlations. APT might offer a non-invasive alternative to the use of a nasogastric tube and acid collection.

The ability of antacids and cholestyramine to bind bile acids: effect of pH.

Reflux of bile into the stomach may be injurious to the gastric mucosa. The ability of antacids and cholestyramine to bind bile acids is therefore potentially valuable in the treatment of reflux gastritis. The ability of antacids and cholestyramine to remove bile acids from gastric juice, hepatic bile, and solutions of commercially available bile acids was investigated in vitro over a pH range likely to occur in the stomach. The percentage of bile acids removed by antacids decreased with decreasing initial bile acid concentration and usually decreased as the incubation pH was increased from 3.6 to 7.0. Glycine-conjugated bile acids were bound to a greater extent than taurine-conjugated bile acids and dihydroxy to a greater extent than trihydroxy bile acids. Cholestyramine bound 97-100% of all bile acids in solution at pH 3.6 and pH 7.0. The effect of pH on adsorption should therefore be considered when antacids are used to treat gastritis.

The effects of steroids and glucagon on the morphological changes in the duct-ligated pancreas of the rat.

Ligation of the rat pancreatic duct produced degeneration of the exocrine acinar tissue, inflammatory cell infiltration and fibrosis. The injection of methyl prednisolone for 5 days following duct ligation produced a marked reduction in the inflammatory-cell infiltrate whereas the administration of glucagon or a combination of glucagon and methyl prednisolone produced only a mild reduction in acinar degeneration. Administration of the drugs for 5 days after duct ligation and examination of the pancreas after 3 months showed no differences in the degree of cellular infiltration and acinar degeneration between controls and those that had received glucagon or glucagon and methyl prednisolone. However, those rats that had received only methyl prednisolone showed fibrosis, a minimal inflammatory-cell infiltrate and a considerable reduction in exocrine tissue. Mild degranulation of the islets of Langerhans was observed in those rats that received methyl prednisolone, alone or in combination with glucagon, and at 3 months the islets appeared normal. The implications for pancreatic transplantation are discussed.

Neonatal islet cell transplantation in the diabetic rat: effect on the renal complications.

PVG/C rats were made diabetic with streptozotocin and after 1 mth received a single intraperitoneal transplant of isogeneic collagenase digested pancreatic tissue. Renal changes have been studied in transplanted and control diabetic rats using light and electron microscopy and immunological techniques. Following transplantation, renal lesions did not increase in severity and progressive basement membrane thickening was prevented. Ultrastructurally many glomeruli showed a significant reduction in the mesangial matrix and the tubular and mesangial cell changes reverted to normal. Immunofluorescent studies demonstrated a similar reduction in the glomerular deposits of IgG. Possibilities for the treatment of diabetes mellitus in human patients are discussed.

Transplantation of pancreatic islet tissue and the control of diabetes mellitus.

The major advances achieved in recent years in pancreatic islet cell transplantation in animals and man are presented and reviewed. In animals, the biochemical and structural changes present in experimentally induced diabetes mellitus can be reversed in part or whole following transplantation. Fetal or neonatal pancreatic islet cell preparations are probably the most appropriate tissue types to employ in the human situation. The optimal conditions for their maintenance to allow such an approach to the therapy of diabetes are under active investigation.

Neonatal islet cell transplantation in the diabetic rat: effect on hepatic enzyme activity and glucose homeostasis.

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.