D. B. A. Silk

The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man.

The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions.

British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome.

### 1.1 PURPOSE OF GUIDELINES These guidelines were compiled by a multidisciplinary group at the request of the chairman of the British Society of Gastroenterologys Clinical Services Committee. The prime targets for these guidelines are consultant gastroenterologists, specialist registrars in training, and general practitioners. The purpose is to identify and inform the key decisions to be made in the management of patients thought to have functional diseases of the gut. As these comprise the commonest conditions seen by gastroenterologists, the working party represented a wide spectrum of practitioners in gastroenterology, including gastroenterologists from both district general hospitals and tertiary referral centres, as well as primary care practitioners, psychiatrists, psychologists, and dietitians. ### 1.2 SPECIFIC DIFFICULTIES Compared with producing guidelines for the management of well defined diseases such as peptic ulcer where there is a clear disease entity, an obvious end point, and highly effective treatments, drawing up guidelines for functional gastroenterological disorders has had many difficulties. Clinical trials have been difficult to design as the conditions being treated are highly variable with many possible end points, and most therapies only marginally more effective than placebo. Early trials were difficult to evaluate because of inadequate patient definition so that many questions have yet to be addressed with good quality randomised controlled clinical trials. Most of our recommendations are therefore supported by clinical experience rather than randomised controlled clinical trials. Finally, because functional diseases, although potentially debilitating, are non-fatal there are few uniformly available audit measures such as mortality or survival times by which to judge or compare different treatment regimens in different areas of clinical practice. ### 1.3 PROCESS OF GUIDELINE CREATION The co-chairmen were approached by the chairman of the British Society of Gastroenterologys Clinical Services Committee and invited to form a working party. Members were chosen to be broadly representative of clinicians and academics with a long term interest and publication record in the …

Effect of catheter tunnelling and a nutrition nurse on catheter sepsis during parenteral nutrition: a controlled trial

In a three-year controlled trial of subcutaneous catheter tunnelling as a method of reducing total parenteral nutrition (TPN) catheter sepsis 99 silicone catheters (52 tunnelled, 47 untunnelled) were inserted into the subclavian (94%) or jugular (6%) veins under aseptic conditions. The influence of a nutrition nurse, who joined the nutrition team after 18 months, on catheter sepsis rate was also documented. Catheter sepsis was confirmed in 13 of 47 (28%) untunnelled catheters and only 6 of 52 (11.5%) tunnelled catheters (p less than 0.05). A nutrition nurse reduced sepsis rate from 33% (tunnelled 6, untunnelled 11) to 4% (0 tunnelled; 2 untunnelled) (p less than 0.001). There was no significant difference between tunnelled and untunnelled catheters in sepsis rates after the arrival of the nutrition nurse. Although 85% patients had concurrent internal sepsis, the pathogens implicated in catheter sepsis came from superficial sites in 16 of 19 cases (p less than 0.01). Rigorous aseptic nursing care is thus the most significant factor in the reduction of TPN catheter sepsis, but tunnelling can reduce sepsis rate when nursing care is suboptimum.

Reversal by short-chain fatty acids of colonic fluid secretion induced by enteral feeding

Diarrhoea complicates enteral feeding in up to 25% of patients. In-vivo perfusion studies in healthy subjects have shown secretion of salt and water in the ascending colon in response to enteral feeding. This study investigated the effect of short-chain fatty acids (SCFA) on this secretory response. Six healthy volunteers underwent segmental in-vivo colonic perfusion. First, baseline fasting colonic water and electrolyte movement was established, then a standard polymeric enteral diet was infused into the stomach while the colon was perfused with either a control electrolyte solution or a test solution containing SCFA. The electrolyte concentrations and osmolality of the two perfusates were identical. In the fasting state water was absorbed throughout the colon. During the control infusion there was significant (p < 0.05) secretion of water in the ascending colon (median rate 1.0 mL per min [95% CI 2.8 mL per min secretion to 0.8 mL per min absorption]). During the SCFA infusion the secretion was significantly reversed (p < 0.05) and there was net absorption (1.6 [0.8-3.7] mL per min). In the distal colon water absorption was significantly greater during the control infusion than during fasting (3.7 [2.5-4.6] vs 1.3 [0.3-2.2] mL per min); during the test infusion this absorption persisted (2.8 [1.3-3.6] mL per min). Movement of sodium, chloride, and potassium ions was similar to that of water in all stages of the study. Bicarbonate movement did not significantly change at any stage. Infusion of SCFA directly into the caecum reverses the fluid secretion seen in the ascending colon during enteral feeding. This finding could have implications for the management of diarrhoea related to enteral feeding.

Influence of protein composition and hydrolysis method on intestinal absorption of protein in man.

An intestinal perfusion technique has been used in normal human subjects to investigate the influence that starter protein composition and hydrolysis procedure have on absorption of amino acid residues from partial enzymic hydrolysates of whole protein. Five starter proteins were studied. Three (egg albumin, casein/soy/lactalbumin, and lactalbumin) were hydrolysed by papain, a second lactalbumin starter protein, and a meat/soy/lactalbumin blend were hydrolysed by a porcine pancreatic enzyme system. Irrespective of starter protein composition or hydrolysis method used, four amino acid residues (threonine, glutamic acid, phenylalanine, and histidine) were absorbed significantly faster from all hydrolysates compared with absorption from their equivalent free amino acid mixtures. In contrast, both starter protein composition and hydrolysis method influenced absorption characteristics of up to nine other amino acid residues.

Use of ethanol-induced tumor necrosis to palliate dysphagia in patients with esophagogastric cancer

Eleven patients with dysphagia caused by inoperable, unresectable, or recurrent esophagogastric cancer were treated by endoscopic injection of ethanol (with or without per-oral dilation) to induce tumor necrosis. Prior to treatment, patients had a mean dysphagia grade of 3. After one treatment, dysphagia grade had improved to a mean of 1.5. An optimum dysphagia grade (mean, 0.9) was achieved after a mean of 1.6 injection treatments. Treatments were repeated as symptoms recurred, with a mean period between repeat treatments of 32 days (median, 26). There were no complications associated with ethanol-induced tumor necrosis (ETN). Mean patient survival was 140 days (median, 109). These results suggest that ETN has considerable potential for palliation of malignant dysphagia in selected patients.

Jejunal water and electrolyte absorption from two proprietary enteral feeds in man: importance of sodium content.

Jejunostomy losses of Na+ and water during enteral nutrition after massive intestinal resection may be severe. We have attempted to analyse this practical problem by using an in vivo perfusion technique in healthy volunteers to study Na+, water and nutrient absorption from a short (25 cm) segment of jejunum during perfusion of an isotonic solution of the elemental diet Vivonex. Further solutions made from the amino acid and carbohydrate components of Vivonex were also perfused in part I of the study in order to determine the causes of the marked Na+ and water secretion seen during Vivonex perfusion. Low initial Na+ concentration was found to be the major determinant of net Na+ secretion, initial Na+ concentration correlating significantly with Na+ absorption (r = 0.95, n = 7 p less than 0.001). Water absorption correlated with net absorption of NaCl (r = 0.82, n = 7 p less than 0.01). There was, however, a better correlation with total absorption of NaCl plus amino acids (r = 0.99, n = 7, p less than 0.01). In part II of the study separate isotonic solutions of NaCl, glucose, and the polymeric diet, Ensure were also studied. Net sodium secretion occurred during glucose and Ensure perfusion, as predicted from their low Na+ concentration. Owing to rapid sucrose absorption from Ensure there was substantial luminal disappearance of osmotically active particles and hence marked water absorption, which was accurately predicted using the regression equation for water absorption derived in part I, substituting sucrose absorption for amino acid absorption. We conclude that the marked Na+ and water secretion observed during Vivonex perfusion is not a unique property of this amino acid based diet but is due to its low Na+ content.

Colonic secretory effect in response to enteral feeding in humans.

Diarrhoea complicating enteral feeding is a common clinical problem affecting up to 25% of patients. Its pathogenesis remains unknown. A new technique of human in vivo segmental colonic perfusion was used to investigate colonic water and electrolyte movement in response to enteral feeding. Four groups of studies were performed in which low and high load polymeric enteral diet infusions were undertaken, either intragastrically or intraduodenally (n = 6 each group). Net absorption of sodium, chloride, and water occurred during fasting throughout the colon in all groups. There was a significant net secretion of sodium, chloride, and water in the ascending colon during low load (sodium: -42 mmol/h; 95% confidence limits -52 to -19, Chloride: -18 mmol/h; -50 to +16, water: -174 ml/h; -348 to -30) and high load (sodium: -24 mmol/h; -60 to +8, chloride: -18 mmol/h; -31 to +16, water: -120 ml/h; -246 to +6) gastric feeding, and during high load duodenal feeding (sodium: -12 mmol/h; -22 to -6, chloride; -6 mmol/h; -16 to +3, water: -72 ml/h; -144 to -6). Net secretion persisted in the distal colon only during high load gastric feeding. In the other three groups there was a net absorption in the distal colon. This study identified a significant colonic secretory response to enteral feeding, which is related to the site and load of the diet infusion. This response may play an important part in the pathogenesis of enteral feeding related diarrhoea.

Delayed mouth-caecum transit of a lactulose labelled liquid test meal in patients with steatorrhoea caused by partially treated coeliac disease.

Mouth-caecum transit time (M-CTT) of a lactulose labelled liquid test meal has been measured in 27 coeliac patients and 10 healthy controls using the breath hydrogen technique. Although all patients were urged to maintain a gluten free diet, not all did, and there was, therefore, a wide range in the severity of fat malabsorption within the patient group. Gastric emptying of a 113Indium DTPA-labelled liquid test meal was also assessed in separate studies on six healthy controls and 11 of the coeliac patients. Fasting breath hydrogen concentrations and the response to lactulose, as assessed both by the rate of rise, and the peak breath hydrogen concentration reached, showed no difference between coeliacs and controls, regardless of the presence or absence of steatorrhoea. Mouth-caecum transit time in the 16 coeliac patients with steatorrhea (faecal fat greater than 7 g/24 h) was, however, significantly prolonged being 158 +/- 18 minutes (mean +/- SEM), compared with 70 +/- 9 minutes for the controls (p less than 0.02), and 83 +/- 15 minutes for the 11 coeliacs without steatorrhoea (p less than 0.002). Mouth-caecum transit time in the coeliac patients was linearly related to the 24 hour faecal fat excretion, r = 0.55, n = 27, p less than 0.01. Slow mouth-caecum transit in the coeliacs with steatorrhoea was not caused by delayed gastric emptying as the t1/2 for coeliacs with steatorrhoea was within the normal range. Coeliacs with delayed mouth-caecum transit had impaired insulin release but the postprandial profiles of the other peptides measured (cholecystokinin, GIP, secretin, motilin, neurotensin, enteroglucagon, and peptide YY) were all within the normal range in this group of partially treated coeliac patients.