Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours.

INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours (n=3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and duodenal ulceration (n=1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.

Management and prevention of adverse effects related to treatment of liver tumours with 90Y microspheres.

BACKGROUND AND AIM: Selective internal radiation therapy with 90Y microspheres (SIR spheres) is increasingly used in the treatment of extensive liver tumours. Careful selection and preparation of patients are necessary to avoid possible adverse effects. We aimed to evaluate the incidence and severity of adverse effects resulting from the administration of SIR spheres during therapy. MATERIALS AND METHODS: Between June 2004 and August 2006, 21 patients (11 women and 10 men; age range 40-75 years; mean, 58 years) with a wide range of extensive liver tumours were treated with SIR spheres. The mean administered dose was 1.87 GBq (range 1.2-2.5 GBq). During the follow-up period of 26 months, all adverse effects were monitored and classified according to the National Cancer Institute criteria. RESULTS: Four patients had adverse effects: one case of cholecystitis followed by fibrosis and portal hypertension, one case of peptic ulceration and two cases of radiation hepatitis. All cases responded to appropriate therapy. CONCLUSION: Proper selection of patients and accurate interpretation of pre-treatment investigations are vital for minimizing adverse effects following therapy with SIR spheres. In our experience, all adverse effects were moderate with no life-threatening consequences.

A new model of human secretory diarrhoea using cholera toxin.

Secretory diarrhoea is a major cause of morbidity and mortality worldwide. However, there is no biologically relevant test system in man for assessing new anti-diarrhoeal therapies prior to clinical trial. We have used highly purified cholera toxin in combination with the triple lumen jejunal perfusion technique to establish a subclinical model of cholera in man. Cholera toxin was administered either by mouth with sodium bicarbonate or directly into a 30 cm 'open' or 'closed' (isolated between two inflated balloons) jejunal segment in healthy adult volunteers. Both oral dosing and direct delivery into an 'open' jejunal segment failed to produce consistent secretion of water and electrolytes. In contrast 15 micrograms or 25 micrograms of cholera toxin elicited secretion of water and sodium 3 h after instillation into the balloon occluded 'closed' jejunal segment (P less than 0.05 vs. controls). The rate of secretion was constant over the maximal period studied (4.5 h) and was similar to that reported in human cholera. None of the subjects experienced troublesome diarrhoea. We believe this model offers a relevant test system for assessing anti-diarrhoeal therapy in man.

Differing effects on gall-bladder motility of lanreotide SR and octreotide LAR for treatment of acromegaly.

BACKGROUND: Octreotide treatment may be associated with gall stone development in up to 50% of patients with acromegaly. Two new sustained-release formulations of somatostatin analogue have been recently developed: lanreotide SR (Somatuline) and octreotide LAR (Sandostatin LAR). The incidence of gall-stone development in patients receiving these drugs has been shown to be less than 20%, but the duration of follow-up has been limited. OBJECTIVE: Prospectively to assess and compare the effects of the two new long-acting somatostatin agonists on gall bladder motility in patients with acromegaly. METHOD AND PATIENTS: Eleven patients with active acromegaly were studied. Three patients had asymptomatic gall stones at the start of the study. Ultrasound scans were performed before commencement of the treatment, and repeated during treatment with lanreotide SR and octreotide LAR. The presence of gall stones, fasting gall bladder volume (FV), residual volume (RV) and maximal percentage gall bladder emptying were measured. RESULTS: One patient developed asymptomatic small gall stones after treatment with octreotide LAR for 4 months. FV and RV were both significantly larger when patients received treatment with lanreotide SR or octreotide LAR compared with pretreatment values (P<0.05 for both). Maximal percentage gall bladder emptying was significantly reduced in patients receiving lanreotide SR or octreotide LAR compared with pretreatment (P<0.01), but was less impaired in patients receiving lanreotide SR than in those receiving octreotide LAR (P<0.01). CONCLUSIONS: Gall bladder motility is impaired in patients receiving either of these new long-acting preparations, and long-term follow-up will be needed to establish the true incidence of gall stones.

Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for a reappraisal?

BACKGROUND: Intravenous cyclosporin is the only new therapy in recent years to have made a significant impact on the management of acute severe ulcerative colitis (UC). It is increasingly recommended for use in patients who prove refractory to the standard regimen of intravenous (i.v.) and rectal hydrocortisone but do not warrant immediate surgery. This practice is based on uncontrolled and controlled studies which suggest a short-term efficacy of 80% and long-term efficacy of 60% in avoiding colectomy. AIM: The aim of this study was to assess the short- and long-term efficacy of i.v. cyclosporin in patients admitted to our hospital with acute severe ulcerative colitis refractory to i.v. steroids, over a 6-year period. METHOD: A retrospective survey of patients admitted to the John Radcliffe Hospital, Oxford, with acute severe UC over a 6-year period (1991-97) was performed. Truelove and Witts criteria for acute severe UC were satisfied by 216 patients. RESULTS: The standard regimen achieved remission in 132 patients (61%). Of the 84 patients who failed to respond, 34 (40%) proceeded directly to colectomy whilst 50 received cyclosporin (4 mg/kg by continuous slow infusion). Remission was achieved by i.v. cyclosporin in 28/50 (56%) patients who were subsequently transferred to oral cyclosporin (5 mg/kg). However, 8/28 (29%) who initially responded later relapsed after discharge from hospital and underwent colectomy. The short-term efficacy of 56% therefore falls to 40% in the longer term (mean follow-up of 19 months). CONCLUSION: This is the largest survey to date of patients with refractory severe UC treated with i.v. cyclosporin. The findings confirm the potential value of i.v. cyclosporin in severe UC but its effectiveness in clinical practice is less dramatic than previously reported.

Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England.

BACKGROUND: Infliximab is used for treatment of Crohn's disease and, following the Active Ulcerative Colitis Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerative colitis (UC). AIM: To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC. METHODS: A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroenterologists from six English centres. RESULTS: Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing response (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4-59), with 21 (55.3%) being in remission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an average of 10 months (range 8-13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurred in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-severe adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media. CONCLUSION: Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC.

Enhancing clinical efficacy of oral rehydration therapy: is low osmolality the key?

Many empirical clinical trials have used complex carbohydrate as substrate in oral rehydration solutions (ORSs) instead of glucose and have shown a number of important clinical benefits. Foremost among these are reduced stool volumes, shorter duration of diarrheal illness, and lower ORS intake. The underlying mechanisms to explain this clinical advantage have not been fully established, but a number of possible factors have been proposed: (1) increased substrate availability, (2) a "kinetic advantage" for glucose absorption by glucose polymer, (3) differential handling of glucose monomer and polymer by the small intestine, (4) low osmolality, (5) a separate effect of peptides and amino acids on solute-linked sodium absorption, (6) an antisecretory moiety in rice, and (6) enhanced mucosal repair and regeneration by luminal nutrients. In this report, we assess the relative contribution of these factors using evidence from laboratory-based studies, mainly in disease-related intestinal perfusion systems in animals and humans, and the relevant clinical studies available to date. We advance the hypothesis that of all the possible mechanisms proposed to underlie the enhanced clinical efficacy of complex carbohydrate ORSs, their hypotonicity plays the dominant role. If confirmed, this concept could guide future development of glucose and complex carbohydrate-based ORSs.

Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea.

Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5-193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1-174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS.

Effective treatment of diabetic diarrhoea with somatostatin analogue, octreotide.

A 22 year old insulin dependent diabetic with high volume, secretory chronic diarrhoea refractory to standard andiarrhoeal drugs was treated with the somatostatin analogue octreotide, 50 micrograms twice daily by subcutaneous injection. She improved markedly with a decrease in mean stool weight from 1170 g/24 h range 440-2900 g) to 440 g/24 h (range 180-800 g) (p < 0.05). Stool frequency also decreased from six (range two to 12) to one (range one to three) bowel movements per day (p < 0.01). Mouth to caecum transit time increased from 45 minutes to > 210 minutes, although total gut transit time was unchanged and remained rapid at nine hours. Thus octreotide can reduce stool volume and frequency in high volume diabetic diarrhoea when conventional antidiarrhoeal agents have failed. Its therapeutic benefit appeared to be predominantly related to a marked increase in mouth to caecum transit time.

Interrelationships between Helicobacter pylori infection, nonsteroidal antiinflammatory drugs and gastroduodenal disease. A prospective study in healthy volunteers.

Helicobacter pylori and nonsteroidal antiinflammatory drugs independently cause gastroduodenal mucosal injury but the relationship between them remains unclear. We have performed a double-blind, parallel-group, placebo-controlled prospective study in 77 healthy volunteers aged 19-35 years who were randomly allocated to indomethacin (N = 15), one of three oxicams (piroxicam, chlortenoxicam, or CHF 1194; N = 36), or placebo (N = 26). Esophagogastroduodenoscopy was performed before and after four weeks of treatment and the mucosal appearances graded. Colonization with H. pylori was established at each endoscopy and gastrointestinal symptoms were assessed by daily diary card. Seven subjects (9%) were positive for H. pylori before treatment (one placebo, one indomethacin, and five an oxicam); their H. pylori status remained unchanged. Two of 70 H. pylori-negative subjects became H. pylori-positive (2.9%), both of whom had received placebo. The endoscopic score deteriorated in 1/6 drug-treated H. pylori-positive subjects and in 0/1 taking placebo. Of the H. pylori-negative subjects whose endoscopic score deteriorated, three (13%) were taking placebo, four (28.6%) indomethacin, and eight (25.8%) an oxicam. Upper gastrointestinal symptoms were reported in eight (30.8%) of the subjects taking placebo (one subject negative for H. pylori became positive), eight (53.3%) indomethacin (one H. pylori-positive), and 10 (27.8%) an oxicam (one H. pylori-positive). There were no statistically significant differences between the H. pylori-negative and H. pylori-positive groups whether on drug or placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Lornoxicam, indomethacin and placebo: comparison of effects on faecal blood loss and upper gastrointestinal endoscopic appearances in healthy men.

Forty-five healthy men aged 21-34 years took part in a double-blind, parallel-group, placebo-controlled study of the effects of 28 days' treatment with lornoxicam 4 mg twice daily or indomethacin 50 mg twice daily on faecal blood loss and the endoscopic appearances of gastric and duodenal mucosa. After an initial endoscopic examination, subjects received, intravenously, on day 0, autologous erythrocytes labelled with 51Cr. Complete daily faecal collections were then made from days 6-12, 20-26 and 34-40. The drug treatments or placebo were given from days 13-41. Faecal blood loss was calculated from 51Cr-specific activity of blood and faeces. Endoscopy was repeated 4-8 hours after the last dose of medication; mucosal appearance was graded on a 5-point scale. Lornoxicam caused no more adverse events than placebo; indomethacin caused more indigestion and central nervous system effects, and one subject in this group was withdrawn from the study. Median total blood losses during the pre-treatment and the second and fourth weeks of treatment were respectively 3.33, 3.95 and 5.71 ml for lornoxicam, 2.87, 7.04 and 7.75 ml for indomethacin, and 4.55, 3.64 and 4.13 ml for placebo. Differences between treatments were not statistically significant (P = 0.081 for second week of treatment, P = 0.383 for fourth week of treatment; Kruskal-Wallis test). The effect of chlortenoxicam on faecal blood loss in this study was thus intermediate between placebo and indomethacin, but within- and between-subject variability was such that the differences were not statistically significant. Endoscopic findings were normal in most subjects before and after all treatments, but indomethacin was associated with a slightly greater deterioration in endoscopic score and was the only treatment associated with Grade 3 appearance (in a single patient) in post-treatment endoscopy.

Glucose polymer in the fluid therapy of acute diarrhoea: studies in a model of rotavirus infection in neonatal rats.

1. Unlike standard glucose-electrolyte oral rehydration solutions, solutions containing polymeric glucose as substrate can significantly reduce stool output, duration of diarrhoea and total oral rehydration solution requirements. However, neither the underlying mechanisms nor the optimal size and concentration of glucose polymer has been defined. 2. We have used a model of rotavirus diarrhoea in neonatal rats to compare the effects on water and solute absorption of varying the concentration of a glucose polymer (mean chain length five glucose residues) in experimental oral rehydration solutions. Three polymer (P) solutions were compared with solutions of identical electrolyte content (mmol/l: sodium, 60; potassium, 20; chloride, 60; citrate, 10) containing equivalent amounts of free glucose (G) as substrate by perfusion of the entire small intestine in situ. The polymer (9, 18, 36 mmol/l; 159, 168, 186 mosmol/kg, respectively) and the monomer (45, 90, 180 mmol/l; 195, 240 320 mosmol/kg) solutions were perfused in normal and rotavirus-infected neonatal rats. 3. In normal intestine polymer solutions promoted greater water absorption [P9, mean 291.4 (SEM 16.4); P18, 331.9 (13.1); P36, 284.3 (11.8) microliters min-1 g-1] than their equivalent monomer solutions [G45, 220.8 (8.4); G90, 240 (21); G180,79.4 (14.5) microliters min-1 g-1; P < 0.02]. In rotavirus-infected intestine, water absorption from all solutions declined, but the fall was much less pronounced from the polymer solutions [P9, 232.8 (6); P18, 277.2 (20.5); P36, 166 (18.2) microliters min-1 G-1] than from their monomeric counterparts [G45, 116.7 (25.5); G90, 68.7 (12.4); G180, 21 (11.6) microliters min-1 g-1; P < 0.005].(ABSTRACT TRUNCATED AT 250 WORDS)

Water and solute absorption from a new hypotonic oral rehydration solution: evaluation in human and animal perfusion models.

Controversy continues regarding the optimal composition of glucose electrolyte oral rehydration solutions for the treatment of acute diarrhoea. Four perfusion models (normal human jejunum, normal rat small intestine, cholera toxin treated secreting rat small intestine and rotavirus infected rat small intestine) have been developed and used to compare the efficacy of a hypotonic oral rehydration solution with standard United Kingdom British National formulary and developing world oral rehydration solutions (WHO). Despite obvious physiological and pathophysiological differences between these models there was general congruence in the water and solute absorption profiles of the different oral rehydration solutions. Hypotonic oral rehydration solution promoted significantly greater water absorption than other oral rehydration solutions in all rat models (p < 0.001) but apparently increased water absorption failed to achieve significance in human jejunum. British National Formulary-oral rehydration solution was unable to reverse net water secretion in both rotavirus and cholera toxin models. Net sodium absorption from hypotonic and WHO-oral rehydration solutions was significantly greater than from the low sodium British National Formulary-oral rehydration solutions (p < 0.001) except in the rotavirus model when absorption was similar to hypotonic-oral rehydration solutions. These findings show that there is agreement in the apparent efficacy of oral rehydration solutions in these animal and human perfusion models, and that improved water absorption with adequate sodium absorption may be achieved by reducing oral rehydration solution osmolality.

Retention of nondeflating balloon in small bowel. Case report and review of the literature.

Intubation of the upper gastrointestinal tract with balloon catheters has a role in the diagnosis, treatment, and research of many gastrointestinal conditions. A potential complication of this procedure, albeit rare, is failure of the balloon to deflate, thereby preventing removal of the intestinal tube. We describe a case where this problem arose and the series of maneuvers that were attempted to resolve it. Attempts at overdistending the balloon, reaching it via endoscopy, and ultrasound localization of the balloon all failed. The tube was successfully removed following CT-guided percutaneous needle puncture of the impacted balloon. The published experience with nondeflating catheter balloons in hollow viscera has been reviewed and the suggested methods for deflation or puncture are discussed.

Diagnostic efficiency of an ultrarapid endoscopy room test for Helicobacter pylori.

There are several reliable methods for detecting Helicobacter pylori but all have as a major disadvantage the time required to yield a definitive result. We have modified the standard urease test so that a positive result is available in one minute. We describe the use of this test in biopsy specimens from the gastric antrum from 220 consecutive patients referred for upper gastrointestinal endoscopy. The performance of the 'one minute test' was compared with a standard urease test, Gram stain, and microbiological culture. Using culture as the 'gold standard' 80 (36%) of the patients were H pylori positive. The one minute test produced no false positives and showed a sensitivity of 89% and specificity of 100%, while the predictive values of a positive and negative test were 100% and 94% respectively. The diagnostic efficiency of the test was 96% compared to 85% for both the Gram stain and direct urease test. All positive results using the one minute test were available within one minute. The test is easy to prepare and costs approximately pounds 0.04. This new modification of the urease test should be superior to the currently available urease tests because a reliable result will be available in almost 90% of infected individuals even before endoscopy is completed.

Jejunal water and electrolyte transport in human cryptosporidiosis.

Cryptosporidiosis may have severe clinical consequences in both immunocompromised and immunocompetent individuals. However, pathophysiological mechanisms that are responsible for diarrhea are poorly understood. We performed jejunal perfusion studies in patients with human immunodeficiency virus-related cryptosporidial diarrhea to measure water and electrolyte transport in vivo. Five patients with human immunodeficiency virus-related cryptosporidiosis and nine healthy volunteers were studied using a triple-lumen steady-state jejunal perfusion technique. Stool volume measurement and distal duodenal biopsy showed that the patients had diarrhea (600-1500 ml/24 hr) and morphological abnormalities of small intestinal mucosa. Net water, sodium, and chloride movement in the jejunum was not significantly different from healthy controls. In these patients with watery diarrhea and morphological mucosal abnormalities, we found no evidence that cryptosporidial diarrhea was due to a secretory state in the proximal small intestine. We conclude that diarrhea may be due to secretion of electrolytes and water efflux more distally or to other abnormalities of gastrointestinal function.

Improving the palatability of oral rehydration solutions has implications for salt and water transport: a study in animal models.

It is believed that improving the taste of oral rehydration solutions (ORSs) might lead to greater patient acceptability. A pilot trial showed that replacing glucose with sucrose and increasing the citrate concentration at the expense of chloride improves palatability. However, the transport implications of such modifications are not known. Three hypotonic experimental ORSs (Suc/cit-ORS, 211 mosmol/kg; Suc/Cl-ORS, 224 mosmol/kg; and Glu-ORS, 224 mosmol/kg) were compared with a standard European ORS (Euro-ORS, 265 mosmol/kg) by in vivo perfusion of entire rat small intestine in normal adult rats and rotavirus-infected neonates. All ORSs were of identical sodium, potassium, chloride, and citrate content except that in the Suc/cit-ORS, chloride was removed in favor of increased citrate, and the chloride concentration in Euro-ORS was higher than in the others. Suc/cit-ORS and Suc/Cl-ORS had glucose partially replaced by sucrose while Glu-ORS and Euro-ORS contained only glucose. In normal small intestine, water absorption was greater from Glu-ORS than Suc/cit-ORS or Euro-ORS, although water absorption was similar from Suc/cit-ORS and Suc/Cl-ORS. In the rotavirus model, Glu-ORS produced more water absorption than Euro-ORS or either sucrose ORS. In both models, Suc/cit-ORS caused sodium and chloride secretion. Glucose absorption was similar from all ORSs. These findings indicate that attempts to improve ORS palatability by adding sucrose or increasing citrate at the expense of chloride would incur a significant penalty in terms of salt and water absorption.

Absorption of a hypotonic oral rehydration solution in a human model of cholera.

The development of oral rehydration solutions (ORSs) has been one of the important therapeutic advances of this century. The optimal formulation, however, of ORSs for both cholera and other infective diarrhoeas is still debated. Part of the problem in developing ORSs has been the lack of adequate test systems for the assessment of new formulations before clinical trial. We have developed a jejunal perfusion, cholera toxin induced, secretory model in humans and have compared net water and solute absorption from a hypotonic ORS (HYPO-ORS: sodium 60 mmol/l, glucose 90 mmol/l, osmolality 240 mOsm/kg) and the British Pharmacopoeia recommended ORS (UK-ORS: sodium 35 mmol/l, glucose 200 mmol/l, osmolality 310 mOsm/kg) in six healthy volunteers. A plasma electrolyte solution (PES) was also perfused in all subjects to confirm a secretory state. Only HYPO-ORS reversed sodium secretion to absorption (p < 0.01). Both ORSs promoted net water absorption but this was greatest with HYPO-ORS (p < 0.01). Glucose and potassium absorption rates were similar for both ORSs whereas chloride absorption mirrored sodium absorption and was greatest from HYPO-ORS (p < 0.05). These results, in a biologically relevant model of secretory diarrhoea, suggest it may be possible to achieve improved rates of rehydration by the use of hypotonic ORS with mid range sodium concentrations.