We used stable-isotope-labelled amino acids to measure the effects of alcoholic liver disease (ALD) on whole-body protein turnover and small-intestinal mucosal protein synthesis. Groups comprising eight patients with ALD and eight healthy control subjects were studied. They received primed, continuous intravenous infusions of L -[1- 13 C]leucine after an overnight fast; after 4 h, duodenal biopsies were obtained via endoscopy. Protein synthesis was calculated from protein labelling relative to intracellular leucine enrichment. Rates of duodenal mucosal protein synthesis were 2.58±0.32%·h -1 (mean±S.D.) in the normal subjects and 2.04±0.18%·h -1 in the ALD patients ( P < 0.003), despite the fact that the protein synthetic capacity ( μ g of RNA/mg of protein) was higher in ALD patients (160±14 compared with 137±6 μ g/mg; P < 0.003). The mucosal cell size (protein/DNA ratio) was lower in ALD patients (9.23±0.91 compared with 13±2.2 μ g/mg; P < 0.002). Although the mean rates of whole-body protein turnover were not significantly different between the two groups (204±18 and 196±44 μ mol leucine·h -1 ·kg -1 for ALD and control subjects respectively), there was, in the ALD patients, an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the severity of ALD; furthermore, there was a direct relationship between the rate of whole-body protein turnover and the severity of ALD. Thus there was an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the rate of whole-body protein turnover in ALD patients, which was not seen in the normal subjects.

Mucosal IgA is important in local immune defence. Helicobacter pylori induces a specific IgA response in antral mucosa, but its immunopathology is unknown. Interleukin-8 (IL-8) has been suggested to be important in H. pylori -induced inflammation. Current information on the relationship between H. pylori -induced IgA and mucosal inflammation is limited. To investigate possible associations between mucosal-specific IgA, the toxinogenicity of H. pylori , mucosal levels of IL-8 and gastric inflammation, 52 endoscoped patients were studied. These comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer dyspepsia. Antral biopsies were taken for histology, H. pylori culture and measurement of mucosal levels of IL-8 (pg/mg) and specific IgA ( A 450 ×1000) by ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H. pylori infection, with a median (interquartile) level of 220 (147, 531) units. There was no significant difference in mucosal levels of the IgA antibodies between patients infected with cytotoxin-positive or cagA -positive strains of H. pylori and those with toxin-negative or cagA -negative strains. The IgA levels in those patients with severe neutrophil infiltration were lower than in those with mild or moderate infiltration ( P < 0.05). There was a weak inverse correlation between antral mucosal IgA and IL-8 in infected patients ( r = -0.36; P = 0.04). H. pylori infection induced a significant local mucosal IgA response in most infected patients. The level of IgA antibodies does not appear to be correlated with the toxinogenicity of H. pylori . However, patients with severe active inflammation appear to have decreased levels of IgA. An inverse correlation between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation compromises the mucosal IgA defence and renders the mucosa susceptible to further damage.

1. Helicobacter pylori infection is characterized by an infiltration of neutrophils in the gastric mucosa. Neutrophil activation is an important source of reactive oxygen radicals, which cause tissue damage. Studies have shown that in Helicobacter pylori -infected patients there is increased mucosal production of interleukin 8. However, the role of interleukin 8 in the Helicobacter pylori -related inflammatory process and its relationship with reactive oxygen radicals remains to be clarified. The aims of this study were to investigate if there is any association between antral mucosal levels of interleukin 8 and reactive oxygen radicals and their relationship to gastric antral inflammation. 2. Fifty-two patients referred for endoscopy were recruited into the study. Gastric antral biopsies were taken for histology, culture and measurement of interleukin 8 and chemiluminescence (measuring reactive oxygen radicals). Interleukin 8 was measured by ELISA and the result expressed as pg/mg biopsy. Luminol-enhanced chemiluminescence was measured as mV min −1 mg −1 biopsy. Antral inflammation was assessed by a pathologist in a blinded fashion. 3. Antral mucosal levels of interleukin 8 and reactive oxygen radicals were significantly higher in Helicobacter pylori -colonized mucosa than in Helicobacter pylori -negative mucosa. After the eradication of Helicobacter pylori in patients with duodenal ulcer the median values (ranges) of interleukin 8 and reactive oxygen radicals fell from 1.21 (0.10-2.40) to 0.65 (0.00-1.60) and from 110.0 (10.0-959.0) to 14.5 (0.0-85.0) respectively. There was a positive correlation between interleukin 8 concentration and chemiluminescence response in the antral mucosa ( r = 0.72). A higher interleukin 8 concentration was associated with greater neutrophil infiltration ( r = 0.72) and mononuclear cell infiltration ( r = 0.55); the magnitude of the chemiluminescence response was also positively associated with neutrophil ( r = 0.77) and mononuclear cell infiltration ( r = 0.59). 4. Interleukin 8 concentration is associated with an infiltration of neutrophils and mononuclear cells and is correlated with the production of reactive oxygen radicals in antral gastric mucosa infected with Helicobacter pylori. These findings suggest that interleukin 8 may be important in attracting and activating phagocytes to release reactive oxygen radicals, thereby causing mucosal damage.

1. 65 Cu/ 63 Cu stable-isotope ratios have been measured in blood serum after oral administration of the stable isotope 65 Cu. The incorporation of the isotope into the plasma protein pool was followed at various times for up to 3 days. The resulting patterns of enrichment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearance to those found by others using copper radioactive isotopes. After an initially high enrichment at 2h after dosage, the Wilson's disease cases, in contrast to the control subjects, did not show a secondary rise in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's disease heterozygotes had variable degrees of impairment of isotope incorporation, not always distinguished from those of control subjects. 2. The stability of the isotope also permits the copper tracer to be followed for a longer period. Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14–26 days). Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper from the plasma pool (median 43 days, 95% confidence interval 32–77 days). 3. The incorporation of 65 Cu in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.

1. Rats were fed with the elemental diet Vivonex for 1 or 3 months and their jejunal histology was compared with that of an equal number of rats fed on a normal diet. 2. After 1 month of Vivonex feeding a significant reduction in the ratio of crypt height: villus height (CH: VH) was found in the Vivonex-fed rats ( n = 4) compared with the control rats ( n = 4) ( P < 0.05). 3. After 3 months the CH:VH ratio was also reduced in the Vivonex-fed rats ( n = 18) compared with control rats ( n = 18) ( P < 0.002). Villus height was significantly increased ( P < 0.002) and crypt height decreased ( P < 0.05). 4. Jejunal protein content, alkaline phosphatase and disaccharidase activity were also determined in 12 control and 12 Vivonex-fed rats from the 3 months study. 5. Alkaline phosphatase activity was increased from a control value of 201 ± 8 to 243 ± 15 munits/cm in the Vivonex-fed rats ( n = 12) ( P < 0.05) but no significant changes in lactase, sucrase or maltase activities were found. 6. The observed decrease in the CH:VH ratio suggested an improved survival of the mature enterocyte population during elemental diet feeding.

1. Pteroylmonoglutamic acid (PteGlu) absorption has been measured by using the technique of small-intestinal perfusion with tritiated PteGlu in normal subjects and in patients with coeliac disease. 2. At similar intrajejunal pH, patients with untreated coeliac disease have significantly less PteGlu than normal subjects and patients with treated coeliac disease. 3. The ‘resting’ pH in the jejunum did not differ markedly between normal subjects and patients with coeliac disease. 4. Increasing pH decreased PteGlu absorption in patients with coeliac disease and in normal subjects. 5. These findings suggest that PteGlu malabsorption in coeliac disease is not due to abnormally high pH in the jejunum.

1. Frusemide, in a dose of 120 nmol (40 mg) administered intravenously, significantly reduced the absorption of water and electrolytes from the human jejunum, a double-lumen perfusion system with proximal occluding balloons being used. Net secretion of water and electrolytes occurred in some subjects. 2. No significant change in water and electrolyte absorption was observed with 60 nmol (20 mg) of frusemide. 3. These findings may explain the diarrhoea which may be induced by frusemide in some patients.

1. The effect of conjugated and unconjugated bile acids in various concentrations on the absorption of water, sodium and chloride in the proximal jejunum in man has been studied using a perfusion system incorporating a proximal occluding balloon. 2. Unconjugated cholic acid and its glycine and taurine conjugates had no significant effect on water and electrolyte absorption. Unconjugated deoxycholic acid significantly inhibited water and electrolyte absorption at 3 m m concentration and net secretion occurred at concentrations of 5 m m , 7 m m and 10 m m . Similar results were found when taurodeoxycholic and glycodeoxycholic acid solutions were used. A greater effect was noted when higher concentrations of bile acids were used. 3. Unconjugated chenodeoxycholic acid caused net water and electrolyte secretion at 3 m m concentration and this effect became more marked with higher bile acid concentrations. Inhibition of absorption also occurred with taurochenodeoxycholic acid in a concentration of 3 m m and net secretion occurred at a concentration of 10 m m . 4. The results show that dihydroxy bile acids, conjugated or unconjugated, inhibit water and electrolyte absorption in the proximal jejunum in low concentration and cause net secretion in high concentration.

1. The transport of water, sodium and chloride across the jejunal mucosa was studied in fourteen patients with untreated adult coeliac disease by using a triple-lumen tube perfusion system. The results were compared with those obtained by identical methods in fifteen normal control volunteers. 2. Evidence was obtained suggesting that not only was absorption impaired in the adult coeliac disease group, but that in some patients there was secretion of water and electrolytes. 3. No significant improvement had occurred in six patients 2–4 months after withdrawal of gluten, nor in one patient after 8 months, in spite of histological improvement and clinical remission.