In septic shock, 'hypocortisolaemia' is not uncommon and does not predict a high mortality; adrenocortical hypo-responsiveness may be associated with poor outcome.

Substantial amounts of phenols are produced in the human colon by bacterial fermentation of protein. In the colonic mucosa of animals, phenols are inactivated predominantly by conjugation with sulphate. The purpose of this study was to confirm sulphation of phenols by isolated colonocytes from man and to evaluate mucosal sulphation in inflammatory bowel disease using the phenol, paracetamol, in rectal dialysis bags. The incubation of paracetamol with colonocytes isolated from resected colon specimens (n=7) yielded a mean (SE) value of 7 0 (0.9) ,tmol/g dry weight of paracetamol sulphate after 60 minutes but virtually undetectable values of paracetamol glucuronide. Paracetamol sulphate was detected in rectal dialysates from all control subjects, with a mean (SE) value of 4-2 (0.8) nmol/hour. Sulphation was significantly impaired (p<0-01) in 19 patients with active ulcerative colitis (0.6 (0 2) nmol/hour) and in 17 patients with ulcerative colitis in remission (1-1 (0-4) nmol/hour). Sulphation in eight patients with Crohn's colitis (4.3 (2.1) nmol/hour) was similar to that in control subjects. Impairment of the capacity of the mucosa to sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic burden on colonic epithelial cells, which are continuously exposed to endogenous phenols from the colonic lumen. The fermentation of protein by bacteria from the human colon generates considerable amounts of phenols and phenylated short chain fatty acids such as phenyl propionate and hydroxyphenyl acetate. ' Some of these volatile phenols may have adverse effects on colonocytes and harmful effects elsewhere in the body.23 In the intact human colon, the concentration of phenols increases progressively from the caecum to the left colon, with maximal concentrations (2 0-3 0 mmol/kg) in the rectosigmoid region.45 Studies in vitro suggest that higher concentrations could be reached under optimal fermentation conditions.6 Although the functional effect of these endogenous phenols remains unclear, the use of an exogenous phenol (paracetamol) has been associated with the onset of exacerbations of ulcerative colitis.7In experimental animals, the inactivation of phenols by the colonic mucosa is mainly achieved by conjugation with sulphate.89 This also seems likely in humans,'0 although studies using colonocytes from resected colon specimens have not been undertaken. The purpose of this study was to examine the sulphation of paracetamol by human colonocytes and to evaluate the sulphation of phenols in inflammatory bowel disease using paracetamol in rectal dialysis bags. Patients and methods STUDIES WITH HUMAN COLONOCYTESColonocytes were isolated from the unaffected mucosa (at least 10 cm from the tumour) of seven colon specimens resected for colonic cancer. Five specimens were from the descending colon and two from the ascending colon. Colonocytes were prepared by mechanical dissociation after incubation in a divalent calcium free solution containing ethylenediaminetetra acetic acid (EDTA

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SUMMARY Conjugation of phenol by the colonic mucosa was assessed in vivo using dialysis tubing containing 15 ml of 1 mmol/l acetaminophen (paracetamol) and 10 mmol/l butyrate. These were allowed to equilibrate in the rectum for one hour. The glucuronidated and sulphated conjugates of acetaminophen were measured by high pressure liquid chromatography and bicarbonate concentrations by gas analysis. In 21 subjects without colonic disease sulphate conjugation was observed in all cases, with a mean (SE) of 3-86 (0-66) nmol/hour, while glucuronide conjugation was found in seven of 21 cases. Mean (SE) bicarbonate output of42 9 (3 9) ,mol/hour (n = 21) indicated healthy colonic mucosal metabolism and phenolic sulphation in dialysate and agreed with published sulphation rates obtained with cultured cells of colonic epithelium.Acetaminophen sulphation suggests that the colonic mucosa has an important role in the conjugation of phenols, and the method reported here would be useful in assessing the detoxification capacity of the colonic mucosa in diseases of the rectal mucosa.Relatively little attention has been directed towards the capacity of the colonic mucosa to inactivate dietary or bacterial phenols. Self

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We report another patient with a circulating alkaline phosphatase/immunoglobulin complex in his blood, and describe a simple method of demonstrating such complexes. On electrophoresis on cellulose acetate, the complex was relatively slow moving and there was no activity in the normal bone/liver isoenzyme region. When the serum was treated with trypsin, the slow band disappeared and the normal pattern was restored.

Circadian rhythms for cortisol, 6-sulphatoxy melatonin and core body temperature were compared in control subjects and patients with functional abdominal pain. There were 20 patients with biliary pain after cholecystectomy, ten with biliary pain without cholecystectomy and 14 with irritable bowel syndrome. Rhythms were determined by urine collections at intervals of 4 h for 48 h and by overnight monitoring of core body temperature using the Vitalog system. Data were fitted to a sine curve to yield the time of maximal urinary excretion/lowest temperature and the amplitude of each rhythm. Urinary excretion of free cortisol was similar in patients and control subjects. For urinary 6-sulphatoxy melatonin, the timing (phase) of rhythms was similar in patients and controls but those with pain had a lower urinary excretion of 6-sulphatoxy melatonin (p less than 0.05) and a rhythm of lower amplitude (p less than 0.02). The amplitude of the temperature rhythm was also lower in patients with biliary pain with and without prior cholecystectomy (p less than 0.05). Functional abdominal pain is associated with 6-sulphatoxy melatonin and temperature rhythms of low amplitude, presumably because of suppression of circadian oscillators.

In 150 patients with undefined biliary pain after cholecystectomy, responses to morphine were compared with responses to morphine combined with neostigmine. The relationship between rises in plasma levels of aspartate aminotransferase (AST) after morphine or morphine-neostigmine and sphincter of Oddi motility as assessed by endoscopic manometry was also examined. When compared with morphine-neostigmine, patients given morphine alone showed a similar frequency (30% versus 33%) of increases in plasma levels of AST (greater than twice the upper limit of the reference range) but had less abdominal pain and a lower frequency of similar increases in plasma levels of amylase (4% versus 25%). Of 92 patients who consented to endoscopic manometry of the sphincter of Oddi, satisfactory manometric records were obtained in 84, 31 with and 53 without increases in AST after morphine or morphine-neostigmine. Those showing rises in AST had a higher frequency of abnormal manometric records (81% versus 57%, P = 0.025), higher basal pressures in the sphincter of Oddi (P = 0.0001) and higher pressures within ducts (P = 0.02). There was a significant correlation between sphincter basal pressures and intraduct pressures (r = 0.51, P less than 0.001). Rises in plasma AST after morphine are similar to those after morphine-neostigmine and are influenced by, or linked to, factors which determine sphincter basal pressures and intraduct pressures.