(Gut 1998;42:42-46)

Because cytomegalovirus (CMV) is an important opportunistic infection after liver transplant, we conducted a prospective study to see if the same applied to human herpesviruses (HHV)-6 and -7. We used polymerase chain reaction (PCR) methods optimised to detect active, not latent, infection and studied patients not receiving antiviral prophylaxis for CMV. Post-transplant, 536 blood samples were tested by PCR (median 7; range 4-50). Active infection with CMV was detected in 28/60 (47%), HHV-6 in 19/60 (32%), and HHV-7 in 29/60 (48%) of patients. The PCR-positive samples were tested by quantitative-competitive PCR to measure the virus load of each betaherpesvirus. The median peak virus load for CMV was significantly greater than that for HHV-6 or HHV-7. Detailed clinicopathological analyses for the whole population showed that CMV and HHV-6 were each significantly associated with biopsy-proven graft rejection. Individual case histories suggested that HHV-6 and HHV-7 may be the cause of some episodes of hepatitis and pyrexia. It is concluded that HHV-6 is a previously unrecognized contributor to the morbidity of liver transplantation, that HHV-7 may also be important and that both viruses should be included in the differential diagnosis of graft dysfunction.

Background-L-Arginine has been shown to induce fluid secretion in human jejunum. Nitric oxide, a derivative of L-arginne is thought to have an important role as an intestinal secretagogue. Aim-To determine the effect of Larginine and the nitric oxide synthase inhibitor, nitro L-arginine methyl ester (L-NAME), on fluid and electrolyte movement in rat jejunum. Methods-A 25 cm segment ofrat jejunum was perfused in situ with iso-osmotic solutions containing either (1) saline, (2) D-arginine 20, (3) L-arginine 20, (4) L-NAME 0-1, 1, or 20 mmol/l, or (5) a combination of L-arginine 20 and L-NAME 0.1, 1, or 20 mmol/l. In further groups the effect of a subcutaneous injection of L-NAME 100 mglkg was examined in rats pretreated with either Dor L-arginine 500 mg/kg. Results-L-Arginine, unlike D-arginine, induced fluid secretion despite being better absorbed (mean -7 3 v 17-0 ,l/min/ g; p<001). L-NAME at 0.1 mmol/l had no effect on basal fluid movement but reversed L-arginine induced secretion (7.8; p<005). L-NAME at 1 and 20 mmol/l induced fluid secretion (-15.4 and -28-4, respectively), which was enhanced by the addition of L-argilnlne (-30.0 and -41-0, respectively; both p<005). A subcutaneous injection of L-NAME resulted in marked fluid secretion (-39.9) and histological evidence of intestinal ischaemia. These changes were attenuated or reversed by pretreatment with subcutaneous L-but not D-arginine. Conclusions-L-Arginine induces intestinal fluid secretion through production of nitric oxide. There is a delicate balance between the effect of nitric oxide as a secretagogue and its effect on maintaining blood flow and thus preventing intestinal ischaemia. (Gut 1996; 39: 539-544) Keywords: arginine, nitric oxide, L-NAME, intestinal transport, bowel ischaemia.Actively transported sugars and most amino acids enhance small intestinal absorption of water and electrolytes.l`However, L-arginine (L-Arg), unlike other amino acids, has been shown by us and others to induce water secretion when perfused in human jejunum.' 5 A satisfactory explanation has never been put forward to explain this phenomenon, though it has been suggested that L-Arg induced secretion by a local effect that could be inhibited by the calmodulin antagonist chlorpromazine.5Over the past few years L-Arg has been found to be the precursor of the free radical nitric oxide (NO), which has an important role as a mediator of neural, cardiovascular, and gastrointestinal function.`8 Nitric oxide is derived from the guanidino terminal of L-Arg by the action of the stereospecific enzyme nitric oxide synthase (NOS) which, in the gut, is present in the myenteric plexus9 10 and submucosal arterioles and venules."' 12 In addition, it has been shown that NO could be produced by enterocytes through both the constitutive and the inducible NOS." In vitro studies have unveiled a role for NO as a secretagogue in the ileum14 '5 and colon, [16][17][18] and in vivo studies have suggested a possible role for NO in the laxative action of castor oil,"9 magnesium sulphat...

Background:5‐hydroxytryptamine type 3 receptor antagonists have been shown to reduce fluid and electrolyte secretion or promote absorption in experimental models of small intestinal secretion. The aim of this study was to compare the effects of a single dose (4 mg) of the 5‐hydroxytryptamine type 3 receptor antagonist alosetron and placebo on jejunal fluid and electrolyte movement in humans under basal conditions (n=7) and following cholera toxin‐induced secretion (n=5) in a randomized, double‐blind, crossover design over two separate study periods.Methods:One hour after oral alosetron or placebo, jejunal intubation was performed. A 30 cm segment of jejunum, isolated by two occluding balloons, was exposed to 15 μg of purified cholera toxin for 2 h prior to triple lumen perfusion with a plasma electrolyte solution containing []> 14C]‐polyethylene glycol as a non‐absorbable volume marker. In the basal study, intestinal perfusion was performed without exposure to cholera toxin. Collection and analysis of the effluent from the jejunal segment allowed fluid and electrolyte movement to be calculated.Results:Alosetron treatment increased basal jejunal fluid absorption (median 5.1 mL/cm/h [interquartile range 4.2 to 7.1] compared with placebo (3.8 [3.6 to 4.3] P=0.028, two sided Wilcoxon matched pairs signed rank test)). However, following establishment of a secretory state by cholera toxin, alosetron failed to significantly promote absorption or reduce secretion (0.3 [−1.2 to 1.2] compared to placebo (−4.3 [−7.7 to −1.3] P=0.14)). Adverse events during the study, which included anorexia, nausea, dizziness and loose bowel movements, were not considered to be clinically important. There were no clinically significant changes in laboratory parameters.Conclusion:The 5‐hydroxytyptamine type 3 receptor antagonist, alosetron increased basal fluid absorption in normal human small intestine but failed to have a beneficial effect in cholera toxin‐induced secretion.