Simulating human sleep spindle MEG and EEG from ion channel and circuit level dynamics.

BACKGROUND: Although they form a unitary phenomenon, the relationship between extracranial M/EEG and transmembrane ion flows is understood only as a general principle rather than as a well-articulated and quantified causal chain. METHOD: We present an integrated multiscale model, consisting of a neural simulation of thalamus and cortex during stage N2 sleep and a biophysical model projecting cortical current densities to M/EEG fields. Sleep spindles were generated through the interactions of local and distant network connections and intrinsic currents within thalamocortical circuits. 32,652 cortical neurons were mapped onto the cortical surface reconstructed from subjects' MRI, interconnected based on geodesic distances, and scaled-up to current dipole densities based on laminar recordings in humans. MRIs were used to generate a quasi-static electromagnetic model enabling simulated cortical activity to be projected to the M/EEG sensors. RESULTS: The simulated M/EEG spindles were similar in amplitude and topography to empirical examples in the same subjects. Simulated spindles with more core-dominant activity were more MEG weighted. COMPARISON WITH EXISTING METHODS: Previous models lacked either spindle-generating thalamic neural dynamics or whole head biophysical modeling; the framework presented here is the first to simultaneously capture these disparate scales. CONCLUSIONS: This multiscale model provides a platform for the principled quantitative integration of existing information relevant to the generation of sleep spindles, and allows the implications of future findings to be explored. It provides a proof of principle for a methodological framework allowing large-scale integrative brain oscillations to be understood in terms of their underlying channels and synapses.

Milk replacers supplemented with either L-arginine or L-carnitine potentially improve muscle maturation of early reared low birth weight piglets from hyperprolific sows.

As a result of the selection for genotypes with greater sow prolificacy, litter size increased and, concomitantly, average litter birth weight and early postnatal survival rates of low birth weight (L-BtW) offspring decreased. This study compared the impact of l-carnitine (CAR) and l-arginine (ARG) supplemented with a milk replacer and fed to L-BtW piglets born from large litters from days 7 to 28 of age on growth performance, carcass composition, organ and Semitendinosus muscle (STM) development. A total of 30 female and castrated Swiss Large White piglets weaned at 7 days of age were assigned to three milk replacer diets containing either no supplement (CON), CAR (0.40 g/piglet per day) or ARG (1.08 g/kg BW per day). Piglets were kept in pairs in rescue decks (0.54 m2). They were weighed daily and daily allowance of both, feed and ARG, was adjusted accordingly. Thus, feed allowance depended on growth. Each day, the milk replacer was prepared with water (1:4). Feed (allowance: 60 g dry matter/kg BW per day) was offered daily in six equal rations. Feed intake and feed efficiency was assessed for the pairs and apparent total tract-energy and -protein digestibility was determined from days 21 to 28 of age. On day 28, piglets were euthanized, blood samples were collected and the whole STM and organs were weighed. In STM, the size and metabolic properties of myofibers were determined. No difference in growth performance was found between dietary treatments, but piglets from the CAR group tended (P<0.10) to grow faster during the 1st experimental week and consume more feed from days 14 to 21 as compared with piglets of the CON group. A setback in growth in the last week in the CAR group coincided with the lower (P<0.05) energy and protein digestibility. Dietary treatments had no effect on STM and organ weight and myofiber size. Compared with the other groups, there were trends (P<0.10) for blood serum urea and glucose level to be greater in CAR and for non-esterified fatty acid level to be greater in ARG piglets. The greater (P<0.05) ratio of lactate dehydrogenase to either citrate synthase or ß-hydroxyacyl-CoA dehydrogenase indicated that the relative importance of the glycolytic compared with the oxidative pathway was greater in STM of CAR and ARG compared with CON piglets. These results suggest that ARG and CAR supplements were beneficial for muscle maturation whereas findings on phenotypic traits were rather unsystematic.

Influence of l-carnitine and l-arginine on protein synthesis and maturation of the semitendinosus muscle of lightweight piglets.

Lightweight (LW) piglets from large litters display impaired growth performance compared with heavier littermates. This study investigated the growth performance and muscle development of early-weaned LW piglets (birthweight <1.2 kg) from large litters (17.3 ± 3.0 total born per litter), fed ad libitum a milk replacer supplemented with either l-carnitine (CAR) or l-arginine (ARG) from day 7 to day 28 of age. In total, 36 female and entire male Swiss Large White piglets, weaned on day 7 of age, were artificially reared in pairs in rescue decks. They were allocated to one of three dietary treatments: unsupplemented control (CON), 0.48 g l-carnitine·piglet-1 ·day-1 (CAR) or 1.20 g l-arginine·kg body weight-1 ·day-1 (ARG). Milk replacer was prepared daily in a 1:4 powder-to-water ratio and fed ad libitum. Piglets were weighed at birth and on days 7, 14, 21 and 28. Feed intake was assessed daily. Piglets were euthanized on day 28. The entire semitendinosus muscle (STM) was collected, and organs were weighed. Subsequently, the STM was divided into the light (STMl ) and dark (STMd ) portion, and contractile and metabolic traits were analysed by ATP histochemistry, enzyme activities and gene expression. No differences in growth performance, organ and STM weight and on contractile traits were found between groups. A tendency (p < .10) for an elevated lipid oxidation enzyme activity in the STMl and STMd and greater (p < .05) phosphorylation of the mammalian target of rapamycin pathway in the STMl of CAR compared with CON piglets was found. Despite these metabolic responses, the lack of effect of CAR and ARG supplementation on growth performance suggests that providing the milk replacer ad libitum in combination with added CAR and ARG is insufficient for eliciting faster growth of LW piglets.

The influence of sacral nerve stimulation on gastrointestinal motor function in patients with fecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is a well-established treatment for fecal incontinence of various etiologies. However, the mechanism of action remains unclear. The aim of the present study was to determine whether SNS affects gastric emptying, small intestinal transit or colonic transit times. METHODS: Seven patients with a permanently implanted sacral nerve stimulator participated in a double-blind randomized cross-over study. The patients were allocated to stimulation ON or OFF for two 7-day periods separated by at least 1week. On days 4-7 of each 7-day period, the patients were examined by gamma camera imaging to measure gastric emptying, small intestinal transit and colonic transit parameters of a radiolabeled, 1600 kJ mixed solid and liquid meal ingested on day 4. KEY RESULTS: Sacral nerve stimulation did not change gastric retention at 15 min, gastric mean emptying time, gastric half emptying time, small intestinal mean transit time or colonic geometric center after 24, 48 and 72 h. CONCLUSIONS & INFERENCES: Sacral nerve stimulation does not induce major changes in the propulsive capacity of the gastrointestinal tract in patients successfully treated for fecal incontinence with permanent sacral nerve stimulator.

Vagus nerve stimulation in pediatric epilepsy: a review.

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.

Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study.

This six-center, retrospective study evaluated the effectiveness, tolerability, and safety of vagus nerve stimulation in children. Data were available for 125 patients at baseline, 95 patients at 3 months, 56 patients at 6 months, and 12 patients at 12 months. The typical patient, aged 12 years, had onset of seizures at age 2 years and had tried nine anticonvulsants before implantation. Collected data included preimplant history, seizures, implant, device settings, quality of life, and adverse events. Average seizure reduction was 36.1% at 3 months and 44.7% at 6 months. Common adverse events included voice alteration and coughing during stimulation. Rare adverse events, unique to this age group, included increased drooling and increased hyperactivity. Quality of life improved in alertness, verbal communication, school performance, clustering of seizures, and postictal periods. We concluded that vagus nerve stimulation is an effective treatment for medically refractory epilepsy in children.

[Irritable colon]. / Colon irritabile.

Irritable bowel syndrome is a chronic, relapsing functional bowel disorder of unknown aetiology. Methods of studying intestinal motor function, nociception, and interactions of the central nervous system and enteric nervous system are not applicable for clinical use. The diagnosis is therefore made on the symptoms, but it is necessary to exclude relevant organic disease. Establishment of the diagnosis, information about the disorder, elimination of foods and other factors that provoke the symptoms, and a change in life-style are sufficient in most cases. Treatment is hampered by the lack of effective treatment and the psychological aspects. The therapeutic gain of drug administration is modest and the rate of response to placebo is high. Fibre supplementation, magnesium oxide or cisapride may be tried for constipation, diphenoxylate or loperamide for diarrhoea, and low dose tricyclic antidepressants or serotonin reuptake blockers for severe pain. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists seems promising.

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon.

BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2. METHODS: Balance studies were performed before and after treatment with GLP-2, 400 microg subcutaneously twice a day for 35 days, in 8 patients (4-17 years from last bowel resection; 6 with Crohn's disease). Four patients received home parenteral nutrition (mean residual jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and body composition was measured by dual-energy x-ray absorptiometry. RESULTS: Treatment with GLP-2 improved the intestinal absorption of energy 3.5% +/- 4.0% (mean +/- SD) from 49.9% to 53.4% (P = 0.04), wet weight 11% +/- 12% from 25% to 36% (P = 0.04), and nitrogen 4.7% +/- 5.4% from 47.4% to 52.1% (P = 0.04). Body weight increased 1.2 +/- 1.0 kg (P = 0.01), lean body mass increased 2.9 +/- 1.9 kg (P = 0.004), fat mass decreased 1.8 +/- 1.3 kg (P = 0.007), and 24-hour urine creatinine excretion increased (P = 0.02). The time to 50% gastric emptying of solids increased 30 +/- 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel transit time was not changed. Crypt depth and villus height were increased in 5 and 6 patients, respectively. CONCLUSIONS: Treatment with GLP-2 improves intestinal absorption and nutritional status in short-bowel patients with impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon have been resected.

Pathophysiology, prevention, and potential treatment of neural tube defects.

Neural tube defects (NTD) remain a major cause of morbidity in spite of the reduction in liveborn incidence with periconceptional folic acid. However, the etiology remains unknown. This article reviews studies that address causation and potential treatment of NTD in humans and in animal models that resemble aspects of the common human NTD. Studies of nutritional markers of vitamin B12 and folic acid support a defect in homocysteine metabolism; a thermolabile variant of methylene tetrahydrofolate reductase, an enzyme that remethylates homocysteine to methionine, correlates with a risk of NTD in some human populations. Numerous mouse mutant models of NTD exist, attesting to the ease of disruption of neurulation, and a genetic basis for this malformation. Of these models, the curly tail mouse mutant most closely resembles the common human NTD. Folic acid does not prevent NTD in this model; however inositol supplementation does result in a significant reduction in incidence. Recent advances in fetal surgery, and evidence from mechanically created myelomeningocele in large animals amenable to surgical intervention suggest that the handicaps associated with myelomeningocele and associated Chiari Type II malformation may be prevented by in utero NTD closure. Success will depend on preservation of neurological tissue until such intervention is possible. Further research in animal models at the genetic and cellular levels, together with technological surgical advances, provide hope that prevention of more NTD and the associated handicaps may be possible. MRDD Research Reviews 6:6-14, 2000.

Ethanol and its effects on fracture healing and bone mass in male rats.

Operatively induced, standardized tibia fractures in 42 10-week-old male rats were fixed with intramedullary nails. 21 of the rats were fed liquid containing 15% ethanol. 5 weeks after inducing the fracture, the rats were killed and the total body bone mineral density (BMD) was analyzed with the DEXA technique, and the mechanical properties of the fractured and the unfractured tibiae as well as the ipsi- and contralateral femoral shaft and femoral neck were tested. The rats given a liquid containing 15% ethanol were found to have significantly lower total BMD and total calcium than the controls. We also found a significantly lower bending moment and bending stiffness both in the fractured and unfractured tibiae among rats fed on ethanol. The energy absorption until refracture was less in rats fed on ethanol. Posttraumatic osteopenia was present, as judged by the mechanical tests of the ipsilateral femoral shaft and the femoral neck in all animals. There was no difference in this respect between the animals fed on ethanol and the controls. We found that ethanol disturbs bone metabolism which reduces the mechanical properties of the tibiae and femora of rats, but the healing process of an induced tibial shaft fracture was not affected.

No adverse effects of clodronate on fracture healing in rats.

Clodronate was administered daily 28 days before and after an experimental tibial fracture in 35 male rats, and the effect on fracture healing and posttraumatic bone loss was studied. 5 groups were tested. The clodronate/clodronate group received clodronate in daily doses of 10 mg/kg body weight for 28 days before being subjected to a standardized fracture of the right tibia, and during the fracture healing period of 28 days. The clodronate/saline group received clodronate before fracture and saline during the healing period. The saline/clodronate group received saline before and clodronate after fracture. The saline/saline group received saline only, while the control group served as unfractured, untreated controls. After 28 days of fracture healing, the tibias were evaluated with dual energy x-ray absorptiometry, and tested mechanically in a 3-point ventral bending test. Bone mineral content and bone mineral density were approximately 30% higher in the groups receiving clodronate during the experiment, compared to the untreated groups. The weight and cross-sectional area of the fracture callus were equal in all groups. Whether clodronate was administered before the fracture, after the fracture or both, did not affect the bone mineral. Ultimate bending moment, energy absorption, stiffness and deflection were not significantly different between the groups. Our findings suggest that clodronate increases bone mineral both when given before and after a tibial shaft fracture, without affecting fracture healing at 28 days.

Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.

Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis.

5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations of leukotriene B4 and prostaglanding E2 in rectal dialysis fluid from 23 males with clinically and sigmoidoscopically active, distally located ulcerative colitis were measured by radioimmunoassays in a double-blind, placebo-controlled, parallel design study before and after rectal administration of an enema containing 0.5% of FPL 64170XX. Repeated measures analysis of leukotriene B4, after adjusting for baseline, showed a significant treatment effect (P = 0.0014). The concentration of leukotriene B4 from rectal dialysates in patients receiving the active drug dropped to 15% (95% confidence interval 5-40%) of the placebo level in the second dialysis following administration of FPL 64170XX 0.5%. By contrast, prostaglanding E2 concentrations doubled (P = 0.0068) in patients receiving FPL 64170XX 0.5% with no change in the placebo group. These findings demonstrate that a single dose of FPL 64170XX 0.5% enema selectively blocks the generation of the 5-lipoxygenase product, leukotriene B4, to a mean of 85% in the target tissue of inflammation. Topical administration of this new leukotriene synthesis inhibitor may prove to be a clinically useful approach to the treatment of active, distally located ulcerative colitis.

[Chronic inflammatory bowel disease]. / Kronisk inflammatorisk tarmsygdom.

Chronic inflammatory bowel disease (IBD) encompasses the disease entities, ulcerative colitis (UC) and Crohn's disease (CD). An aetiologic agent has not yet been defined and the diagnosis is based, therefore, on the sum of clinical, paraclinical, radiologic, endoscopic and histopathologic features. In recent years pathogenetic studies have focused on immune mechanisms, transmissible infectious agents, the potential role of the normal intestinal flora, dietary factors, enzymatic alterations and genetic features, in addition to vascular, neuromotor, allergic and psychologic factors. The corner stones in medical therapy of IBD are still corticosteroids and sulphasalazine (SAZ). The new oral salicylates, which are analogues of SAZ or "slow release" preparations of 5-aminosalicylic acid (mesalazine), have provided a therapeutic progress, because they are tolerated better than SAZ. Immunosuppressive agents, such as azathioprine and 6-mercaptopurine, reduce the requirement for corticosteroids and are effective in refractory CD, but the effect is delayed up to several months. The therapeutic action of cyclosporine A is not sustained, but often associated with side effects. Metronidazole has a beneficial effect on perineal disease. The efficacy of antimycobacterial drugs, sodium-cromoglycate, lidocaine, clonidine and sucralfate has been reported only in optimistic case stories and small open trials. A diet, rich in omega-3-fatty acids, modifies leukotriene (LT) production, but its clinical efficacy is insufficient. The first anti-leukotriene-drug, zileuton, has recently been evaluated and a significant, although insufficient, clinical response was obtained by a 70 per cent inhibition of rectal LTB4 synthesis. Dietary therapy may be useful as an adjunct to treatment of local complications in CD.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous oral N-acetylcysteine treatment and development of nitrate tolerance in patients with stable angina pectoris.

The presence of sulfhydryl (SH) groups appears to be fundamental to nitrate-induced vasodilation and N-acetylcysteine (NAC), a sulfhydryl (SH)-donor substance, potentiates hemodynamic responsiveness to nitrates. We investigated the effect of simultaneous administration of NAC and isosorbide dinitrate (ISDN) on development of nitrate tolerance. In a double-blind, randomized, placebo-controlled cross-over study, seven patients with stable angina pectoris were treated for two 8-day periods with ISDN (40 mg four times daily, q.i.d.) together with NAC (controlled release 600 mg q.i.d.) or matching placebo. Bicycle exercise tests were performed before treatment was started, 1 h after treatment was started, and at day 8. After 8-day treatment with ISDN + placebo, responses determined by exercise testing were diminished as compared with responses obtained during acute therapy and did not differ from baseline values, suggesting development of tolerance to ISDN. During treatment with ISDN + NAC, time to 1-mm ST depression was significantly prolonged (441 +/- 44 vs. 381 +/- 40 s, mean +/- SEM) and total ST segment depression significantly reduced (1.9 +/- 0.7 vs. 3.5 +/- 0.8 mm) as compared with baseline values. The reduction in ST segment depression was significantly more pronounced during ISDN + NAC (46%) as compared with ISDN + placebo (23%). Although exercise time and time to angina pectoris were unaffected. NAC augmented the antiischemic effects of ISDN as assessed by ECG. This finding may suggest that development of nitrate tolerance is modified by chronic oral high-dose NAC administration.

Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients.

Six patients with chronic relapsing diarrhoea caused by Clostridium difficile were treated with rectal instillation of homologous faeces (one patient) or a mixture of ten different facultatively aerobic and anaerobic bacteria diluted in sterile saline (five patients). The mixture led to a prompt loss of Cl difficile and its toxin from the stools and to bowel colonisation by Bacteroides sp, which had not been present in pre-treatment stool samples. Strains of Escherichia coli, Cl bifermentans, and Peptostreptococcus productus in the mixture inhibited the in-vitro growth of Cl difficile, which in turn inhibited the growth of Bacteroides ovatus, Bacteroides vulgatus, and Bacteroides thetaiotaomicron. The finding that Bacteroides sp had been absent during the patients' illness but was present after recovery suggests that the absence of Bacteroides sp may result in chronic relapsing Cl difficile diarrhoea, and that its presence may prevent colonisation by Cl difficile.

Immunoreactivity in pituitary gonadotropes and hypothalamic vasopressinergic neurons for the monoclonal antibody INO.

The monoclonal antibody INO (inhibitor of neurite outgrowth) has been shown to bind to a complex of laminin and a heparan sulfate proteoglycan and to block the action of this complex in promoting neurite outgrowth. We now report that the same antibody binds to cytoplasmic constituents in rat adenohypophyseal gonadotropes, as well as to vasopressinergic neurons in the hypothalamus and their terminals in the neurohypophysis. INO immunoreactivity in fixed sections of pituitary does not colocalize with the immunoreactive laminin in blood vessels and glandular basement membranes, although when unfixed tissue is washed in buffer prior to fixation, the INO immunoreactivity appears in these laminin-rich structures. These observations suggest similarities between the INO hypophyseal antigen and the neurite-promoting proteoglycan complex characterized in conditioned media. Presence of this complex in specific neurosecretory cell types suggests that it is involved with specific secretory products with function yet to be determined.

Maintenance of constant 95% neuromuscular blockade by adjustable infusion rates of pancuronium and atracurium.

In a double-blind study, 39 patients (ASA groups I-II,) were given either pancuronium or atracurium as an infusion during surgery. The drugs were given as an initial loading dose of 0.064 mg kg-1 or 0.30 mg kg-1, respectively, followed by an infusion, the rate of which was regulated to produce a constant 95% depression of the evoked twitch response throughout surgery. No significant difference in the number of corrections of the infusion rate per hour was found (4.6 v. 4.9). Mean infusion maintenance doses were 35 and 356 micrograms kg-1 h-1, respectively. The inter-individual variability of maintenance doses for the two drugs did not differ, the coefficients of variation being 0.32 and 0.24. On stopping the infusion, the patients given atracurium recovered to a 15% twitch faster than those given pancuronium. In addition neostigmine produced a quicker recovery in this group. Thus atracurium may be a more satisfactory drug for use by infusion.

Does vitamin E supplementation modulate in vivo arachidonate metabolism in human inflammation?

To determine whether supplementation with the physiological radical scavenger, vitamin E, would modulate arachidonate metabolism in human inflammation, we performed equilibrium dialysis of rectum in eight patients with active ulcerative colitis confined to the rectum. The patients, all off drug treatment, were supplemented with 1920 IU/day of alpha-tocopherol and had rectal dialysis done at entry and after three and 14 days. Luminal concentrations of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), determined by radioimmunoassay in purified dialysates, were significantly raised compared to healthy controls. Supplements caused no change in these levels either at day 4 or 15, although serum-tocopherol showed a 3-fold increase. Also disease activity was unaffected. This failure of vitamin E supplementation to suppress the mucosal release of PGE2 and LTB4 in active inflammation does not encourage controlled trials on the effect of oral vitamin E in ulcerative colitis.