John B. Rodgers

Dietary Supplementation with Fish Oil in Ulcerative Colitis

OBJECTIVE To determine the efficacy of fish oil supplementation in patients with active ulcerative colitis. DESIGN Multicenter, randomized, double-blind, placebo-controlled, crossover trail with 4-month treatment periods (fish oil and placebo) separated by a 1-month washout. SETTING Four gastroenterology divisions. PATIENTS Twenty-four patients with active ulcerative colitis entered the study. Five dropped out, and one was noncompliant. Eighteen patients completed the study. All patients had active disease as manifested by diarrhea and rectal inflammation. INTERVENTIONS Treatment with prednisone and sulfasalazine was continued. Fish oil supplementation consisted of 18 Max-EPA (eicosapentaenoic acid) capsules daily (eicosapentaenoic acid, 3.24 g; and docosahexaenoic acid, 2.16 g). Placebo supplementation consisted of 18 identical capsules containing isocaloric amounts of vegetable oil. MEASUREMENTS Patients were evaluated at study entry and after each diet period. Evaluations included a review of symptoms, flexible sigmoidoscopy, rectal biopsy, and rectal dialysis to measure prostaglandin E2 and leukotriene B4 levels. RESULTS Fish oil supplementation resulted in a significant decrease in rectal dialysate levels of leukotriene B4 from 71.0 to 27.7 pg/mL (average change, -43.3 pg/mL; 95% CI, -83 to -3.6). Significant improvements were seen in acute histology index (average change, -8.5 units from a baseline of 10.5 units; CI, -12.9 to -4.2) and total histology index (average change, -8.5 units from a baseline of 14.80; CI, -13.2 to -3.8) as well as significant weight gain (average weight gain, 1.74 kg, CI, 0.94 to 2.54). No significant changes occurred in any variable during the placebo period. Seven patients received concurrent treatment with prednisone. During the fish oil supplementation period, the mean prednisone dose decreased from 12.9 mg/d to 6.1 mg/d and rose from 10.4 mg/d to 12.9 mg/d during the placebo diet period (P greater than 0.20). CONCLUSIONS Four months of diet supplementation with fish oil in patients with inflammatory bowel disease resulted in reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain.

Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia☆

This multicenter trial evaluated the safety and efficacy of escalating doses of Niaspan (niacin extended-release tablets) and placebo (administered once-a-day at bedtime) in patients with primary hyperlipidemia on the percent change from baseline in levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Extended-release niacin was initiated at a dose of 375 mg/day, raised to 500 mg/day, and further increased in 500-mg increments at 4-week intervals to a maximum of 3,000 mg/day. A total of 131 patients (n = 87, extended-release niacin; n = 44, placebo) were treated for 25 weeks with study medication after a 6-week diet lead-in/drug washout phase and 2-week baseline LDL cholesterol stability phase. Significant decreases from baseline in levels of LDL cholesterol and apolipoprotein B became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or =0. 05), reaching 21% and 20%, respectively, at the 3,000-mg/day dose. Significant increases from baseline in levels of high-density lipoprotein cholesterol became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or = 0.05), reaching 30% at the 3,000-mg dose. Significant decreases from baseline in triglycerides and lipoprotein(a) occurred at the 1,000-mg dose and were apparent at all subsequent doses (p < or =0.05), reaching 44% and 26%, respectively, at the 3,000-mg dose. The most common adverse events were flushing and gastrointestinal disturbance. Transaminase increases were relatively small, and the proportion of patients who developed liver function abnormalities on extended-release niacin was not significantly different from placebo. Thus, extended-release niacin was generally well tolerated and demonstrated a dose-related ability to alter favorably most elements of the lipid profile.

Adaptive changes of the rat small intestine in response to a high fat diet

Abstract 1. 1. Rats exposed to increased dietary lipid were studied for evidence of adaptive changes in the small intestine. Two experimental groups were used. One was fed regular chow supplemented to 20% lipid with additional lard. The other was fed a synthetic diet with a similar lipid but a greater carbohydrate content and devoid of fibrous filler. 2. 2. After four weeks fecal fat output was determined. Absorption of oleate was also studied by the everted sac technique and assays of one of the mucosal lipid re-esterifying enzymes were performed. 3. 3. Rats on a high fat diet excreted significantly less radioactive fat in feces. Sacs from the jejunum of these animals absorbed more oleic acid than controls. The same trend was observed in the ileum but this was of greater significance in ileal sacs from rats on the synthetic diet. Enzyme content in the jejunum was the greatest in rats on regular chow supplemented with lard while in the ileum the highest levels were found in animals on the synthetic high fat diet. 4. 4. It is concluded that the small intestine adapts to increased dietary lipid. Other components of the diet, however, can influence the site at which these adaptive changes occur.

Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism

Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.

Effects of Changes in Dietary Lipids on Intestinal Fluid Loss in the Short-Bowel Syndrome

Abstract Seven patients underwent massive intestinal resection. Fecal losses of water and electrolytes were life threatening in four patients, who required constant or repeated intravenous replacem...

Effect of phosphatidylcholine on fatty acid and cholesterol absorption from mixed micellar solutions

Using the experimental model of the everted sac prepared from rat jejuna, kinetic studies on [14C]oleic acid uptake from bile salt micelles were conducted in the presence and absence of phosphatidylcholine. The concentration of oleic acid was varied between 0.625 and 5 mM. At every level of fatty acid concentration studied the addition of 2 mM phosphatidylcholine produced a significant inhibition of fatty acid uptake. It was further noted that the intact phospholipid molecule was required for this effect as lysophosphatidylcholine produced little, if any, inhibition of [14C]oleic acid uptake. The effect of varying the concentration of phosphatidylcholine on fatty acid uptake was also studied. The degree of inhibition was noted to be correlated grossly with media concentrations of this phospholipid although the decrease of fatty acid uptake was not strictly proportional to concentration of this material in the medium. Studies were also performed analyzing in vitro absorption of [14C]oleic acid and [3H]cholesterol simultaneously from mixed micelles composed of sodium taurocholate, oleic acid, monoolein and cholesterol. Control medium contained no phospholipid while experimental medium contained either diester or diether phosphatidylcholine, 2 mM. Both types of phosphatidylcholine caused significant inhibition of fatty acid and cholesterol uptake. In vivo absorption studies were also performed using the isolated jejunal segment technique. A mixed micellar solution containing [3H]cholesterol and [14C]oleic acid was used as the test dose. Phospholipid in the test dose for controls was supplied as lysophosphatidylcholine and for experimentals it was in the form of diether phosphatidylcholine. Significantly less radioactively labeled cholesterol and fatty acid was absorbed by experimentals as compared to controls over a 10-min period. It is concluded that the intact molecule of phosphatidylcholine inhibits intestinal uptake of cholesterol and fatty acid from mixed micellar solutions under both in vitro and in vivo conditions.

Bouveret's syndrome complicated by distal gallstone ileus after laser lithotropsy using Holmium: YAG laser

BackgroundBouverets syndrome is an unusual presentation of duodenal obstruction caused by the passage of a large gallstone through a cholecystoduodenal fistula. Endoscopic therapy has been used as first-line treatment, especially in patients with high surgical risk.Case presentationWe report a 67-year-old woman who underwent an endoscopic attempt to fragment and retrieve a duodenal stone using a Holmium: Yttrium-Aluminum-Garnet Laser (Ho:YAG) which resulted in small bowel obstruction. The patient successfully underwent enterolithotomy without cholecystectomy or closure of the fistula.ConclusionWe conclude that, distal gallstone obstruction, due to migration of partially fragmented stones, can occur as a possible complication of laser lithotripsy treatment of Bouverets syndrome and might require urgent enterolithotomy.

Effect of polyol detergents on cholesterol and triglyceride absorption. Hypolipidemic action of chronic administration of hydrophobic detergent.

Nonionic detergents were found to affect absorption of neutral lipid and cholesterol. The effects of these detergents were related to their physicochemical properties. The most effective detergents for producing an inhibition of lipid absorption were detergents containing 90% hydrophobic components. Hydrophilic detergents did not interfere with lipid absorption and in some cases, it was facilitated. Studies done over a period of one month demonstrate that addition of a hydrophobic detergent to a high fat-high cholesterol diet results in lower serum levels of cholesterol and triglyceride and prevents cholesterol accumulation in the liver of the rat. This effect was also associated with significant loss of body weight.

The absorption and subsequent utilization of lecithin by the rat jejunum

Labeled lecithin (32P, 2-3H-glycerol, 1-14C-palmitate) was prepared for studying absorption of lecithin by rat intestine and its incorporation into microsomal and prechylomicron-chylomicron lecithin. Bile fistula rats were perfused intraduodenally with bile salts and lecithin plus a liquid diet. Intestinal samples were obtained after sacrifice and specific activities (DPM/μmol) of isotopes in lecithin were determined. Ratios of specific activities of isotopes were calculated and compared to respective ratios in the original perfusate lecithin. Radioactivity rapidly appeared in jejunal lecithin following perfusion. When specific activities of isotopes in prechylomicron-chylomicron lecithin were compared to those in microsomal lecithin, specific activities were always greater in prechylomicron-chylomicron lecithin. Analysis of ratios of specific activities of isotopes in jejunal lecithin showed that the ratios were nearly identical to those in perfusate phospholipid, indicating that the lysolecithin portion of luminal lecithin can be absorbed intact and can then be utilized for jejunal lecithin synthesis.Labeled lecithin (32P, 2-3H-glycerol, 1-14C-palmitate) was prepared for studying absorption of lecithin by rat intestine and its incorporation into microsomal and prechylomicron-chylomicron lecithin. Bile fistula rats were perfused intraduodenally with bile salts and lecithin plus a liquid diet. Intestinal samples were obtained after sacrifice and specific activities (DPM/μmol) of isotopes in lecithin were determined. Ratios of specific activities of isotopes were calculated and compared to respective ratios in the original perfusate lecithin. Radioactivity rapidly appeared in jejunal lecithin following perfusion. When specific activities of isotopes in prechylomicron-chylomicron lecithin were compared to those in microsomal lecithin, specific activities were always greater in prechylomicron-chylomicron lecithin. Analysis of ratios of specific activities of isotopes in jejunal lecithin showed that the ratios were nearly identical to those in perfusate phospholipid, indicating that the lysolecithin portion of luminal lecithin can be absorbed intact and can then be utilized for jejunal lecithin synthesis.

Effect of hydrophobic detergent on lipid absorption in the rat and on lipid and sterol balance in the swine.

The effects of hydrophobic detergent on fat absorption in the rat were determined under two conditions. In the first, a high dose of detergent was given in a test lipid meal to rats not previously exposed to this agent. A marked delay in digestion of triglyceride in association with malabsorption was observed. In the second, a relatively small dose of detergent was given to rats pretreated with dietary supplement of detergent. No delay of digestion or uptake was observed but absorbed, reesterified lipid was noted to accumulate in the mucosa. Morphologic studies showed abnormal collections of fat droplets in the enterocytes. Sterol and fat balance studies were done on swine on chronic dietary detergent supplement. Mild steatorrhea with excess fecal excretion of neutral sterols was observed. It is concluded that hydrophobic detergents can have an inhibitory effect on both intraluminal and intracellular events of fat absorption.