Laxatives: clinical pharmacology and rational use.
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Hyperlipidemia is now established as a major risk factor for causation of coronary heart disease (CHD) in adults; however, there is much debate on the level of coronary risk at which lipid-lowering drugs should be used. These issues of possible harm or lack of benefit from long-term use of lipid-lowering therapy, and cost effectiveness, are also pertinent in the pediatric setting. Evidence from several countries indicates that children have an increasing prevalence of obesity, hyperlipidemia and type 2 diabetes mellitus. Children who have high serum lipids 'track' these increased levels into adulthood. In some countries there is a trend to screen children for hypercholesterolemia. Family history itself is a poor discriminator in determining which children need to be screened and treated. Estimation of apolipoprotein B and/or apolipoprotein E genotype can improve prediction. Measuring high density lipoprotein cholesterol also helps, but obesity appears to be the best marker for screening children at high risk. These considerations should not cloud the need for case finding and treatment of children with genetic disorders. Low fat diets have been shown to be well tolerated and effective in children; however, there are no major long-term studies demonstrating harm or benefit in those on lipid-lowering drugs. Nevertheless, concerns regarding the psychological effect and the theoretical metabolic effects of long-term lipid lowering remain. Lipid-lowering drugs should be generally restricted to children with genetic disorders of lipid metabolism. Children with diabetes mellitus, hypertension or nonlipid-related inherited disorders leading to premature CHD in adults should be treated with diet, and with lipid-lowering drugs when they reach adulthood. Children with secondary hyperlipidemia should be assessed individually. A number of drugs and nutriceuticals are available for use in children, but only a few drugs are licensed for use in children.
The aim of this prospective randomized study is to describe the effects of laxative plantago ovata after open hemorrhoidectomy (Milligan-Morgan). Sixty patients divided into 2 equal groups were included in this study. The first group was treated postoperatively with 2 sachets of bulk agent Laxomucil (3.26 g plantago ovata), twice daily, for a period of twenty days, while the control group was treated with glycerin oil. The p.ovata group patients had a statistically significant shorter postoperative length of hospital stay (2.9 v.s. 4.1 days). Pain after stool was statistically significant more tolerable in the p.ovata group. In conclusion, the application of bulk agent plantago ovata after hemorrhoidectomy shortens the mean postoperative hospital stay, expedites digestive function recovery and lessens the pain after stool.
Plantago ovata is a high fibre bulk forming laxative. It absorbs water and expands to provide increased bulk and moisture content to the stool. The increased bulk encourages normal peristalsis and bowel motility. Clinical Indications: Constipation, Fecal Incontinence, Hemorrhoids, Ulcerative Colitis, Appetite, Hyperlipidemia, Diabetes mellitus.
A double-blind cross-over long-term trial (18 months) with randomized supplementation with wheat fibre or ispaghula for two periods of six months, separated by a six-month wash-out period with placebo, was performed in ten patients with juvenile ulcerative colitis to study the effect on faecal bile acid (BA) excretion. All patients were in remission since 0.5-2 years and orally treated with sulphasalazine. The average intake of either fibres was 16 g day-1. Faecal samples were collected (72 h) before and after each fibre period. Faecal water were prepared by centrifugation of faeces at 15,000 g for 2 h. BA in faeces and faecal water were studied using capillary column gas-liquid chromatography-mass spectrometry. Faecal excretion of total BA were not significantly changed by the two fibres. Supplementation with wheat fibre, but not with ispaghula, decreased the faecal concentration of total BA by 43% (p < 0.05), unconjugated BA by 41% (p < 0.01), and taurine conjugated BA by 58% (p < 0.05). Addition of wheat fibre decreased the concentration of chenodeoxycholic acid by 66% (p < 0.05) and isomers of cholic acid by 51% (p < 0.05) in faeces. The mean faecal water concentration of taurine-conjugated BA decreased by 55% when wheat fibre was added (p < 0.05) and the concentration of isomers of deoxycholic acid increased by 39% when ispaghula was supplemented (p < 0.05). The ratio isomeric deoxycholic acid to deoxycholic acid in faecal water increased significantly when wheat fibre was added (p < 0.05). The percentage distribution of secondary and ketonic BA was not influenced by the dietary fibre supplementation. The concentration of BA in faeces and faecal water decreased only by wheat fibre, suggesting that it is superior in obtaining an affect on faecal BA concentration.
To evaluate factors influencing the short-chain fatty acid (SCFA) concentrations in stools, three different experiments were performed: faecal concentrations of SCFA at defecation were determined by gas liquid chromatography in nine healthy volunteers on a free diet. SCFAs were 114 +/- 15.0 mmol/l (means +/- SD). The coefficient of variation (CV) of the assay was 4-15%, the intraindividual CV 12-33%, and the interindividual CV 11-29%. On incubation of faeces at 37 degrees C concentrations of SCFA doubled in 6 h and rose fourfold in 72 h. In three volunteers the experiments were extended by adding ispaghula husk or lactulose to the diet for two 14-day periods each; no change in faecal SCFA concentrations was seen, either at defecation or after incubation. When ispaghula husk or lactulose was added to faeces in an in vitro incubation system, the concentrations of SCFA were five times higher than those of controls. We conclude that instant handling of faeces is essential for determinations of SCFA concentrations to obtain interpretable and comparable results; that determination of total SCFA output is of limited value; that addition of fibre to the diet does not influence faecal SCFA concentrations; and that the capacity for SCFA production in faeces is large provided a sufficient amount of substrate is available.
The binding of iron to different fibers suggest in vitro that dietary fibers might interfere with the bioavailability of iron in the diet. As it is difficult or impossible to translate in vitro studies to in vivo bioavailability and even to translate results from animal studies to man, it is necessary to study the effect of fiber in man. With the extrinsic tag method and two different radioiron tracers it is possible in the same subject to compare the iron absorption from a meal with and without a certain component of dietary fiber. With a standard reference dose of 3 mg iron it is possible to "calibrate" each subject which makes it possible to compare the absorption in different groups given different components of dietary fiber.
A commercial product of fibre-enriched wheat fibre (Fiberform R) was tested for its binding of bile salts in vitro. The wheat fibre preparation was standardized and through enzymatic digestion of protein and starch contained 78 per cent fibre (w/w). Fibre-enriched wheat fibre bound with high capacity both conjugated and unconjugated bile salts. Binding was saturable, reversible and showed no specificity towards tauro- or glycine-conjugated bile salts. Binding was rapid, dependent on pH, was enhanced by the presence of high salt concentrations and partially inhibited by 6 M urea. This indicated that binding was a combination of hydrophobic and hydrophilic interactions.
Twenty-five patients with chronic diarrhoea were included in an open, randomized crossover trial comparing the effect of loperamide with ispaghula and calcium. Nineteen patients completed both treatments. Before treatment the median number of daily stools was 7 (range, 4-13), stool consistency was loose in all, and urgency was present in 16 out of 19 patients. Both treatments halved stool frequency, but with regard to urgency and stool consistency ispaghula and calcium was significantly better. A combination of ispaghula and calcium seems to be a cheap and effective alternative to conventional treatment of chronic diarrhoea. Moreover, side effects were minimized.
The efficiency of ispaghula husk in relieving gastrointestinal symptoms in patients with ulcerative colitis in remission was studied in a placebo-controlled trial running for 4 months. Twenty-nine patients (81%) completed the trial; four withdrew after colitis relapse (three while receiving placebo). Grading of symptoms judged ispaghula to be consistently superior to placebo (p less than 0.001) and associated with a significantly higher rate of improvement (69%) than placebo (24%) (p less than 0.001). The results show that ispaghula can be helpful in the management of gastrointestinal symptoms in quiescent ulcerative colitis.
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Immature male rats were fed a purified, low-fiber diet containing massive doses of sodium cyclamate or amaranth (FD and C Red No. 2). Sodium cyclamate when incorporated at a 5% level in the purified, low-fiber diet resulted in toxic manifestations which were counteracted by the concurrent administration of the anion exchange resin cholestyramine at a 2 1/2% level in the diet. Other anion exchange resins were also active in this regard. Cholestyramine at a 2 1/2% level of supplementation was also active in counteracting the toxic effects induced by amaranth when the latter was incorporated at a 5% level in the purified, low-fiber diet.
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