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Biomedical subjects

K Ewe

Publications and source records attributed to K Ewe.

At least 37 records · Page 2Linked to original sources

Effect of 4 x 250 mg erythromycin on human gastrointestinal transit.

The motilin agonist erythromycin affects gastrointestinal motility. We studied its influence on gastric, intestinal, and colonic transit of indigestible solids. Ten healthy volunteers measured the gastrointestinal transit of a 6-8 mm metal sphere by metal detector with oral intake of 250 mg erythromycin q.i.d. or placebo in randomized order. Postprandial gastric emptying of the sphere after a standard meal was measured after a single i.v. dose of 250 mg erythromycin, subsequently followed by determination of small and large bowel transit. Motilin serum levels were measured for one hour. Gastric transit of the sphere was shortened from 243 +/- 34 to 72 +/- 46 min (mean +/- SD) (p = 0.002) and shifted from the interdigestive to the digestive phase. Small and large bowel transit were not influenced, and gastric transit times and motilin serum levels were not correlated. In conclusion, 250 mg erythromycin shortened postprandial gastric emptying of indigestible solids, most likely due to overcoming of pyloric sieving function by strong gastric antral contractions without effecting the transit through the lower part of the gastrointestinal tract.

Adult↗

Azathioprine combined with prednisolone or monotherapy with prednisolone in active Crohn's disease.

BACKGROUND: The role of azathioprine (AZA) in the treatment of active Crohn's disease (CD) is still controversial. This study examined whether AZA combined with standard prednisolone therapy improved the therapeutic outcome compared with monotherapy with prednisolone. METHODS: Forty-two patients with a Crohn's Disease Activity Index (CDAI) of > 150 were randomized into two groups. Both received 60 mg of prednisolone daily in a tapering regimen to a maintenance dose of 10 mg. In addition, group 1 received 2.5 mg AZA/kg body wt and group 2 received a placebo over the whole study period of 4 months. RESULTS: At the end of the trial, 16 of 21 patients (76%) in group 1 were in remission (CDAI < 150), compared with 8 of 21 (38%) in group 2 (P = 0.03). The CDAI in group 1 dropped from 290 +/- 97 (SD) to 72 +/- 84 and from 285 +/- 110 to 155 +/- 105 in group 2. The differences between activity indices in groups 1 and 2 became statistically significant after 8 weeks. The average prednisolone dose per day was 20.9 mg in group 1 and 26.7 mg in group 2 (P = 0.02). No major side effects were observed in this study. CONCLUSION: The combination of prednisolone and AZA was superior to the treatment with prednisolone alone in active CD. Patients receiving AZA showed remission more frequently, more quickly, and with lower doses of prednisolone.

Adolescent↗

Influence of senna, fibre, and fibre + senna on colonic transit in loperamide-induced constipation.

Retarded colonic transit and disturbed defecation are the most prominent pathophysiological mechanisms in constipation. Both may be influenced by bulking agents and by laxatives such as senna. Direct measurements of the influence of such substances on colonic transit are rare mainly because of technical problems. We measured gastric emptying, small and large intestinal transit in 24 healthy volunteers by a newly developed method employing a metal detector. Twelve persons taking a normal diet received loperamide in a dose sufficient to double the individual transit time. All subjects measured gastrointestinal transit time under normal conditions and with Sennatin containing purified sennosides 20 mg, Agiocur (30 g) as a fibre product containing 20 g Plantago ovata seeds/husks, or Agiolax (10 g) as a combination of 5.4 g P. ovata seeds/husks + 1.2 g senna pod with a sennoside content of 30 mg. Colonic transit was reduced by Sennatin and by Agiolax from 39 +/- 4 h to 17 +/- 3 h (p < 0.005). Agiocur did not influence colonic transit (39 +/- 3 h). Loperamide prolonged colonic transit from 27 +/- 0.7 to 72 +/- 12 h. This effect was abolished by Sennatin (30 +/- 5 h) and Agiolax (27 +/- 1 h) (p < 0.005), but not by Agiocur (64 +/- 13 h). The same effects were seen when right and left colonic transit were analyzed separately. Neither gastric emptying nor small intestinal transit were affected by either substance. All of the three study drugs increased stool weight significantly (p < 0.05). When stool frequency and consistency were compared, the effects were less clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Crohn disease and ulcerative colitis--newer therapeutic approaches].

Most of the progress in the treatment of chronic inflammatory bowel diseases (IBD) is derived from the long known basic treatment drugs: aminosalicylates and glucocorticoids. 5-aminosalicylic acid (5-ASA) was prevented from being absorbed by coupling it to less toxic molecules than sulfapyridine especially to another 5-ASA molecule or by coating it with acid fast resins of different solubility. From these properties special indications may be derived for the different preparations according to the localisation of the IBD. New topical highly active glucocorticoids with high first pass effect in the liver are intensively investigated at present. It is hoped that the local steroid effect in the bowel can be achieved without systemic side effects. The cascade of inflammation in IBD comprises different phases, it's immunological basis is under intense scrutiny. New forms of treating IBD are based upon the attempt to inhibit specifically isolated factors of inflammation such as cytokines and mediators of inflammation (f.i. inhibition of PAF, LTB4, CD4-T-cells or scavenging O2-radicals) Whether the specific inhibition of a single factor in the inflammatory cascade will finally abolish the whole inflammatory process has to be proven in the future.

Aminosalicylic Acids↗

[The effect of food intake on the gastric emptying of gastric juice-resistant tablets and capsules].

To test the effect of food intake on gastric emptying of gastric juice-resistant drugs, emptying time of a 11 x 6 mm tablet and a 20 x 7 mm capsule was measured by means of a metal detector in 10 healthy persons (5 men and 5 women; mean age 25 [18-30] years) after fasting and after eating three main and three in-between meals. After fasting the tablets left the stomach after 78 +/- 18 min, the capsules after 60 +/- 16 min, while meal intake delayed emptying by a factor of 10 to 12 +/- 1.3 hours and 10 +/- 1.8 hours, respectively. The slightly shorter emptying time of capsules was statistically not significant. The results indicate that gastric juice-resistant tablets taken during day-time may, if several meals are eaten, accumulate in the stomach and then be emptied together at night. It is recommended that such drugs be taken in the fasting state in the morning and between meals, while avoiding in-between meals.

Adolescent↗

Influence of loperamide and loperamide oxide on the anal sphincter. A manometric study.

The objective of this study was to investigate the effects of the opioid loperamide and its recently synthesized pharmacologically inactive prodrug loperamide oxide on the anal sphincter. In a double-blind, placebo-controlled crossover study, anorectal manometry was performed in 12 healthy volunteers five hours after oral bolus application of 10 mg of loperamide, loperamide oxide, or placebo. Loperamide significantly increased the threshold volumes for minimal perception and urgency to defecate (P less than 0.05) and raised the volume required to abolish recovery of the rectoanal inhibitory reflex (P less than 0.05). These findings suggest that loperamide has a specific continence-improving action on the anal sphincter. However, anal resting pressure and maximal squeeze pressure were unaffected in our study and do not seem to be responsible for this effect. The effects under loperamide oxide showed a similar tendency but were without statistical significance.

Adult↗

Intraindividual variability of anorectal manometry parameters.

The present study investigates the intraindividual day-to-day variability of anorectal manometry parameters. Manometric studies were performed in twelve healthy volunteers on three different days. A low compliance capillary perfusion system was used. The values measured on day 1 and day 2, as well as those on day 2 and day 3, showed no significant (p greater than 0.05) differences for any parameter in Wilcoxon's test. Mean percentage of differences as a measure for intraindividual day-to-day variation was relatively low for anal resting (mean: 13.5%) and maximal squeeze (17.5%) pressure. However, it was high for the threshold volumes for minimal perception (71.8%) and urgency to defecate (38.5%) during rectal balloon distention as well as for the minimal volume required to abolish recovery of the rectoanal inhibitory reflex (41.2%). We conclude that anal resting pressure and maximal squeeze pressure both are the most stable anorectal manometry parameters in man, at least over a period of a few days.

Adult↗

[Pancreatitis associated with 5-aminosalicylic acid].

Acute pancreatitis with severe belt-like upper abdominal pain developed within 1-4 weeks of starting medication in three patients (29-year-old man with ulcerative colitis; 43-year-old woman and 22-year-old woman with Crohn's disease) treated, for the first time, with 5-aminosalicylic acid (mesalazine), 500 mg three times daily. Concentrations of lipase initially were 545, 1182 and 3000 U/l, and of amylase 243, 449 and 129 U/l, respectively. Symptoms receded within a few hours after the drug had been discontinued, enzyme levels returning to normal in the course of the next 2-3 weeks. On repeating the drug in two of the patients, in lower dosage, the pancreatitis recurred within a few days. These observations support the view that 5-aminosalicylic acid can cause acute pancreatitis, perhaps as an allergic reaction.

Acute Disease↗

Effect of loperamide on jejunal electrolyte and water transport, prostaglandin E2-induced secretion and intestinal transit time in man.

Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit. In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2-8 mg.l-1). The volunteers were pretreated with 1 mg.l-1 prostaglandin E2 (PgE2) in the perfusate before addition of 4 mg.l-1 loperamide. Phenolsulphonphtalein (PSP) boluses (2 ml) were given to measure mean transit time (MTT). Loperamide 2 mg.l-1 converted the minor secretion after perfusion with the standard solution (water -145 ml.min-1, Na -0.09 and Cl -0.04 mmol.min-1) to absorption (water 0.93 ml.min-1, Na 0.23, Cl 0.25 mmol.min-1) within 15 min. Higher doses of loperamide did not increase absorption. The addition of PgE2 induced net secretion of water (-4.48 ml.min-1) and electrolytes (Na -0.57, Cl -0.51 mmol.min-1). Loperamide 4 mg.l-1 significantly diminished the PgE2-induced net secretion by approximately 50%. Loperamide dose dependently increased the MTT from 6 (2 mg.l-1) to 13.3 min (8 mg.l-1). MTT was still delayed 60 min after a wash out period (10.5 min). It is concluded that loperamide had a dual effect or intestinal activities stimulating absorption and prolonging intestinal transit time with rising doses.

Adolescent↗

Gastric emptying of indigestible tablets in relation to composition and time of ingestion of meals studied by metal detector.

Enteric-coated tablets leave the stomach mainly during the interdigestive phase. Composition as well as time of ingestion of meals may influence their gastric emptying considerably. In 12 normal volunteers gastric emptying of a plastic tablet with a metal core was followed by a metal detector in relation to different compositions and various times of ingestion of meals. With an empty stomach and after ingestion of 250 ml water, the mean time for gastric emptying of the tablet was 38 +/- 11 min (mean +/- SEM) and 38 +/- 8 min. Two hundred fifty milliliters of milk (652 kJ) and a formula diet (1000 kJ) delayed gastric emptying time to 128 +/- 14 and 152 +/- 6 min, respectively (P less than 0.05). Breakfast (2200 kJ) further retarded gastric emptying compared with both liquids to 249 +/- 24 min (P less than 0.05). There was a close correlation between nutritive density and gastric emptying of the tablet (r = 0.92; P less than 0.001). Main meals also delayed gastric emptying of tablets when compared to empty stomach (P less than 0.05). A snack after breakfast further delayed gastric emptying from 201 +/- 10 to 278 +/- 19 min (P less than 0.05). The largest delay was observed following ingestion of breakfast, lunch, dinner, and additional snacks (509 +/- 220 min). We conclude that the delay of gastric emptying of enteric-coated tablets by food is related to its nutritive density and eating habits. The gastric emptying of an enteric coated tablet that is ingested early in the morning may be delayed until late at night when several meals and snacks are ingested during the day, leading to unwanted alterations in bioavailability and to possible adverse effects.

Adult↗

[Increased serum alpha 1-antitrypsin does not produce a rise in fecal alpha 1-antitrypsin in patients with healthy intestines].

Fecal alpha-1-Antitrypsin (alpha-1-AT) was related to serum alpha-1-AT concentration in 50 healthy controls, 51 patients with extraintestinal inflammatory disease as well as in 23 patients with ulcerative colitis with mild or severe disease activity. alpha-1-AT concentrations were measured by radial immunodiffusion. Even though serum alpha-1-AT concentration was elevated above normal limits in all patients, a concomitant increase of fecal alpha-1-AT was found only in patients with ulcerative colitis. In these patients a positive correlation between fecal alpha-1-AT-clearance and -concentration and severity and extension of inflammation could be demonstrated. It is concluded that elevated blood levels of alpha-1-AT do not cause increases in fecal alpha-1-AT loss and that fecal alpha-1-AT excretion is increased specifically in patients with intestinal inflammation.

Adult↗

[The treatment of irritable colon. Efficacy and tolerance of buscopan plus, buscopan, paracetamol and placebo in ambulatory patients with irritable colon].

A double-blind, randomized parallel group trial comparison involving 712 patients with irritable bowel syndrome was performed. Over a treatment period of 4 weeks hyoscine-N-butylbromide (30 mg/day p.o.) plus paracetamol (1 500 mg/day p.o.), hyoscine-N-butylbromide (30 mg/day p.o.), paracetamol (1. 500 mg/day p.o.) or placebo (3 tablets/day p.o.) were administered. Patients kept a diary and entered a daily rating of their symptoms (visual analogue scale). At the end of the four weeks 81% of the patients in the Buscopan plus group were deemed "responder" (marked or some improvement in symptoms). In the Buscopan group 76%, in the paracetamol group 72% and in the placebo group 64% of the patients were responders. The differences between the Buscopan plus group and the placebo group, and between the Buscopan group and the placebo group were statistically significant. The daily rating on the analogue scale showed a statistically significant improvement in abdominal pain intensity in the Buscopan plus group versus the placebo group and in the Buscopan plus group versus the paracetamol group. Thirty-eight patients ( = 5%, no differences between the treatment groups) experienced adverse effects, that did not require treatment. Buscopan plus and Buscopan are suitable for the treatment of the irritable bowel syndromes.

Acetaminophen↗

[The early recurrence of Crohn's disease after "curative" ileocecal resection. A prospective endoscopic and histological study].

The postoperative course of 44 patients (24 women, 20 men; mean age 31.5 [18-63] years) treated by ileocaecal resection for Crohn's disease was investigated prospectively. None of the patients received any prophylactic drug treatment during the 12-month postoperative period of observation. Recurrence of Crohn's disease was endoscopically diagnosed in 21 of the 44 patients during the 12-month period, and in 14 patients recurrence was suspected. Histological confirmation of recurrent Crohn's disease, however, was obtained unequivocally in only 11 patients, while in further 20 patients there was suspicion of recurrence. A large proportion of the recurrences was already confirmed endoscopically and histologically by the end of the third postoperative month. It is concluded that recurrences are frequent and early after a "curative" operation, raising the question of early prophylaxis with drugs.

Adolescent↗

Antibodies to cytoskeletal proteins in patients with Crohn's disease.

The immunologic basis of inflammatory bowel disease has been the focus of interest of a series of studies on Crohn's disease and the process of immune sensitization at the gastrointestinal mucosal level is functionally poorly understood. To date only few contradictory reports concerning the incidence of autoantibodies in patients with this disease exist. The aim of this study was to investigate the sera drawn from 60 patients suffering from biopsy-proven Crohn's disease to evaluate the prevalence of autoantibodies against nuclear antigens and cytoskeletal proteins. Using standard methods, no anti-nuclear antibodies or antibodies to extractable nuclear antigens could be detected. All sera were also negative for antibodies to double-stranded DNA, anti-mitochondrial antibodies, and antibodies to gastric parietal cells. Using sensitive enzyme-linke immunosorbent assays with purified antigens and Western blotting with cytoskeletal proteins of human intestinal cells, the following antibodies could be demonstrated: cytokeratin 18 autoantibodies (IgG 20.0%; IgM 6.7%; IgA 13.3%), actin antibodies (IgG 36.7%; IgM 48.3%, IgA 26.7%), desmin antibodies (IgG 6.7%; IgM 15.08%; IgA 5.0%), vimentin antibodies (IgG 3.3%; IgM 16.7%; IgA 10.0%) and tropomyosin antibodies (IgG 3.3%; IgM 3.3%, IgA 5.0%). Statistically significant correlations could be found for levels of cytokeratin 18 antibodies (IgM-type) and the BEST index of activity, and for levels of desmin antibodies (IgM-type) and the van HEES index of activity. Highest levels could be measured for actin antibodies (IgG-type) in patients with isolated disease manifestation in the colon. The mechanism of induction of autoantibodies against cytoskeletal components in Crohn's disease still remains obscure. Unmasking of hidden antigens after cell injury during the inflammatory process of disease might lead to sensitization and antibody production. The pattern of antibodies in patients with Crohn's disease seems to be different compared with that of connective tissue diseases.

Adolescent↗

Feasibility and effectiveness of a defined-formula diet regimen in treating active Crohn's disease. European Cooperative Crohn's Disease Study III.

In a randomized multicenter trial the efficacy of treatment of active Crohn's disease by means of a liquid defined formula diet (DFD) was tested and compared with a combination of 6-methyl-prednisolone and sulfasalazine. A total of 95 patients participated in the study. By the end of 6 weeks, among 44 patients randomized to drug treatment, 32 showed improvement of the Crohn's disease activity index (CDAI) as compared with 21 of 51 patients receiving oral DFD (p less than 0.05). The proportion of withdrawals in the DFD group (29 of 51) was sevenfold higher than in the drug group (4 of 44). However, most patients (20 of 29) receiving DFD withdrew because of the unpalatability of the liquid diet. Analysis of patients in each group who finished the study showed equal effectiveness of DFD and the drug regimen. In these subsets of patients the CDAI decreased from 280.8 +/- 90.6 to 151.7 +/- 86.5 (DFD) and from 263.7 +/- 86.3 to 129.3 +/- 63.7 (drug), respectively. Improvement of inflammation factors was similar in both groups at the end of the study, although improvement was delayed in the DFD group. In conclusion, our data show a superiority of the drug combination over DFD in the treatment of Crohn's disease under the conditions of this trial. The results do suggest, however, that DFD offers a therapeutic alternative to prednisolone and sulfasalazine in a subgroup of patients, which has to be closer characterized in further studies.

Adult↗