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Biomedical subjects

G Olaison

Publications and source records attributed to G Olaison.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mechanism of absorption enhancement in humans after rectal administration of ampicillin in suppositories containing sodium caprate.

PURPOSE: The medium chain fatty acid sodium caprate (C10) is approved as an absorption enhancer but its mechanism of action has not been studied in humans. The aim of this study was to investigate the mechanism of action of C10 in human subjects after rectal administration. METHODS: Twelve healthy human subjects were randomised to receive ampicillin suppositories with (AM-C10) or without (AM) C10. Serum and urine samples were collected and analysed for ampicillin by HPLC. Rectal biopsies were taken before and 25 min (approximate time of maximum serum concentration, Cmax, for ampicillin) and 185 min (during the final part of the elimination phase) after rectal administration of the suppositories. The osmolality of the rectal fluid was also measured. RESULTS: AM-C10 administration increased Cmax, area under the serum concentration-time curve (AUC) and urinary recovery of ampicillin 2.6-, 2.3- and 1.8-fold, respectively, compared to AM. Histological examination of the biopsies showed that AM-C10 exposure resulted in reversible mucosal damage that occurred at the same time as the Cmax for ampicillin while AM prolonged mucosal damage. A reversible increase in rectal fluid osmolality was observed with both treatments. CONCLUSIONS: AM-C10-enhanced absorption of ampicillin coincides with non-specific damage to the rectal mucosa. C10 itself as well as the suppository base and the hyperosmolality of the rectal fluid contributed to this effect. However, the histological damage was reversible with AM-C10, suggesting that C10 also has a protective effect on the rectal mucosa.

Adult↗
PubMed1997

Absorption profiles for polyethylene glycols after regional jejunal perfusion and oral load in healthy humans.

The study aimed at applying closed segmental intestinal perfusion with a multichannel tube (Loc-I-Gut) for studies of regional small bowel permeability to different-sized polyethylene glycols and to compare jejunal absorption with absorption after oral load in healthy subjects. Intestinal perfusion was performed in 10 healthy volunteers and recovery of (14)C-labeled polyethylene glycol 4000 was used to detect leakage. Absorption of polyethylene glycols 546-942 was measured as urinary recovery after perfusion and oral load, and as disappearance from the lumen during steady-state perfusion. Steady-state conditions were obtained during the second hour of perfusion. Absorption of polyethylene glycols during perfusion was size-selective for molecular weights 546-766, but not for 810-942. After oral load, absorption was size-selective throughout 546-942. Segmental perfusion with Loc-I-Gut may be used to study regional jejunal permeability. Our data support the hypothesis of a dual pore system for absorption of hydrophilic molecules in the human jejunum.

Administration, Oral↗
PubMed1996

The endoscopic picture reflects transmural inflammation better than endoscopic biopsy in Crohn's disease.

OBJECTIVE: To investigate how the histopathological picture of endoscopic biopsy specimens related to that of transmural sections and also how these related to the endoscopic findings. DESIGN: Prospective controlled study. PATIENTS AND METHODS: Intraoperative endoscopy was performed on 19 patients with Crohn's disease and mucosal biopsies were obtained from various bowel segments that were to be resected. The histopathological appearance of mucosal biopsies was compared to that of transmural bowel sections and to endoscopic findings. Ten patients undergoing surgery for colonic cancer were used as controls. RESULTS: Poor agreement was found between the pathologist's assessment of biopsy specimens and transmural bowel sections (kappa < 0.38) for all histological variables. The endoscopic assessment of inflammatory severity had a better correlation with global histological assessment of transmural bowel wall sections (r = 0.75) than with a global histological assessment of endoscopic biopsy specimens (r = 0.65). CONCLUSION: Endoscopic assessment of inflammation in Crohn's disease better reflects transmural histopathology than mucosal biopsy and thus the severity and extent of inflammation. Routine biopsy sampling is of limited value in Crohn's disease.

Adult↗
PubMed1996

Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study.

BACKGROUND AND AIMS: To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD). PATIENTS AND METHODS: Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment. RESULTS: Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups. CONCLUSION: 6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects.

Administration, Oral↗
PubMed1996

Increased gastric absorption of polyethylene glycols in atrophic gastritis.

Atrophic gastritis increases the risk of developing gastro-intestinal tumours. An impaired barrier function of the gastric mucosa could contribute to this risk. The absorption of polyethylene glycols (molecular weights 414-766), expressed as recovery in 6-hour urine, was studied both after oral and duodenal loads in patients with atrophic gastritis (n = 18) and compared with controls without gastritis (n = 9). The patients had a higher absorption after oral than after duodenal load for molecular weights 502-546. The differences in absorption after oral and duodenal loads were correlated with the severity of the atrophy in the antrum. No differences were found in the controls. Absorption after the duodenal load did not differ between the study groups. The increased gastric absorption of polyethylene glycols in patients with atrophic gastritis may be caused by a permeability disturbance of the gastric mucosa.

Administration, Oral↗
PubMed1995

Endoscopic and external bowel changes and histopathology in patients with Crohn's disease.

The relationships between intraoperative endoscopic findings, exterior bowel wall changes and transmural histopathology were investigated in 23 patients with Crohn's disease (24 resections). Villous atrophy and leucocyte infiltration of the epithelium, lamina propria and submucosa were common in intestine without endoscopic lesions. Minor endoscopic ulcers were associated with leucocyte infiltration, ulcers and pyloric metaplasia, and large endoscopic ulcers and stricture with severe transmural inflammation, fibrosis and fissures. In ileal Crohn's disease (19 resections), correlation was close between endoscopic stage and histopathology (rs = 0.77, P < 0.0001), but an exterior lesion index showed worse correlations with endoscopy and histology (rs = 0.57 and rs = 0.59 respectively). The difference was attributable to patients with previous resection and/or fistula showing exterior lesions without concomitant histological or endoscopic abnormalities. Intraoperative surgical decisions should be guided by endoscopic observations rather than by assessment of exterior bowel wall changes.

Adolescent↗
PubMed1995

Effect of postoperative insulin-like growth factor I supplementation on protein metabolism in humans.

Insulin-like growth factor I (IGF-I) has been shown experimentally to exert a nitrogen-sparing effect in both animals and humans. Its effects on protein metabolism during the first 5 days after radical large bowel resection were investigated. Nineteen patients were randomly allocated to receive either human recombinant IGF-I (2 x 80 micrograms/kg body weight subcutaneously, n = 10) or placebo (n = 9) starting on the morning of the first day after operation. All patients received parenteral nutrition (glucose 3 g and nitrogen 0.1 g/kg/day). The mean(s.e.m.) urinary nitrogen:creatinine ratio was significantly reduced in patients who received IGF-I compared with those given placebo (275.0(17.1) compared with 386.3(23.6), P < 0.01). The mean urinary 3-methylhistidine:creatinine ratio and nitrogen balance were lower in the IGF-I group, but not significantly so. Plasma IGF-I concentrations were four times higher in the treated group compared with those in the placebo group. Insulin-like growth factor binding protein 3 (IGFBP-3) increased significantly after the start of IGF-I treatment, compared with mean postoperative levels. The mean blood glucose concentration was significantly lower in the IGF-I group than the placebo group (P < 0.05) but no patient had a hypoglycaemic attack. The authors conclude that IGF-I does not significantly influence the nitrogen balance, but that results indicate a possible nitrogen-sparing effect in patients after major abdominal operations. IGF-I therapy is safe, and may be of value in catabolic patients after serious injury and major operations.

Blood Glucose↗
PubMed1995

Clusters of acute appendicitis: further evidence for an infectious aetiology.

BACKGROUND: The aetiology of appendicitis, the commonest cause of acute abdomen, is unknown. Infection has been proposed but the evidence has been unconvincing. The purpose of the present study was to investigate if temporo-spatial clustering and outbreaks, characteristics of infectious diseases, could be found in appendicitis cases in a defined Swedish population. METHODS: Temporo-spatial clustering among 1155 cases from three districts of Jönköping County in 1984-1990 was identified by Knox space-time cluster analysis. Outbreaks were identified by retrospective study of temporal variations in 3590 consecutive cases of acute appendicitis from the city of Jönköping in 1969-1990. RESULTS: Space-time clustering was found among patients with operations less than 60 days apart (observed/expected [O/E]-ratio 1.46, P = 0.016). Subset analysis revealed clustering to be commonest among patients from the same households (O/E-ratio 6.52, P = 0.012), among patients younger than 15 years (O/E-ratio 3.61, P = 0.004) and among females (O/E-ratio 2.28, P = 0.004). Three outbreaks with a significantly increased number of cases were observed during the 22-year study period (O/E-ratio 1.6-2.2, P = 0.001-0.049). CONCLUSIONS: The finding of temporo-spatial interaction and outbreaks among appendicitis cases supports the concept that appendicitis may be caused by infectious agents.

Acute Disease↗
PubMed1995

Phospholipase A2 gene expression and activity in histologically normal ileal mucosa and in Crohn's ileitis.

Increased activity of phospholipase A2 (PLA2) in the ileal mucosa may contribute to the inflammation in Crohn's disease. The results of this study showed that (a) three months after ileocolonic resection for Crohn's disease the neoterminal ileal mucosa showed endoscopically new inflammation and had higher PLA2 activity than at the time of the operation (n = 8); no such findings were seen in controls (n = 7), (b) histologically normal ileal mucosa (n = 3) contained mRNA for three isoforms of PLA2 (PLA2-I, PLA2-II, and cPLA2), but the amounts of PLA2-II mRNA clearly exceeded the amounts of mRNA for PLA2-I and cPLA2, (c) ileal mucosa from Crohn's patients (n = 2) contained higher values of PLA2-II mRNA than ileal mucosa from two controls, (d) ileal mucosa from Crohn's patients (n = 4) showed increased PLA2-II mRNA three months after ileocolonic resection. In conclusion, these results show that the predominating PLA2 mRNA in the human ileal mucosa is type II PLA2, and the increased synthesis of PLA2-II might be responsible for the increased PLA2 activity found in the ileal mucosa accompanying recurrent ileal inflammation in Crohn's disease.

Adolescent↗
PubMed1995

Interobserver variation of colonoileoscopic findings in Crohn's disease.

BACKGROUND: Colonoileoscopy is increasingly used to evaluate Crohn's disease, but the reproducibility of endoscopic findings is not clear. METHODS: The interobserver variation of endoscopic findings and the influence of experience on assessments were investigated in 82 colonoileoscopies in Crohn's disease. RESULTS: In colonic assessment there was excellent agreement for most endoscopic features (kappa values > 0.75; p < 0.001). In ileal assessment agreement was excellent with regard to detection of large ulcers and strictures and endoscopic staging on the basis of ulcer size and stricture (kappa > 0.76; p < 0.001). Observer experience was an important factor in ileal assessments: agreement was excellent for 13 features within experienced pairs, compared with 3 when only 1 of a pair was experienced. In colonic assessment experience was less important. CONCLUSION: The study showed that acceptable agreement can be obtained on some well-defined inflammatory lesions in Crohn's disease even when investigator experience is limited. Endoscopic staging on the basis of ulcer size and stricture, being excellently reproducible, can serve as a simple summarizing assessment.

Adult↗
PubMed1995

Importance of endoscopically visualized recurrent ileitis and small-bowel resection for symptoms in Crohn's disease.

BACKGROUND: The relationship between the endoscopic appearance of the ileal mucosa in Crohn's disease and the symptoms has not been studied. Although surgery is important, morbidity caused by intestinal resections and its relation to recurrent inflammation have been poorly evaluated. METHODS: The relationship of symptoms to various ileoscopic signs of inflammation and previous intestinal resection was prospectively studied in 75 postresection Crohn patients. RESULTS: Multivariate analysis showed that a combination of anastomotic width, pus, and length of previous small-bowel resection best explained a symptom score (r = 0.53, p < 0.001). Of 40 patients with the anastomosis strictured to less than 15 mm, only 9 had moderate to severe symptoms. Patients with a stricture diameter < 10 mm differed significantly in symptom score (p < 0.05) from those with wider anastomoses. CONCLUSIONS: The study indicated that intestinal resection was as important for symptoms as endoscopically viewed recurrent ileal inflammation. The diameter at which an intestinal stricture produces symptoms is less than previously argued, and the association of small-bowel resection with symptoms underlines the advisability of minimal surgery.

Adult↗
PubMed1995

Intestinal permeability to polyethylene glycols in monozygotic twins with Crohn's disease.

BACKGROUND: A deranged mucosal permeability, demonstrated in several studies, has been proposed to play a role in the pathogenesis of Crohn's disease. The possibility of a genetically determined alteration of paracellular transport has been indicated in some investigations. The identification of a group of monozygotic twin pairs concordant and discordant for Crohn's disease, prompted this investigation. METHODS: Intestinal absorption after an oral load of different-sized polyethylene glycols (mol.wt, 458-810) was studied as 6-h urinary recovery. The study groups comprised twins with Crohn's disease (n = 19) and their healthy twin siblings (n = 9), non-twin patients with Crohn's disease (n = 14), and healthy controls (n = 30). RESULTS: No differences were found in the absorption of polyethylene glycols between the study groups. CONCLUSION: The results give no support to the hypothesis of a genetically determined intestinal leakiness in Crohn's disease.

Adult↗
PubMed1995

Small intestinal absorption of polyethylene glycol 400 to 1,000 in the portacaval shunted rat.

Functional changes of the intestinal barrier that may occur after the creation of a portacaval shunt (PCS) were investigated. After chronic PCS in the rat, the intestinal absorption of and the jejunal permeability to the inert polymer marker polyethylene glycol (PEG) with molecular weight (Mw) ranging from 400 to 1,000 g/mol were investigated. The PEG mixture was orally fed to PCS and sham-operated rats, and urine was collected for 24 hours to obtain the urinary recovery of the different PEG polymers as a measure of intestinal absorption. To study the intestinal permeability, segments from the proximal small intestine were incubated in diffusion chambers with the PEG mixture on the mucosal side, and samples were withdrawn from the serosal side for analysis. The urinary recovery for the PEGs increased (P < .01) while the tissue permeability decreased (P < .001) in the PCS group rats in comparison with Sham-operated rats. The increased absorption in vivo was caused neither by altered renal clearance, nor by changed portal blood pressure. The decreased jejunal permeability in the PCS rats could be explained by a reduction of the mucosal area by shortening of the microvilli. This discrepancy indicates that changes in permeability and absorption may not be parallel during PCS. It is possible that these changes also may be affected by nutritional factors, drug therapy, as well as toxic substances.

Animals↗
PubMed1994

A comparison of budesonide with prednisolone for active Crohn's disease.

BACKGROUND: Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low. METHODS: We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week. RESULTS: At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score < or = 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P < 0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks. CONCLUSIONS: Among patients with active Crohn's disease, both controlled-release budesonide and prednisolone are effective in inducing remission. In this trial, prednisolone reduced scores on the Crohn's disease activity index more, whereas with budesonide there were fewer glucocorticoid-associated side effects and less suppression of pituitary-adrenal function.

Adult↗
PubMed1994

Indications for operation in suspected appendicitis and incidence of perforation.

OBJECTIVE: To clarify poorly understood epidemiological features of appendicitis. DESIGN: Retrospective study of consecutive cases from a defined population and analysis of data from published studies. SETTING: County of Jönköping, Sweden. 3029 patients who underwent operation in 1984-9 and 4717 patients from the county town who underwent operation in 1970-89, all for suspected appendicitis, plus 48,426 cases from six reported studies. MAIN OUTCOME MEASURES: Incidences specific for age and sex and temporal trends of perforating and non-perforating appendicitis and removal of a normal appendix. Associations between diagnostic accuracy, rate of perforation, and incidences of removal of a normal appendix and of perforating and non-perforating appendicitis. RESULTS: The incidence of appendicitis was 116/100,000 inhabitants. Appendicitis was more common in male patients. The incidence of perforating appendicitis was independent of age, stable over time, and uninfluenced by the rate of laparotomy, whereas the incidence of non-perforating appendicitis was age dependent, decreasing over time, and related to the diagnostic accuracy and rate of removal of a normal appendix. CONCLUSIONS: Perforating and non-perforating appendicitis seem to be separate entities, and appendicitis that resolves spontaneously is common. This may have important implications for managing suspected appendicitis.

Adolescent↗