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| 12. |
- Hellström, Per M., 1954-, et al.
(författare)
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Luminal Nitric Oxide and Plasma Nitrite/Nitrate As Predictors of Colectomy in Corticosteroid-Treated Acute Colitis
- 2015
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Ingår i: Gastroenterology. - Uppsala. - 0016-5085 .- 1528-0012. ; 148:4, suppl. 1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nitric oxide (NO) is known to be up-regulated by the induction of induciblenitric oxide synthase (iNOS) in inflammatory conditions. NO gas can be used as a markerof inflammatory activity in hollow organs. In parallel, plasma nitrite + nitrate (NOx) canreflect the ongoing inflammatory activity. We analyzed rectal NO before and after threedays, as well as plasma NOx in patients on glucocorticosteroid (GC) therapy in hospitalizedpatients. The aim of the study was to evaluate the relationship of rectal luminal NO andcirculating plasma NOx in acute fulminant colitis to the outcome as therapeutic responseor colectomy.Methods: 50 patients with median age 41 (range 20-78) years were hospitalizeddue to acute fulminant colitis and received treatment with high-dose GCs. Luminal nitricoxide was analyzed with chemiluminescence before therapy onset of therapy with GC andon day 3 of treatment. NOx was measured by nitrite/nitrate colorimetric assay. NO levelsand plasma NOx were compared to clinical disease activity index and C-reactive protein(CRP).Results: 32 responded to GC treatment and 18 did not, resulting in colectomy.The responders had higher luminal NO than non-responders (day 1: 12525±2600, day 3:15590±4157 ppb) vs non-responders (day 1: 2874±1283, day 3: 1137±297 ppb) (p<0.0114).Using an optimal cut-off NO level of 2250 ppb, sensitivity and specificity was 86% and81% for colectomy (p<0.0001). The area under the curve was 0.88 and likelihood ratio4.8. Similarly, plasma NOx was higher in responders vs non-responders (day 1: 6.2±0.3 vs3.9±0.4 umol/L) (p<0.0001). Using plasma NOx, we found a corresponding cut-off at 5umol/L with sensitivity 87% and specificity 87%. The area under the curve was 0.88 andlikelihood ratio 6.7. Luminal NO was also correlated to plasma NOx (r=0.33, p=0.0205).In the responder group, CRP levels decreased (day 1: 22.31±2.95, day 3: 15.69±3.57mg/L), whereas among non-responders CRP levels increased (day 1: 45.83±11.10, day 3:76.35±16.96 mg/L) (p<0.0167). Kaplan-Meier analysis showed that patients with baselineNO levels lower than 2250 ppb were at a significantly higher risk of colectomy within onemonth from onset of GCS treatment (p<0.0001). Twelve out of 18 (67%) in patients withday 1 NO <2250 ppb were colectomized, the corresponding number of patients with NO>2250 ppb was 3 out of 32 (9%). In a similar manner, using plasma NOx <5 uml/L foranalysis, we found 13 (72%) to be colectomized, and with >5 umol/L only two (6%).Conclusion: NO and its oxidation product NOx are markers of inflammatory activity in thegut. However, with more intense inflammation and mucosal damage, the less NO is produced.Luminal NO as well as plasma NOx can be used as a sensitive biomarker to predict colectomyin the outcome of acute fulminant colitis
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| 15. |
- Lind, Tore, et al.
(författare)
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The MACH2 study : Role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies
- 1999
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 116:2, s. 248-253
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established. This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance.Methods: Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori screening test result were randomized into 4 groups. OAC group received 20 mg omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg, and clarithromycin, 250 mg) groups received no omeprazole. All doses were administered twice daily for 1 week. H. pylori status was assessed before and after therapy by 13C-urea breath test. Susceptibility testing was performed at entry and in patients with persistent infection after therapy.Results: Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001). Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and clarithromycin resistance each developed in 12 patients: 8 treated with omeprazole and 16 without omeprazole.Conclusions: Addition of omeprazole achieves high eradication rates, reduces the impact of primary resistance, and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics.
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| 20. |
- Söderholm, Johan D, 1958-, et al.
(författare)
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Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?
- 1999
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 117:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Crohn's disease (CD) is associated with a disturbed intestinal barrier. Permeability studies have focused on inert molecules, but little is known about transepithelial transport of macromolecules with antigenic potential in humans. The aim of this study was to quantify permeation and to characterize passage routes for macromolecules in ileal mucosa in CD.Methods: Noninflamed and inflamed ileal mucosa specimens from patients with CD (n = 12) and ileal specimens from patients with colon cancer (n = 7) were studied regarding transmucosal permeation of ovalbumin, dextran (mol wt, 40,000), and 51Cr-EDTA for 90 minutes in vitro in Ussing chambers. Transepithelial passage routes for fluorescent ovalbumin and dextran 40,000 were investigated by confocal microscopy.Results: Noninflamed ileum from CD patients showed increased permeation of ovalbumin compared with ileum from colon cancer patients (P < 0.05). Dextran permeation was equal in the three groups, whereas 51Cr-EDTA permeability was increased in inflamed ileum. Ovalbumin passed both transcellularly and paracellularly, but dextran followed a strictly paracellular route. Both markers were subsequently endocytosed by cells of the lamina propria.Conclusions: Noninflamed ileal mucosa from patients with CD shows increased epithelial permeability to ovalbumin, probably by augmented transcytosis. This increase in antigen load to the lamina propria could be an initiating pathogenic event in CD.
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