Biomedical subjects

Juan-R Malagelada

Publications and source records attributed to Juan-R Malagelada.

23 records · Page 2Linked to original sources

PubMed2003

Sucralfate therapy in NSAID bleeding gastropathy.

BACKGROUND AND AIMS: A randomized, double-blind, placebo-controlled, multicenter study was conducted to assess the efficacy of 2 g sucralfate suspension in treating gastric mucosal lesions caused by long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Only patients given NSAIDs continuously for at least 2 months with positive fecal occult blood (FOB) and endoscopically confirmed mild to moderate mucosal lesions (Lanza scale, grades 2-4) were included. After 1-week run-in phase, patients were stratified into 2 groups according to gastropathy-related symptoms during the preceding 7 days (symptomatic vs. asymptomatic) and randomized to 2 g (10 mL) of sucralfate suspension or placebo twice a day over a 6-week period. NSAIDs were given according to each patient's dosage schedule and always after meals. RESULTS: Twenty-five patients received sucralfate and 25 received placebo. At the end of the study, 68% (17/25) of patients given sucralfate had no lesions (Lanza grade 0) on endoscopy compared with 35% (8/23) in controls (P = 0.042). The Lanza grades in patients given sucralfate were significantly improved compared with the placebo patients (P = 0.022). CONCLUSIONS: In this target population selected according to positive FOB test and endoscopic evidence of mucosal injury, chronic administration of sucralfate significantly decreased NSAID-induced gastric erosions.

Adult↗

PubMed2002

Increased activity and expression of matrix metalloproteinase-9 in a rat model of distal colitis.

Matrix metalloproteinases may play a role in tissue remodelling and destruction associated with inflammation. We investigated activity and expression of matrix metalloproteinases in a rat model of colitis and tested the therapeutic potential of a synthetic inhibitor (CGS-27023-A). Colitis was induced by dextran sulphate sodium (at 5% in drinking water for 5 days) in a group of eight rats, whereas a matched control group received plain water. Activity and expression of matrix metalloproteinases were measured in colonic tissue homogenates using zymography and Western blot on days 3 and 5 after induction of colitis. In another set of experiments, two groups of colitic rats (20 per group) were treated with CGS-27023-A (20 mg/kg) or vehicle, respectively. On days 5 and 14, colonic mucosal lesions were blindly scored by microscopic examination. Induction of colitis led to a significant upregulation of matrix metalloproteinase-9 protein and its activity, but no change in matrix metalloproteinase-2 activity was observed. Treatment with CGS-27023-A significantly decreased the extent and severity of epithelial injury but did not influence mucosal repair. We conclude that increased activity of matrix metalloproteinases may contribute to epithelial damage in this model of colitis.

Animals↗

PubMed2002

Lipid-induced intestinal gas retention in irritable bowel syndrome.

BACKGROUND & AIMS: We hypothesized that lipids, which induce various motor and sensory effects on the gut, modulate intestinal gas dynamics and that alteration of this regulatory mechanism may result in impaired gas transit in patients with irritable bowel syndrome (IBS). METHODS: In 45 healthy subjects and 30 patients with IBS, evacuation of gas infused into the jejunum (at 12 mL/min) was measured for 2 hours. The effect of simultaneous duodenal perfusion of lipids at 0 kcal/min (saline), 0.5 kcal/min, and 1 kcal/min was tested in groups of 15 subjects each. RESULTS: In healthy subjects, duodenal lipids at 1 kcal/min but not at 0 kcal/min or 0.5 kcal/min produced significant gas retention (281 +/- 53 mL vs. 22 +/- 64 mL at 0 kcal/min and -65 +/- 72 mL at 0.5 kcal/min; P < 0.05 for both). Patients with IBS exhibited gas retention during saline perfusion (259 +/- 85 mL at 0 kcal/min; P < 0.05 vs. healthy subjects) and were hypersensitive to duodenal lipids (505 +/- 61 mL retention at 0.5 kcal/min; P < 0.05 vs. saline and vs. healthy subjects). The "gas plus lipids" challenge test discriminated patients with 100% sensitivity and 93% specificity. CONCLUSIONS: Physiologic concentrations of intestinal lipids exert an inhibitory control on intestinal gas transit, and this mechanism is up-regulated in patients with IBS. Hence, impaired gas propulsion, shown by the gas challenge test, may be useful as a diagnostic test if replicated in a larger series of patients.

Adult↗

PubMed2002

Significance of pelvic floor muscles in anal incontinence.

BACKGROUND & AIMS: The pathophysiology of anal incontinence may be elusive using current parameters. Our aim was to establish the role of the levator ani in anal continence. METHODS: In 53 patients with anal incontinence, 30 with constipation as disease controls, and 15 healthy controls, we evaluated incontinence severity by a 0-12 scale, anorectal function by standard manometric tests, and levator ani contraction by a perineal dynamometer. RESULTS: Patients with incontinence exhibited various physiologic abnormalities (3.2 +/- 0.3 per patient), but multiple regression analysis showed that levator ani contraction was the independent variable with strongest relation to the severity of incontinence (R = -0.84; P < 0.0001), as well as a predictive factor of the response to treatment (R = 0.53; P < 0.01). Furthermore, in contrast to other physiologic parameters, clinical improvement in response to treatment (4.4 +/- 0.5 score vs. 7.9 +/- 0.5 score pre; P < 0.001) was associated with a marked and significant strengthening of levator ani contraction (448 +/- 47 g vs. 351 +/- 35 g pre; P < 0.05). CONCLUSIONS: We have shown the importance of levator ani failure in understanding the etiology of anal incontinence and in predicting response to treatment.

Adult↗

PubMed2002

Gut perception in humans is modulated by interacting gut stimuli.

Digestive symptoms depend on multiple interacting gut stimuli, but integration of visceral afferent traffic is poorly understood. Our aim was to elucidate the contribution of simultaneous intestinal stimuli to conscious perception. In 17 healthy subjects, we performed stimulus-response trials of jejunal distensions (1-min duration at 5-min intervals in 8-ml increments) either alone or with a background electrical stimulus, and stimulus-response trials of electrical stimuli (1-min duration at 5-min intervals in 6-mA steps) either alone or with a background intestinal distension. The four stimulus-response trials were performed concomitantly applying the different types of stimuli in random order. Perception was measured on a scale of 0 to 6. Background stimulation markedly increased perception of test stimuli, reducing tolerance from 44 +/- 3 to 32 +/- 3 ml and from 67 +/- 6 to 33 +/- 4 mA (P < 0.05 for both). However, whereas jejunal distensions below the perception threshold did not modify perception of the background stimulus (4 +/- 1% change; not significant), unperceived electrical stimuli exerted a sensitizing effect and increased perception of the background distension up to uncomfortable levels (111 +/- 40% increment; P < 0.05). In conclusion, activation of different pools of jejunal afferents produces summative effects on perception, and this sensitizing effect can be exerted by unperceived stimulation of mechanoinsensitive jejunal afferents.

Adult↗