Biomedical subjects

J-R Malagelada

Publications and source records attributed to J-R Malagelada.

17 recordsLinked to original sources

PubMed2006

Selective effects of nutrients on gut sensitivity and reflexes.

BACKGROUND: Intestinal nutrients induce gut reflexes and modulate perception. AIM: To elucidate the relative potency and putative relationship of motor and sensory effects induced by different nutrients. METHODS: By paired tests carried out in sequence on healthy patients, the effect of isocaloric duodenal infusions of carbohydrates and lipids was determined on gastric compliance and on perception of gastric distension. Gastric distension at stepwise tension increments was applied using a tensostat, and perception at each tension level was measured on a 0-6 scale. In separate groups (n = 8 each), three nutrient loads were tested: (A) low (0.2 kcal/min), (B) medium (0.5 kcal/min) and (C) high (1 kcal/min). RESULTS: Values are mean (standard error). (A) Low caloric loads: both gastric perception and compliance were similar with lipids (45 (2) g, 451 (28) ml tolerated) and carbohydrates (46 (1) g, 449 (22) ml tolerated). (B) Medium caloric loads: although perception remained unchanged (46 (1) g and 46 (2) g tolerated, respectively), lipids, but not carbohydrates, partially relaxed the stomach (559 (18) v 442 (31) ml intragastric volume, respectively; p<0.05). (C) High caloric loads: lipids markedly reduced gastric tolerance and increased compliance (22 (3) g, 635 (34) ml tolerated), whereas carbohydrates did not affect perception and induced only a partial gastric relaxation (46 (1) g, 565 (46) ml tolerated; p<0.05 v lipids for both). CONCLUSION: The effects of intestinal nutrients on gastric tone are more potent than those on gastric sensation, and both depend on the caloric load and the type of nutrient.

Adult↗

PubMed2006

Intestinal sensitivity testing by transmucosal electrical nerve stimulation: stimulus parameters to induce conscious perception.

Intestinal sensitivity can be tested using transmucosal electrical nerve stimulation. The aim of this study was to establish the stimulus characteristics that determine perception. In six healthy subjects constant current electrical stimuli were applied via an intrajejunal bipolar electrode while measuring perception. Intensity-response tests with stimuli trains of various frequencies (5 and 100 Hz) and pulse durations (50 and 1000 mus) were performed. All stimuli within the broad range tested induced similar-type abdominal sensations, but the intensity of the stimuli to produce perception differed depending on both pulse duration and frequency. A 20-fold increase in pulse duration decreased the intensity of perceived stimuli by a factor of 0.34 +/- 0.04 (P < 0.05); a similar increase in pulse frequency decreased the intensity by a 0.63 +/- 0.07 factor (P < 0.05). When the frequency and duration concomitantly increased, the stimulus intensity decreased by the product of both factors (0.22 +/- 0.04). Transmucosal electrical nerve stimulation of the intestine induces perception within a broad range of stimuli. However, the intensity of the stimuli required to activate sensory pathways is primarily weighted by the duration rather than by the frequency of the pulses.

Adult↗

PubMed2006

Intramuscular interstitial cells of Cajal associated with mast cells survive nitrergic nerves in achalasia.

Achalasia is dominated by injury to inhibitory nerves. As intramuscular interstitial cells of Cajal (ICC-IM) are proposed to form functional units with nitrergic nerves, their fate in achalasia may be critically important. We studied the relationship between loss of nitrergic nerves and injury to ICC-IM in patients with achalasia and determined associations between ICC-IM and mast cells (MC), using quantitative immunohistochemistry and electron microscopy. Loss of neuronal nitric oxide synthase (nNOS) immunoreactivity was completed within 3 years of acquiring achalasia. Thereafter, progressive ultrastructural injury to remaining nerve structures was evident. Within the first 2 years, the number of ICC-IM did not decline although ultrastructural injury was already present. Thereafter, loss of ICC-IM occurred unrelated to duration of disease. Damage to ICC-IM appeared unrelated to nerve injury. A significant MC infiltration was observed in the musculature; the number of MC was positively related to the persistent number of ICC-IM. Mast cell formed close contacts with ICC-IM and piecemeal-degranulation occurred towards ICC-IM. In conclusion, injury to ICC-IM in achalasia is variable, but not related to duration of disease and injury to nitrergic nerves. MC are prominent and form close functional contact with ICC-IM which may be responsible for their relatively long survival.

Aged↗

PubMed2006

Intestinal tone and gas motion.

The intestine propels and evacuates large gas loads without detectable phasic contractions by manometry. We hypothesized that intestinal gas motion is produced by changes in gut tone and capacitance. In 13 healthy subjects, changes in duodenal tone were measured by a barostat during continuous perfusion of lipids (Intralipid, 1 kcal min(-1)) into the duodenum for 60 min. In separate groups, the effects of jejunal gas infusion (N2, CO2 and O2 in venous proportions at 12 mL min(-1) starting after 15 min lipid perfusion) and sham infusion were tested. Gas outflow was collected continuously via an intrarectal cannula. Duodenal lipid perfusion produced a rapid duodenal relaxation (volume increased by 48 +/- 18%; P < 0.01 vs basal). Gas infusion increased gas evacuation (184 +/- 59 mL), and this was associated with a tonic contraction of the duodenum (R = 0.86; P < 0.01) that completely reverted the lipid-induced duodenal relaxation (volume decreased by 42 +/- 13%; P < 0.05). During sham infusion only 52 +/- 28 mL of gas were evacuated (P < 0.05 vs gas infusion), and the duodenum remained relaxed due to the effect of lipids (0 +/- 1% volume reduction; ns). In conclusion, intestinal gas propulsion and clearance is associated with a tonic contraction of the gut wall and reduced gut capacitance.

Adult↗

PubMed2006

A symptom-based approach to making a positive diagnosis of irritable bowel syndrome with constipation.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Characterised by abdominal pain or discomfort, bloating and altered bowel habit, IBS is a chronic recurring condition, typically affecting up to 15% of the Western population, IBS can be subclassified into IBS with constipation (IBS-C), IBS with diarrhoea (IBS-D), or IBS with alternating constipation or diarrhoea symptoms (IBS-A). Conventional clinical diagnosis focuses on excluding all potential organic causes of patient symptoms. However, a positive diagnosis of IBS may be established using published criteria such as the Manning and/or Rome criteria. While these methods are useful to identify patients with IBS who are suitable for enrollment into clinical trials, the criteria are relatively complex and not readily applicable to general practice. In this review we present an 'identify, eliminate, probe' algorithm that may be appropriate to establish a positive diagnosis of patients with IBS-C, as symptoms characteristic of patients in this IBS subgroup are least likely to be confused with symptoms reflecting serious organic disease.

Algorithms↗

PubMed2005

Selective inhibition of phosphodiesterase-4 ameliorates chronic colitis and prevents intestinal fibrosis.

The phosphodiesterase-4 (PDE4) inhibitors may be an important target in the treatment of several inflammatory conditions. The anti-inflammatory effect of PDE4 inhibitors bears similarities with that of steroids, without interfering with the hypophysary-adrenal-axis. We compared the effect of rolipram, a selective PDE4 inhibitor, with steroids on the clinical course of experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Three groups of rats (n = 20) received TNBS. One group received methylprednisolone from day 7, another group received rolipram from the same day, and control group received no further treatment. On days 14 and 21 after TNBS instillation, sets of 10 rats underwent colonic dialysis to measure eicosanoid release. Colonic lesions were blindly scored, and colons were homogenized for quantification of myeloperoxidase (MPO) activity and collagen content. Concentration of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) in colonic tissue was also measured. Both treatments reduced significantly the eicosanoid release and MPO activity. On day 14, both rolipram and methylprednisolone significantly reduced TNF-alpha content, but TGF-beta1 was only inhibited by rolipram. On day 21, lesion scores and collagen content were significantly reduced only in rolipram-treated group. In conclusion, PDE4 inhibition by rolipram markedly ameliorates the course of chronic colitis and it is superior to methylprednisolone in preventing late collagen deposition.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Impairment of health-related quality of life in patients with inflammatory bowel disease: a Spanish multicenter study.

BACKGROUND: Inflammatory bowel disease impairs patients' perception of health and has a negative impact on health-related quality of life (HRQOL). Most studies include patients from a single hospital. This may bias limit results through the use of small patient samples and/or samples within a restricted disease spectrum. METHODS: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) from 9 hospitals located in different geographical areas in Spain using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. RESULTS: The study included 1156 patients (528 patients with UC and 628 with CD; median age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in parallel with disease severity to a similar extent in both UC (IBDQ scores of 6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between clinical activity and quality of life was observed when EuroQol preference values were used. All 5 dimensions of the IBDQ showed significantly lower scores in patients with active UC and CD than in patients in remission. The pattern of scores by IBDQ dimensions differed between patients in relapse (who scored worse on the digestive symptoms dimension) and patients in remission. Variables related with disease activity, time of evolution since diagnosis and female sex, were significantly associated with having a worse perception of HRQOL. The type of disease or geographical area of residence did not influence results on the IBDQ. CONCLUSIONS: UC and CD impair patients' HRQOL, and the degree of impairment depends on disease activity but is independent of the type of disease and place of residence.

Adult↗

PubMed2005

Impaired reflex control of intestinal gas transit in patients with abdominal bloating.

BACKGROUND: Patients with abdominal bloating and distension exhibit impaired transit of intestinal gas which may lead to excessive gas retention and symptoms. Furthermore, we have previously shown that intestinal gas transit is normally accelerated by rectal distension. We hypothesise that in patients with functional bloating this modulatory mechanism fails and impairs gas transit. METHODS: In 12 healthy subjects and eight patients with abdominal bloating we compared, by paired studies, the effect of rectal versus sham distension on intestinal gas transit. Gas was infused into the jejunum (12 ml/min) for three hours with simultaneous perfusion of lipids into the duodenum (Intralipid 1 kcal/min) while measuring evacuation of gas per rectum. RESULTS: In healthy subjects, duodenal lipid infusion produced gas retention (409 (68) ml) which was prevented by rectal distension (90 (90) ml; p<0.05 v sham distension). In contrast, rectal distension in patients with abdominal bloating failed to reduce lipid induced gas retention (771 (217) ml retention during rectal distension v 730 (183) ml during sham distension; NS; p<0.05 v healthy controls for both). CONCLUSION: Failure of distension related reflexes impairs intestinal gas propulsion and clearance in patients with abdominal bloating.

Abdomen↗

PubMed2005

Mucosal colonisation with Lactobacillus casei mitigates barrier injury induced by exposure to trinitronbenzene sulphonic acid.

BACKGROUND: Trinitrobenzene sulphonic acid (TNBS) induces chronic transmural inflammatory lesions in the rat colon. Injury is facilitated by barrier disruption and invasion of commensal bacteria. However, certain bacteria have shown anti-inflammatory properties in in vitro models. AIM: To investigate in vivo the anti-inflammatory effect of Lactobacillus casei DN-114 001. METHODS: Rats with a colonic segment excluded from faecal transit were surgically prepared. After washing the lumen with antibiotics, the excluded segment was recolonized (control group: standard flora of rat origin; test group: standard flora and L casei). Microbial colonisation was confirmed by culture of segment washing, and colitis was then induced by instillation of TNBS. One day after, intestinal lesions were blindly graded by macro- and microscopic scores, and myeloperoxidase activity measured in tissue homogenates. Translocation of bacteria to mesenteric lymph nodes, spleen and liver was investigated. RESULTS: Test rats showed a smaller area of mucosal injury than control rats (p<0.05). Maximum depth lesion scores were similar in both groups but myeloperoxidase activity was lower in test than in control rats (p<0.05). Remarkably, bacterial translocation was quantitatively lower (p<0.01) and less frequent (p<0.05) in test than in control rats. CONCLUSION: In rats colonised with L casei, mucosal injury, inflammatory response, and barrier disruption after TNBS challenge were attenuated. Bacterial communities colonising the mucosa can modify inflammatory responses to luminal challenges.

Animals↗

PubMed2004

Shortened questionnaire on quality of life for inflammatory bowel disease.

Questionnaires for measuring quality of life in patients with inflammatory bowel disease usually include a large number of items and are time-consuming for both administration and interpretation. Our aim was to elaborate and validate a short quality-of-life questionnaire with the most representative items from the Spanish version of the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) using the Rasch analysis. The responses to 311 IBDQ-36 questionnaires from 167 patients with ulcerative colitis (UC) and 144 with Crohn's disease (CD) were analyzed. IBDQ-36 was shortened with successive Rasch analyses until all the remaining items showed acceptable separation and goodness-of-fit properties. Validation of the short questionnaire was studied in a new group of 125 patients by determining its validity and reliability. A 9-item short questionnaire was obtained (IBDQ-9). Its correlation with IBDQ-36 was excellent (r = 0.91). Correlation between IBDQ-9 and clinical indices of activity was statistically significant in UC (r = 0.70) and CD (r= 0.70). IBDQ-9 score discriminates adequately between patients in clinical remission or relapse (P < 0.01). Sensitivity to change was determined in 14 patients who improved clinically, showing significant IBDQ-9 changes between both determinations (P < 0.01), with an effect size of -2.67 in UC and -5.29 in CD. IBDQ-9 was also homogeneous, with a Cronbach's alpha of 0.95 in UC and 0.91 in CD. In 35-clinically stable patients, test-retest reliability was good, with a statistically-significant correlation between both questionnaires (r = 0.76 in UC and 0.86 in CD, P < 0.01) and an intraclass correlation coefficient of 0.82 in UC and 0.84 in CD. In conclusion, a short and valid questionnaire to measure quality of life in patients with inflammatory bowel disease was obtained using a new measurement model. Its use should facilitate comprehension of the impact of inflammatory bowel disease.

Adult↗

PubMed2004

Sites of symptomatic gas retention during intestinal lipid perfusion in healthy subjects.

BACKGROUND: Gas pooling within the gut may produce abdominal symptoms but the segment of the intestine responsible for gas retention is unknown. Our aim was to determine the role of the proximal and distal bowel in symptomatic gas accumulation using an experimental model of gas retention triggered by intraluminal lipids. SUBJECTS: Sixteen healthy subjects. METHODS: A gas mixture (N2, O2, and CO2 in venous proportions) was infused into the intestine at12 ml/min for three hours and gas evacuation was continuously measured via an anal cannula connected to a barostat. Abdominal perception and girth changes were measured at 10 minute intervals. Lipids (1 kcal/min) were simultaneously perfused either into the duodenum (n = 8) or into the ileum (n = 8). Each subject was studied twice on separate days, with gas infused into the jejunum or ileum. RESULTS: Duodenal lipids produced retention of gas infused into the jejunum (646 (62) ml) but the volume retained was much smaller when gas was infused directly into the ileum (262 (90) ml; p<0.05). The effects on gas retention were even more pronounced during ileal perfusion of lipids (1546 (184) ml during jejunal gas infusion and 847 (142) ml during ileal gas infusion; p<0.05). Abdominal distension correlated with the volume of gas retained (r = 0.87; p<0.001). Healthy subjects tolerated gas retention, and significant symptoms (score 3.7 (0.8)) developed only during jejunal gas infusion plus ileal lipid perfusion when gas retention was very large. CONCLUSION: Intraluminal lipids induce intestinal gas retention, predominantly acting on the proximal small bowel.

Abdomen↗

PubMed2004

Response of first attack of inflammatory bowel disease requiring hospital admission to steroid therapy.

INTRODUCTION: Corticoid administration is the usual treatment of Crohńs disease (CD) and ulcerative colitis (UC) attacks. However, information available on response rates and their predictive factors is scarce. OBJECTIVE: To establish response to steroidal treatment in an homogeneous group of patients with CD or UC during their first admission to hospital. METHODS: Restrospective analysis of 86 patients who received systemic steroidal treatment for a severe flare-up during their first hospital admission between 1995 and 2000. Patients were treated per protocol with fluid therapy, absolute diet, IV 6-methyl-prednisolone 1 mg/kg/day, and enoxaparin at prophylactic doses. Clinical response at 30 days was considered good in case of complete remission, and poor in case of partial or absent remission. Univariate and multivariate analyses according to non-parametric statistics were performed for sociodemographic and biologic variables. RESULTS: 45 patients with CD and 41 with UC were included. Good response rates were 64.4% for CD and 60.9% for UC. The univariate analysis showed that patients with good response have shorter evolution times and fewer previous flare-ups (p < 0.05) regarding CD. However, the multivariate analysis showed that none of the analyzed variables had predictive value. CONCLUSION: The response rate of severe inflammatory bowel disease attacks to corticoids is around 60% in CD and UC. Data resulting from the current study cannot predict which patients will ultimately respond to therapy.

Adult↗

PubMed2003

Intestinal gas distribution determines abdominal symptoms.

BACKGROUND: Patients with functional gut disorders manifest poor tolerance to intestinal gas loads but the mechanism of this dysfunction is unknown. AIM: Our aims were firstly, to explore the relative importance of the amount of intestinal gas versus its distribution on symptom production, and secondly, to correlate gut motility and perception of gas loads. SUBJECTS: Fourteen healthy subjects with no gastrointestinal symptoms. METHODS: In each subject a gas mixture was infused (12 ml/min) either into the jejunum or rectum for one hour during blocked rectal gas outflow, and subsequently gas clearance was measured over one hour of free rectal evacuation. We measured abdominal perception, distension, and gut tone by duodenal and rectal barostats. RESULTS: Similar magnitude of gas retention (720 ml) produced significantly more abdominal symptoms with jejunal compared with rectal infusion (perception score 4.4 (0.4) v 1.5 (0.5), respectively; p<0.01) whereas abdominal distension was similar (15 (2) mm and 14 (1) mm girth increment, respectively). Jejunal gas loads were associated with proximal contraction (by 57 (5)%) and colonic loads with distal relaxation (by 99 (20)%). CONCLUSION: The volume of gas within the gut determines abdominal distension whereas symptom perception depends on intraluminal gas distribution and possibly also on the gut motor response to gas loads.

Abdomen↗

PubMed2003

Severe idiopathic gastroparesis due to neuronal and interstitial cells of Cajal degeneration: pathological findings and management.

Delayed gastric emptying can be due to muscular, neural, or humoral abnormalities. In the absence of an identified cause, gastroparesis is labelled as idiopathic. We present the case of a patient with severe idiopathic gastroparesis. Pharmacological approaches failed, as well as reduction in gastric emptying resistance with pyloric injection of botulinum toxin and pyloroplasty. Therefore, subtotal gastrectomy was performed. Histological and immunohistochemical study of the resected specimen showed hypoganglionosis, neuronal dysplasia, and a marked reduction in both myenteric and intramuscular interstitial cells of Cajal. To our knowledge, this is the first time these rare histological findings have been described in a patient with idiopathic gastroparesis.

Adult↗

PubMed2003

Influence of body posture on intestinal transit of gas.

BACKGROUND: Patients describe that body posture may affect their abdominal bloating, distension, and flatulence, but whether changes in position have objectively demonstrable effects, either beneficial or deleterious, has not been investigated. AIM: To determine the effect of body posture, upright versus supine, on intestinal transit of gas loads. SUBJECTS: Eight healthy subjects without gastrointestinal symptoms. METHODS: In each subject a gas mixture was continuously infused into the jejunum (12 ml/min) for three hours, and gas evacuation, clearance of a non- absorbable gaseous marker, perception, and abdominal girth were measured. Paired studies were randomly performed in each subject on separate days in the upright and supine positions. RESULTS: In the upright position, intestinal gas retention was much smaller than when supine (13 (52) ml v 146 (75) ml retention at 60 minutes, respectively; p<0.05), and clearance of the gas marker was expedited (72 (10)% clearance v 49 (16)% at 60 minutes, respectively; p<0.05). The gas challenge test was well tolerated both in the upright and supine positions without abdominal distension. CONCLUSION: Body posture has a significant influence on intestinal gas propulsion: transit is faster in the upright position than when supine.

Adult↗

PubMed2002

Role of microecology in chronic inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology. Current therapy mitigates the severity of acute bouts of mucosal inflammation but an eradication therapy is lacking. Growing incidence of IBD is associated with social development. Epidemiology suggests a relationship between the establishment of the individual gut flora and the risk of developing IBD. Patients show an impaired tolerance towards commensal bacteria of the resident flora. Unrestrained activation of the intestinal immune system against some commensal bacteria appears to be responsible for the characteristic relapsing course of these diseases. Wide-spectrum antibiotic therapy reduces bacterial load and mitigates intestinal inflammation in human IBD and in animal models. Current research aims at the identification of probiotics for bacterial antagonism therapies. Probiotics are living microorganisms which upon ingestion in certain numbers exert health benefits beyond inherent basic nutrition. Colonization with a Lactobacillus reuteri strain can prevent the development of colitis in genetically susceptible mice. Other studies have used a bacterium genetically engineered to secrete the antiinflammatory cytokine IL-10 and demonstrated a therapeutic effect in animal models of colitis. Moreover, some probiotics may naturally exhibit antiinflammatory properties when interacting with the human gut mucosa. Prebiotics such as inulin have also been shown to prevent colonic inflammation in animal models. Preliminary clinical trials with probiotics in IBD are encouraging. Probiotics offer a valuable tool for the prevention and control of inflammatory bowel diseases.

Animals↗

PubMed2002

Sensation and gas dynamics in functional gastrointestinal disorders.

Our current knowledge of motor and sensory functions in the human gut is critically reviewed, showing how the two may interact to produce symptoms in patients with functional gastrointestinal disorders. A local stimulus is necessary to activate the pathogenetic symptom generation process, and in many patients abnormal pooling of gas at various or extensive sites in the bowel and focal gut distension may provide the local stimulus, compounded by spatial summation phenomena and conscious visceral hypersensitivity. The interplay of these mechanisms results in the clinical expression of symptoms.

Colonic Diseases, Functional↗