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Biomedical subjects

J R Malagelada

Publications and source records attributed to J R Malagelada.

At least 19 recordsLinked to original sources

Guidelines for adults on self-medication for the treatment of acute diarrhoea.

Acute uncomplicated diarrhoea is commonly treated by self-medication. Guidelines for treatment exist, but are inconsistent, sometimes contradictory, and often owe more to dogma than evidence. An ad hoc multidisciplinary group has reviewed the literature to determine best practice. In general it is recognized that treatment of acute episodes relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. Self-medication in otherwise healthy adults is safe. Oral loperamide is the treatment of choice. Older anti-diarrhoeal drugs are also effective in the relief of symptoms but carry the risk of unwanted adverse effects. Oral rehydration solutions do not relieve diarrhoea, and confer no added benefit for adults who can maintain their fluid intake. Probiotic agents are, at present, limited in efficacy and availability. Antimicrobial drugs, available without prescription in some countries, are not generally appropriate for self-medication, except for travellers on the basis of medical advice prior to departure. Medical intervention is recommended for the management of acute diarrhoea in the frail, the elderly (> 75 years), persons with concurrent chronic disease, and children. Medical intervention is also required when there is no abatement of the symptoms after 48 h, or when there is evidence of deterioration such as dehydration, abdominal distension, or the onset of dysentery (pyrexia > 38.5 degrees C and/or bloody stools).

Acute Disease↗

Gastrointestinal, liver, and pancreatic involvement in adult patients with cystic fibrosis.

BACKGROUND: The clinical prevalence of cystic fibrosis (CF) in adults continues to rise, with a consequent impact on adult gastroenterology practice. AIM: To characterize the gastrointestinal manifestations of CF in adult patients. PATIENTS AND METHODS: The clinical records of 89 adult CF patients treated at our institution from 1992 to 1999 were reviewed. Patients were distributed into two groups: group A (39 patients), which consisted of patients who were diagnosed with CF at when they were younger than 14 years old and who survived into adulthood; and group B (50 patients), who were diagnosed with CF at the age of 14 years or older. Data on CF genetic mutations, nutritional state, evidence of pulmonary, gastrointestinal, liver, or pancreatic involvement were collected for each patient. RESULTS: The most prevalent genetic mutation in our series was deltaF508, present in 50 patients (56.2%), 29 of whom belonged to group A and 21 who belonged to group B. In group A, the deltaF508 mutation was associated with exocrine pancreatic insufficiency (PI) in 26 of 29 patients (89.6%), whereas in group B it was associated with PI in only four patients (19%). Overall, PI was present in 33 of 39 patients (84.6%) in group A and in eight of 50 patients (16%) in group B. Four patients in group B had experienced previous episodes of acute pancreatitis; two of them had associated PI. Of the 89 patients, 12 (10 in group A) were malnourished. Malnutrition was invariably associated with PI. Hepatic and biliary tree abnormalities were particularly prevalent in patients in group A and was usually associated with PI. Intestinal manifestations were uncommon. CONCLUSIONS: Diagnosis of CF before the age of 14 years is associated with greater gastrointestinal compromise than diagnosis at an older age, particularly with regard to PI. CF carriers of the deltaF508 mutation have an increased risk of developing gastrointestinal manifestations.

Acute Disease↗

Influence of inflammatory bowel disease on different dimensions of quality of life.

OBJECTIVE: To establish the impairment of different dimensions of quality of life in inflammatory bowel disease (IBD). DESIGN: Prospective observational study. PARTICIPANTS: 289 patients [160 with ulcerative colitis (UC) and 129 with Crohn's disease (CD)]. MEASURES: Health-related quality of life was assessed by means of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Psychological General Well Being Index (PGWBI). RESULTS: In active IBD, all dimensions of the quality of life scored significantly lower than in inactive IBD, indicating a poor quality of life. Social impairment was the least impaired dimension of the IBDQ in active UC and CD, compared with digestive and systemic symptoms. In inactive IBD, the systemic symptoms domain received the lowest score (P < 0.01). In a subgroup of 22 patients studied before and after remission, emotional function was the most impaired dimension after achieving remission. The Psychological General Well Being Index was significantly impaired in active UC [78.5 (range 64-89)] and CD [76.5 (range 69-97)] relative inactive IBD [104 (range 93-111)] vs 106 (95-113), respectively; P < 0.05]. CONCLUSIONS: Quality of life is impaired in IBD. During relapse, clinicians should pay attention to digestive symptoms and psychological distress. In remission, they should be sensitive to systemic symptoms.

Adult↗

Pancreatitis and haemobilia due to arterioportal fistula after percutaneous liver biopsy resolved by selective arterial embolization.

Haemobilia and arterioportal fistula are uncommon complications secondary to percutaneous liver biopsy. We report the case of a patient who developed haemobilia and subsequently acute pancreatitis as a result of a liver biopsy. Selective hepatic angiogram showed an arterioportal fistula. Transcatheter arterial embolization successfully occluded the fistula. The patient remained asymptomatic 4 months later. We review the published literature concerning acute pancreatitis associated with haemobilia and draw conclusions for management of similar cases in the future.

Acute Disease↗

Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat.

OBJECTIVES: Inulin stimulates intracolonic generation of butyrate and growth of lactic acid bacteria. This study investigated whether inulin protects against colitis. METHODS: Rats with dextran sodium sulfate colitis received inulin either orally (1% in drinking water, or 400 mg/day) or by enema. Matched groups received vehicle. In addition, fecal water obtained from inulin-fed rats was administered by enema to rats with colitis and compared with fecal water from control rats. Finally, rats with colitis received daily enemas of either butyrate (at 40 or 80 mmol/L) or vehicle. Inflammation was assessed by eicosanoid asssay in rectal dialysates and MPO activity in colonic tissue. Mucosal lesions were blindly scored by microscopic examination. Luminal pH was measured from cecum to rectum by a surface microelectrode. RESULTS: Oral inulin prevented inflammation, as evidenced by lower lesion scores (p < 0.05), decreased release of mediators (p < 0.05), and lower tissue MPO (p < 0.05) as compared with controls. Inulin induced acidic environment (pH <7.0) from cecum to left colon and increased counts of lactobacilli. Fecal water from inulin-fed rats also reduced scores (p < 0.05) and inflammation (p < 0.05). However, inulin or butyrate enemas had no effect. CONCLUSIONS: Oral inulin reduces the severity of dextran sodium sulfate colitis. The effect seems to be mediated by modification of the intracolonic milieu.

Animals↗

Prospective evaluation of esophageal motor dysfunction in Down's syndrome.

OBJECTIVE: The aim of this study was to determine the prevalence and way of presentation of esophageal motor dysfunction in a nonselected population of subjects with Down's syndrome. METHODS: The study was conducted in 58 Down's syndrome patients and 38 healthy controls. A global symptom score and individual scores for dysphagia for liquids and solids, heartburn, vomiting/regurgitation, and chest pain were obtained. Esophageal function was evaluated initially by scintigraphy using liquid and semisolid bolus. Time-activity curves based on the mean condensed images were used to calculate residual activity at 100 s after swallowing. According to both scintigraphy and clinical evaluation results, participants underwent a radiological and manometric study. RESULTS: The most frequent symptoms in Down's syndrome patients were: dysphagia for liquids (n = 9), dysphagia for solids (n = 10), vomiting/regurgitation (n = 8), and chest pain (n = 2). Liquid and semisolid retention of the tracer was significantly higher in Down's syndrome patients than in controls (p < 0.05). In 15 participants with Down's syndrome, tracer retention was higher than the 95 percentile of controls' retention. No correlation was found between the global or individual symptom score and esophageal retention quantified by scintigraphy. Hypothyroidism was unrelated to esophageal symptoms or retention. Five of the 15 esophagograms performed were abnormal, showing barium retention and/or esophageal dilation. Manometry showed achalasia in two subjects, total body aperistalsis in one, and nonspecific esophageal motor disorder in two. CONCLUSION: Esophageal motor disorders, particularly achalasia, are frequent in individuals with Down's syndrome. Awareness of esophageal dysmotility in this population is important, even though symptoms are not evident, to avoid potential complications.

Adolescent↗

Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome.

BACKGROUND: Patients with irritable bowel syndrome (IBS) frequently complain of excessive gas but their fasting volume of intestinal gas is apparently normal. We hypothesised that the pathophysiological mechanism involved may be impairment of intestinal gas transit. AIM: To investigate intestinal gas transit and tolerance in IBS patients compared with healthy subjects. METHODS: A gas mixture (N(2), O(2), and CO(2) in venous proportions) was infused into the jejunum of 20 patients with IBS and 20 healthy controls at 12 ml/min for four hours. Gas evacuation, initially flatus from the anus (two hours) and then intrarectally (two hours), was continuously recorded. Symptom perception (0-6 scale) and abdominal distension were measured at 10 minute intervals. RESULTS: After two hours of external gas (flatus) collection, 18 of 20 IBS patients had developed gas retention (>400 ml), increased gastrointestinal symptoms (score >3), or abdominal distension (>3 mm girth increment) compared with only four of 20 control subjects. During intrarectal gas collection, 13 of 17 patients still exhibited abnormal responses. CONCLUSION: A large proportion of patients with IBS can be shown to have impaired transit and tolerance of intestinal gas loads. This anomaly may represent a possible mechanism of IBS symptoms, specifically pain and bloating.

Abdomen↗

Modulation of colonic barrier function by the composition of the commensal flora in the rat.

BACKGROUND AND AIMS: Altered intestinal permeability is a key pathogenetic factor of idiopathic bowel inflammation. We investigated in the rat if changes in the composition of the bowel flora can alter colonic permeability. METHODS: A colonic segment was surgically excluded from faecal transit and brought out as a loop to the abdominal wall through two colostomies. The loop was used for colonisation with specific bacterial strains after eradication of the native flora with antibiotics. Lumen to blood clearance of dextran (molecular weight 70 000) and mannitol (molecular weight 182) was measured in rats recolonised with a single bacterial strain from rat colonic origin, and in control rats whose colonic loop was kept free of bacteria by antibiotics. Actual colonisation was confirmed by culture of segment effluents. RESULTS: Colonisation with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased lumen to blood clearance of mannitol. Colonisation with Lactobacillus brevis had the opposite effect and reduced permeability to mannitol. Bacteroides fragilis did not induce significant changes. Permeability to dextran was not altered by any of the strains tested. CONCLUSIONS: Certain commensal bacteria can modify colonic wall permeability to luminal substances.

Analysis of Variance↗

Modification of small bowel mechanosensitivity by intestinal fat.

BACKGROUND: Lipids may exacerbate symptoms induced by gut stimuli. AIM: To determine the mechanism whereby fat exerts this effect. SUBJECTS: Twenty four healthy subjects were studied during fasting. METHODS: We measured perception (0-6 scale) in response to jejunal balloon distension and transmucosal electrical nerve stimulation; phasic stimuli (one minute) were randomly applied at five minute intervals during intestinal infusion (2 ml/min) of saline and then Intralipid 2 kcal/min (high fat; n=8 subjects), Intralipid 0.5 kcal/min (low fat; n=8), or saline (n=8). RESULTS: Intestinal lipids increased the perception of jejunal distension regardless of concentration (by 53% with high fat, 49% with low fat, and 17% with saline; p<0.05 for both fat loads). This effect could not be attributed to changes in intestinal compliance as intraballoon pressures remained unchanged during lipid infusion (2% change; NS). Sensitisation induced by lipids seemed to be specifically related to intestinal mechanoreceptors because electrical stimulation, which non-specifically activates gut afferents, was perceived equally during saline and lipid administration (10%, 11%, and 15% change during high fat, low fat, and saline, respectively; NS). CONCLUSION: Physiological amounts of lipids heighten intestinal sensitivity by modulating intestinal mechanoreceptor response.

Adult↗

Epidermal growth factor increases surface hydrophobicity and resistance to acid in the rat duodenum.

Epidermal growth factor (EGF) is produced in Brunner's glands and plays a role in healing and repair of duodenal ulcers. We examined the participation of zwitterionic phospholipids of mucus in the effects of EGF. Under anesthesia, groups of rats received an intraduodenal bolus of either saline or EGF. Some rats received subcutaneous indomethacin followed by EGF or EGF followed by a detergent (5% Brij 35, a nonionic detergent that solubilizes luminal phospholipids). Thirty minutes after treatment, mucosal surface hydrophobicity and phospholipid concentration in the mucus layer were measured. Matched groups of rats were challenged with 0.5 M HCl, instilled intraduodenally 30 min after treatment, and mucosal damage was assessed 1 h after acid challenge. Exogenous EGF significantly increased surface hydrophobicity and phosphatidylcholine concentration in the mucus layer. EGF treatment also reduced mucosal damage induced by acid. However, indomethacin pretreatment or detergent administration after EGF abolished both protection against acid and changes in the mucus layer. These data suggest that EGF increases duodenal resistance to luminal acid via stimulation of mucosal zwitterionic phospholipids.

Animals↗

Mechanisms of intestinal gas retention in humans: impaired propulsion versus obstructed evacuation.

To explore the clinical role of intestinal gas dynamics, we investigated two potential mechanisms of gas retention, defective propulsion and obstructed evacuation. In healthy subjects, a gas mixture was continuously infused into the jejunum (4 ml/min) 1) during a 2-h control period of spontaneous gas evacuation and 2) during a 2-h test period either with impaired gut propulsion caused by intravenous glucagon (n = 6) or with obstructed (self-restrained) anal evacuation (n = 10) while anal gas evacuation, symptom perception (0-6 scale), and abdominal girth were measured. Impaired gut propulsion and obstructed evacuation produced similar gas retention (558 +/- 68 ml and 407 +/- 85 ml, respectively, vs. 96 +/- 58 ml control; P < 0.05 for both) and abdominal distension (8 +/- 3 mm and 6 +/- 3 mm, respectively, vs. 1 +/- 1 mm control; P < 0.05 for both). However, obstructed evacuation increased symptom perception (2.3 +/- 0.6 score change; P < 0.05), whereas gas retention in the glucagon-induced hypotonic gut was virtually unperceived (-0.4 +/- 0.7 score change; not significant). In conclusion, the perception of intestinal gas accumulation depends on the mechanism of retention.

Adult↗

[Clinical relevance of immunoglobulin A deficiency in celiac disease].

BACKGROUND: To determine the prevalence of the IgA deficiency in patients with celiac disease and its influence on the presentation and evolution of celiac disease. PATIENTS AND METHOD: 47 patients with clinical and histological diagnosis of celiac disease were included. Seric immunoglobulin levels were determined in all patients. RESULTS: Five patients presented a low level of IgA (IgA-deficient group) and 42 patients presented normal levels (non-IgA-deficient group). The age and the relation male/female were similar between both groups. Presentation, clinical manifestations, analytic data of intestinal malabsorption, and the radiologic pattern were also similar between both groups of patients. There were bronchiectasies in two out of 5 IgA-deficient patients and in only one out of 42 non-IgA- deficient patients (p < 0.05). None of the IgA-deficient group showed complications due to the celiac disease, meanwhile 3 non-IgA deficient patients developed intestinal lymphoma (p = NS). CONCLUSIONS: The IgA deficiency is frequently associated to celiac disease. This association does not seem to influence in a significant way the presentation or the evolution of celiac disease.

Adult↗

[Infection by cytomegalovirus in patients with ulcerative colitis requiring colonic resection].

BACKGROUND: The objective was to determine the rate of colonic infection by cytomegalovirus (CMV) in patients with ulcerative colitis (UC) who have required colonic resection because of lack of response to medical treatment or complications. PATIENTS AND METHODS: Thirty nine patients (26 males, 13 females) colectomized because of refractory or complicated UC were included. Clinical and pharmacological characteristics were analyzed. Specific immunohistochemistry for CMV was performed in biopsic samples of all specimens. RESULTS: Immunohistochemistry was positive for CMV in 7 out of the 39 patients. Since 1985 to 1994 there was only one case of CMV that contrasts with the 6 cases diagnosed from 1995 to 1998 (p < 0.05). All patients with CMV infection have received systemic corticosteroids before surgery, and additionally cyclosporine in 5 of them. Twenty two out of the 32 patients without CMV infection have also received corticosteroids, cyclosporine, azatioprine or methotrexate before surgery. The rate of immunosuppression was not different between the patients with or without CMV infection. Length of treatment before surgery was also similar for both groups of patients: (17 months (18-89) in non-infected group and 30 months (13-49) in CMV infected group; p = NS). Four patients infected by CMV died in the postoperatory. CONCLUSIONS: CMV infection in patients with refractory or complicated UC is a serious complication due to its frequency and prognosis. A significant increase in the prevalence of CMV infection, not related with differences in therapeutic immunosupression, has been observed in recent years.

Adult↗

[Patient assessment of the long-term benefits of surgery in inflammatory bowel disease].

UNLABELLED: The objective of surgical treatment in ulcerative colitis (UC) and Crohn's disease (CD) differs. Surgery in UC is more aggressive and potentially curative whereas in CD it is more conservative and palliative. OBJECTIVE: To assess the opinion of patients with inflammatory bowel disease who underwent surgery in the distant past about the results and timing of surgery. MATERIAL AND METHODS: A total of 50 surgical patients (36 with CD and 14 with UC) who had undergone an intestinal surgical procedure at least one year before. The clinical characteristics of patients and details of surgery procedures were recorded. Also, a personal interview was conducted. Patients were asked about their current clinical status, surgical consequences and their opinion about the appropriate timing of surgery. RESULTS: Surgery for UC was total proctocolectomy in 85% of patients and it was on an emergency basis in 43% of them. Surgery for UC was partial intestinal or colonic resection, and it was on an emergency basis in 22% of them. Postsurgical complications were more common in UC than CD patients (50% versus 20%; p < 0.05). In CD surgery, recurrence of disease occurred in 78% of patients within a 2.6 years interval. Among UC and CD patients, 71% and 50%, respectively, reported that their presurgical expectatives had been fulfilled (p = 0.17). CONCLUSIONS: Surgery for UC is associated with an appreciable rate of complications; however, most patients had their expectatives fulfilled with surgery as long-term symptoms were controlled. As for CD, the patient's satisfaction degree was lower than or UC.

Adult↗

Improved screening for intestinal villous atrophy by D-xylose breath test.

The hydrogen breath test (H2BT) with D-xylose has proven valid in both early recognition and follow-up of intestinal malabsorption. To further evaluate the specificity of the H2BT with D-xylose in the diagnosis of intestinal malabsorption as compared to the conventional urinary D-xylose test, we analyzed the result in 49 patients referred to our unit with a clinical diagnosis of intestinal malabsorption. These patients had an abnormal 25-g D-xylose H2BT but a normal conventional urinary D-xylose test. Jejunal biopsy with Watson capsule was performed in all patients. H&E staining was prepared from each biopsy specimen, and histological changes were classified according to the Marsh criteria. Jejunal biopsy showed mucosal atrophy in 5 patients (10%), hyperplastic lesion in 11 (22.5%), infiltrative lesion in 14 (28.5%), and normal appearance in 19 (39%). G. lamblia infection was additionally diagnosed in two patients. Histological changes were independent of the presence of diarrhea, weight loss, abdominal pain, or anemia. H2 excretion, assessed as increase over baseline and area under the curve, was similarly independent of the histological pattern. In conclusion, performance of a D-xylose H2BT in patients with a normal urinary test reveals a significant number of patients with intestinal mucosal atrophy who might otherwise remain undiagnosed.

Adolescent↗

Achalasia presenting as acute airway obstruction.

Achalasia presenting as acute airway obstruction is an uncommon complication. We report the case of an elderly woman with previously undiagnosed achalasia who presented with acute respiratory distress due to megaesophagus. Emergency endotracheal intubation and insertion of a catheter into the esophagus, with continuous aspiration was required. Upon introduction of the esophageal catheter an abruptand audible air decompression occurred, with marked improvement of the clinical picture. Endoscopic injection of botulinum toxin was chosen as the definitive treatment with good clinical result. The pathophysiology of the phenomenon of esophageal blowing in achalasia is unclear, but different hypothetical mechanisms have been suggested. One postulated mechanism is an increase in upper esophageal sphincter (UES) residual pressure or abnormal UES relaxation with swallowing in achalasia patients. We reviewed the UES manometric findings in 50 achalasia patients and compared it with measurement performed in 45 healthy controls. We did not find any abnormalities in UES function in any of our achalasia patients group, or in the case under study. An alternative hypothesis postulates that airway compromise in patients with achalasia results from the loss UES belch reflex (abnormal UES relaxation during esophageal air distension), and in fact, an abnormal UES belch reflex was evidenced in our case.

Aged↗

Accuracy of helical computed tomographic angiography for the diagnosis of colonic angiodysplasia.

BACKGROUND & AIMS: The diagnosis of colonic angiodysplasia is often challenging and relies on endoscopy or catheter angiography. We investigated whether computed tomographic angiography (CTA) contributes to the diagnosis of colonic angiodysplasia. METHODS: Twenty-eight patients with suspected bleeding from colonic angiodysplasia were prospectively evaluated. Gastrointestinal bleeding was investigated by colonoscopy plus visceral angiography and by CTA. The level of agreement between CTA and the former procedures was determined. RESULTS: CTA images of diagnostic quality were obtained in 26 patients. Eighteen patients were diagnosed with colonic angiodysplasia by colonoscopy plus visceral angiography, and 14 by CTA (kappa = 0.68; P < 0.001). Sensitivity, specificity, and positive predictive values of CTA for detection of colonic angiodysplasia were 70%, 100%, and 100%, respectively. CTA signs including accumulation of vessels in the colonic wall, early filling vein, and supplying enlarged artery were present in 55%, 50%, and 22% of cases, respectively. None of these signs were present in the 8 patients with obscure gastrointestinal bleeding and negative diagnostic investigation of the digestive tract. CONCLUSIONS: CTA is a sensitive, specific, well-tolerated, and minimally invasive tool for the diagnosis of colonic angiodysplasia.

Aged↗

Mechanical properties of the gastro-esophageal junction in health, achalasia, and scleroderma.

BACKGROUND: Manometric assessment of the gastro-esophageal junction (GEJ) is deceptive in that ignores key dynamic properties of the junction, such as resistance to flow and compliance. Our aim was to investigate the mechanical properties of the GEJ comprising intraluminal pressure (measured by manometry), resistance to flow and compliance (measured by resistometry). METHODS: We studied 8 healthy subjects, 11 patients with achalasia and 11 patients with scleroderma. We used a pneumatic resistometer, previously developed and validated in our laboratory. The resistometer consists of a flaccid polyurethane 5-cm cylinder connected to an electronically regulated nitrogen-injection system; the instrument records nitrogen flow through the cylinder while maintaining a constant pressure gradient between its proximal and distal ends. By placing the cylinder successively in the proximal stomach and along the GEJ we measured the GEJ-gastric resistance gradient (GEJ resistance minus gastric resistance) and were able to calculate the cumulative resistance (sum of resistance exerted at each pressure level), peak resistance (at any injection pressure), nil resistance point (injection pressure in mmHg at which GEJ resistance equals gastric resistance), and compliance slope (flow/pressure relationship). RESULTS: We found that GEJ resistance to flow (cumulative resistance, peak resistance, and nil resistance point) is significantly increased in achalasia and decreased in scleroderma (P < 0.05 versus health) while GEJ compliance is diminished in achalasia (P < 0.05 versus health) and normal in scleroderma. CONCLUSION: Achalasia is a disease characterized by increased GEJ resistance and rigidity. By contrast, although scleroderma is characterized by decreased GEJ resistance, GEJ compliance may be normal.

Adult↗