[Highlights in gastroenterology 2006].
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Adult↗
Biomedical subjects
M Fried
Publications and source records attributed to M Fried.
The effects of tegaserod on oesophageal function and bolus transport in healthy volunteers: studies using concurrent high-resolution manometry and videofluoroscopy.
BACKGROUND: Tegaserod is a partial 5-hydroxytryptamine 4 receptor agonist with prokinetic effects on the gastrointestinal tract, its effects on oesophageal function are unknown. AIM: A randomized, placebo controlled, double-blind trial assessed the effect of tegaserod on the oesophagus in healthy, asymptomatic subjects. METHOD: A 7-day course of tegaserod 6 mg b.d. vs. placebo was prescribed (n = 17/21 completed both phases of study). High-resolution manometry and pH measurements were performed before and after a test meal. Bolus transport of liquids and solids was studied by high-resolution manometry and videofluoroscopy. RESULTS: Tegaserod had no effect on lower oesophageal sphincter pressure compared with placebo, peristaltic velocity increased (P < 0.001) and distal contractile pressure decreased slightly (P < 0.05). Transient lower oesophageal sphincter relaxations and reflux were infrequent regardless of treatment. During the studies of bolus transport, high-resolution manometry revealed that tegaserod promoted mid-oesophageal contractility (P < 0.02) and shortened the 'proximal transition zone' (P < 0.05), the level where bolus escape occurred most frequently. These effects had no effect on liquid bolus transport; however a non-significant trend to improved solid bolus transport was observed (66% vs. 31%;P = 0.07). CONCLUSION: Tegaserod did not alter lower oesophageal sphincter pressure, but had significant effects on peristaltic function. High-resolution manometry promoted mid-oesophageal contractility during bolus transport. This effect was associated with a non-significant trend to improved solid bolus transit.
Adult↗
[Infliximab--practical guidelines for the treatment of Crohn's disease].
Infliximab is a monoclonal chimeric antibody, with high affinity and specificity for tumour necrosis factor alpha (TNFalpha) that plays a central role in the pathogenesis of immune mediated inflammatory disorders including Crohn's disease and ulcerative colitis. Globally over 600000 patients have been treated with infliximab to date. This global experience led to a better definition of the overall safety and efficacy profile of this medication. The goal of the present recommendations is to provide practical information to physicians involved in the care of patients with inflammatory bowel disease.
Antibodies, Monoclonal↗
Systematic review: the efficacy of treatments for irritable bowel syndrome--a European perspective.
BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder, characterized by abdominal pain/discomfort, bloating and altered bowel habit. AIM: To conduct a systematic evidence-based review of pharmacological therapies currently used, or in clinical development, for the treatment of IBS in Europe. The safety and tolerability of these therapies are the subject of an accompanying review. METHODS: A literature search was completed for randomized controlled studies which included adult patients with IBS and an active or placebo control, assessed IBS symptoms, and were published in English between January 1980 and June 2005. The level of evidence for efficacy was graded according to the quality of the trial design and the study outcome. RESULTS: There is some evidence for improvement of individual IBS symptoms with antidiarrhoeals (diarrhoea), antispasmodics (abdominal pain/discomfort), bulking agents (constipation), tricyclic antidepressants (abdominal pain/discomfort) and behavioural therapy. In contrast, there is strong evidence for the improvement of global IBS symptoms with two new serotonergic agents: the 5-HT4 selective agonist tegaserod (IBS with constipation) and the 5-HT3 antagonist alosetron (IBS with diarrhoea). Further data are required for the 5-HT3 antagonist, cilansetron, and the mixed 5-HT3 antagonist/5-HT4 agonist renzapride before their utility in IBS can be appraised. CONCLUSIONS: There is limited evidence for the efficacy, safety and tolerability of therapies currently available in Europe for the treatment of IBS. Overall, there is an absence of pharmacological agents licensed specifically for the treatment of IBS subtypes, and new agents are awaited in Europe that will allow changes in clinical practice to focus on and improve global IBS symptoms.
Adult↗
Chromosomal instability at a mutational hotspot in polyoma middle T-antigen affects its ability to activate the ARF-p53 tumor suppressor pathway.
We have isolated spontaneous mutants of polyoma virus middle T-antigen (PyMT) that do not activate the ARF-p53 pathway based on their inability to block REF52 cell division. The REF52 cells containing these mutants have a flat untransformed morphological phenotype and do not express the ARF protein. The PyMT mutations in the different cell isolates so far analysed occur at a mutational hotspot in the PyMT sequence between nucleotides 1241 and 1249, which contains nine consecutive cytosines. In one set of mutants a single cytosine was deleted, while in another mutant set an additional cytosine was inserted. Both these mutations result in frameshifts, generating altered PyMT proteins containing amino-acid sequences derived from each of the two other alternative reading frames of the polyoma virus early region. Both types of mutations result in the loss of the C-terminal PyMT region containing the membrane-binding hydrophobic region and result is mislocalization of the PyMT mutant proteins. Revertant wild-type PyMT (containing nine cytosines) was easily detected in transformants generated after infection of REF52 cells expressing high amounts of dominant negative p53 with retroviruses containing either mutation. We demonstrate that wild-type PyMT revertants are derived from mutations in the hotspot sequence of the integrated mutant PyMT sequences.
Amino Acid Sequence↗
[Functional magnetic resonance imaging of the gastrointestinal tract--clinical application possibilities?].
Magnetic resonance imaging (MRI) is a versatile medical imaging tool for which several new applications have been developed. Beside its broad clinical use for the detection of anatomical structures and pathologies MRI has been successfully applied for the non-invasive imaging of human organ functions, including the brain and the cardiovascular system. The use of MRI for the assessment and analysis of gastrointestinal (GI) function is a new approach that is currently performed in only a few research sites. Several characteristics make MRI an ideal technique for the direct assessment of GI physiology: MRI acquires high resolution images with excellent soft tissue contrast, it does not expose subjects to ionizing radiation, is non-invasive, and the acquisition and analysis of the images can be independently verified. In this article we summarize recent developments of MRI techniques in GI research. We will also discuss the advantages and limitations of MRI for this purpose in relation to established medical imaging tools and investigations.
Forecasting↗
Bedside sonographic control for positioning enteral feeding tubes: a controlled study in intensive care unit patients.
BACKGROUND AND STUDY AIM: The correct placement of an enteral feeding tube in the duodenum in critically ill patients is usually controlled radiographically. However, a direct bedside method that obviates the need for exposure to radiation would be preferable. The aim of this study was to demonstrate the usefulness of bedside sonographic position control for placing enteral feeding tubes in critically ill patients. PATIENTS AND METHODS: After placement of the enteral feeding tube, the position of the tip was determined using bedside transabdominal ultrasound. Native ultrasound was enhanced by injection of air bubbles into the feeding tube. The tube was regarded as being correctly positioned when the tube was visualized within the second or third parts of the duodenum. Plain abdominal radiographs with contrast served as the gold standard test. RESULTS: A total of 76 consecutive examinations were analyzed. In 12 patients, access to the upper abdominal wall was not possible because of open wounds; in another 13 patients who had undergone extensive abdominal surgery, the duodenum could not be identified and so no conclusion could be reached regarding the position of the tube. In 51/76 patients (67 %) ultrasound identified the duodenum and it was possible to determine the position of the tube (46 true positives and 2 true negatives); the position was incorrectly diagnosed in three patients. The sensitivity was 96 % (95 %CI 87 % - 98 %) and the specificity was 50 % (95 %CI 36 % - 65 %), with a positive predictive value of 94 %. CONCLUSIONS: Bedside sonographic control of the positioning of enteral feeding tubes is very sensitive and can be a valuable alternative to radiological control, especially in patients without open abdominal wounds, external installations, or extensive abdominal surgery.
Adult↗
Clearance mechanisms of the aperistaltic oesophagus: the "pump gun" hypothesis.
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Deglutition Disorders↗
[Gastro-highlights 2004].
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Education, Medical, Continuing↗
[Highlights in gastroenterology 2004].
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Colonoscopy↗
Malaria in the pregnant woman.
Women become more susceptible to Plasmodium falciparum malaria during pregnancy, and the risk of disease and death is high for both the mother and her fetus. In low transmission areas, women of all parities are at risk for severe syndromes like cerebral malaria, and maternal and fetal mortality are high. In high transmission areas, where women are most susceptible during their first pregnancies, severe syndromes like cerebral malaria are uncommon, but severe maternal anemia and low birth weight are frequent sequelae and account for an enormous loss of life. P. falciparum-infected red cells sequester in the intervillous space of the placenta, where they adhere to chondroitin sulfate A but not to receptors like CD36 that commonly support adhesion of parasites infecting nonpregnant hosts. Poor pregnancy outcomes due to malaria are related to the macrophage-rich infiltrates and pro-inflammatory cytokines such as tumor necrosis factor-alpha that accumulate in the intervillous space. Women who acquire antibodies against chrondroitin sulfate A (CSA)-binding parasites are less likely to have placental malaria, and are more likely to deliver healthy babies. In areas of stable transmission, women acquire antibodies against CSA-binding parasites over successive pregnancies, explaining the high susceptibility to malaria during first pregnancy, and suggesting that a vaccine to prevent pregnancy malaria should target placental parasites. Prevention and treatment of malaria are essential components of antenatal care in endemic areas, but require special considerations during pregnancy. Recrudescence after drug treatment is more common during pregnancy, and the spread of drug-resistant parasites has eroded the usefulness of the few drugs known to be safe for the woman and her fetus. Determining the safety and effectiveness of newer antimalarials in pregnant women is an urgent priority. A vaccine that prevents pregnancy malaria due to P. falciparum could be delivered before first pregnancy, and would have an enormous impact on mother-child health in tropical areas.
Animals↗
Cultural recovery and determination of antimicrobial susceptibility in Helicobacter pylori by using commercial transport and isolation media.
BACKGROUND: Antimicrobial resistance of Helicobacter pylori is the main reason for eradication failure. We have studied the feasibility of a commercial transport medium for cultural recovery and subsequent drug susceptibility testing. PATIENTS AND METHODS: From March to December 2000, 79 consecutive gastric biopsies, positive in a rapid urease test, were transferred into a commercial transport medium and sent within 24 hours from the district hospital to the microbiological laboratory for culture and susceptibility testing. A commercial agar plate and an in-house Wilkins-Chalgren agar plate were used for culture. Susceptibility data were compared with data collected from 1992 to 2003 in the University Hospital of Zurich. RESULTS: Cultural recovery and susceptibility testing of H. pylori was successful in 55 of 79 patients. In 17 cases cultural recovery failed because of technical problems (n = 14), long transport time (n = 1) and unknown reason (n = 2). Failure of susceptibility testing (n = 7) was mainly due to fungal overgrowth. Resistance to metronidazole and clarithromycin was found in 15 (27%) and in 12 patients (22%), respectively; resistance to amoxicillin was not observed. Five patients (9%) showed resistance both to metronidazole and to clarithromycin. Eradication therapy failed in all patients with macrolide resistance. Resistance rates were higher in females than in males; 30% vs 12% for clarithromycin and 33% vs 20% for metronidazole. Resistance to metronidazole was significantly lower in Swiss patients (15%) than in non-Swiss patients (39%). CONCLUSION: Antimicrobial resistance data can reliably be obtained by sending the biopsy specimen in a commercial transport medium to a microbiological laboratory. This is especially important after eradication failure. Resistance to metronidazole and clarithromycin is highly prevalent and more common in women and non-Swiss patients.
Amoxicillin↗
Gastroscopic real-time 13C-urea breath test.
BACKGROUND AND STUDY AIMS: Biopsy-based Helicobacter urease testing (HUT) may constitute a hazard in patients with bleeding disorders, those receiving anticoagulant therapy, and those with communicable diseases. In addition, definitive test results may not immediately be available. The aim of this study was to investigate the feasibility of breath testing for H. pylori during gastroscopy (gastroscopic breath testing, GBT) in comparison with the standard HUT in a prospective, randomized, and controlled study. PATIENTS AND METHODS: A total of 119 patients were randomly allocated to undergo H. pylori testing with either HUT (n = 61) or GBT (n = 58) with 75 mg of 13C-labeled urea by endoscopic instillation. Breath samples were continuously analyzed using molecular correlation spectroscopy, displaying real-time results. The procedure time and time until definitive test results were obtained (mean plus or minus standard deviation) were recorded. RESULTS: H. pylori was detected in 10 of 49 patients (20.4 %) with HUT and in 16 of 53 (30.2 %) with GBT. Contraindications to biopsy prevented HUT in 12 of 61 patients. GBT results could not be obtained in one of the 58 patients due to respiratory disease and in four for technical reasons. Slightly less time was required to carry out HUT than GBT (121 +/- 30 s vs. 164 +/- 36 s; P < 0.001). Definitive test results were available within 14.0 +/- 2.2 min using GBT in comparison with 19.6 +/- 9.1 h for HUT ( P < 0.001). GBT prolonged the time spent by the patient in the endoscopy room by only 5.6 min in comparison with HUT (45.1 +/- 8.5 min vs. 39.5 +/- 10.3 min; P < 0.01). CONCLUSIONS: GBT provides immediate, definitive results and allows H. pylori testing in patients in whom biopsies are contraindicated, with only minimal prolongation of the procedure time.
Adolescent↗
[Highlights in gastroenterology 2003].
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APACHE↗
Thiopurine S-methyltransferase polymorphisms: efficient screening method for patients considering taking thiopurine drugs.
OBJECTIVE: More than 11% of the Caucasian population are heterozygous or homozygous carriers of thiopurine S-methyltransferase (TPMT) mutants and are at risk for toxic side effects when treated with thiopurine drugs. Therefore, screening for TPMT polymorphisms in a patient prior to prescribing these agents is recommended. The goal of this study was to determine a cut-off concentration of the TPMT activity assay beyond which genotyping of the TPMT gene should be performed. METHODS: The TPMT activity of 240 unrelated Caucasian subjects was measured using high-performance liquid chromatography. Genotyping for the most frequent allelic variants, TPMT*2, *3A, *3B, *3C and *7 was performed by LightCycler technology and sequencing. RESULTS: The inter-individual TPMT activity showed a range from 23 nmol MTG/g*Hb*h(-1) to 97 nmol MTG/g*Hb*h(-1) with a median of 56 nmol MTG/g*Hb*h(-1). Using a cut-off concentration of 45.5 nmol MTG/g*Hb*h(-1), a test sensitivity of 100% and a specificity of 89% were reached for heterozygous carriers of a TPMT mutation. We identified 1 carrier of TPMT*2, 14 carriers of TPMT*3A and 3 carriers of TPMT*3C, resulting in a TPMT heterozygosity prevalence of 7.5%. CONCLUSIONS: This study defines the cut-off value for the TPMT phenotyping assay at 45.5 nmol/g*Hb*h(-1), beyond which additional genotyping elucidates the individual risk for drug therapy. Using this cut-off concentration, the number of genotyping assays could be reduced by about 60%.
Female↗
The pathophysiology of faecal spotting in obese subjects during treatment with orlistat.
BACKGROUND: The intermittent loss of oil or liquid faeces ('spotting') is an adverse effect that occurs in obese patients during treatment with the lipase inhibitor orlistat; the pathophysiology is unknown. AIM: To investigate the effects of orlistat on anorectal sensorimotor function and continence. METHODS: Obese subjects susceptible to spotting were identified by an unblind trial of orlistat. Obese spotters (n = 15) and non-spotters (n = 16) completed a randomized, double-blind, cross-over trial of orlistat and placebo. Anorectal function was assessed by rectal barostat and anal manometry, together with a novel stool substitute retention test, a quantitative measurement of faecal continence. RESULTS: Orlistat increased stool volume and raised faecal fat and water. Treatment had no effect on anorectal motor function, but rectal sensation was reduced; on retention testing, the volume retained was increased. Subjects susceptible to spotting had lower rectal compliance, heightened rectal sensitivity and weaker resting sphincter pressure than non-spotters. On retention testing, gross continence was maintained; however, spotters lost small volumes of rectal contents during rectal filling. CONCLUSION: Treatment with orlistat has no direct adverse effects on anorectal function or continence. Spotting occurs during treatment with orlistat when patients with sub-clinical anorectal dysfunction are exposed to increased stool volume and altered stool composition.
Adult↗
Dietary protein precipitation properties have effects on gastric emptying in healthy volunteers.
BACKGROUND & AIMS: Strategies that reduce the size of particles in the stomach accelerate gastric emptying. Partial dephosphorylation of casein reduces the size of protein precipitates (curds) in acid conditions and facilitates peptic digestion. We hypothesized that changing the precipitation properties of casein by partial dephosphorylation would accelerate gastric emptying. METHODS: Eight healthy male volunteers entered a prospective, double blind, randomized study with crossover design. Gastric emptying of milk based formula containing either unmodified or dephosphorylated casein was assessed by scintigraphy. Gastric pH measurements were acquired concurrently. RESULTS: A trend to faster gastric emptying was observed for the unmodified preparation, with lower median half time (unmodified 133; dephosphorylated 214 min, P = 0.09) and area under the curve (unmodified 8425 min%; dephosphorylated 9135 min%, P = 0.08). A positive correlation was found between half time for the dephosphorylated preparation and the treatment effect (r2 = 0.81, P < 0.02). Gastric pH was unaffected. CONCLUSIONS: The study hypothesis was rejected; indeed gastric emptying tended to be faster for the unmodified than the dephosphorylated protein. This effect was more pronounced in subjects with slow gastric emptying on the dephosphorylated preparation. Properties other than the size of protein precipitates determine the rate of gastric emptying for milk based formula.
Adult↗