Department of Medicine, Ullevâl University Hospital, Oslo, Norway. asle.medhus@ioks.uio.no
BACKGROUND: Erythromycin is a motilin agonist and its effects on gastrointestinal motility are dependent on both dose and whether it is administered during the postprandial or fasting state. AIM: To study the motility response of the small bowel to a low dose of intravenous erythromycin after meal intake and during fasting. METHODS: Eighteen healthy subjects with mean age of 25 years were studied by small bowel manometry. Erythromycin was administered intravenously (0.75 mg per kg body weight) during 20 min in the postprandial (n=9) and the fasting state (n=9), and the motility response was recorded. RESULTS: Erythromycin significantly reduced the frequency of propagated contractions (P < 0.001) and the amplitude of contractions (P < 0.02) in the small bowel during established postprandial motility. During the fasting state, erythromycin invariably initiated a phase III-like activity, which was similar to the spontaneous nocturnal phase III and migrated significantly more slowly than the diurnal phase III (P < 0.01). CONCLUSIONS: A low dose of erythromycin administered intravenously during the postprandial state significantly inhibits small bowel motility, whereas administration during the fasting state initiates a phase III resembling the nocturnal rather than the diurnal phase III. These effects of erythromycin may indicate interference with vagal pathways. Due to its inhibitory effects, the clinical use of erythromycin in patients with hypomotility should be reconsidered, and the potential usefulness of these effects in patients with exaggerated intestinal motility deserves further attention.
Latest citations:
Elin M Matsson,
Ulf G Eriksson,
Lars Knutson,
Kurt-Jürgen Hoffmann,
Ulrika Logren,
Patrik Fridblom,
Niclas Petri,
Hans Lennernäs
Department of Pharmacy, Uppsala University, Uppsala, Sweden.
The biliary excretion of the oral thrombin inhibitor ximelagatran and its metabolites was investigated by using duodenal aspiration in healthy volunteers following intraintestinal dosing. In the first investigation, radiolabeled [(14)C]ximelagatran was administered, enabling quantification of the biliary excretion and identification of metabolites in the bile. In the second study, the effect of erythromycin on the biliary clearance of ximelagatran and its metabolites was investigated to clarify the reported ximelagatran-erythromycin interaction. Approximately 4% of the intraintestinal dose was excreted into bile with ximelagatran and its active form, melagatran, being the most abundant compounds. Four novel ximelagatran metabolites were identified in bile (<0.1% of dose). Erythromycin changed the pharmacokinetics of ximelagatran and its metabolites, with an elevated ximelagatran (78% increase), OH-melagatran (89% increase), and melagatran (86% increase) plasma exposure and higher peak plasma concentrations of the compounds being measured. In parallel, the biliary clearance was moderately reduced. The results suggest that inhibition of hepatobiliary transport is a likely mechanism for the interaction between erythromycin and ximelagatran. Furthermore, the study demonstrated the value of direct bile sampling in humans for the identification of primary biliary metabolites.
Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN 46202, USA. jason.dranove@carolinashealthcare.org
PURPOSE: Erythromycin is successfully used as a gastroduodenal prokinetic agent. Given the limited available treatments for colonic dysmotility, further investigation into erythromycin's effect on colonic motility is warranted. We aimed to study the effect of erythromycin on colonic motility in pediatric patients with recalcitrant chronic constipation/encopresis and other suspected colonic motility disorders. METHODS: Patients referred for colonic manometry were eligible for enrollment. Fasting motility was recorded for 1 to 2 hours, then erythromycin lactobionate (EL), 3 mg/kg, was administered intravenously, and colonic motility was monitored for 1 to 2 hours after erythromycin. Manometry was then continued per routine. The motility index (MI) of pressure tracings at each pressure transducer was calculated for each patient for a period of 15 and 60 minutes before and after EL infusion. Change in MI was compared by Wilcoxon signed rank test. RESULTS: Twenty patients were enrolled. The most common indication was constipation with encopresis. Seventy percent of patients had normal colonic manometry, and 30% of patients demonstrated a neuropathy. Average MI for the 60-minute period before and after EL infusion were 254 +/- 74 mm Hg/h and 253 +/- 94 mm Hg/h, respectively (P =.55). Average MI for the 15-minute period before and after EL infusion were 64 +/- 23 mm Hg/15 min and 69 +/- 32 mm Hg/15 min, respectively (P =.45). CONCLUSIONS: Administration of intravenous EL resulted in no changes in colonic MI in pediatric patients referred for colonic manometry. Further studies on potential colokinetic agents are warranted in this population of patients.
Can Vet J. 2006 Jun ;47 (6):551-9
16808227
Cit:6
Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1. jkoenig@ovc.uoguelph.ca
Colic is a common problem encountered in equine practice. Alteration of gastrointestinal motility is often the underlying cause for abdominal pain. Gastrointestinal motility can be measured as myoelectric activity, mechanical activity, and transit of intraluminal contents. Regulation of motility is based on a complex interaction between central innervation, autonomic innervation, and the enteric nervous system. Various humoral and neurochemical substances are required to interact flawlessly to allow propulsive motility. Ileus is defined as the absence of propulsive aboral movement of gastrointestinal contents, irrespective of its pathophysiology. Potential etiologies for ileus are described in this review. The prokinetic drugs available for clinical use are discussed. Choosing the appropriate prokinetic drug requires knowledge about the complex nature of gastrointestinal motility and its abnormalities.
Clinic for Ruminants, Vetsuisse-Faculty of Berne, Bremgartenstrasse 109a, PO Box 8466, 3001 Berne, Switzerland. patrik.zanolari@knp.unibe.ch
The effects of erythromycin on myoelectric activity of the spiral colon of dairy cows were investigated in a prospective study. Four Simmental x Red-Holstein crossbred cows of similar body weight and condition with seven pairs of bipolar electrodes implanted in the intestine (one each in the distal ileum, caecum and proximal colon, and four in the spiral colon) were included. Erythromycin lactobionate (1 mg kg(-1)) and 0.9% sodium chloride solution (NaCl) were administered to each cow in a random order. Erythromycin was diluted with NaCl and both treatments were administered slowly intravenously over a period of 5 min 1 h after onset of a phase III of the bovine colonic migrating myoelectric complex (bcMMC). A 3-6-day washout period was scheduled between trials. Significant differences between the results of the treatments were observed for spike duration in phase I as well as for spike duration and duration of spiking activity during phase II of the second bcMMC, which were significantly higher after erythromycin treatment than after NaCl. These findings suggest an indirect effect of erythromycin on colonic motility in cattle.
Obes Surg. 2002 Dec ;12 (6):765-72
12568180
Cit:4
Department of Surgery, Eisenhower Army Medical Center, Fort Gordon, GA, USA. Neal.Wilkinson@RoswellPark.org
BACKGROUND No conclusive data exists supporting the use of any prokinetic agent in the postoperative setting. The study was designed to examine the effect of erythromycin on small bowel motility in a placebo-controlled trial of post gastric bypass patients utilizing a standardized nuclear medicine test. METHODS A consecutive series of 21 patients undergoing elective gastric bypass surgery for morbid obesity between September 1999 and March 2001 were enrolled in this prospective double-blind randomized controlled trial. Standard open, divided gastric bypass was performed. Patients were randomized to receive either erythromycin 250 mg i. v.(11 patients) or placebo (10 patients) every 8 hours. On postoperative day 2, a hepatic iminodiacetic acid (HIDA) scan was obtained. Tracer movement through the biliary tree and proximal small bowel was quantified and compared. RESULTS Tracer clearance from the liver and biliary tree was no different between groups from time of injection through 1 hour. Tracer material clearance from the duodenum into the jejunum was no different between the erythromycin and control groups at 1 hour, 37%+/- 13% and 37%+/- 22% respectively (P = 0.95). At 4 hours, clearance was greater in the erythromycin group, 77%+/- 6%, compared to control, 60%+/- 20%(P = 0.036). The rate of tracer change between hour 1 and 4 (slope) was steeper in the erythromycin group (P = 0.048). CONCLUSIONS Erythromycin increases intestinal transit in the postoperative setting.
Stimulation of the small intestine by nutrients in relation to phase of the migrating motor complex.
Dept. of Medicine, Ullevål University Hospital, Oslo, Norway.
BACKGROUND The relationship between the preceding phase of the migrating motor complex (MMC) and postprandial motility in the small intestine was studied. METHODS In eight healthy subjects small-bowel manometry was performed, and a 55-ml caloric liquid bolus (280 kJ) containing paracetamol and 14C-D-xylose was instilled into the duodenum during phase I and late phase II of the intestinal MMC, respectively, in randomized order. Blood samples were drawn at regular intervals and analysed for insulin, gastrin, glucose, paracetamol, and 14C-D-xylose. RESULTS After bolus administration during late phase II a phase-III-like activity succeeded by quiescence occurred in the duodenum in seven of eight subjects, whereas administration during phase I initiated irregular contractions in seven of eight subjects (P < 0.05). The caloric bolus induced a significant increase in serum insulin and gastrin. Areas under the curves for serum insulin, gastrin, glucose, paracetamol, and 14C-D-xylose were not modulated by the preceding phase of the MMC. CONCLUSIONS The present study shows that a nutrient bolus instilled into the intestinal lumen induces MMC-like activity when administered during late phase II. These findings provide further evidence of interference between MMC and postprandial motility.
Other papers by authors:
Department of Gastroenterology, Oslo University Hospital, Ullevål, Oslo, Norway.
Abstract Background Dysmotility of the upper gastrointestinal (GI) tract has been reported in children with Hirschsprung's disease (HD). To study the motility of the oesophagus and the small bowel in adults treated for HD during early childhood to elucidate whether there are alterations in motility of the upper GI tract in this patient group. Methods Ambulatory small bowel manometry with recording sites in duodenum/jejunum was performed in 16 adult patients with surgically treated HD and 17 healthy controls. In addition, oesophageal manometry was performed with station pull-through technique. Key Results The essential patterns of small bowel motility were recognized in all patients and controls. During fasting, phase III of the migrating motor complex (MMC) was more prominent in patients with HD than in controls when accounting for duration and propagation velocity (P = 0.006). Phase I of the MMC was of shorter duration (P = 0.008), and phase II tended to be of longer duration (P = 0.05) in the patients. During daytime fasting, propagated clustered contractions (PCCs) were more frequent in the patients (P = 0.01). Postprandially, the patients demonstrated a higher contractile frequency (P = 0.02), a shorter duration of contractions (P = 0.008) and more frequent PCCs (P < 0.001). The patients had normal oesophageal motility. Conclusions & Inferences This study demonstrates that adult patients with HD have preserved essential patterns of oesophageal and small bowel motility. However, abnormalities mainly characterized by increased contractile activity of the small bowel during fasting and postprandially are evident. These findings indicate alterations in neuronal control of motility and persistent involvement of the upper GI tract in this disease.
Department of Medicine, Ullevål University Hospital, Oslo, Norway.
Hirschsprung's disease (HD) is considered a focal disease usually confined to the distal colon and rectum. However, autonomic dysfunction and dysmotility in the upper gastrointestinal tract have been reported, suggesting that this disease is not only confined to the distal gastrointestinal tract. This study examines the fasting and postprandial levels of glucose and insulin in adult patients with HD to elucidate whether there might also be an endocrine involvement in this disease. Sixteen patients with surgically treated HD during early childhood and 17 healthy subjects were studied. All subjects ingested a caloric liquid meal containing glucose, lactose, maize oil, and water (2,020 kJ) after an overnight fast. Blood samples were collected at regular intervals for insulin and glucose analyses. Fasting levels of both glucose (P <.05) and insulin (P <.02) were significantly higher in patients compared with healthy controls. Peak concentration of insulin following meal intake was significantly higher in the patient group (P <.05), and peak concentration of glucose tended to be higher in patients compared with controls (P =.06). There was no correlation between body mass index and serum levels of glucose or insulin. The present study shows that adult patients treated for HD during childhood have an impaired glucose and insulin homeostasis, indicating a mild degree of insulin resistance. This may imply susceptibility towards development of non-insulin-dependent diabetes mellitus.
Department of Medicine, Ullevål University Hospital, Oslo, Norway. asle.medhus@ioks.uio.no
An algorithm for the paracetamol absorption test for gastric emptying, adjusting for individual pharmacokinetics, was recently developed. The aim of the present study was to validate the use of this algorithm. Furthermore, the algorithm was applied to elucidate whether a gastric tube interferes with the rate of gastric emptying. A caloric liquid meal with paracetamol was administered orally to nine healthy volunteers on two separate days. On one occasion, the subjects were intubated with a nasogastric tube and the meal was aspirated from the stomach 45 min after meal intake. The percentage of the meal retained in the stomach at the time of aspiration was determined by analyses of paracetamol in the aspirate and compared with calculations by the algorithm. On the other examination day, the same meal was ingested without tube and aspiration. The median percentage of the meal retained in the stomach at aspiration was 47%(range 33-70%) calculated by the algorithm and 48%(range 23-61%) based on the aspiration data. The correlation between the emptying parameters was r=0.97 (P < 0.001). The median of gastric emptying parameters was similar when the number of samples included in the calculation by the algorithm was reduced, but the range tended to increase. The gastric tube moderately inhibited gastric emptying during the period 20-40 min after meal intake (P < 0.05), but for the period from meal intake until start of aspiration, no inhibition was found. The present study demonstrates that the novel algorithm for the paracetamol absorption test provides valid estimates for gastric emptying.
Stimulation of the small intestine by nutrients in relation to phase of the migrating motor complex.
Dept. of Medicine, Ullevål University Hospital, Oslo, Norway.
BACKGROUND The relationship between the preceding phase of the migrating motor complex (MMC) and postprandial motility in the small intestine was studied. METHODS In eight healthy subjects small-bowel manometry was performed, and a 55-ml caloric liquid bolus (280 kJ) containing paracetamol and 14C-D-xylose was instilled into the duodenum during phase I and late phase II of the intestinal MMC, respectively, in randomized order. Blood samples were drawn at regular intervals and analysed for insulin, gastrin, glucose, paracetamol, and 14C-D-xylose. RESULTS After bolus administration during late phase II a phase-III-like activity succeeded by quiescence occurred in the duodenum in seven of eight subjects, whereas administration during phase I initiated irregular contractions in seven of eight subjects (P < 0.05). The caloric bolus induced a significant increase in serum insulin and gastrin. Areas under the curves for serum insulin, gastrin, glucose, paracetamol, and 14C-D-xylose were not modulated by the preceding phase of the MMC. CONCLUSIONS The present study shows that a nutrient bolus instilled into the intestinal lumen induces MMC-like activity when administered during late phase II. These findings provide further evidence of interference between MMC and postprandial motility.
Dept. of Medicine, Ullevål University Hospital, Oslo, Norway.
BACKGROUND: The phase of the migrating motor complex (MMC) in the proximal small intestine at meal intake modulates gastric emptying, which is accelerated after intake during phase II. In the present study the relationship between phase of the MMC at meal intake and the postprandial endocrine response was studied. METHODS: Eight healthy subjects ingested a caloric liquid meal of 2020 kJ during phase I and late phase II of the intestinal MMC, respectively, in a randomized order. Blood samples were drawn at regular intervals after meal intake and analysed for insulin, gastrin, neurotensin, cholecystokinin, motilin, and somatostatin by radioimmunoassays. RESULTS: The area under the curve (AUC) until 15 min for serum insulin (P<0.05) and plasma neurotensin (P<0.02) and AUC until 120 min for serum gastrin (P<0.05) were higher after intake during late phase II than after phase I. Plasma cholecystokinin increased earlier (P<0.05) after intake during late phase II than after phase I. Plasma motilin and somatostatin were not influenced by preceding phase of the MMC. CONCLUSIONS: This study shows that the phase of intestinal MMC at meal intake modulates the postprandial endocrine response, which may be explained by the prior entry of nutrients to the small intestine after intake during phase II.
Department of Medicine, Ullevål University Hospital of Oslo, Norway. asle.medhus@ioks.uio.no
AIMS: To examine the influence of duodenal intubation on gastric emptying measured by the paracetamol absorption test using a new algorithm developed to estimate emptying parameters, and to determine the sensitivity of this test. METHODS: A caloric liquid meal with paracetamol as marker of emptying was administered orally to eight healthy volunteers during phase I and phase II of the migrating motor complex (MMC) and without intubation on 3 separate days, and to 10 patients with partial gastrectomy. RESULTS: Healthy subjects: With duodenal tube, time until 25% of the meal had emptied (t25%) was 24+/-7 (phase I, P<0.02) and 21+/-6 min (phase II, P<0.02) compared with 14+/-4 min for meal intake without intubation. Time until 50% of the meal had emptied (t50%) was 45+/-8 (phase I, P<0.001) and 35+/-8 min (phase II, P<0.02) compared with 26+/-9 min for meal intake without intubation. Intraduodenal instillation of 10-20 mL of the liquid meal was reliably detected. Patients: In 9 out of 10 patients with partial gastrectomy t25% was below the lower limit of the range for healthy controls, and t25% detected accelerated emptying with a higher degree of sensitivity than the commonly applied pharmacokinetic parameters Cmax and Tmax. CONCLUSIONS: A duodenal tube delays gastric emptying of a caloric liquid meal. The paracetamol absorption test emerges as a sensitive method suitable for detecting both delayed and accelerated gastric emptying of caloric liquid meals.
Clin Microbiol Infect. 2011 Apr 4;:
21745258
ment of Paediatrics, Oslo University Hospital Institute of Clinical Medicine, University of Oslo Division of Infectious Disease Control, Norwegian Institute of Public Health Unit of Biostatistics and Epidemiology, Oslo University Hospital Department of Microbiology, Oslo University Hospital, Oslo, Norway.
Clin Microbiol Infect ABSTRACT: A longitudinal, prospective study was conducted intermittently in Norway, from 1999 to 2008, to investigate the Candida colonization rates and species distributions in the tonsillopharyngeal and faecal flora in:(i) children with cancer;(ii) children with cystic fibrosis (CF); and (iii) healthy children. The effect of antibiotic treatment on Candida colonization was also studied, and we looked for changes in antifungal susceptibility over time within each child and between the different groups of children. In total, 566 tonsillopharyngeal swabs and 545 faecal samples were collected from 45 children with cancer, 37 children with CF, and 71 healthy, age-matched controls. The overall colonization rate with Candida was not significantly higher in the two groups of children undergoing extensive treatment with broad-spectrum antibiotics than in healthy controls. Approximately one-third of the cancer patients had a total lack of Candida colonization or had only one Candida-positive sample, despite multiple samples being taken, treatment with broad-spectrum antibiotics, long hospital stays, and periods with neutropenia. Children with CF had the highest prevalence of Candida albicans. Amoxycillin, azithromycin, third-generation cephalosporins and oral vancomycin resulted in a significantly increased Candida colonization rate. Phenoxymethylpenicillin, second-generation cephalosporins, metronidazole, trimethoprim-sulphamethoxazole, ciprofloxacin, penicillinase-resistant penicillins and inhaled tobramycin or colistin showed minimal effects on the Candida colonization rate. We found no evidence of development of antifungal resistance over time.
Clin Microbiol Infect. 2011 Jan 2;:
21199154
Cit:2
A Skiada,
L Pagano,
A Groll,
S Zimmerli,
B Dupont,
K Lagrou,
C Lass-Florl,
E Bouza,
N Klimko,
P Gaustad,
M Richardson,
P Hamal,
M Akova,
J F Meis,
J-L Rodriguez-Tudela,
E Roilides,
A Mitrousia-Ziouva,
G Petrikkos
1st Department of Propaedeutic Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece Institute of Hematology, Catholic University, Rome, Italy Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, Children's University Hospital, Münster, Germany Institute for Infectious Diseases, University of Bern, Bern, Switzerland Hôpital Necker, Maladies Infectieuses et Tropicales, Paris, France Department of Medical Diagnostic Sciences, K.U. Leuven, Leuven, Belgium Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria Department of Clinical Microbiology and Infectious Diseases, Hospital General 'Gregorio Marañón', Madrid, Spain Department of Clinical Mycology, Allergiology and Immunology, Saint Petersburg Medical Academy of Postgraduate Education, Saint Petersburg, Russia Institute of Medical Microbiology, Rikshospitalet University Hospital, Oslo, Norway Regional Mycology Laboratory, University Hospital of South Manchester, Wythenshawe Hospital and The University of Manchester, Manchester Academic Health Science Centre, School of Translational Medicine, Manchester, UK Institute of Microbiology, Palacky University, Faculty of Medicine, Olomouc, Czech Republic Hacettepe University School of Medicine, Section of Infectious Diseases, Ankara, Turkey Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain 3rd Department of Pediatrics, Aristotle University School of Medicine, Hippokration Hospital, Thessaloniki, Greece Department of Microbiology, National and Kapodistrian University of Athens, Athens, Greece 4th Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens,'Αttikon' Hospital, Athens, Greece.
Clin Microbiol Infect ABSTRACT: Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp.(34%), Mucor spp.(19%) and Lichtheimia (formerly Absidia) spp.(19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival.
J Hosp Infect. 2010 Sep ;76 (1):56-9
20542590
Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. a.warris@cukz.umcn.nl
Published data implicate hospital water as a potential source of opportunistic fungi that may cause life-threatening infections in immunocompromised patients. Point-of-care filters are known to retain bacteria, but little is known about their efficacy in reducing exposure to moulds. We investigated the effect of point-of-use filters (Pall-Aquasafe) on the level of contamination of Aspergillus fumigatus and other filamentous fungi. The point-of-use filters were applied to several outlets (taps and showers) on the paediatric bone marrow transplantation (BMT) unit of the National Hospital in Oslo, Norway. In addition the efficacy was investigated using a test rig. The laboratory experiments showed that the filters were highly effective in reducing the number of colony-forming units for a period of at least 15 days. In the BMT unit the filters eliminated the fungi from the water on day 1 but due to particles present in the water the filters occluded, which prevented further evaluations. Our results show that point-of-use filtration might be an effective preventive measure to eliminate filamentous fungi at individual points of water use, thereby reducing patients' exposure.
University of Oslo, Oslo, Norway. ilobmaier@gmail.com
In cases of sudden unexpected death in infants and children (SUDI), microbiological investigation has been an important part of the autopsy protocol at the University of Oslo for the last 15 years. The purpose of this study was to compare the microbiological findings in samples taken at hospital admittance shortly after death and at autopsy. Blood cultures and cerebrospinal fluid (CSF) were collected both at the hospital and at autopsy; organ samples were additionally collected at autopsy. Hospital samples were collected at a median of 4.5 h (95% confidence interval [CI] 3.25-5) and autopsy samples at a median of 24.25 h (95% CI 22-25.5) after death. The proportion of positive cultures was stable over time; the post mortal time had no influence on bacterial growth. As long as the autopsy is performed within 48 h after death, prior microbiological examination is unnecessary. Blood culture, CSF and lung specimens are the best predictors in our study.
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Roberto Gomez,
Sergio Fernandez,
Ann Aspirot,
Jaya Punati,
Beth Skaggs,
Hayat Mousa,
Carlo Di Lorenzo
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, Columbus, OH, USA. rgomezsu@wfubmc.edu
AIM The aim of the present study was to evaluate the effect of amoxicillin/clavulanate (A/C) on gastrointestinal motility. METHODS Twenty consecutive pediatric patients referred for antroduodenal manometry received 20 mg/kg of A/C into the small bowel lumen. In 10 patients (group A), A/C was given 1 hour after and in 10 (group B), 1 hour before ingestion of a meal. Characteristics of the migrating motor complex, including presence, frequency, amplitude, and propagation of duodenal phase III and phase I duration and phase II motility index (MI), were evaluated 30 minutes before and after A/C administration. RESULTS There were no statistically significant differences in age and sex between the 2 groups. Manometry studies were considered normal in 8 patients in each group. In group A, 2 patients developed duodenal phase III after receiving A/C, and no significant difference was found in the MI before and after the drug administration. In group B, 9 patients developed duodenal phase III (P <0.05 vs group A). All phase III occurred within a few minutes from the medication administration. Most duodenal phase III contractions were preceded by an antral component during fasting but never after the medication was administered in either of the 2 groups (P<0.001 vs fasting). In group B, the duration of duodenal phase I was shorter after drug administration (P<0.05). There was no significant difference in duodenal phase II MI before and after A/C administration for the 2 study groups. CONCLUSIONS In children, administration of A/C directly into the small bowel before a meal induces phase III-type contractions in the duodenum, with characteristics similar to those present in the fasting state. These data suggest the possible use of A/C as a prokinetic agent. Further studies are needed to clarify its specific mechanism of action and the group of patients most likely to benefit from its use.
Gastroenterology Unit, Massachusetts General Hospital, Boston, MA, USA.
BACKGROUND Assessment of phase III MMC is often not performed due to the invasive nature of antroduodenal manometry used to detect it. The aim of the study was to evaluate the ability of wireless motility capsule (WMC) to detect phase III MMC and correlate it with the simultaneous measurements by antroduodenal manometry (ADM). METHODS Eighteen patients underwent simultaneous ADM and WMC. MMCs were identified first on ADM and then correlated with WMC events occurring simultaneously. Frequency of contractions per min, AUC, MI, and criteria for amplitude thresholds of contractions representing MCCs on WMC tracings were defined. KEY RESULTS In 18 patients, a total of 29 MMCs were recorded by ADM. WMC detected 86% of MMC events measured by ADM. Hundred percent (10/10) of MMCs in stomach were detected by WMC, whereas 79%(15/19) of MMCs were detected in SB. The sensitivity and specificity of WMC high amplitude contractions to represent phase III MMC were 90% and 71.8% in the stomach; 73.7% and 84.7% in SB, respectively, and negative predictive value was 99.9% in both regions. CONCLUSIONS & INFERENCES Wireless motility capsule was able to detect the phase III MMCs as the high amplitude contractions with good fidelity. WMC does not detect the propagation of MMC. Using the pressure thresholds, WMC can detect high amplitude contraction representing phase III MMC with favorable sensitivity/specificity profile and 99.9% negative predictive value. This observation may have clinical significance, as the absence of high amplitude contractions recorded by WMC during fasting state suggests absence of MMCs.
Department of Anatomy, Sapporo Medical University, School of Medicine, Chuo-ku, Sapporo 060-8556, Japan. fujimiya@sapmed.ac.jp
Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of these peptides, we applied the manometric measurement of gastrointestinal motility in freely moving conscious rat models. Ghrelin exerts stimulatory effects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum, but not on the motility of duodenum in the fasted state of animals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state, but not in the fasted state of animals. NPY Y2 or Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptors in the brain mediate the action of des-acyl ghrelin, whereas CRF type 1 and type 2 receptors in the brain mediate the action of obestatin. Vagal afferent pathways might be involved in the action of ghrelin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.
Research Institute, Taiko Pharmaceutical Co Ltd, Osaka, Japan.
Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.
Div. of Gastroenterology, Univ. of Texas Medical Branch,, Rte. 0632, 1108 The Strand, Rm. 221, Galveston, TX 77555, USA.
The aim of this study was to investigate effects of synchronized intestinal electrical stimulation (SIES) on small intestinal motility in dogs. Seventeen dogs were equipped with a duodenal cannula for the measurement of small bowel motility using manometry; an additional cannula was equipped in six of the dogs with 1.5 m distal to the first one for the measurement of small intestinal transit. Two pairs of bipolar electrodes were implanted on the small intestinal serosa with an interval of 5 cm; glucagon was used to induce postprandial intestinal hypomotility. Eleven dogs were used for the assessment of the small intestinal contractions in both fasting and fed states. The other six dogs were used for the measurement of small intestinal transit. We found that 1) SIES induced small intestinal contractions during phase I of the migrating motor complex (MMC)(contractile index or CI: 5.2 +/- 0.6 vs. 10.3 +/- 0.7, P = 0.003); 2) in the fed state, SIES significantly improved glucagon-induced small intestinal postprandial hypomotility (CI: 3.4 +/- 0.5 vs. 6.0 +/- 0.3, P = 0.03); 3) SIES significantly accelerated small intestinal transit delayed by glucagon (70.4 +/- 3.1 vs. 44.5 +/- 3.1 min, P < 0.01); 4) there was a negative correlation between the CI and transit time (r =-0.427, P = 0.048); and 5) the excitatory effect of SIES was blocked by atropine. SIES may have a therapeutic potential for treating patients with small intestinal disorders.
Veterans Research Foundation, Oklahoma City, Oklahoma, USA.
The aim of this study was to determine the effects and mechanism of synchronized gastric electrical stimulation (SGES) on gastric contractions and gastric emptying. The first experiment was designed to study the effects of SGES on antral contractions in four randomized sessions. Sessions 1 (control) and 2 (atropine) were performed in the fasting state, composed of three 30-min periods (baseline, stimulation, and recovery). Sessions 3 (control) and 4 (SGES performed during 2nd 20-min period) were performed in the fed state, consisting of two 20-min periods; glucagon was injected after the first 20-min recording. The second experiment was designed to study the effect of SGES on gastric emptying and consisted of two sessions (control and SGES). SGES was delivered with train duration of 0.5-0.8s, pulse frequency of 40 Hz, width of 2 ms, and amplitude of 4 mA. We found that 1) SGES induced gastric antral contractions in the fasting state. The motility index was 1.3 +/- 0.5 at baseline and 6.1 +/- 0.7 (P = 0.001) during SGES. This excitatory effect was completely blocked by atropine. 2) SGES enhanced postprandial antral contractions impaired by glucagon. 3) SGES significantly accelerated glucagon-induced delayed gastric emptying. Gastric emptying was 25.5 +/- 11.3% without SGES and 38.3 +/- 10.7% with SGES (P = 0.006 vs. control). This novel method of SGES induces gastric antral contractions in the fasting state, enhances glucagon-induced antral hypomotility in the fed state, and accelerates glucagon-induced delayed gastric emptying. The effect of SGES on antral contractions is mediated via the cholinergic pathway.
Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University. Xi'an 710004, Shaanxi Province, China. miss.wangyan@gmail.com
OBJECTIVE Ghrelin is an orexigenic peptide with remarkable prokinetic effects. However, its mechanisms in regulating feeding and gastrointestinal migrating myoelectrical complex (MMC) are not fully understood. The aim of this study was to examine the effects of ghrelin on feeding regulation and duodenal motility in rats. MATERIAL AND METHODS Feeding regulation was investigated at different times after intravenous injection of ghrelin and its receptor antagonist (D-Lys3)GHRP-6 in fasted rats. Rats were supplied with a pair of silver bipolar electrodes embedded in the duodenal serosa for electromyography. Ghrelin was injected intravenously into the rats during the fed state or fasted state. Some rats were pretreated with atropine, phentolamine, propranolol, L-arginine, the 5-hydroxytryptamine3 receptor antagonist ondansetron, and (D-Lys3)GHRP-6. RESULTS Ghrelin had little effect on food intake in the first 30 min after administration, but was found to increase feeding during the subsequent hours.(D-Lys3)GHRP-6 decreased feeding and antagonized the effect of ghrelin. Ghrelin induced duodenal MMC after administration in the fed state, and shortened the duodenal MMC cycle length and the duration of phase III during fasting. The amplitude and frequency of phase III were increased without affecting the percentage of phase III in the MMC cycle. Pretreatment with atropine, L-arginine, ondansetron, and (D-Lys3)GHRP-6 inhibited the effects of ghrelin. Propranolol and phentolamine had little influence on these effects. CONCLUSIONS Ghrelin appears to be closely related to feeding and intestinal motility. The excitatory effects of ghrelin are dependent on the cholinergic pathway, and it has a close relationship with the NOS-NO or 5-HT pathway. The ghrelin receptor is involved in its activities.
Naruo Kawasaki,
Koji Nakada,
Tomoko Nakayoshi,
Yoshiyuki Furukawa,
Yutaka Suzuki,
Nobuyoshi Hanyu,
Katsuhiko Yanaga
Department of Surgery, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan. naruk@jikei.ac.jp
The purpose of this study was to investigate the effects of the herbal medicine dai-kenchu-to on gastrointestinal motility based on differences in the administration site and timing. We sutured strain-gauge transducers to the stomach (three), duodenum (one), jejunum (one), ileum (one), and colon (two) and inserted indwelling tubes into the stomach, jejunum, and proximal colon of beagles. Dai-kenchu-to was administered to each site during the fasting or fed state. During the fasting state, the prokinetic effects of dai-kenchu-to were evident at all administration sites. The effects were attenuated during the fed state. With intracolonic administration, a contraction similar to the giant migrating contraction-like contraction was induced during the fasting and the fed state, and defecation occurred. Despite the differences in administration site and timing, no contraction complex appeared orad to the administration sites. These results indicate that the prokinetic effects of dai-kenchu-to differ with the site or timing of administration.
III Department of Paediatrics, Medical University of Białystok, Poland. mirusc@o2.pl
PURPOSE Cholecystokinin regulates gut motility and visceral sensation. The aim of the study was to determine the diagnostic value of plasma cholecystokinin octapeptide (CCK-8) concentration in children with functional abdominal pain (FAP). MATERIAL AND METHODS Fifty-two children (33 girls and 19 boys) aged 6-17 years with chronic abdominal pain were included in this study. On the basis of clinical data, results of endoscopy and Criteria for Functional Disorders the patients were divided into three groups: group 1--functional dyspepsia (FD), group 2--irritable bowel syndrome (IBS), group 3--non-specific FAP. The control group consisted of children without abdominal pain in anamnesis. CCK-8 concentrations in plasma were measured with radio immunoassay technique, after plasma extraction. In study protocol we analysed CCK-8 levels in fasting state and 15, 30, 60 minutes after a standard test meal. RESULTS In the fasting state plasma levels of CCK-8 were similar in each group and in controls. In the IBS patients CCK-8 levels were not increased after meal. In groups 1, 3 and controls postprandial levels were higher when compared to fasting state (p<0.05). Area under curve of CCK-8 plasma concentration was the lowest in group 2, but not significant compared to controls and other groups. No correlation was found between main symptoms of FD and IBS and CCK-8 concentration in plasma. CONCLUSIONS We conclude that gut dysmotility and symptoms of functional abdominal pain in children are not concerned with alteration of plasma CCK-8 levels before and after meal.
Department of Pathological Biochemistry, Glasgow Royal Infirmary, 4th Floor, Queen Elizabeth Building, Glasgow, UK. j.gill@clinmed.gla.ac.uk
This study aimed to determine whether changes in plasma heparin-releasable lipoprotein lipase (LPL) activity following a brisk walk were associated with decreases in fasting and/or postprandial triglyceride (TG) concentrations. Two groups of pre-menopausal women participated. In one group (fasting study group, n=10), TG concentrations and post-heparin plasma LPL activity were measured in the fasted state on two occasions: approximately 18 h after a 2-h treadmill walk at 50% maximal oxygen uptake (exercise trial); and after a day of no exercise (control trial). The other group (postprandial study group, n=9) undertook two oral fat tolerance tests (blood samples taken fasting and for 6 h after a high-fat meal), with plasma LPL activity measured 6 h after meal ingestion. Pre-conditions were the same as for the fasting study group (i.e. control and prior exercise). Prior exercise reduced fasting TG concentrations by 23 (7)%(fasting study group)[mean (SEM)] and by 18 (9)%(postprandial study group)(both P<0.05), and the postprandial TG response by 23 (6)%(postprandial study group)(P<0.01). Plasma LPL activity was not significantly increased by exercise in either the fasting or postprandial study groups. However, exercise-induced changes in both fasting and postprandial LPL activity were significantly correlated with the respective exercise-induced changes in fasting TG concentration and the postprandial TG response (r=-0.70 and -0.77 respectively, P<0.05 for both). These data suggest that increased LPL activity may contribute to the hypotriglyceridaemic effect of moderate exercise, although other mechanisms are also likely to be involved.
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