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Colonic postoperative inflammatory ileus in the rat.

OBJECTIVE: To investigate local inflammatory events within the colonic muscularis as a causative factor of postoperative ileus. SUMMARY BACKGROUND DATA: Surgically induced intestinal muscularis inflammation has been hypothesized as a mechanism for postoperative ileus. The colon is a crucial component for recovery of gastrointestinal motor function after surgery but remains unaddressed. The authors hypothesize that colonic manipulation initiates inflammatory events that directly mediate postoperative smooth muscle dysfunction. METHODS: Rats underwent colonic manipulation. In vivo transit and colonic motility was estimated using geometric center analysis and intraluminal pressure monitoring. Leukocyte extravasation was investigated in muscularis whole mounts. Mediator mRNA expression was determined by real-time reverse transcriptase-polymerase chain reaction. In vitro circular muscle contractility was assessed in a standard organ bath. The relevance of iNOS and COX-2 inhibition was determined using DFU or L-NIL perfusion. RESULTS: Colonic manipulation resulted in a massive leukocyte recruitment and an increase in inflammatory mRNA expression. This inflammatory response was associated with an impairment of in vivo motor function and an inhibition of in vitro smooth muscle contractility (56%). L-NIL but not DFU significantly ameliorated smooth muscle dysfunction. CONCLUSIONS: The results provide evidence for a surgically initiated local inflammatory cascade within the colonic muscularis that mediates smooth muscle dysfunction, which contributes to postoperative ileus.

Animals↗

Churg-Strauss syndrome diagnosed and followed with gastrointestinal fiberscopic studies and electroneuromyography.

Churg-Strauss syndrome (CSS) is a disorder characterized by hypereosinophilia and systematic vasculitis occurring in individuals with bronchial asthma. We present a case of 24-year-old woman with CSS diagnosed by and followed with gastrointestinal fiberscopic examination and electroneuromyography. The duodenal biopsy showed granulomatous angiitis with eosinophilic infiltration, and the electroneuromyography showed peripheral nerve dysfunction. After steroid treatment, the duodenal erosion and ulcer were almost completely resolved. There was no improvement in electroneuromyography, but the patient was able to walk independently after intensive rehabilitative training.

Adult↗

[Ibuprofen versus indomethacin in the treatment of patent ductus arteriosus in preterm infants].

INTRODUCTION: Persistent patent ductus arteriosus (PDA) is a common entity in preterm infants. The most commonly used pharmacological treatment to close the ductus is indomethacin but it can affect cerebral, renal and mesenteric blood flow. Ibuprofen has recently been shown to be effective in closing PDA with fewer hemodynamic effects. In this study we compared the safety and efficacy of ibuprofen and indomethacin in the treatment of PDA in preterm infants. MATERIAL AND METHODS: A randomized trial was performed. Premature infants with symptomatic PDA confirmed by echocardiography in the first week of life and who required respiratory support were included. The patients were randomly assigned to receive either intravenous indomethacin or ibuprofen. The rate of ductal closure, need for additional treatment, complications, and clinical course were evaluated. RESULTS: Twenty-four patients were treated with indomethacin and 23 with ibuprofen. The clinical characteristics before treatment were similar in both groups. Both treatments were effective in closing PDA (87.5% in the indomethacin group and 82.6% in the ibuprofen group). The two cohorts did not differ in the rate of reopening, need for a second pharmacologic treatment, or surgical ductal ligation. No patient in the ibuprofen group developed gastrointestinal adverse effects, but two infants in the indomethacin group had isolated bowel perforation and one had necrotizing enterocolitis. Transient renal dysfunction developed in seven patients (29%) in the indomethacin group versus two (9%) in the ibuprofen group. Transient renal insufficiency was found in one patient in the indomethacin group and in none in the ibuprofen group. The rate of other complications was similar in both groups. CONCLUSIONS: In our trial ibuprofen was as effective as indomethacin in closing PDA. No significant differences were found in the incidence of complications but fewer renal complications and no gastrointestinal complications were found in the ibuprofen group.

Anti-Inflammatory Agents, Non-Steroidal↗

Effects of intermittent tail shock or water avoidance on proximal colonic motor contractility in rats.

Changes in proximal colonic mechanical activity and defecation during exposure to three different types of experimental stressors were examined in rats chronically implanted with 2 force transducers on the proximal colon. To validate the integrity of the recording system, meal-induced changes in proximal colonic contractility were initially measured in all rats 1-2 days prior to stress induction. Different groups of ad lib fed rats were then exposed to tail shock, re-exposure to the shock chamber or water avoidance for 1 h over the next 1-2 days. Two types of phasic colonic contractions, long (0-3/min) and short (6-8/min) duration, were analyzed separately using a computer. Long duration contractions were significantly elevated 21-71% over fasting basal values from 61-120 min following a meal. No other consistent changes during the prandial or postprandial period were observed. Tail shock significantly suppressed proximal colonic contractility from pre-shock values and increased fecal output and fluid content when compared to ad lib fed rats that were not shocked. Fecal output increased but proximal colonic contractility did not change when previously shocked rats were re-exposed to the tail shock chamber but not shocked. In rats exposed to water avoidance, proximal colonic contractility was minimally suppressed but defecation was significantly greater than home cage control animals. These results indicate that proximal colonic contractile activity is differentially altered by exposure to different environmental stressors and may be a contributing factor in stress-induced bowel dysfunction.

Animals↗

Guanylins--agents with natriuretic effect.

Guanylins and uroguanylins are natriuretic peptides with different effects in many of tissues. In context with guanylins, the intestine-renal axis is presented. The overproduction of guanylin or uroguanylin leads to secondary diarrhea with stimulation of Cl(-) secretion. A diet high in salt lead especially to increased guanylin and uroguanylin secretion. Interesting applications with guanylins measurement could to be in hypertension diagnosis, monitoring of heart dysfunction treatment, intensive care etc.

Gastrointestinal Hormones↗

Pathogenesis of slow transit and pelvic floor dysfunction: from bench to bedside.

The colon and anorectum function together to provide intraluminal mixing, absorption of water, electrolytes, and short chain fatty acids, dehydration of fecal material, storage, and ultimately, elimination in a socially appropriate manner. Normal function and continence require accommodation of the colon and rectum to the entry of fecal materials, which includes receptive relaxation, perception, and discrimination of rectal contents, and voluntary and reflex motor function of the anorectum. Defecation, on the other hand, requires the reflex relaxation of the internal anal sphincter, voluntary and reflexive relaxation of the external anal sphincters and pelvic floor structures, and adequate rectosigmoid tone to allow funneling of contents through the anal canal. The sensation of urgency with rectal filling, and the motivation and prior learning of the appropriate responses are also required. Continence and defecation, therefore, involve complex sensory, structural, and motor mechanisms that involve both the colon and pelvic floor. These mechanisms and their relative importance to the pathogenesis of slow-transit constipation and pelvic floor dysfunction will be reviewed.

Chronic Disease↗

Is irritable bowel syndrome more likely to be persistent in those with relatives who suffer from gastrointestinal symptoms? A population-based study at three time points.

BACKGROUND: We tested the hypothesis that subjects with relatives who suffered from abdominal pain or bowel dysfunction would be at an increased risk of more persistent irritable bowel syndrome. METHODS: A valid, self-report questionnaire was mailed to an age- and gender-stratified random sample of residents, aged 30-64 years, in Olmsted County, MN, USA, on three occasions over a 4-year period. Persistent irritable bowel syndrome was defined as the presence of irritable bowel syndrome on at least two of the three surveys, and fluctuating irritable bowel syndrome was defined as the presence of irritable bowel syndrome on only one of the surveys. RESULTS: Subjects were less likely to have persistent irritable bowel syndrome over the age of 50 years [odds ratio (OR), 0.20; 95% confidence interval (CI), 0.09, 0.47]. A positive family history was reported by 23%. A family history of gastrointestinal symptoms was independently associated with persistent irritable bowel syndrome (vs. no irritable bowel syndrome: OR, 2.5; 95% CI, 1.3, 4.9) and fluctuating irritable bowel syndrome (vs. no irritable bowel syndrome: OR, 2.4; 95% CI, 1.3, 4.4). However, subjects reporting a positive family history were not more likely to report persistent vs. fluctuating irritable bowel syndrome (OR, 1.2; 95% CI, 0.5, 2.9). The use of non-steroidal anti-inflammatory drugs (OR, 2.3; 95% CI, 1.2, 4.3) and a history of food sensitivity (OR, 3.6; 95% CI, 1.9, 6.9) were the only other predictors of persistent irritable bowel syndrome. CONCLUSIONS: A history of abdominal pain or bowel troubles in first-degree relatives appears to be independently associated with both persistent and fluctuating irritable bowel syndrome.

Adult↗

Vincristine-induced dysphagia suggesting esophageal motor dysfunction: a case report.

Transient esophageal motor dysfunction with dysphagia was observed in a 62-year-old man receiving vincristine-containing chemotherapy for non-Hodgkin's lymphoma. Neurological examinations, including muscle strength of extremities, deep tendon reflexes and cranial nerves, were normal. However, the patient complained of severe numbness in the fingertips and toes. The results of esophagogram and esophagoscopy were unremarkable. However, a significantly prolonged esophageal transit time was observed. Vincristine was considered as the causative agent. Empirical vitamin and metoclopramide were prescribed for his neurological symptoms but there was no improvement. The symptoms of dysphagia subsided spontaneously 2 weeks later. However, prompt recurrence of severe dysphagia was observed again after administration of the second and third courses of treatment, which again disappeared upon discontinuation of the drug. Peripheral nerves and the gastrointestinal tract are often affected by vincristine. Common gastrointestinal tract symptoms of vincristine neuropathy may be colicky abdominal pain and constipation. However, vincristine-induced esophageal motor dysfunction with dysphagia is uncommon but generally reversible. The oncologist and chemotherapist should be aware of this complication.

Antineoplastic Agents, Phytogenic↗

[Phase II study of SM-108 (4-carbamoylimidazolium-5-olate) in hematological malignancies].

A total of 165 patients were entered into this study and 140 were evaluate for effects and 165 for toxicities. Of 39 patients with chronic myelogenous leukemia (CML) 21 achieved complete remission (CR), 6 achieved partial remission (PR) with a response rate of 69.2%. In MDS, of 11 patients with chronic myelomonocytic leukemia (CMMoL), one good partial response and 4 partial response were observed (CR + PR:45.5%); of 14 patients with RAEB, one complete response, 4 partial response (CR + PR: 35.7%); of 11 patients with RAEB in T, 3 partial response were observed (response rate: 27.3%). Of 13 patients with polycythemia vera, 4 excellent effect and 7 moderate effect (84.6%) were observed. Seven of 30 patients with acute myelocytic leukemia achieved partial response (23.3%). Mean dosages of SM-108 until remission were 400-500 mg/m2/day on CMMoL, RAEB in MDS, polycythemia vera and CML, and 600-800 mg/m2/day on RAEB in T and AML. In the analysis of adverse effects of SM-108, a subjective side effects including mainly gastrointestinal toxicities were observed in 38 cases (23.0%) of the patients : 26 patients (15.8%) showed objective side effects including liver dysfunction, but these symptoms were transient and not serious. Our study indicates that SM-108 is useful agent against MDS, especially CMMoL, RAEB, RAEB in T, polycythemia vera and CML.

Administration, Oral↗

The association of Streptococcus bovis bacteremia and gastrointestinal diseases: a retrospective analysis.

There is a well-established association between Streptococcus bovis bacteremia (SBB) and colorectal cancer. However, SBB is also frequently associated with chronic liver disease and has been described with other gastrointestinal disorders. The aim of the study was to evaluate the prevalence of gastrointestinal disease in patients with SBB. Retrospective analysis of the microbiology database at Jackson Memorial Medical Center, Miami, Florida, between 1992 and 2002, was performed. Patients' clinical records were reviewed, with special focus on underlying gastrointestinal disease or other major comorbidities. Thirty-eight patients (83%) were adults and eight (17%) were pediatric patients. Nineteen patients presented with gastrointestinal disorders associated with SBB (41%). Nine adult patients (19%) had end-stage liver disease (five female). Six patients had alcohol-induced liver disease (one with concomitant chronic hepatitis C), with the remaining three cases related to autoimmune hepatitis, primary biliary cirrhosis, and nonalcoholic steatohepatitis. Colonic neoplasms (adenocarcinoma in 3 and adenomatous polyps in 3) were found in 6 of 10 adult patients in whom colonoscopic evaluation was performed. Seven adult patients had acquired immunodeficiency syndrome (AIDS) (18%). Mortality in the patients with AIDS and SBB was high (71%). No significant association with gastrointestinal diseases was found in the pediatric population. Bacteremia due to S. bovis in adults is frequently associated with hepatic dysfunction (1:4), colonic neoplasms (1:6), and AIDS (1:6). This association was valid for our adult population only. SBB is an early clue to the likely presence of these serious underlying conditions and warrants rigorous investigation when recognized.

Adolescent↗

Side effects of NSAIDs and dosing recommendations for ketorolac.

We reviewed the pathogenesis of the most important side effects of non-steroidal antiinflammatory drugs (NSAIDs). Short-term treatments for postoperative pain are not generally associated with gastric damage. Pharmacoepidemiological studies have shown that for ketorolac the risk of gastrointestinal bleeding was only important in older patients and when doses > 90 mg/day were used. Although NSAIDs cause platelet dysfunction resulting in prolonged bleeding time, these drugs do not affect clot formation. Therefore, NSAIDs should be used with caution in surgical procedures involving considerable dissection of tissues and where any reduction in hemostatic function could be hazardous. Acute reversible renal dysfunction may occur when volume depletion or reduced renal function are present, in particular in elderly patients. NSAIDs should also be used with great caution in asthmatic patients. In general, the adverse events associated with ketorolac are similar to other NSAIDs. Provided the current European Community label prescription of ketorolac is not exceeded and with due observation of the contra-indications for use of NSAIDs, this agent is not likely to induce an increased risk of adverse events.

Aged↗

[Current status of endocarditis prevention].

There are currently no randomized and carefully controlled human trials to definitively prove that endocarditis prophylaxis is efficient. Furthermore, most cases of endocarditis are not attributable to a medical procedure. Thus, even with a high level of application of endocarditis prophylaxis only a minority of cases could be prevented. Endocarditis is a rare disease. On the other hand, its morbidity is increasing! In addition, infective endocarditis remains still a major medical concern because of its mortality between 5% and 76%. In addition, in up to 40% of all patients suffering from endocarditis one or more heart valves have to be replaced in the following 5 to 8 years. Without treatment endocarditis has a lethality of 100%. Therefore, there is worldwide agreement that endocarditis prophylaxis is necessary. Combining the recommendations of the German and the American Heart Association, as well as the results of the European consensus conferences, with newer insights into the pathophysiology of endocarditis the following aspects are elucidated: depending on their risk of endocarditis patients are allocated into 3 groups. In the first group there are patients with prosthetic cardiac valves, patients who suffered from previous endocarditis and patients with complex cyanotic congenital heart disease and surgically constructed shunts or conduits of the aorta and/or pulmonary circulation. In these high-risk patients the prophylactic regimen for dental, oral, respiratory tract procedures is oral amoxycillin. In genitourinary and gastrointestinal procedures ampicillin and gentamicin i.v. is recommended. In patients with mostly congenital cardiac malformations, acquired valvular dysfunction, hypertrophic obstructive cardiomyopathy and mitral valve prolapse or thickened leaflets and valvular regurgitation oral amoxycillin is recommended for all medical procedures (second group). The third group consists of patients with isolated secundum atrial defect, previous coronary bypass graft surgery, patients with cardiac pacemakers or defibrillators. In this patient cohort the individual risk of endocarditis is not higher than in the general population. Therefore, endocardits prophylaxis is not recommended.

Antibiotic Prophylaxis↗

Familial occurrence of intestinal obstruction in children with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is an uncommon neuromuscular disorder caused by mitochondrial dysfunctions that result in headaches, seizures, and progressive dementia. The authors describe a clinical case study of gastrointestinal manifestations in a pedigree with MELAS, in which all three children, ages 11, 8, and 6, demonstrated acute onset of intestinal obstruction. They unexpectedly showed severe abdominal distension and vomiting. Their parents had no clinical manifestation. The first female sibling underwent an emergent laparotomy because she was diagnosed to have intestinal strangulation. She had postoperative complications caused by progressive lactic acidosis and died the next day. The second and third sisters had similar onsets of the disease and were treated with gastrointestinal decompression and intravenous administration of lactate-free fluid and coenzyme Q10. Genetic testing using blood samples showed an A-to-G point mutation at nucleotide position 3243 in the tRNALeu(UUR) region in the mitochondrial DNA. In MELAS children who demonstrate acute onset of gastrointestinal manifestations, a careful review of family history and an elevation of serum lactate and pyruvate levels may enable a differential diagnosis to be made of acute abdomen to avoid unnecessary surgical intervention.

Child↗

Angioedema presenting in the retropharyngeal space in an adult.

PURPOSE: Hereditary angioedema is a rare disorder of deficient or dysfunctional C1-esterase inhibitor and usually manifests as edema of the face, tongue, supraglottis, extremities, or gastrointestinal tract. We report the case of a 40-year-old man with known hereditary angioedema who presented with a sore throat and a sensation of evolving airway obstruction. After a thorough search of the medical literature, we believe this to be the first reported case of angioedema manifesting in the retropharyngeal space. The pathophysiological factors of angioedema are discussed, along with its variable presentation and management issues. METHOD: Laryngoscopic examination was suggestive of posterior pharyngeal fullness; therefore, a computed tomographic scan of the neck was obtained, which showed a non-contrast-enhancing retropharyngeal edema from the base of the skull to below the level of the glottis. The patient had a history of multiple episodes of angioedema requiring hospitalization and three prior tracheotomies. RESULTS: Familiarity with the patient's history directed his rapid treatment course (including intravenous stanozolol, Solu-Medrol, and diphenhydramine), which significantly reduced his edema and avoided the need for tracheotomy. CONCLUSION: Hereditary angioedema may present in atypical locations, and expeditious treatment in a patient with a known history may avert the sequelae of evolving airway obstruction.

Adult↗

Altered anion handling by choroid plexus in renal insufficiency.

Abnormal localization of 99mTc pertechnetate was detected in the choroid plexus of patients with renal insufficiency despite the administration of potassium perchlorate. This was found in 8 of 21 studies on patients on conservative medical treatment, in 35 of 41 studies in patients on hemodialysis, in 12 of 22 studies in renal transplant recipients, and in 1 of 5 with acute renal insufficiency, but not in any of 33 persons free of renal disease. Abnormal retention of pertechnetate was also observed in the salivary glands of 21 renal patients. The increased localization of 99mTc pertechnetate could not be related to high blood levels of radioactivity, altered protein binding, increased erythrocyte labeling or to impaired gastrointestinal absorption of potassium perchlorate. It is proposed that this finding represents a manifestation of choroid plexus dysfunction resulting in altered handling of anions by this organ. A possible relation to neurological disease in chronic renal insufficiency is suggested.

Choroid Plexus↗