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Biomedical subjects

G Triadafilopoulos

Publications and source records attributed to G Triadafilopoulos.

At least 91 records · Page 5Linked to original sources

Oropharyngeal and esophageal interrelationships in patients with nonobstructive dysphagia.

Normal swallowing requires the close functional coordination of the mouth, pharynx, and esophagus, and if one of these components becomes functionally impaired, it is likely that the others may be affected. Using videofluoroscopy and manometry in this study, we examined the esophageal phase of swallowing in 12 patients with oropharyngeal dysphagia (group A) and the oropharyngeal components of swallowing in 29 patients with esophageal motor dysfunction and nonobstructive dysphagia (group B). A wide range of esophageal function abnormalities was seen in the first group, including delayed esophageal body peristalsis, spontaneous or simultaneous (tertiary) contractions, esophageal body dilation, proximal bolus redirection, and poor lower esophageal sphincter relaxation. Manometrically, 92% of group A patients were classified as having nonspecific esophageal motility disorder (NSEMD). In a similar fashion, group B patients exhibited many oropharyngeal function abnormalities on videofluorography including disturbed lingual peristalsis, slowed pharyngeal transit time with poor constriction of pharyngeal muscles, and laryngeal vestibular and tracheal bolus penetration. Manometrically, group B patients were classified as having NSEMD, achalasia, diffuse esophageal spasm, nutcracker esophagus, scleroderma, and chronic intestinal pseudoobstruction. In conclusion, oropharyngeal function is significantly altered in patients with esophageal motility disorders and dysphagia, and esophageal motor dysfunction occurs in patients with oropharyngeal dysphagia. These changes may represent either a compensatory mechanism or concomitant involvement of the oropharynx or the esophagus by the underlying neuromotor disorder. We suggest that assessment by esophageal motility and videofluoroscopy of both the oropharyngeal and esophageal phases of swallowing may improve diagnosis and therapy in patients with nonobstructive dysphagia.

Adult↗

Blood group-related antigen expression in normal and metaplastic human upper gastrointestinal mucosa.

Lewis antigen expression in upper gastrointestinal epithelium was studied using four monoclonal antibodies to determine the relationship between aberrant differentiation and antigen expression. Specific patterns of type 1 and type 2 Lewis blood group antigen expression were found in the surface and glands of the esophagus, gastric fundus, and duodenum. In biopsy specimens of Barrett's esophagus, gastric fundic-type columnar metaplasia expressed Lewis antigens indistinguishable from those in the normal stomach. In Barrett's junctional and specialized columnar metaplasia, Lewis a antigen was aberrantly expressed on the surface in secretors and in the glands independent of secretor state. Lewis x reactivity was markedly diminished in the glands of Barrett's junctional and specialized columnar epithelium irrespective of secretor state. There was no significant aberrancy observed in the expression of Lewis b and y antigens. The observed aberrant expression of Lewis antigens may be caused by an altered differentiation program in Barrett's metaplastic epithelium and may define a role for these glycoconjugates in the process of metaplasia and carcinogenesis in Barrett's epithelium.

Barrett Esophagus↗

Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study.

Arachidonic acid metabolites formed by both the cyclooxygenase and lipoxygenase pathways may contribute to the clinical diarrhea and colitis of inflammatory bowel disease. Patients with active ulcerative colitis have increased levels of leukotriene B4 in their rectal mucosa, and these levels tend to correlate with severity of the disease. In this study, we evaluated the efficacy of ingestion of fish oil n-3-omega-fatty acids, inhibitors of leukotriene synthesis, in the treatment of ulcerative colitis. Eleven patients with ulcerative colitis of mild to moderate severity were studied in a 8-month, double-blind, placebo-controlled, crossover trial of dietary supplementation with fish oil, which provided about 4.2 g of omega-3- fatty acids per day. A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy. Mucosal leukotriene B4 production was measured by radioimmunoassay. Mean disease activity index declined 56% for patients receiving fish oil and 4% for patients on placebo (p less than 0.05). There were no statistically significant differences in histopathologic scores or colonic mucosal leukotriene B4 levels. All patients tolerated fish oil ingestion and showed no alteration in routine blood studies. No patient worsened; anti-inflammatory drugs could be reduced or eliminated in eight patients (72%) while receiving fish oil. We conclude that fish oil dietary supplementation results in clinical improvement of active mild to moderate ulcerative colitis but is not associated with significant reduction in mucosal leukotriene B4 production, compared with placebo therapy. Further studies are needed to elucidate the mechanism of action and optimal dose and duration of fish oil supplementation in ulcerative colitis.

Adult↗

Bowel dysfunction in fibromyalgia syndrome.

Fibromyalgia and irritable bowel syndrome frequently coexist. In this study, we utilized a previously validated self-administered questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome in 123 patients with fibromyalgia as compared to 54 patients with degenerative joint disease (DJD) and 46 normal controls. Ninety (73%) of the fibromyalgia patients reported altered bowel function as compared to 20 (37%) DJD patients and none of the normal controls (P less than 0.001). Ninety-nine patients (81%) reported normal alternating with irregular bowel pattern, and 77 (63%) had alternating diarrhea and constipation. In contrast, only 24 (44%) of DJD patients and six (13%) of controls had regular alternating with irregular bowel pattern and only 12 (22%) of the DJD patients and none of the healthy controls had alternating constipation and diarrhea (P less than 0.01). Other bowel dysfunction complaints noted in the fibromyalgia group were abdominal gas (59%), nausea (21%), diarrhea (9%), and constipation (12%). Seventy-nine (64%) fibromyalgia patients reported frequent abdominal pain that was stress-related 47% of the time. Laxative use was frequent in the fibromyalgia group (19%) and absent in the other two groups. Fifty percent of fibromyalgia patients, compared to 28% of DJD patients, felt that their bowel complaints were worse during exacerbations of their joint disease (P less than 0.05). In conclusion, patients with fibromyalgia have a high prevalence of gastrointestinal complaints that should be carefully assessed. If the diagnosis of IBS is confirmed, appropriate treatment may improve patients' symptoms, although this approach requires further study.

Adult↗

Medical treatment of esophageal achalasia. Double-blind crossover study with oral nifedipine, verapamil, and placebo.

Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebo-controlled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia.

Administration, Oral↗

Acute abdomen as the first presentation of pseudomembranous colitis.

Acute abdomen was the presenting manifestation of pseudomembranous colitis in six men who had previously been treated with antibiotics and presented with abdominal distention, pain, fever, and leukocytosis with absent or mild diarrhea. Plain abdominal radiographs revealed megacolon in two, combined small and large bowel dilation in three, with one of them showing volvuluslike pattern, and isolated small bowel ileus in one. Emergency colonoscopy was performed successfully in all patients and revealed pseudomembranes in five and nonspecific colitis in one. All patients had positive latex test results for Clostridium difficile, and two tested positive for cytotoxicity. All patients were treated with IV metronidazole, resulting in resolution of symptoms and abdominal findings. In addition, two patients underwent colonoscopic decompression with improvement. Endoscopically, complete resolution of the pseudomembranes occurred at 4 weeks in all cases. No patient had a recurrence. It is concluded that (a) pseudomembranous colitis may present as abdominal distention mimicking small bowel ileus. Ogilvie's syndrome, volvulus, or ischemia; (b) in such cases, emergency colonoscopy is safe and useful for diagnosis and therapeutic decompression and may obviate the need for surgery; and (c) treatment with IV metronidazole is effective. Colitis due to C. difficile should be considered in the differential diagnosis of acute abdomen in patients previously treated with antibiotics.

Abdomen, Acute↗

Failure of initial 24-hour esophageal pH monitoring to predict refractoriness and intractability in reflux esophagitis.

Prolonged esophageal pH monitoring is considered to be the most sensitive and specific test for the diagnosis of gastroesophageal reflux disease (GERD). However, the role of pH monitoring in predicting the clinical and endoscopic response of reflux esophagitis is not well defined. In this study, 106 patients with moderate to severe symptoms of GERD and esophagitis (grades 0-IV) by endoscopy were initially studied by ambulatory esophageal pH monitoring, and their clinical response to standard H2 antagonist therapy was monitored at 8 wk. Refractory patients were defined as those who failed to heal and/or had intractable reflux symptoms after 8 wk of H2 antagonist therapy, and who required continuous therapy with higher doses of H2 antagonists, addition of prokinetic agents, or omeprazole. There was a positive correlation (r = 0.89) between endoscopic severity of esophagitis upon entry into the study and refractoriness to standard medical therapy. However, there were no differences in the various pH parameters analyzed between the 58 patients who responded and the 48 patients who were refractory to medical therapy, regardless of the endoscopic grading of their esophagitis. We conclude that 24-h ambulatory esophageal pH monitoring does not predict refractoriness of reflux esophagitis to standard therapy. The decision for more aggressive methods of treatment probably requires assessment of symptomatic and endoscopic response after 8 week standard H2 antagonist therapy.

Adult↗

Same-day upper and lower inpatient endoscopy: a trend for the future.

Performance of same-day upper and lower endoscopy has many potential advantages, as it may reduce costs, shorten hospital stay, and expedite patient care, but its feasibility, efficacy, and potential have not been carefully defined. We report here our experience with a group of 87 patients who underwent same-day upper and lower endoscopy (174 procedures) over a 2-yr period at a tertiary care VA Hospital, compared with an alternate-day upper and lower endoscopy group of 50 patients (100 procedures) over the same time period. Most patients were elderly males. Common indications for endoscopy were occult or overt gastrointestinal bleeding, previous or concomitant history of pertinent pathology (i.e., polyps, ulcers), abdominal pain, diarrhea, or other symptoms, abnormal radiological studies, and iron deficiency anemia. Both groups required similar amounts of intravenous sedation. There were no complications in either group. In both groups, common positive findings were inflammation (i.e., colitis, esophagitis), benign neoplasms, diverticulae, peptic ulcer, and cancer. In both groups, only 2-6% had negative upper and lower endoscopy, whereas either one procedure was negative in 25% and 18% of cases, respectively. We conclude that the practice of same-day inpatient upper and lower endoscopy is feasible, has excellent diagnostic yield, even in the elderly, and carries no increased risks. When indicated, the practice of same-day upper and lower endoscopy should be encouraged.

Adult↗

The chemotactic response of human granulocytes to Clostridium difficile toxin A is age dependent.

Elderly patients are at high risk for developing diarrhea and colitis as a complication of antimicrobial therapy. Clostridium difficile, the causative agent of antibiotic-associated diarrhea and colitis produces an enterotoxin (toxin A) and a cytotoxin (toxin B). Of these two exotoxins, toxin A appears to be largely responsible for the inflammatory phenomena of C. difficile colitis, because it produces secretion, pronounced granulocytic infiltration, and epithelial cell necrosis and ulceration in ligated ileal loops of experimental animals. We have recently demonstrated that the inflammatory effects of C. difficile toxin A in the intestine may be related to its ability to mobilize intracellular calcium and elicit a chemotactic response by human granulocytes. In this study, in order to explain why the elderly are at greater risk for developing antibiotic-associated colitis, we investigated the effects of toxin A on activation of granulocytes from healthy elderly and young subjects. Highly purified toxin A and the chemotactic factor N-formyl-Met-Leu-Phe (FMLP) at concentrations of 10(-7) M both elicited a significant (p less than 0.001) and comparable chemotactic and chemokinetic response in human granulocytes from both age groups. A significantly (p less than 0.001) increased chemotactic effect in elderly subjects compared with young subjects was elicited by toxin A and not by FMLP. These findings suggest that the enhanced intestinal inflammatory effects of C. difficile in the elderly, compared with the young, may be related to the ability of its enterotoxin to elicit a more pronounced chemotactic response by granulocytes.

Adult↗

Nonpropulsive esophageal contractions and gastroesophageal reflux.

Nonpropulsive esophageal contractions radiologically described as tertiary contractions or "corkscrew" esophagus suggest the presence of an underlying motility disorder and may lead to impaired acid clearance. The goals of this study were to determine the prevalence and role of gastroesophageal reflux (GER) in patients with tertiary contractions. Thirty-five consecutive patients with spontaneous, repetitive, nonpropulsive esophageal contractions noted on esophagography were studied with endoscopy, infusion esophageal manometry, and 24-h ambulatory pH monitoring. All patients had esophageal symptoms, mainly dysphagia, heartburn, and chest pain, but only three were found to have esophagitis by endoscopy and biopsy. Nineteen patients had repetitive, nonlumen-obliterating, nonperistaltic (tertiary) contractions, six had corkscrew esophagus, and 10 had forceful, lumen-obliterating simultaneous contractions (rosary bead esophagus). Twenty patients (58%) had GER by pH criteria with mean values: % time pH less than 4, 40.9; %upright pH less than 4, 41; %supine pH less than 4, 44.3%; number of episodes with greater than 5 min of pH less than 4, 12. Esophageal motility revealed "nutcracker" esophagus in eight, low LESP in two, and nonspecific esophageal motility disorder in 10. Symptoms or severity of nonperistaltic contractions did not correlate with GER. Radiologically demonstrable free reflux or the presence of heartburn did not predict GER. We conclude that 1) GER occurs in up to 58% of patients with nonpropulsive (tertiary) esophageal contractions on esophagography, and may play a role in the induction of abnormal peristaltic activity of the esophageal body; 2) GER is usually not associated with endoscopic evidence of esophagitis or characteristic symptoms, and is recognized by 24-h pH monitoring. We speculate that detection and treatment of GER may improve the symptomatic management of patients with nonpropulsive esophageal contractions.

Adult↗

"Spontaneous sump syndrome": Successful treatment by duodenoscopic sphincterotomy.

"Sump syndrome" is a rare complication of side-to-side choledochoenterostomy operations which develops in the distal, nonfunctioning limb of the common bile duct where lithogenic bile, gastrointestinal contents, and debris accumulate. We report here a patient who developed spontaneous sump syndrome as a result of the formation of choledochoduodenal fistula, and who presented with multiple pyogenic liver abscesses. The patient's symptoms and liver abscesses resolved completely after treatment by endoscopic sphincterotomy and antibiotics. This case demonstrates that sump syndrome may occur spontaneously, that it can be a cause for pyogenic liver abscess formation, and that it may be treated effectively by endoscopic sphincterotomy.

Biliary Fistula↗

Nodular duodenitis and single duodenal nodules.

Duodenal nodules are an uncommon endoscopic finding generally thought to indicate duodenal inflammation. This study examines the incidence and histologic correlates of multiple and single duodenal nodules in 2,966 consecutive male patients who underwent esophagogastroduodenoscopy during the past five years. Five per cent had duodenal nodules. When two or more discrete nodules, with or without apical ulceration, were present, the finding was termed nodular duodenitis, which was seen five and one-half times more frequently than single nodules. There were 127 patients with nodular duodenitis (4.3%); seven had chronic renal disease and 33 (26%) had concomitant peptic ulcer disease. Biopsies showed either normal mucosa or histologic aberrations typical of nonspecific duodenitis. Single nodules were seen in only 23 patients (0.8%). Biopsies of these nodules revealed benign or malignant tumors in five instances and infrequently showed only normal mucosa. It is concluded that nodular duodenitis is a visually distinct, morphologic variant of nonspecific duodenitis bearing some yet-to-be-defined relationship to peptic ulcer disease. Single nodules are much less likely to represent duodenitis and, in fact, they have significant neoplastic potential, mandating biopsy whenever they are found.

Aged↗

Comparative study of Clostridium difficile toxin A and cholera toxin in rabbit ileum.

The purpose of this study was to compare the effects of Clostridium difficile toxin A and cholera toxin on fluid secretion, intestinal permeability, and arachidonate metabolites in rabbit ileum. Injection of 25 micrograms of either purified toxin into 10-cm ileal loops caused significant increases in fluid secretion and intestinal permeability to mannitol as well as release of prostaglandin E2 into the lumen. Toxin A, but not cholera toxin, caused a severe inflammatory reaction of the lamina propria and necrosis of enterocytes as well as increased release of leukotriene B4. The toxin A-mediated increases in prostaglandin E2 and leukotriene B4 could be blocked by prior instillation of 10 mg of 5-aminosalicylic acid into ileal loops. 5-Aminosalicylic acid also significantly diminished the expected increase in mannitol permeability after both toxins, but had no significant inhibitory effect on fluid secretion or, in the case of toxin A, intestinal inflammation. Our results indicate that C. difficile and cholera enterotoxins differ substantially in their effects on the rabbit intestine. Clostridium difficile toxin A, an inflammatory toxin, produces a striking infiltration of the lamina propria with neutrophils that is associated with increased release of leukotriene B4. In contrast, cholera toxin does not cause inflammation or leukotriene B4 release. Increased release of prostaglandin E2 occurs after exposure to both toxins and appears to be correlated with increased intestinal permeability.

Animals↗

Effect of purified Clostridium difficile toxins on intestinal smooth muscle. I. Toxin A.

In these studies we determined the effects of purified Clostridium difficile toxin A, an enterotoxin, on the electrophysiological and contractile properties of rabbit intestinal circular smooth muscle and correlated these effects with changes of smooth muscle morphology. Simultaneous measurements of intracellular membrane potential and contractility were determined in excised ileal muscle strips after administration of toxin A in vivo (60 micrograms/ml) into an isolated rabbit ileal loop or directly in vitro (0.1-60 micrograms/ml) to a normal muscle strip. Toxin A injection in vivo resulted in membrane depolarization and increased slow wave and action potential frequency. Toxin A injection in vivo also caused increased amplitude of spontaneous and carbachol-induced phasic contractions. The electrophysiological effects of in vivo administration of toxin A were correlated with an inflammatory infiltrate of the lamina propria, but no light or electron microscopic evidence of injury to smooth muscle cells was seen. In contrast to the in vivo studies, direct in vitro exposure of normal ileal muscle strips to toxin A had no effect on either spontaneous or carbachol-induced electromechanical activity. Our results indicate that in vivo administration of C. difficile toxin A into a rabbit ileal loop, but not direct in vitro exposure, causes significant alterations of smooth muscle excitation-contraction coupling that may be mediated by products of local inflammatory cells.

Action Potentials↗

Nonobstructive dysphagia in reflux esophagitis.

Dysphagia in the absence of organic esophageal stricture may occur in patients with reflux esophagitis. Although the exact mechanism of this "nonobstructive dysphagia" (NOD) is not known, it is believed to be related to transient segmental esophageal motor disorder. The goals of this study were to determine the frequency of NOD in patients with reflux esophagitis and correlate it with esophageal pH and motility changes. Sixty-three consecutive patients with symptoms of esophageal dysfunction were studied with endoscopy, infusion esophageal manometry, and 24-h ambulatory esophageal pH monitoring. Forty-seven had severe erosive esophagitis unresponsive to medical therapy; 16 with esophageal motility disorders were used as symptomatic controls. Twenty-eight of 63 patients studied experienced NOD during the 24-h pH study; 22 had esophagitis and six had esophageal dysmotility without esophagitis. NOD was noted with similar frequency in the two groups; 22/47 (46.8%) of patients with esophagitis and 6/16 (37.5%) with esophageal dysmotility experienced NOD during the period of study. NOD correlated with pH less than 4.0 in 88.6% of patients with esophagitis but in only 7% of patients with esophageal dysmotility (p less than 0.001). There was no difference in acid reflux patterns in esophagitis patients who experienced NOD (22/47), and in those who did not (25/47). There was no correlation between NOD and baseline esophageal motility abnormalities. In summary, 1) NOD is a common, intermittent symptom that occurred in up to 46.8% of esophagitis patients and 37.5% of symptomatic controls during the 24-h period of this study; 2) NOD correlates with esophageal pH less than 4.0 in patients with esophagitis and not in patients with esophageal dysmotility. These data strongly suggest that acid in the distal esophagus frequently triggers the sensation of dysphagia in esophagitis patients, but not in patients with esophageal motility disorders. Combined ambulatory intraesophageal motility and pH monitoring may further elucidate the mechanism of dysphagia in these patients.

Deglutition Disorders↗

Hiccups and esophageal dysfunction.

Presented herein are the detailed esophageal manometric, radiologic, ambulatory pH, and scintigraphic findings from a patient who developed protracted and recurrent hiccups (singultus) after a lateral medullary infarction. Because of the usually transient and benign nature of hiccups, previous reports on esophageal dysfunction during hiccups have been sporadic and confined to manometric findings. Utilizing various esophageal function techniques, the main features observed during hiccups were esophageal body dilation and aperistalsis, absent lower esophageal sphincter relaxation in response to swallowing, poor emptying of the distal two-thirds of the esophageal body, and low distal esophageal pH. Most of these features normalized in the absence of hiccups. A comparison is made of these findings during prolonged hiccups with those of esophageal achalasia.

Aged↗