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Biomedical subjects

J Tack

Publications and source records attributed to J Tack.

At least 127 records · Page 7Linked to original sources

Self-expandable metallic stents in the palliation of rectosigmoidal carcinoma: a follow-up study.

BACKGROUND: Currently applied endoscopic palliative treatment of advanced rectosigmoidal carcinoma is hampered by the cost of the equipment, the need for repeated, often painful treatment sessions, and the occurrence of complications. Metallic expandable stents are effective in the palliation of malignant esophageal and biliary stenoses. We evaluated the use of a new type of self-expandable nitinol stent in the palliation of rectosigmoidal carcinoma. METHODS: In 10 patients with advanced obstructing rectosigmoidal carcinoma, initial Nd:YAG laser treatment was performed if necessary to allow passage of a gastroscope. Subsequently, a self-expanding nitinol stent with flanged ends was inserted under combined fluoroscopic and endoscopic control. Endoscopic and clinical follow-up was carried out at regular intervals. RESULTS: After 2+/-0.4 sessions of initial laser therapy, minimal lumen diameter was 9+/-1 mm. Stent insertion was successful in 9 patients, increasing minimal lumen diameter to 14+/-1.2 mm (p < 0.005). In one patient, stent deployment was complicated by a sigmoid perforation, requiring surgery. After insertion, colorectal stents remained adequately positioned and free of obstruction for 103+/-31 days. Patient survival after stent placement was 204 +/-43 days. Stent migration occurred in 3 patients, after 38+/-10 days. Obstruction of the stent because of tumor ingrowth was observed in only one patient, after 268 days. CONCLUSION: Insertion of self-expandable nitinol stents in patients with rectosigmoidal carcinoma is technically feasible. Metallic stents are effective in the palliation of malignant rectosigmoid obstruction; they provide an alternative to repeated palliative laser therapy or palliative surgery.

Aged↗

The influence of cisapride on gastric tone and the perception of gastric distension.

BACKGROUND: Delayed gastric emptying, impaired gastric accommodation to a meal and hypersensitivity to gastric distension have been implied in the pathophysiology of functional dyspepsia. Dyspeptic patients are often treated with the prokinetic drug cisapride. AIM: To assess the effects of cisapride on perception of gastric distension and gastric accommodation to a meal. METHODS: Eighteen healthy volunteers underwent a gastric barostat study on two occasions, after pretreatment with placebo or cisapride 10 mg q.d.s. Graded isobaric and isovolumetric distensions were performed until the subjects reported discomfort. Volume and pressure changes were recorded and perception was scored by a questionnaire. In 10 volunteers, the amplitude of the gastric accommodation to a mixed liquid meal was also measured. RESULTS: Pre-treatment with cisapride significantly lowered thresholds for perception and for discomfort, both during isobaric (4.3 +/- 0.7 vs. 3.2 +/- 0.7 and 12.2 +/- 1.2 vs. 9.2 +/- 0.9 mmHg above minimal distending pressure (MDP), respectively, P < 0.05) and isovolumetric (256 +/- 46 vs. 200 +/- 35 and 644 +/- 36 vs. 511 +/- 40 mL, respectively, P < 0.05) distensions. Cisapride significantly enhanced the size of the meal-induced fundus relaxation (143 +/- 37 vs. 270 +/- 50 mL, P < 0.05). CONCLUSIONS: Cisapride enhances both the perception of gastric distension and the gastric accommodation to a meal. These data suggest that cisapride may provide benefit to patients with impaired postprandial relaxation of the fundus.

Adult↗

Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man.

BACKGROUND: Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex. AIMS: To study the effect of sumatriptan, an agonist of enteric neuronal 5HT1p receptors, on interdigestive motility in man. SUBJECTS AND METHODS: In 12 healthy subjects, interdigestive motility was recorded manometrically in the upper gastrointestinal tract. In seven subjects blood samples were drawn every 15 minutes for radioimmunoassay of motilin and somatostatin. After two phase 3s of the migrating motor complex, 6 mg of sumatriptan was administered subcutaneously. Recording continued until two more phase 3s had occurred. RESULTS: Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of the migrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilin concentrations and the occurrence of plasma motilin peaks were not affected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented the induction of a gastric phase 3 by the motilin agonist erythromycin. CONCLUSIONS: Administration of the 5HT1P receptor agonist sumatriptan induces a premature intestinal phase 3, suppresses gastric phase 3s, prevents induction of a gastric phase 3 by erythromycin, and reduces plasma somatostatin concentrations.

Adult↗

Ambulatory gastrojejunal manometry in severe motility-like dyspepsia: lack of correlation between dysmotility, symptoms, and gastric emptying.

BACKGROUND: Previous studies have failed to identify manometric patterns of gastrointestinal motor activity that can distinguish dyspepsia from health. AIMS: To test the hypothesis that the combined use of prolonged, ambulatory, antrojejunal manometry and computer aided analysis in patients selected for the severity of their symptoms could reveal new insights into gastrointestinal motor activity in patients with severe motility-like dyspesia. METHODS: Twenty four hour antrojejunal ambulatory manometry was performed in 14 patients and 10 healthy volunteers. Parameters characterising digestive and fasted motility were obtained by a validated computer program and visual analysis. Scoring systems quantified the degree of dysmotility as well as the severity of symptoms. Gastric emptying times were measured in each patient. RESULTS: There was a high prevalence of antral and jejunal dysmotility both during the interdigestive period (71% of patients) and in the postprandial period (78%). During the interdigestive period there was a reduced incidence of antral and jejunal phases, a larger contribution of phase 2 during migrating motor complex cycles, and aberrant configuration of jejunal phase 3 in 29% of patients. Postprandially, the most frequent finding was antral (29% of patients) or jejunal (29%) hypomotility or hypermotility. Minute rhythm was present both during the postprandial (29% of patients) and the interdigestive period (21%). There was no positive correlation between symptom scores, gastric half emptying times, or motility scores. CONCLUSION: Even with the use of prolonged recordings and advanced computer aided analysis, it is not possible to identify a specific motor pattern which can discriminate patients with severe motility-like dyspepsia from those with other diseases or even healthy individuals. Clinical symptoms or gastric half emptying times are poor predictors of gastrointestinal dysmotility in patients with functional dyspepsia.

Adolescent↗

Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans.

BACKGROUND: During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity. AIMS: To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1 receptor agonist sumatriptan. METHODS: In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n = 10), atropine (15 micrograms/kg intravenous bolus plus 15 micrograms/kg/h over 30 minutes; n = 10), or sumatriptan (6 mg subcutaneously; n = 10) was administered, followed by infusion of erythromycin 40 mg or 200 mg. RESULTS: After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p < 0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p < 0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo. CONCLUSIONS: The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.

Anti-Bacterial Agents↗

5-Hydroxytryptamine-1 receptor activation inhibits endocrine pancreatic secretion in humans.

The selective 5-hydroxytryptamine-1 receptor agonist sumatriptan inhibits exocrine pancreatic function in humans. No data are available on the effect of sumatriptan on fasting and postprandial endocrine pancreatic function in humans. To elucidate the influence of 5-hydroxytryptamine-1 receptor activation by sumatriptan on endocrine pancreatic function and blood glucose homeostasis, we determined plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin, and C-peptide before and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers, and we measured blood glucose and insulin plasma levels during an oral glucose tolerance test after placebo and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers. Sumatriptan significantly decreased the mean plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin and C-peptide (P < 0.001) and also significantly decreased mean and peak plasma levels of insulin after an oral glucose challenge (P < 0.02 and P = 0.04, respectively) without affecting glucose homeostasis. From our study, we speculate that activation of the 5-hydroxytryptamine-1 receptor inhibits endocrine pancreatic secretion.

Adult↗

Ambulatory small intestinal manometry. Detailed comparison of duodenal and jejunal motor activity in healthy man.

The aim of this study were to provide a detailed comparison of duodenal and jejunal motor activity in healthy individuals by utilizing prolonged ambulatory manometry in combination with computer-aided analysis. Intraluminal pressure profiles were studied in the duodenum and jejunum of 18 healthy volunteers over 24 hr. The subjects ingested two meals, both of 800 kcal and of equal chemical composition, at two different times of the day. Over the whole interdigestive period, phase III motor activity started more frequently distal than proximal to the ligament of Treitz. However, an increasing time of fasting was linearly related to an increasing number of phase IIIs originating proximal to the ligament of Treitz (r = 0.95). Both meals induced a postprandial motor pattern of similar duration and contractile activity. As compared to the jejunum, individual duodenal contractions during the postprandial period and during phase II had a higher duration and amplitude. Propagated clustered contractions occurred more frequently in the duodenum than in the jejunum, both in the interdigestive and digestive state. Jejunal clusters comprised a higher number of individual contractions of lower amplitude and duration. In healthy man duodenal and jejunal motor activity are different, both in the digestive and interdigestive state. The differences include the number of activity fronts traversing these segments of the gut, the number and organization of propagated clustered contractions, and subtle changes in the amplitude, duration, and coordinated propagation of individual contractions. These changes presumably reflect a regulatory capability of the small intestine to modulate the rate of transit of intraluminal content through different segments of the gut.

Adult↗

Sumatriptan, a selective 5-HT1 receptor agonist, induces a lag phase for gastric emptying of liquids in humans.

Sumatriptan, a 5-hydroxytryptamine1 (5-HT1) receptor agonist at enteric neuronal 5-HT receptors, causes a relaxation of the gastric fundus and inhibition of antral contractile activity. The present study examined the effect of sumatriptan on gastric emptying of solids and liquids in humans. In eight healthy subjects the gastric emptying rate for liquids and solids was measured using the carbon-labeled glycine and octanoic acid breath test after subcutaneous administration of placebo or sumatriptan. Sumatriptan increased the gastric half-emptying time of liquids (P < 0.0005) and induced a prolonged lag phase for liquids (P < 0.0005) in all subjects. Sumatriptan increased gastric half-emptying time (P < 0.005) and the lag phase of solids (P < 0.05) in all subjects. In two healthy subjects gastric emptying of liquids and solids after subcutaneous administration of sumatriptan was studied by radioscintigraphy. Radioscintigraphy confirmed the delayed emptying and the prolonged lag phases after sumatriptan. In conclusion, sumatriptan delays gastric emptying of solids and liquids in healthy subjects. Moreover, sumatriptan induces a lag phase for liquids. The mechanism by which sumatriptan alters gastric emptying remains to be studied.

Adult↗

Biosynthesis of riboflavin. Lumazine synthase of Escherichia coli.

A gene located at 443 kilobases on the Escherichia coli chromosome (subsequently designated ribE) was expressed in a recombinant E. coli strain and was shown to code for the enzyme 6, 7-dimethyl-8-ribityllumazine synthase. The recombinant enzyme was purified to homogeneity. The protein is an icosahedral capsid of 60 subunits with a mass of about 1 MDa as shown by hydrodynamic studies and by electron microscopy. In contrast to the icosahedral lumazine synthase-riboflavin synthase complex of Bacillus subtilis, the lumazine synthase of E. coli is not physically associated with another enzyme of the riboflavin pathway, and the core of the icosahedral capsid is empty. The RIB4 gene of Saccharomyces cerevisiae was also expressed to a high level (about 40% of cellular protein) in E. coli. The recombinant protein is a pentamer of 90 kDa. An insertion of 4 amino acids into helix alpha4 is likely to hinder the formation of an icosahedral capsid by the yeast protein. The kinetic properties of lumazine synthase of E. coli, B. subtilis, and S. cerevisiae are similar.

Amino Acid Sequence↗

A risk-benefit assessment of cisapride in the treatment of gastrointestinal disorders.

Cisapride is a substituted benzamide compound that stimulates motor activity in all segments of the gastrointestinal tract by enhancing the release of acetylcholine from the enteric nervous system. Cisapride is administered orally in the treatment of gastro-oesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction syndromes and chronic constipation. In gastro-oesophageal reflux disease in both adults and children, cisapride provides symptomatic improvement and mucosal healing. Long term treatment with cisapride is effective in the prevention of relapse of oesophagitis. Cisapride improves gastric emptying rates and improves symptoms in patients with gastroparesis of various origins. Unlike domperidone and metoclopramide, long term administration of cisapride seems to result in persistently enhanced gastric emptying. Cisapride is also effective in improving symptoms in patients with functional dyspepsia. In comparative studies in patients with functional dyspepsia, cisapride was at least as effective as metoclopramide, domperidone, clebopride, ranitidine and cimetidine. Cisapride increases stool frequency and reduces laxative consumption in patients with idiopathic constipation. Severe cases of slow transit constipation seem refractory to cisapride. Clinical studies also indicate that cisapride might be effective in the treatment of chronic intestinal pseudo-obstruction, postoperative ileus, peptic ulcer and irritable bowel syndrome. Further clinical studies are warranted to define the role of cisapride in these conditions. The dosage of cisapride ranges from 5mg 3 times daily to 20mg twice daily. Cisapride is generally well tolerated, both during short and long term treatment. In children, cisapride is also well tolerated in doses of 0.2 to 0.3 mg/kg, 3 to 4 times daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Ulcer Agents↗

Significance of arrhythmias during the first 24 hours of acute myocardial infarction treated with alteplase and effect of early administration of a beta-blocker or a bradycardiac agent on their incidence.

BACKGROUND: Although early intravenous beta-blocker therapy during acute myocardial infarction (AMI) reduces the incidence of fatal arrhythmias in patients not treated with thrombolytic agents, its antiarrhythmic effect in thrombolysed patients remains controversial. We investigated prospectively the arrhythmia incidence in 244 patients with AMI receiving alteplase and a double-blind randomized adjunctive therapy with intravenous atenolol, alinidine, or placebo. Moreover, the characteristics and prognostic significance of early arrhythmias and their relation with infarct size and coronary patency were evaluated. METHODS AND RESULTS: All patients underwent 24-hour Holter monitoring on day 1 and were clinically followed in the hospital for 10 to 14 days. Coronary angiography was performed on day 10 to 14. Atenolol and alinidine significantly decreased the basic heart rate without causing more sinus arrest or higher-degree atrioventricular block. The prevalence of atrial fibrillation in alinidine patients was lower than in the atenolol patients (P = .007) but not lower than in placebo patients (P = .11). There was no effect of either agent on the incidence and frequency distribution of ventricular or supraventricular premature beats or on the incidence and characteristics of nonsustained ventricular tachycardia, accelerated idioventricular rhythm, sustained ventricular tachycardia (VT), or ventricular fibrillation (VF). On day 1, seven VF episodes were recorded in six patients (2.5%) and five VT episodes in five patients (2%). VF always started at < 2.5 hours after start of thrombolytic treatment and VT always at > 2.5 hours (average of 6 hours). Five of the seven VF and three of the five VT episodes started with an R-on-T. However, for all VT, the morphology of the first beat was the same as that of the following beats, suggesting that the sustained arrhythmia was not induced by an extrasystole. After day 1 and before hospital discharge, VF and VT developed in one and six patients, respectively. Three of the seven patients who developed VF during the first 2 weeks underwent coronary angiography; all three had an occluded infarct-related artery. In contrast, only one of nine patients with early or late VT had an occluded vessel. Patients with VT and VF on day 1 had a significantly larger enzymatic infarct size than those without the arrhythmia (P = .02), and a similar trend was noted for VT or VF after day 1 (P = .19). However, none of the patients with VT or VF on day 1 developed a life-threatening arrhythmia later during the hospital stay. Also, none of the seven patients with VT or VF after day 1 had experienced a major rhythm disturbance during the first 24 hours. CONCLUSIONS: (1) Our data do not support the hypothesis that beta-blockers or bradycardiac agents might reduce the incidence of major arrhythmias when used in conjunction with thrombolytic therapy. (2) The pathogeneses of VT and VF early during AMI are clearly distinct. (3) VT or VF during the first 2 weeks is a marker for a larger infarct. (4) We could not detect a relation between malignant arrhythmias on day 1 and recurrences within the following 2 weeks.

Anti-Arrhythmia Agents↗

5-hydroxytryptamine-3 receptors are involved in the initiation of gastric phase-3 motor activity in humans.

BACKGROUND: 5-hydroxytryptamine-3 (5-HT3) receptor antagonists inhibit gastric phase-3 motor activity in the dog. This study examined the role of 5-HT3 receptors in the generation of gastric phase 3 of the migrating motor complex in humans. METHODS: Interdigestive motor activity was recorded manometrically in 16 subjects before and after administration of ondansetron, a selective 5-HT3 receptor antagonist. Plasma motilin values were also assayed in 7 individuals. The incidence of gastric activity fronts before and after ondansetron was compared with a control group that had not received ondansetron. The ability of erythromycin to induce a gastric activity front in the presence of ondansetron was also evaluated in 7 subjects. RESULTS: The incidence of gastric activity fronts was 69% before ondansetron vs. 19% after ondansetron. In contrast, in the control group there was no significant change in the incidence of gastric activity fronts over time. Activity fronts preceding ondansetron were associated with motilin peaks while activity fronts after ondansetron were not. Despite the previous administration of ondansetron, erythromycin induced gastric activity fronts in 89% of cases. CONCLUSIONS: Selective antagonism of 5-HT3 receptors suppresses the gastric component of phase-3 motor activity and simultaneously suppresses plasma motilin peaks. The results suggest that the suppression of gastric activity fronts is achieved via the suppression of plasma motilin peaks because in the presence of ondansetron a motilin agonist like erythromycin restores the gastric phase 3.

Adult↗

Suppression of nicotinic synaptic transmission by adenosine in myenteric ganglia of the guinea-pig gastric antrum.

Conventional intracellular recording techniques were used to investigate actions of adenosine on nicotinic cholinergic transmission in myenteric neurons of the gastric antrum. Adenosine or the more potent derivatives, 5'-N-ethylcarboxamidoadenosine (NECA), 5'-N-cyclopropylcarboxamidoadenosine, 1-deaza-2-chloro-N6-cyclopentyladenosine or N6-cyclopentyladenosine reversibly and dose dependently inhibited the fast excitatory postsynaptic potentials (fast EPSPs) in 60% of the gastric neurons. Neither adenosine nor NECA affected excitatory responses to the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium iodine. The EC50 concentration for inhibition of the fast excitatory postsynaptic potential (EPSP) by adenosine was 55 microM NECA was a more potent inhibitor than adenosine. The specific adenosine receptor antagonists 1,3-dipropyl-8-p-sulfophenyl xanthine or 1,3-dipropyl-8-(cyclopentyl) xanthine blocked the inhibitory effects of adenosine or NECA. Fast EPSPs were enhanced by superfusion of the antagonists alone, suggestive of ongoing inhibition of nicotinic transmission by endogenous adenosine. The antagonists had no effect on resting membrane properties, excitability or antidromic action potentials. In neurons with suppression of fast EPSPs, adenosine did not suppress all cholinergic inputs to the same neuron. The results suggest that adenosine inhibits nicotinic transmission by interacting with presynaptic P1 adenosine receptors located at cholinergic release sites.

Action Potentials↗

Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination.

Erythromycin has been shown to act as a motilin agonist by binding to motilin receptors on gastrointestinal smooth muscle and to improve the severely impaired gastric emptying in patients with diabetic gastroparesis. To elucidate the motor pattern that accounts for this accelerated emptying, the effect of 200 mg erythromycin vs. placebo on postprandial motility of the stomach and the upper small intestine was examined in 13 normal subjects. Erythromycin significantly increased the amplitude of the antral contractions during the 2-hour postprandial study period (maximal difference in mean amplitude of distal antral contractions between erythromycin and placebo recorded from 80 to 90 minutes after meal: 123 +/- 17 vs. 44 +/- 12 mm Hg; P less than 0.005). The total number of antral contractions was not affected, but the contractions could be recorded manometrically higher up in the stomach after erythromycin than after placebo (9-12 vs. 3-6 cm above the pylorus). Antroduodenal coordination was significantly improved during the first postprandial hour, and the first normal phase 3 of the migrating motor complex, indicating the reappearance of fasting motility, occurred earlier after erythromycin than after placebo (128.3 +/- 14.3 vs. 173.4 +/- 16.1 minutes; P less than 0.05). These changes in postprandial motility induced by erythromycin may well account for its accelerating effect on gastric emptying.

Adult↗

Effect of erythromycin on gastric motility in controls and in diabetic gastroparesis.

The effect of three doses of erythromycin on interdigestive gastrointestinal motility and on plasma motilin levels was studied in healthy volunteers and patients with diabetic gastroparesis. Abnormalities of interdigestive motility were observed in 40% of the patients. In healthy volunteers, 40 mg erythromycin elicited a premature phase 3 that started in the stomach. In contrast to the spontaneous gastric phase 3, this erythromycin-induced phase 3 was not accompanied by a motilin peak. In patients with diabetic gastroparesis, 40 mg erythromycin induced a premature phase 3 in three patients, no response in one patient, and a burst of antral contractions in another patient. Doses of 200 and 350 mg erythromycin elicited a burst of antral phase-3-like contractions in both volunteers and patients, which was not accompanied by a motilin peak. This phase-3-like activity did not migrate to the small intestine and was not followed by a phase 1, but by a prolonged period of antral contractile activity. The number and amplitude of antral contractions after 200 or 350 mg erythromycin were significantly higher than after 40 mg. The motor patterns induced by different doses of erythromycin offer potential therapeutic applications.

Adult↗

Endobronchial tuberculosis mimicking lung cancer in elderly patients.

We report four elderly patients with cough who were referred with the presumptive diagnosis of bronchial carcinoma based on chest X-ray and the macroscopic view on fibreoptic bronchoscopy, but whose final diagnosis was endobronchial tuberculosis. Chest X-ray showed atypical pulmonary infiltrates in three patients, but was normal in one. Bronchoscopic examination revealed ulcerative and/or stenotic lesions. Endobronchial tuberculosis should be considered in differential diagnosis, especially in the elderly.

Aged↗