Sample records for cisapride

  1. Influence of Cisapride on food-stimulated gastro-oesophageal reflux: A radiological study

    The influence of Cisapride on food-stimulated gastro-oesophageal reflux meachanisms was studied in a double-blind cross-over investigation in 24 consecutive patients selected by endoscopy, 12 with microscopical evidence of gastro-oesophageal reflux and 12 with additional macroscopic oesoghagitis. 63% had food-stimulated gastro-oesophageal reflux, and Cisapride significantly reduced the tendency to gastro-oesophageal reflux and mucosal contact time between gastric content and the oesophageal mucosa in 73% of these patients. It is concluded that Cisapride could be valuable in the treatment of gastro-oesophageal reflux. (orig.)

  2. Effects of cisapride on ulcer formation and gastric secretion in rats: comparison with ranitidine and omeprazol.

    Alarcón de la Lastra, C; Martin, M J; La Casa, M; López, A; Motilva, V


    1. The antiulcerogenic effects of cisapride, a potent benzamide-stimulating gastrointestinal motility agent, were studied on cold-resistant and pylorus-ligated gastric ulcers. Acidity, composition of gastric secretion, and quantitative and qualitative changes on mucus glycoprotein content were also determined. These effects were compared with those of ranitidine (50 mg/kg) and omeprazol (10 mg/kg). 2. Oral cisapride (10-100 mg/kg) dose-relatedly and significantly (P < 0.01, P < 0.05) decreased the severity of the lesions induced by cold-resistant stress. In stressed rats, cisapride increased the amount of mucus secretion and markedly enhanced the glycoprotein content. Morphometric evaluation of mucus secretion revealed a significant increase in both the PAS area (neutral glycoproteins) and Alcian blue area (sulfated glycoproteins). 3. In 4 h pyloric-ligated animals, cisapride (10-100 mg/kg) showed a significant reduction in the number and severity of ulcers (P < 0.01) and histamine concentration (P < 0.01, P < 0.001). In addition, at the highest doses (50-100 mg/kg), cisapride produced a significant decreases in acidity; however, it did not alter the gastric volume secretion or pepsin concentrations. 4. These results suggest that cisapride shows antiulcerogenic effects which could possibly be explained through antisecretory and cytoprotective mechanisms involving an enhancement of cuality and production of gastric mucus. PMID:9304418

  3. Effect of cisapride on symptoms and biliary drainage in patients with postcholecystectomy syndrome

    The study evaluates the effect of 20 mg cisapride twice daily on symptoms and biliary drainage in patients with the postcholecystectomy syndrome. 19 patients, all female, went through a randomized, double-blind, placebo-controlled, crossover trial with two 4-week treatment periods separated by a 2-week washout period. Symptoms were registered on diary cards. Biliary drainage was studied with dynamic cholescinitigraphy. The down slope of the time-activity curve was used as a measure of the biliary drainage. More symptoms were registered during cisapride therapy than with placebo. This unfavourable effect of cisapride was statistically significant in a subgroup of patients with postcholecystectomy complaints identical to the biliary pain they experienced during injection of contrast at the endoscopic retrograde cholangiopancreatographic examination. Cisapride statistically significantly hastened biliary drainage. The median T1/2 values were 24 and 28 min after cisapride and placebo, respectively. In conclusion, cisapride promoted biliary drainage in patients with the postcholecystectomy syndrome, but had an unfavourable symptomatic effect in those with bile duct triggered postcholecystectomy complaints. 22 refs., 3 figs

  4. Cisapride does not alter gastric volume or pH in patients undergoing ambulatory surgery.

    Lydon, A


    PURPOSE: To evaluate the efficacy of 20 mg cisapride p.o. in reducing residual gastric volume and pH in adult ambulatory surgical patients. METHODS: Using a prospective randomised double-blind controlled design, we administered either 20 mg cisapride p.o. or placebo preoperatively to 64 ASA 1-2 ambulatory surgical patients. Following induction of anesthesia we measured volume and pH of residual gastric contents, using blind aspiration through an orogastric tube. Parametric data were analysed using unpaired, one tail Students\\' t test. Non-parametric data were analysed using Fishers Exact test and Chi square analysis. Statistical significance was accepted at the probability level of < 0.05. RESULTS: Residual gastric volumes were similar in the two groups (19.5 +\\/- 23.8, 23.9 +\\/- 24.4 ml), in the cisapride and placebo groups respectively, P=0.24). Data shown are mean (+\\/- SD). The proportions of patients with a residual gastric volume exceeding 0.4 ml x kg(-1) were similar in the two groups (4 of 28, and 8 of 23 patients in the cisapride and placebo groups respectively, P=0.09). The pH of the residual gastric contents were similar in the cisapride and placebo groups (1.6 +\\/- 0.5, 1.4 +\\/- 0.5, respectively, P=0.26). The proportions of patients with pH < 2.5 was also similar in the cisapride and placebo groups (21 of 25, and 20 of 21 patients respectively, P=0.2). CONCLUSIONS: Preoperative administration of 20 mg cisapride p.o. to patients scheduled for outpatient surgery does not alter either the volume or the pH of gastric contents. Its use in this setting is of no apparent clinical benefit.

  5. Study on Gastric Empty Disorder after the Gastric Ulcer Healing and Therapeutic Effect of Cisapride

    ZOU Kaifang; LIU Shi; LIU Jinsong; LIU Yongge; HOU Xiaohua; YI Cuiqiong


    Gastric emptying time of liquid meal was detected by using ultrasonography in 28 gas tric ulcer patients with continual or recurrent dyspepsia symptoms after the ulcer healing. Sixteen out of 28 patients (57.1%) with a delay of gastric emptying time (T1/2) were randomly divided into two groups: 8 cases were treated with cisapride 5 mg three times a day and 8 cases with cis apride 10 mg three times a day respectively. The results showed that cisapride could relieve the symptoms with the effective rate being 68.8% in the two groups. T1/2 in the patients after treat ment with cisapride was significantly shorter than before treatment (P<0.001). It was concluded that there is a delay of T1/2 in some patients with gastric ulcer healing. Cisapride could promote gastric empty of liquid meal and relieve the symptoms efficiently. The effect of lower dose of cis apride is similar to that of higher dose.

  6. Therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation in rats

    ZHANG Lian-yang; WANG Zheng-guo; ZHU Pei-fang; XU Yan


    Objective: To investigate the therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation.Methods: 108 Wistar rats weighing (200 g±30 g) were randomly divided into a sham shock (SS) group (n=36), a hemorrhagic shock resuscitation (HS) group (n=36) and a hemorrhagic shock cisapride treated (HSC) group (n=36). Sampling at 1, 2 and 4 hours after resuscitation was done and 6 samples for each observation item were taken. The gastric blood flow volume was measured by isotope label biological microglobulin. Gastric pHi, gastric emptying, MDA and Na+-K+-ATPase of gastric mucosa were measured.Results: In the HSC group, the relative residual rate of gastric pigment decreased significantly, the gastric blood flow volume elevated; gastric pHi increased significantly at 2 hours; the level of mucosal MDA decreased at 4 hours, the activity of Na+-K+-ATPase increased and the lactic acid level in the portal vein decreased significantly compared to the HS group.Conclusions: After hemorrhagic shock resuscitation, cisapride contained the following functions,1) promoting gastric emptying, 2) increasing the blood flow of gastric blood flow volume and gastric pHi, 3) depressing the lactic acid concentration of the portal vein and improving MDA volume and Na+-K+ -ATPase activity of gastric mucosa. It suggests that after comple menting effective circulating blood volume for hemorrhagic shock resuscitation, early use of cisapride for gastric motility is helpful for an improvement of lasting ischemia and hypoxia in stomach.

  7. Effects of cisapride on parameters of oesophageal motility and on the prolonged intraoesophageal pH test in infants with gastro-oesophageal reflux disease.

    Cucchiara, S; Staiano, A.; Boccieri, A; De Stefano, M; Capozzi, C; Manzi, G.; Camerlingo, F; Paone, F M


    The effect of cisapride, a new gastrointestinal prokinetic drug, on oesophageal motility and acid reflux was studied in 14 children with gastro-oesophageal reflux disease, receiving either placebo or cisapride 0.15 mg/kg intravenously. Cisapride significantly (p less than 0.01) increased the lower oesophageal sphincter pressure (+124%), the amplitude (+84%) and duration (+24%) of oesophageal peristaltic waves, whereas the placebo treatment did not produce any changes. Subsequently, all 14 chi...

  8. Clinical Comparative Study on Massage Therapy and Cisapride in Treating Functional Dyspepsia

    ZHANG Jia-fu; LIN Qiang; LIU Hong-bo; ZHOU Ping; XIAO Yuan-chun


    To observe the clinical efficacy of massage therapy and Cisapride in the treatment of functional dyspepsia (FD).Methods:Eighty subjects were randomized into two groups:treatment group in which 40 cases were treated by massage therapy and control group in which 40 cases were treated by Cisapride,with a course of 4 weeks;meanwhile,another 40 healthy people were taken as normal group.Abdominal fullness,acid regurgitation,diminished appetite and anorexia,nausea and vomiting and health survey were observed;symptom scores were recorded.Results:These two treatment methods were effective for FD.Conclusion:Mental disorder is one cause of FD;massage therapy is quite effective for it.

  9. Modulatory role of verapamil treatment on the cardiac electrophysiological effects of cisapride.

    Morissette, Pierre; Hreiche, Raymond; Turgeon, Jacques


    The role of transport proteins in the distribution of drugs in various tissues has obvious implications for drug effects. Recent reports indicate that such transporters are present not only in the liver, intestine, or blood-brain barrier but also in the heart. The objective of our study was to determine whether treatment of animals with verapamil, a well-known L-type calcium channel blocker with modulatory properties of membrane transporters, would alter distribution and cardiac electrophysiological effects of an I(Kr) blocker. Male guinea pigs (n = 72) were treated with either saline or verapamil at various doses (1.5 to 15 mg/kg) and for various durations (1 to 7 d). Animals were sacrificed 24 h after the last dose of verapamil (or saline), and their hearts were isolated and retroperfused with cisapride, a gastrokinetic drug with I(Kr) blockade properties. In hearts obtained from animals treated with vehicle, 50 nmol/L cisapride prolonged MAPD90 by 15 +/- 5 ms vs. 36 +/- 8 ms in hearts from animals treated with verapamil 15 for 5 d (p access to intracellular binding sites on I(Kr) channels. PMID:17487237

  10. Gastric emptying time and the effect of cisapride in cirrhotic patients with autonomic neuropathy.

    Gumurdulu, Yuksel; Yapar, Zeynep; Canataroglu, Abdullah; Serin, Ender; Gumurdulu, Derya; Kibar, Mustafa; Colakoglu, Salih


    GOALS To investigate the relationships between gastric emptying and autonomic dysfunction in hepatic cirrhosis and to assess the effects of cisapride on gastric emptying in cirrhotic patients. STUDY Twenty-four cirrhotic patients (8 patients in each Child-Pugh classification) and 25 healthy controls were enrolled. All the patients had viral (B or C) hepatitis. Patients with DM, alcoholic cirrhosis, active peptic ulcer, gastric malignancy and pyloric obstruction were excluded by esophagogastroduodenoscopy. Parasympathetic and sympathetic functions were assessed by the criteria set forth by Ewing and Clark. Drugs affecting GI motility and smoking were discontinued 48 hours and 12 hours prior to the study respectively. A solid-phase of gastric emptying study was conducted by scintigraphic method for the calculation of gastric half-emptying time (GET1/2). RESULTS The study revealed that 9 patients with Child-Pugh B and C cirrhosis had autonomic neuropathy and none of Child-Pugh A cirrhosis had autonomic neuropathy. Prolonged GET1/2 was noted in cirrhotics compared with the control group (p hepatitis may cause prolonged gastric emptying. Cisapride can shorten gastric emptying time in such patients. PMID:12544204

  11. Gastric Emptying in Patients with Diabetes: Gastric Emptying Time, Retention Rate and Effect of Cisapride

    Gastic emptying scan in diabetic patients is widely used to assess the degree of motility disturbance and the symptoms such as nausea, vomiting, bloating, abdominal pain and early gastric fullness which we can't find anatomic lesion by fiberoscopic or barium study. In order to determine the relationship among diabetic gastropathy, neropathy, retinopathy and disease duration, gastric emptying scan using 99mTc-tin colloid labeled scramble egg in hamburger was performed in 10 healthy male controls and 50 diabetic patients which were subdivided to no neuropathy, peripheral neuropathy and autonomic neuropathy groups according to the degree of diabetic neuropathy and no retinopathy, background retinopathy and proliferative retinopathy groups according to the degree of diabetic retinopathy. After medication of cisapride for 2 weeks, we observed the presence of improvement of gastric motility in diabetics. The results were as following: 1) In controls, gastric emptying time (GET1/2) was 75 ± 13.6 min and 2 hour gastric retension rate(GRR2) was 32 ± 11.1%. 2) In diabetics, GET/2 was prolonged more than 2 hours and GRR2 was 58 ± 23.1%. According to degree of neuropathy, GET1/2 was prolonged more than 2 hours in all three groups and GRR2 was 54± 24.1% in no neuropathy group, 57 ± 24.3% in peripheral neuropathy group and 69 ± 24.6% in autonomic neuropathy group. According to degree of retinopathy, GET1/2 was 110 ± 23.4 min in no retinopathy group and prolonged more than 2 hours in other two groups and GRR2 was 45 ± 21.6% in no retinopathy group, 71 ± 19.7% in background retinopathy group and 73 ± 21.5% in proliferative retinopathy group. 3) After cisapride for 2 weeks, GET1/2 and GRR2 were improved as 90 ± 14.6 min and 40 ± 13.8% (initial GET1/2 and GRR2 were above 2 hours and 61 ± 15.4%). We can conclude from above findings that gastropathy in diabetic neuropathy suggesting main underlying factor in motility disorder. The degree of retinopathy and disease

  12. Simultaneous noninvasive evaluation of gastric emptying and orocaecal transit times. Use in studying the actions of cisapride in diabetic patients.

    Bergmann, J F; Chassany, O; Guillausseau, P J; Bayle, M; Chagnon, S; Caulin, C; Sallenave, J R


    The aim of the study was to use a novel combination of two methods for the simultaneous evaluation of two effects of oral cisapride in 10 diabetic patients with autonomic neuropathy; gastric empyting time was measured by following radio-opaque markers and orocaecal transit time by the sulphasalazine-sulphapridine method. The study was of double-blind, randomized, placebo-controlled, cross-over design. It was possible to evaluate the effect of a prokinetic drug on gastric emptying and orocaecal transit times using these two noninvasive techniques at the same time. Cisapride significantly reduced both the gastric empyting (1.2 h versus 2.1 h) and orocaecal tansit (5.9 h versus 7.7 h) times. PMID:1425866

  13. Design and evaluation of hydrophobic coated buoyant core as floating drug delivery system for sustained release of cisapride

    Jacob, Shery; Nair, Anroop B; Patil, Pandurang N


    An inert hydrophobic buoyant coated–core was developed as floating drug delivery system (FDDS) for sustained release of cisapride using direct compression technology. Core contained low density, porous ethyl cellulose, which was coated with an impermeable, insoluble hydrophobic coating polymer such as rosin. It was further seal coated with low viscosity hydroxypropyl methyl cellulose (HPMC E15) to minimize moisture permeation and better adhesion with an outer drug layer. It was found that sta...

  14. Effect of hydroxypropyl-β-cyclodextrin on the stability of cisapride in oral suspensions

    Jutima Boonleang


    Full Text Available Cisapride (CIS is a gastrointestinal prokinetic agent. It has been associated with rare, but serious cardiac side effects.However, it does not affect psychomotor functions or induce central depressant adverse effects. As liquid formulations arerequired in a number of cases, an oral suspension of CIS was developed from CIS tablets. The objective of this study was toinvestigate the effect of hydroxypropyl--cyclodextrin (HP--CD on the stability of CIS in oral suspension with an ultimateaim to formulate a more stable CIS oral suspension. Six batches of CIS oral suspensions, namely, 0 (control, 0.3, 1.6, and 3%HP--CD containing formulations were prepared. They were stored at 5°C and 30°C. The amounts of CIS in the suspensionswere determined by a validated stability-indicating HPLC-DAD method. The stability was assessed based on the 90%remaining. The changes in the amounts of CIS over time were statistically analyzed by ANOVA and ANCOVA. At 5°C, HP--CD had no significant effect on the stability of CIS. CIS in all four formulations was stable for at least 12.5 months. At 30°C,HP--CD affected the stability of CIS. CIS was most stable in 0.3% HP--CD containing formulation with the observed t90 ofapproximately 11 months as compared to 7 months in control formulation.

  15. Simultaneous stability-indicating HPLC method for the determination of cisapride, methylparaben and propylparaben in oral suspension

    Jutima Boonleang


    Full Text Available A simultaneous stability-indicating HPLC method for the determination of cisapride, methylparaben and propylparabenin oral suspensions has been developed and validated. Baseline separation was achieved on a C18 column at room temperature(25°C by gradient elution with mobile phase consisting of solvent A: 10% v/v acetonitrile in 0.13% w/v sodium-1-pentanesulfonate pH 8 and solvent B: acetonitrile. The gradient program was as follows: 0-5 min: 20 to 56% solvent B; 5-7min: 56 to 85% solvent B; 7-10 min: 85% solvent B. The flow rate of mobile phase was 1.2 mL/min. The injection volume was20 L. Detection and peak purity assessments were performed by photo-diode array detector set at 275 nm with scan modein the range of 190-400 nm. The method was selective, accurate and precise. It provided chromatograms with good peak shapeand acceptable resolutions of greater than 4.4 for all analytes including the degradation products formed in oral suspensionsin about 8.5 min. All analyte peaks were pure. The accuracy of all analytes was in the range of 99.20-100.6%. The within-runand between-run relative standard deviations were less than 1.50%. The calibration curves for cisapride, methylparaben, andpropylparaben were linear over the concentration range of 10.0-75.0 g/mL, 8.0-100.0 g/mL, and 0.8-10.0 g/mL, respectivelywith r2 greater than 0.999. This developed method was successfully applied to the stability study of cisapride, methylparabenand propylparaben in oral suspension formulations.

  16. Efecto de cisapride sobre el sobrecrecimiento bacteriano intestinal y la translocación bacteriana en la cirrosis

    Pardo Balteiro, Alberto


    La alteración de la motilidad intestinal que se detecta con frecuencia en la cirrosis puede facilitar la presencia de sobrecrecimiento bacteriano intestinal (SBI). Este, a su vez, puede conducir a la aparición de translocación bacteriana (TB). El objetivo principal del estudio fue evaluar el efecto de la administración de cisapride sobre el SBI y la TB en la cirrosis. Se utilizó el modelo de cirrosis experimental en ratas mediante la administración de tetracloruro de carbono. Dos grupos de r...

  17. Effects of ranitidine and cisapride on acid reflux and oesophageal motility in patients with reflux oesophagitis: a 24 hour ambulatory combined pH and manometry study.

    Inauen, W; Emde, C; Weber, B; Armstrong, D; Bettschen, H U; Huber, T; Scheurer, U; Blum, A L; Halter, F; Merki, H S


    The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH upright reflux (p conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis. PMID:8174947

  18. Cisapride a green analytical reagent for rapid and sensitive determination of bromate in drinking water, bread and flour additives by oxidative coupling spectrophotometric methods

    Al Okab, Riyad Ahmed


    Green analytical methods using Cisapride (CPE) as green analytical reagent was investigated in this work. Rapid, simple, and sensitive spectrophotometric methods for the determination of bromate in water sample, bread and flour additives were developed. The proposed methods based on the oxidative coupling between phenoxazine and Cisapride in the presence of bromate to form red colored product with max at 520 nm. Phenoxazine and Cisapride and its reaction products were found to be environmentally friendly under the optimum experimental condition. The method obeys beers law in concentration range 0.11-4.00 g ml-1 and molar absorptivity 1.41 × 104 L mol-1 cm-1. All variables have been optimized and the presented reaction sequences were applied to the analysis of bromate in water, bread and flour additive samples. The performance of these method was evaluated in terms of Student's t-test and variance ratio F-test to find out the significance of proposed methods over the reference method. The combination of pharmaceutical drugs reagents with low concentration create some unique green chemical analyses.

  19. 阿片样物质介导多潘立酮和西沙必利对小鼠的镇痛作用%Opioid mediated anti-nociceptive effect of domperidone and cisapride in mice

    Isabella TOPNO; Mohammed ASAD; Deepak Gopal SHEWADE; Chanolean SHASHINDRAN; Subramanyan RAMASWAMY


    AIM: To study the anti-nociceptive effect of domperidone and cisapride in mice. METHODS: Initially, the effect of these drugs on motor activity was tested using rotarod. The anti-nociception was tested using chemical and mechanical assay. In the chemical assay, the number of abdominal constrictions either in the saline treated animals or in the domperidone/cisapride (1, 5, or 10 mg/kg either po or ip) treated mice, were recorded for a period of 30 main after acetic acid challenge (10mL/kg, of 0.6 % acetic acid ip). In the tail clip assay, the time taken by the mouse to make attempts to dislodge the bulldog clamp placed at the tail (reaction time) was recorded with a cut off time of 30 s. The role of opioid pathways was examined by pretreating the animals with naloxone (1 mg/kg, ip) 30 min prior to domperidone and cisapride. RESULTS: Domperidone and cisapride, both reduced the number of abdominal constrictions when given orally or intraperitoneally.Domperidone (5 mg/kg) inhibited it to the extent of 57.0 % after po and 54.6 % after ip. The inhibition after cisapride ( 5 mg/kg ) was 65.1% ( po ) and 71.6 % (ip). Naloxone pretreatnent reduced this inhibition (57.0 % vs 10.3 % for domperidone and induced hyperalgesia by antagonizing the inhibition and enhanced analgesia to the extent of 28.4 % for cisapride ). The reaction time was increased by domperiidone (10 mg/kg, ip) from 1.6 s±l.0 s to 14.8s ±0.5 s and cisapride (10 mg/kg, ip) from 3.3 s ± 1.0s to 14.8 s ± 0.5 s. CONCLUSION: Domperidone and cisapride exhibited a significant anti-nocicepfve activity after oral as well as intraperitoneal administration.A role for opioid pathways is indicated. Since domperidone is likely to exert less extrapyramidal effects,it can be substituted for metoclopramide, which is now widely used as an analgesic either alone or as an adjuvant.

  20. Efeito da cisaprida e da fisioterapia respiratória sobre o refluxo gastroesofágico de lactentes chiadores segundo avaliação cintilográfica Effects of cisapride and chest physical therapy on the gastroesophageal reflux of wheezing babies based on scintigraphy

    Maria Angela G.O. Ribeiro


    Full Text Available OBJETIVO: analisar o efeito da cisaprida e da fisioterapia respiratória em lactentes chiadores (LC, com doença do refluxo gastroesofágico (DRGE. MÉTODOS: avaliamos, prospectivamente, em 13 LC com DRGE e 12 sem DRGE, a densidade nuclear de tecnécio (99Tc em 3 topografias esofágicas. Os 2 grupos foram submetidos à investigação clínica, exames laboratoriais, radiológicos e cintilográficos para investigação etiológica da síndrome do LC e DRGE. A técnica fisioterápica denominada aceleração de fluxo expiratório (AFE foi realizada antes e após tratamento com cisaprida. O tempos totais de RGE(TTRGE, primeiramente durante a cintilografia basal, e em seguida, durante a AFE, foram analisados e somados, para cada topografia esofágica. RESULTADOS: a cisaprida diminuiu o TTRGE, com significância estatística somente no terço superior do esôfago (p OBJECTIVE: to evaluate the effect of cisapride and chest physical therapy on the gastroesophageal reflux of wheezing babies. METHODS: we prospectively assessed the presence of technetium (99Tc in the upper, middle, and lower esophagus of 25 wheezing babies (13 with GERD and 12 without GERD using scintigraphy. Both groups underwent clinical investigation, including laboratory, X-ray and scintigraphy tests, for the etiology of the wheezing baby syndrome (WBS and GERD. Expiratory Flow Acceleration (EFA was performed before and after treatment with cisapride. The total time of GER episodes was accounted for each portion of the esophagus during scintigraphy and during EFA. RESULTS: cisapride significantly reduced the total reflux time in the upper esophagus (P < 0.05, but showed no influence during EFA. After cisapride therapy, EFA increased the total reflux time in the upper and medium esophagus; however, no statistical significance was found. Infants with GERD presented a shorter total reflux time in the distal esophagus (P<0.05 during EFA. After cisapride treatment, no statistical

  1. Drug: D02092 [KEGG MEDICUS

    Full Text Available D02092 Drug Cisapride (JAN); Cisapride monohydrate; Propulsid (TN) C23H29ClFN3O4. H...TINAL DISORDERS A03F PROPULSIVES A03FA Propulsives A03FA02 Cisapride D02092 Cisapride...rotonin 5-HT4-receptor [HSA:3360] [KO:K04160] Cisapride [ATC:A03FA02] D02092 Cisapride (JAN) CAS: 260779-88-

  2. Drug: D00274 [KEGG MEDICUS

    Full Text Available D00274 Drug Cisapride (USAN/INN) C23H29ClFN3O4 465.1831 465.9455 D00274.gif Stimula...L GASTROINTESTINAL DISORDERS A03F PROPULSIVES A03FA Propulsives A03FA02 Cisapride D00274 Cisapride...hodopsin family Serotonin 5-HT4-receptor [HSA:3360] [KO:K04160] Cisapride [ATC:A03FA02] D00274 Cisapride (US

  3. Erythromycin

    ... especially other antibiotics, anticoagulants ('blood thinners'), astemizole (Hismanal), carbamazepine (Tegretol), cisapride (Propulsid), clozapine (clozaril), cyclosporine (Neoral, Sandimmune), digoxin (Lanoxin), disopyramide (Norpace), ...

  4. Drug treatment


    950229 A controlled multi—center clinical trial oncisapride in treatment of functional dyspepsia.WANGBaoen(王宝恩),et al.Beijing Friendship Hosp,Bei-jing.100050.Chin J Intern Med 1995;34(3):180—184.A controlled muhi-centre clinical trial was con-ducted for evaluating the efficacy and safety of cis-apride in the treatment of 414 cases of functional dys-pepsia with 169 cases as control.Cisapride were given

  5. Relative efficacy of some prokinetic drugs in morphine-induced gastrointestinal transit delay in mice

    AD Suchitra; SA Dkhar; DG Shewade; CH Shashindran


    AIM: To study the relative efficacy of cisapride,metoclopramide, domperidone, erythromycin and mosapride on gastric emptying (GE) and small intestinal transit (SIT)in morphine treated mice.METHODS: Phenol red marker meal was employed to estimate GE and SIT in Swiss albino mice of either sex. The groups included were control, morphine 1 mg/kg (s.c. 15min before test meal) alone or with (45 min before test meal p.o.) cisapride 10 mg/kg, metoclopramide 20 mg/kg,domperidone 20 mg/kg, erythromycin 6 mg/kg and mosapride 20 mg/kg.RESULTS: Cisapride, metoclopramide and mosapride were effective in enhancing gastric emptying significantly (P<0.001)whereas other prokinetic agents failed to do so in normal mice. Metoclopramide completely reversed morphine induced delay in gastric emptying followed by mosapride.Metoclopramide alone was effective when given to normal mice in increasing the SIT. Cisapride, though it did not show any significant effect on SIT in normal mice, was able to reverse morphine induced delay in SIT significantly (P<0.001)followed by metoclopramide and mosapride.CONCLUSION: Metoclopramide and cisapride are most effective in reversing morphine-induced delay in gastric emptying and small intestinal transit in mice respectively.

  6. Prokinetic Therapy Reduces Aspiration Pneumonia in Tube-Fed Patients With Severe Developmental Disabilities

    Pareek, Namita; Williams, John; Hanna, Deborah; Johnson, William D.; Minocha, Anil; Abell, Thomas L.


    To evaluate the clinical benefit of prokinetic therapy in aspiration pneumonia in patients with developmental disabilities, we conducted a retrospective study; records of 22 tube-fed patients were reviewed from December 1990 to October 1998 for a mean of 22.7 months before and 38.9 months during Cisapride therapy. Numbers of hospital admissions…

  7. Paracetamol, widely used hardly understood

    Marel, Caroline


    markdownabstract__Abstract__ Paracetamol (APAP), in the USA known as acetaminophen, is widely used both in hospital settings and at home for antipyresis and mild (postoperative) pain. Although APAP is available over the counter and is ranked on the third place, following nystatin and cisapride, when looking at the most commonly prescribed drugs in our Pediatric Surgical Intensive Care Unit (PSICU), it is surprising that there are still little data available concerning the pharmacokinetics (i....

  8. Postoperative ileus: a preventable event

    Holte, Kathrine; Kehlet, H


    BACKGROUND: Postoperative ileus has traditionally been accepted as a normal response to tissue injury. No data support any beneficial effect of ileus and indeed it may contribute to delayed recovery and prolonged hospital stay. Efforts should, therefore, be made to reduce such ileus. METHODS: Mat...... only cisapride is proven beneficial; the effect of early enteral feeding remains unclear. However, postoperative ileus may be greatly reduced when all of the above are combined in a multimodal rehabilitation strategy....

  9. Effect of megestrol acetate and prepulsid on nutritional improvement in patients with head and neck cancers undergoing radiotherapy

    Background and purpose: Anorexia is a common problem in cancer patients who receive radiotherapy. In this current study, we attempt to determine the effect of megestrol acetate and prepulsid on appetite and nutritional improvement in patients with head and neck cancers undergoing radiotherapy. Materials and Methods: One hundred twenty-nine consecutive patients with head and neck cancers treated between July 1993 and June 1994 were prospectively randomized to receive either megestrol acetate, 40 mg qid (megace group), prepulsid, 5 mg tid (cisapride group), or a placebo treatment (control group) during radiotherapy. Before radiotherapy, body weight (kg), appetite score, performance status, biochemical parameters and hematological parameters were evaluated, and the above-noted clinical and biochemical parameters were assessed and recorded every other week. All patients received 6- 10 MV X-rays or Co-60 γ-ray to head and neck region for a full course of radiotherapy, 61.2-75.6 Gy/7-9 weeks. Results: Forty-eight patients were enrolled in the megace group, 41 patients in the cisapride group, and 40 patients in the control group. At the 2nd, 4th, 6th and 8th week, as the radiation dose escalated, the megace group had significantly less body weight loss than did the cisapride and control groups (P = 0.045, 0.024, 0.006, 0.003, respectively). The appetite scores of the megace group were significantly higher than those of the cisapride and control groups (P 0.0001). However, there were no statistically significant differences in the change of albumin level among these three groups at the 2nd, 4th, 6th and 8th week (P > 0.05, respectively). Conclusions: Megestrol acetate can significantly decrease the degree of body weight loss, and can prevent the deterioration of appetite in patients with head and neck cancers receiving radiotherapy. However, prepulsid lacks the above-mentioned clinical benefits

  10. Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: in vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma.

    Dall'Asta, C; Ballarè, E; Mantovani, G; Ambrosi, B; Spada, A; Barbetta, L; Colombo, P; Travaglini, P; Loli, P; Beck-Peccoz, P


    Regulation of cortisol secretion by aberrant hormone receptors may play a role in the pathogenesis of ACTH-independent Cushing's syndrome. In this study, the topic was evaluated by combining in vivo and in vitro approaches. Cortisol responses to various stimuli (standard meal, GnRH + TRH, cisapride, vasopressin, glucagon) were assessed in 6 patients with clinical or subclinical adrenal Cushing's syndrome, and non-functioning adrenal adenoma in two cases. Abnormal responses were observed in three patients with Cushing's syndrome; one patient showed a gastric inhibitory polypeptide (GIP)-dependent cortisol rise after meal, together with responses after GnRH and cisapride; the second patient showed an LH-dependent cortisol response to GnRH, and in the third cortisol rose after cisapride. The pattern of receptor expression performed by RT-PCR showed that while GIP-R was only expressed in tumor from the responsive patient, 5-hydroxytryptamine type 4 receptor and LH-R were also present in normal adrenal tissues and tissues from non-responsive patients. Interestingly, an activating mutation of Gsalpha gene was identified in one of these tumors. Therefore, cortisol responses to agents operating via Gs protein coupled receptors (in one case associated with Gsalpha mutation) were found in Cushing's patients, while these responses were absent in the others. The finding of receptor expression in normal and non-responsive tumors suggests that different mechanisms are probably involved in inducing in vivo cortisol responses. PMID:15326569

  11. Is this a reflux patient or is it a patient with functional dyspepsia with additional reflux symptoms?

    Funch-Jensen, P


    complications. The therapeutic goals in GORD are symptom relief, healing of lesions, prevention of complications, and omittance of adverse effects at the lowest possible costs. Patients with functional dyspepsia usually have symptoms of less severe intensity and as, per definition, no organic substrate is...... functional dyspepsia is less documented and in most studies the symptomatic pattern could not predict the pharmacologic principle of clinical benefit. This may be because a separation between presence of symptoms and presence of symptoms as a major problem has not been taken into account. Cisapride is the...

  12. Experimental transfer of adult Oesophagostomum dentatum from donor to helminth naive recipient pigs: a methodological study.

    Bjørn, H; Roepstorff, A; Grøndahl, C; Eriksen, L; Bjerregaard, J; Nansen, P


    This study was carried out to compare potential methods of transplanting adult Oesophagostomum dentatum from experimentally infected donor pigs to helminth naive recipient pigs. The following methods were each tested in five pigs: A. Transfer of worms by stomach tube to the gastric ventricle of pigs per os pretreated with 0.5 mg/kg cisapride to increase gastrointestinal peristalsis; B. Transfer by stomach tube to the gastric ventricle of pigs per os pre-treated with cisapride (0.5 mg/kg) and omeprazol 20 mg which blocks hydrochloric acid secretion; C. Surgical transfer of worms to caecum of pigs. Worms for transplantation to pigs were obtained after slaughter of experimentally infected donor pigs and following isolation from the contents of the large intestine, using an agar gel migration technique. A mean of 1054 nematodes were transferred into each recipient pig within 2 hours. Procedures A and B resulted in establishment rates corresponding to only 0.5% and 7.6% of the transferred worms. In contrast, surgical transfer allowed 74.2% of the transplanted worms to be established. In all groups the transplanted worms migrated to the normal predilection site, i.e. the middle part of the large intestine. More female than male worms established in all groups. It was concluded from this study that surgical transfer was the most reliable of the methods tested for experimental establishment of adult O. dentatum in helminth naive pigs. PMID:8583123

  13. Comparison between empirical prokinetics, Helicobacter testand-treat and empirical endoscopy in primary-care patients presenting with dyspepsia: A one-year study

    Wayne HC Hu; CK Chan; Gabriel M Leung; WM Hui; SK Lam; Cindy LK Lam; WM Wong; KF Lam; KC Lai; YH Wong; Benjamin CY Wong; Annie OO Chan


    AIM: To investigate the optimal strategy to treat dyspeptic patients in primary care.METHODS: Dyspeptic patients presenting to primary care outpatient clinics were randomly assigned to:(1) empirical endoscopy, (2)Hpylori test-and-treat,and (3) empirical prokinetic treatment with cisapride.Early endoscopy was arranged if patients remained symptomatic after 2 wk. Symptom severity, quality-oflife (SF-36) as well as patient preference and satisfaction were assessed. All patients underwent endoscopy by wk 6. Patients were followed up for one year.RESULTS: Two hundred and thirty four patients were recruited (163 female, mean age 49). 46% were H pylori positive. 26% of H pylori tested and 25% of empirical prokinetic patients showed no improvement at wk 2follow-up and needed early endoscopy. 15% of patients receiving empirical cisapride responded well to treatment but peptic ulcer was the final diagnosis. Symptom resolution and quality-of-life were similar among the groups. Costs for the three strategies were HK$4343,$1771 and $1750 per patient. 66% of the patients preferred to have early endoscopy.CONCLUSION: The three strategies are equally effective. Empirical prokinetic treatment was the least expensive but peptic ulcers may be missed with this treatment. The H pylori test-and-treat was the most cost-effective option.

  14. Effect of drug utilization reviews on the quality of in-hospital prescribing: a quasi-experimental study

    Chabot Isabelle


    Full Text Available Abstract Background Drug utilization review (DUR programs are being conducted in Canadian hospitals with the aim of improving the appropriateness of prescriptions. However, there is little evidence of their effectiveness. The objective of this study was to assess the impact of both a retrospective and a concurrent DUR programs on the quality of in-hospital prescribing. Methods We conducted an interrupted time series quasi-experimental study. Using explicit criteria for quality of prescribing, the natural history of cisapride prescription was established retrospectively in three university-affiliated hospitals. A retrospective DUR was implemented in one of the hospitals, a concurrent DUR in another, whereas the third hospital served as a control. An archivist abstracted records of all patients who were prescribed cisapride during the observation period. The effect of DURs relative to the control hospital was determined by comparing estimated regression coefficients from the time series models and by testing the statistical significance using a 2-tailed Student's t test. Results The concurrent DUR program significantly improved the appropriateness of prescriptions for the indication for use whereas the retrospective DUR brought about no significant effect on the quality of prescribing. Conclusion Results suggest a retrospective DUR approach may not be sufficient to improve the quality of prescribing. However, a concurrent DUR strategy, with direct feedback to prescribers seems effective and should be tested in other settings with other drugs.

  15. Correlation of bowel symptoms with colonic transit, length, and faecal load in functional faecal retention

    Raahave, Dennis; Christensen, Elsebeth; Loud, Franck B.; Knudsen, Lisbet L.


    INTRODUCTION: Abdominal pain, bloating, and defecation disturbances are common complaints in gastrointestinal functional disorders. This study explores whether bowel symptoms are correlated to colon transit time (CTT), faecal loading (coprostasis), and colon length; and whether prokinetic....... Interventions included a low-fat, high-fiber diet, cisapride or domperidone, and exercise for a mean of 21.6 months. RESULTS: The mean CTT was 40.71 h in patients vs 24.75 h in controls (p = 0.013). In patients, faecal loading was significantly greater than in controls (p<0.001). Bloating correlated.......030), and symptoms increased significantly with increase in the number of redundancies (p<0.001). A subgroup of patients (n = 90) with normal CTTs (< or = 24.75 h) had significantly higher faecal loading compared to controls (p = 0.033). Factor analysis showed that bloating correlated significantly with...

  16. [Irritable colon].

    Madsen, J R


    Irritable bowel syndrome is a chronic, relapsing functional bowel disorder of unknown aetiology. Methods of studying intestinal motor function, nociception, and interactions of the central nervous system and enteric nervous system are not applicable for clinical use. The diagnosis is therefore made on the symptoms, but it is necessary to exclude relevant organic disease. Establishment of the diagnosis, information about the disorder, elimination of foods and other factors that provoke the symptoms, and a change in life-style are sufficient in most cases. Treatment is hampered by the lack of effective treatment and the psychological aspects. The therapeutic gain of drug administration is modest and the rate of response to placebo is high. Fibre supplementation, magnesium oxide or cisapride may be tried for constipation, diphenoxylate or loperamide for diarrhoea, and low dose tricyclic antidepressants or serotonin reuptake blockers for severe pain. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists seems promising. PMID:11530562

  17. Cholescintigraphy in the evaluation of gastroduodenal reflux in children with gastritis - preliminary report

    We assessed by means of Tc-99m-HEPIDA cholescintigraphy the gastroduodenal reflux in 28 children with endoscopic signs of gastric biliary reflux. Those children were selected from a group of 190 children who underwent endoscopy because of abdominal pain disorders. We found the positive cholescintigraphic test in 67% of children. In 6 control tests after 4-months treatment with cisapride we found the withdrawal of cholescintigraphic signs, which corresponded with the improvement of clinical signs. The authors consider the cholescintigraphic examination useful in evaluation of biliary reflux in children, for the sake of more non-invasive character in comparison to endoscopy and X-ray contrast imaging after catheterizing of duodenum. (author). 9 refs

  18. Effect of antiemetic drugs on decrease in gastric emptying in experimental model of motion sickness in rats



    AIM:To study the effect of pretreatment with different antiemetic drugs on the motion sickness-induced inhibition in gastric emptying.METHODS:The rats were rotated for a period of 45 min at the rate of 30 rotations per min.RESULTS:Rotating the rats caused a significant decrease in gastric emptying as cvompared to the non-rotated group.Pretreatment with scopolamine(5 mg/kg,ip)did not reverse the delay in gastric emptying,while it per se caused inhibition of gastric emptying in the non-rotated group.Similarly other drugs mepyramine,cisapride,and granisetron did not have any effect on delay in gastric emptying caused by rotation.However beta blocker propranolol could partially but significantly reverse the decrease in gastric emptying.CONCLUSION:The present study demonstrated the potential use of propranolol as adjuvant with conventional antiemetics for motion sickness to combat associated secondary symptoms.

  19. 止吐药物对大鼠实验性晕动病模型产生的胃排空抑制的影响%Effect of antiemetic drugs on decrease in gastric emptying in experimental model of motion sickness in rats

    Gupta YK; Chaudhary G


    AIM: To study the effect of pretreatment with different antiemetic drugs on the motion sickness-induced inhibitionin gastric emptying. METHODS: The rats were rotated for a period of 45 min at the rate of 30 rotations per min.RESULTS: Rotating the rats caused a significant decrease in gastric emptying as compared to the non-rotatedgroup. Pretreatment with scopolamine (5 mg/kg, ip) did not reverse the delay in gastric emptying, while it per secaused inhibition of gastric emptying in the non-rotated group. Similarly other drugs mepyramine, cisapride, andgranisetron did not have any effect on delay in gastric emptying caused by rotation. However beta blocker propra-nolol could partially but significantly reverse the decrease in gastric emptying. CONCLUSION: The present studydemonstrated the potential use of propranolol as adjuvant with conventional antiemetics for motion sickness tocombat associated secondary symptoms.

  20. Measurement of gastric emptying and antral motor activity in patients with primary anorexia nervosa

    The quantification of gastric motor activity is of great clinical importance. This investigation was aimed at critically evaluating a scintigraphic method of measuring gastric emptying of a semi-solid meal and antral motor activity in patients with primary anorexia nervosa (PAN). Data obtained from 50 patients were evaluated. Twelve patients participated each in two studies, in which the effects of the prokinetic drug, cisapride, were compared to those of placebo under random double-blind conditions. A dual head gamma camera with camera heads in anterior and posterior positions, respectively, was used. After ingestion of the radiolabelled meal, recording with 1 min frames continued for 50 min. Half-emptying times as determined under the assumption of a mono-exponential emptying pattern correlated perfectly with the emptying rate per minute as determined under the assumption of a linear emptying pattern, suggesting the validity of both assumptions. No initial lag phase was observed, which can be attributed to the semi-solid meal consistency but also the measurement geometry improved by simultaneous ventral and dorsal recording. PAN patients had significantly slower emptying rates than 24 healthy volunteers studied earlier. Antral motor activity was recorded in minutes 7-10, 27-30 and 47-50 with 3 s frames. Time/activity curves were analysed using data obtained from three small regions of interest positioned across the antrum. The modulation depth of the time/activity curves corresponding to the amplitude of contractions and the contraction frequency could be computed reliably in most; the propagation velocity of contractions, however, could only be computed reliably in a few instances. Patients showed significantly lower modulation depths than controls, whereas frequency and propagation velocity did not differ. After cisapride, slightly higher modulation depths and significantly lower frequencies occurred than after placebo. It is concluded that the employed

  1. 糖尿病神经源性膀胱临床常用治疗方法疗效研究%Study to treatment effect of clinical useful method about diabetie neurogenic blader

    范可军; 邓丽娜


    Objective The study about comparison of the used treatments,to identify the best clinical treat-ment of diabetic neurogenie bladder.Methods 120 in-patients or out-patients with type 2 diabetes ale randomly di-vided into four groups.On the basis ofthe combined treatment,3 groups of A,B and C are given vitamin B12,B and C group are added respectively cisapride or neostigmine,D group are given methycobal.Results Before and after con-trast,the effects of four groups ale significant,but the effects of B,C and D group ale early and very significant;inter-group differences in contrast,between B,C,D group and A group is significant;between B,C and A group is signifi-cant;between B and C group is no significant.Conclusion The effect of neostigmine or cisapride and vitamin jointly can signifiCalltly reduce tlle DNB patients'residual urine in bladder and urinary retention.the effect is better than a simple application of vitamin or mecobalamin;For DNB milds,as appropriate,can use the treatment of mecobalamin.%目的 将常用治疗方法进行比较研究,以期找出糖尿病神经源性膀胱的临床最佳治疗方案.方法 将住院及门诊2型糖尿病患者120例随机分为四组,在综合治疗基础上A、B、C三组均予维生素B12治疗,B组、C组分别加用西沙比利、溴吡斯的明,D组予羟钴胺治疗.结果 治疗前后对比,四组疗效均显著,但B、C、D显效早且疗效非常显著;组间差异对比,B、C、D组与A组相比差异显著,B、C组与A组相比差异显著,B、C组疗效无显著差异.结论 溴吡斯的明、西沙比利联合维生素治疗的可显著改善DNB残余尿增多及尿潴留,疗效优于单纯应用维生素B12及羟钴胺;DNB轻症,可酌情使用羟钴胺治疗.

  2. Pharmacological Therapy of Gastroesophageal Reflux in Preterm Infants

    Luigi Corvaglia


    Full Text Available Although gastroesophageal reflux (GER is a very common phenomenon among preterm infants, its therapeutic management is still an issue of debate among neonatologists. A step-wise approach should be advisable, firstly promoting nonpharmacological interventions and limiting drugs to selected infants unresponsive to the conservative measures or who are suffering from severe GER with clinical complications. Despite of this, a concerning pharmacological overtreatment has been increasingly reported. Most of the antireflux drugs, however, have not been specifically assessed in preterm infants; moreover, serious adverse effects have been noticed in association to their administration. This review mainly aims to draw the state of the art regarding the pharmacological management of GER in preterm infants, analyzing the best piecies of evidence currently available on the most prescribed anti-reflux drugs. Although further trials are required, sodium alginate-based formulations might be considered promising; however, data regarding their safety are still limited. Few piecies of evidence on the efficacy of histamine-2 receptor blockers and proton pump inhibitors in preterm infants with GER are currently available. Nevertheless, a significantly increased risk of necrotizing enterocolitis and infections has been largely reported in association with their use, thereby leading to an unfavorable risk-benefit ratio. The efficacy of metoclopramide in GER’s improvement still needs to be clarified. Other prokinetic agents, such as domperidone and erythromycin, have been reported to be ineffective, whereas cisapride has been withdrawn due to its remarkable cardiac adverse effects.

  3. From association to alert--a revised approach to international signal analysis.

    Lindquist, M; Edwards, I R; Bate, A; Fucik, H; Nunes, A M; Ståhl, M


    From the inception of the WHO international drug monitoring programme, the main aim has been to detect signals of adverse reaction problems as early as possible. The Uppsala Monitoring Centre (UMC), is now in a better position to fulfil this mission. Using the latest technology, new tools have been developed which allow for rapid, robust and comprehensive data mining of the WHO database. Based on retrospective time scans made during the pilot phase the current threshold used is the 97.5% confidence level of difference from the generality of the database. To maximize the capacity for picking up signals, we intend to extend today's panel of expert consultants, as well as doing our own review. The new system includes an enhanced follow-up list of signals, a 're-signalling' procedure and a cumulative historical file of all drug-ADR associations. Already we produce some 50 signals per year, cisapride and tachycardia being an example of a controversial signal only recently accepted. With the addition of new tools for follow-up of important signals such as complex variable data mining techniques, and the combination of WHO ADR data with sales and prescription figures from the IMS, we will be able to provide more information that should benefit regulators, producers, prescribers, and most importantly, the users of medicines. PMID:15073883

  4. Pharmacological treatment of irritable bowel syndrome--from concept to sales.

    Kamm, Michael A


    Functional gastrointestinal disorders are characterised by central and peripheral physiological changes, associated with psychological factors. Successful drug development has been hindered by lack of adequate characterisation of the nature of symptoms and their physiological and psychological correlates. Animal models of chronic stress are lacking. High levels of drug safety are now demanded for treating non-life threatening conditions. Once close to market, patient pressure groups, health care providers and insurers, government, and the internet can all influence a drug's success. Serotonin-modifying drugs have been the main recent focus of development, with mixed results. Cisapride has been withdrawn because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists have been developed on the questionable assumption that they modify visceral sensation in patients. Problems have arisen with alosetron being associated with ischaemic colitis and a high incidence of constipation. The 5-HT4 agonists have their major effect on inducing peristalsis, and may modify gut secretion and sensory function. Tegaserod and prucalopride show promise in patients with constipation and related symptoms. 5-HT1 agonists may play a role in treating functional dyspepsia, partly by improving impaired gastric accommodation to a meal. Antidepressants, often found to be clinically beneficial in these disorders, also affect serotonin metabolism. Past successes, such as loperamide or the somatostatin analogue octreotide, involved targeting end organ receptors influencing motor function or secretion. Modifying sensory function is much more challenging. Future research with novel compounds need to keep these recent lessons in mind. PMID:16144196

  5. Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology.

    Sebastian Schaaf

    Full Text Available Human embryonic stem cell (hESC progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple and robust protocol for the generation of fibrin-based human engineered heart tissue (hEHT in a 24-well format using an unselected population of differentiated human embryonic stem cells containing 30-40% α-actinin-positive cardiac myocytes. Human EHTs started to show coherent contractions 5-10 days after casting, reached regular (mean 0.5 Hz and strong (mean 100 µN contractions for up to 8 weeks. They displayed a dense network of longitudinally oriented, interconnected and cross-striated cardiomyocytes. Spontaneous hEHT contractions were analyzed by automated video-optical recording and showed chronotropic responses to calcium and the β-adrenergic agonist isoprenaline. The proarrhythmic compounds E-4031, quinidine, procainamide, cisapride, and sertindole exerted robust, concentration-dependent and reversible decreases in relaxation velocity and irregular beating at concentrations that recapitulate findings in hERG channel assays. In conclusion this study establishes hEHT as a simple in vitro model for heart research.


    Singh Nidhi


    Full Text Available Drug interaction is an increasingly important cause of adverse reactions (ADR, and is the modification of the effect of one drug (object by the prior or concomitant administration of another drug (precipitant drug. Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. The aim of present review is to throw light on the concept of drug interaction.

  7. High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays.

    Gilchrist, Kristin H; Lewis, Gregory F; Gay, Elaine A; Sellgren, Katelyn L; Grego, Sonia


    Microelectrode arrays (MEAs) recording extracellular field potentials of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) provide a rich data set for functional assessment of drug response. The aim of this work is the development of a method for a systematic analysis of arrhythmia using MEAs, with emphasis on the development of six parameters accounting for different types of cardiomyocyte signal irregularities. We describe a software approach to carry out such analysis automatically including generation of a heat map that enables quick visualization of arrhythmic liability of compounds. We also implemented signal processing techniques for reliable extraction of the repolarization peak for field potential duration (FPD) measurement even from recordings with low signal to noise ratios. We measured hiPS-CM's on a 48 well MEA system with 5minute recordings at multiple time points (0.5, 1, 2 and 4h) after drug exposure. We evaluated concentration responses for seven compounds with a combination of hERG, QT and clinical proarrhythmia properties: Verapamil, Ranolazine, Flecainide, Amiodarone, Ouabain, Cisapride, and Terfenadine. The predictive utility of MEA parameters as surrogates of these clinical effects were examined. The beat rate and FPD results exhibited good correlations with previous MEA studies in stem cell derived cardiomyocytes and clinical data. The six-parameter arrhythmia assessment exhibited excellent predictive agreement with the known arrhythmogenic potential of the tested compounds, and holds promise as a new method to predict arrhythmic liability. PMID:26232523

  8. Chronic intestinal pseudo-obstruction as an expression of inflammatory enteric neuropathy

    Rita Pimentel


    Full Text Available Chronic intestinal pseudo-obstruction (CIPO is characterised by inadequate digestive tract motility and can lead to severely disordered motility. CIPO manifests as recurrent episodes of intestinal sub-occlusion without an anatomical obstruction. We present the case of a 41-year-old female, with severe chronic constipation and several episodes of intestinal sub-occlusion. Investigation revealed colonic inertia and marked distension of the small bowel and colon with no evidence of stenosis or obstructive lesions, compatible with CIPO. After several treatments were tried (domperidone, erythromycin, cisapride, octreotide, total enteral nutrition, with partial or no response, further work-up was done trying to identify an etiology. Gastrointestinal manometry showed neuropathic type abnormalities, transmural biopsy of the jejunum revealed degenerative enteric neuropathy and anti-HU antineuronal antibody screen was positive, suggesting an autoimmune type neuropathy with diffuse involvement of the digestive tract. Corticosteroids showed partial improvement of short duration and azathioprine was also tried but discontinued due to intolerance. Marked dietary intolerance and malnutrition lead to total parenteral nutrition (TPN at home since October 2011. Since then, symptoms and nutritional status improved, with rare episodes of pseudo-obstruction, not requiring hospitalisation.

  9. Tratamento cirúrgico da doença de refluxo gastroesofágico na esclerose sistêmica Surgical treatment of gastroesophageal reflux disease in systemic sclerosis

    Percival D. Sampaio-Barros


    Full Text Available OBJETIVO: Os autores descrevem sua experiência com o tratamento cirúrgico da doença de refluxo gastroesofágico (DRGE em pacientes com esclerose sistêmica (ES. MÉTODOS: Foram selecionados 10 pacientes com DRGE que apresentavam esofagite grave e estenose esofágica, tratados previamente com doses recomendadas de drogas anti-secretórias (ranitidina e/ou omeprazol e pró-cinéticas (cisapride por mais de seis meses, sem melhora significativa. Todos os pacientes eram do sexo feminino e 8 eram caucasóides, sendo 7 com ES limitada e 3 com ES difusa. RESULTADOS: O tratamento cirúrgico foi realizado através de videolaparoscopia em 9 pacientes e por cirurgia aberta no outro paciente. Sete pacientes foram submetidos à técnica de Nissen modificada e 3 à técnica de Lind. Seis pacientes com estenose esofágica significativa necessitaram de dilatações endoscópicas no período pré-operatório. Avaliação pós-operatória três meses após a cirurgia revelou que 70% dos pacientes apresentaram resultado favorável, com melhora significativa da azia e da disfagia; 1 paciente necessitou de nova intervenção cirúrgica em conseqüência de uma hérnia paraesofágica no período pós-operatório, sendo realizada uma gastrectomia em Y de Roux. Uma boa evolução foi referida por 80% dos pacientes um ano após cirurgia e por 70% dois anos após cirurgia, observando-se dois óbitos. CONCLUSÕES: Os autores concluem que o tratamento cirúrgico da DRGE representa uma eficiente opção terapêutica em pacientes com ES e esofagite grave com estenose.OBJECTIVE: The authors describe the experience with the surgical treatment of gastroesophageal reflux disease (GERD in 10 patients with systemic sclerosis (SSc. METHODS: Criteria for surgery included GERD with severe chronic esophagitis and stricture, treated previously with recommended doses of antisecretory (ranitidine and/or omeprazole and prokinetic (cisapride drugs for more than six months, without

  10. Chronic Intestinal Pseudo-Obstruction.

    Panganamamula, Kashyap V; Parkman, Henry P


    Chronic intestinal pseudo-obstruction (CIP) is a gastrointestinal motility disorder characterized by chronic symptoms and signs of bowel obstruction in the absence of a fixed, lumen-occluding lesion. Radiographic findings consist of dilated bowel with air-fluid levels. Pseudo-obstruction is an uncommon condition and can result from primary or secondary causes. The management is primarily focused on symptom control and nutritional support to prevent weight loss and malnutrition. The principles of management of patients with CIP involve 1) establishing a correct clinical diagnosis and excluding mechanical obstruction; 2) differentiating between idiopathic and secondary forms; 3) performing a symptomatic and physiologic assessment of the parts of the gastrointestinal (GI) tract involved by manometric and whole gut transit scintigraphic studies; 4) careful assessment of nutritional status of the patient; and 5) developing a therapeutic plan addressing the patient's symptoms and nutritional status. Treatment of CIP includes frequent small meals with a low-fat, low-fiber diet, liquid nutritional supplements may be needed; prokinetic agents such as metoclopramide may help to reduce upper GI symptoms. Trials of drugs such as erythromycin, domperidone, cisapride, and tegaserod may be considered if there is no response. Subcutaneous octreotide may be helpful to improve small bowel dysmotility especially in patients with scleroderma. In patients with symptoms suggestive of bacterial overgrowth, courses of antibiotics such as metronidazole, ciprofloxacin, and doxycycline may be needed. Nutritional assessment and support is an important aspect of management. Enteral nutrition is usually preferred. In carefully selected patients, feeding jejunostomy with or without decompression gastrostomy may be tried. Long term parenteral nutrition should be reserved for patients who can not tolerate enteral nutrition. Complications associated with total parenteral nutrition include

  11. Study on the treatment effect of Bx decoction on rat models of reflux esophagitis

    Objective: To explore the mechanism of BAN-XIA-XIE-XIN Decoction (Bx Decoction) treatment in rat models of reflux esophagitis. Methods: Rat models of reflux esophagitis were prepared with the method previously reported from this laboratory. Twenty-five models each were left untreated, treated with cisapride (2.5 mg/kg/d) or treated with BAN-XIA-XIE-XIN Decoction (BX) 5.78m/kg/d) respectively. All the models were sacrificed after 4 weeks, acid contents in gastric juice, cholic acid contents in duodenal juice as well as calcitonin-gene-related peptide (CGRP) (with RIA) contents in lower esophageal tissue and plasma were measured. Histologic examination of lower esophageal tissue for degree of esophagitis was also performed in all the models. Besides, 25 animals underwent sham operation only and served as controls. Results: The positive rates of pathologic changes (mucosal inflammation, squamous cell hyperplasia, lamina propria extension and mucosal erosion) were all significantly higher in the non-treated models than those in the BX treated models (P<0.01). Acid contents in gastric juice were significantly lowered with pH significantly increased in the BX treated group (P<0.01). The CGRP contents in esophageal tissue in the BX treated models, though remains lower than those in the 25 animals with sham operation only, were significantly higher than those in non-treated models (P<0.01). The plasma contents of CGRP in the BX-treated models remained significantly higher than those in sham-operation animals (P<0.01), decrease from the very high levels in untreated model was not large enough to be significant. Conclusion: BX-decoction might exert its protective effect on esophageal mucosa through lowering of gastric acidity with modulation of CGRP synthesis. (authors)

  12. Clinical Observation on Xiaoyu Decoction (

    JIANG; Bo


    [1]ZHOU B, LI QG, REN SB, et al. The determination of gastric emptying function of Spleen-Stomach Qi stagnation type dyskinetic dyspepsia patients. J Chin Integr of Trad and West Med of Spleen-Stomach 1997;5(2)∶84-86.[2]Drossman DA, Richter JE, Talley NJ, et al. The functional gastrointestinal disorders. Boston: Little Brown & Co, 1994∶1-74.[3]WANG XD. Handbook of mental health assessment quantitative scale. J Chin Ment Health 1993;(Suppl)∶31-36.[4]KE MY, PAN GZ, YI CQ, et al. Clinical observation with multi-centric double blind controlled on cisapride in treating regurgitational esophagitis. J Chin Digest 1995;15(5)∶253-255.[5]LI YY. Psychic factor of functional gastrointestinal disorder and its treatment. Medicine Abroad, Medicine Fascicle 1998;25(3)∶105-107.[6]CHEN D, WANG CH, WU CF. Progress in study of kinetic drugs of GI tract. J Chin Integr of Trad and West Med of Spleen-Stomach 1996;4(2)∶120-123.[7]CHEN SF, LI YQ, HE FY, et al. Effect of Aucklandia on gastric acid secretion and serum gastrin, growth inhibitor, motilin levels. CJITWM 1994;14(7)∶406-408.[8]WANG YM. Chinese drug pharmacology. Shanghai: Shanghai Science and Technology Press, 1985∶300.[9]China Academy of TCM, chief edited. Concise dictionary of TCM. Beijing: People's Health Publishing House, 1980∶186, 584.

  13. Neurobiological and psychopharmacological basis in the therapy of bulimia and anorexia.

    Mauri, M C; Rudelli, R; Somaschini, E; Roncoroni, L; Papa, R; Mantero, M; Longhini, M; Penati, G


    1. Eating disorders can be found in several psychiatric pathologies: schizophrenia, delusional disorder (somatic type), bipolar disorders, major depressive disorder, borderline personality disorder, generalized anxiety disorder, body dysmorphic disorder, somatization disorder and conversion disorder. 2. Although their clinical features have been defined, relatively little is known about the role of neurobiological patterns in the pathogenesis of these disorders. Several CNS neurotransmitters and neuromodulators are involved in the regulation of eating behavior in animals and have been implicated in symptoms such as depression and anxiety often observed in patients with eating disorders. The authors will review some studies on NA, DA, 5-HT, beta-endorphins, CRH, VP, OT, CCK, NPY and PYY involved in eating disorders. Furthermore, we will highlight some of the studies on drug therapy of eating disorders taking into account the effects of these agents on neurotransmitters and neuromodulators. 3. Antidepressant drugs have long been used for anorexia nervosa and bulimia, these disorders been claimed to be affective equivalent. Antidepressant agents seem to be effective in reducing the frequency of binge-eating episodes, purging behavior and depressive symptomatology. It is notable that antidepressant agents have been proved to be effective in patients with chronic bulimic symptoms, even in cases persisting for many years and in patients who had repeatedly failed courses of alternative therapeutic approaches. In all of the positive studies, antidepressant agents appeared effective even in bulimic subjects who did not display concomitant depression. 4. Few controlled studies on use of medications for anorexia nervosa have been published. Central serotonergic receptor-blocking compounds such as cyproheptadine cause marked increase in appetite and body weight. Zinc supplementation or cisapride could be a therapeutic option in addition to psychological and other approaches in

  14. [Functional dyspepsia: the past, the present and the Rome III classification].

    Buzás, György Miklós


    The author summarizes the historical development of our knowledge about functional dyspepsia and overviews the so-called "road to Rome" process. Between 1988 and 2006, expert committees developed using the Delphi method subsequent classifications of functional gastrointestinal disorders (Rome I-III). The Rome III classification reassessed the diagnostic criteria for functional dyspepsia and distinguished new subgroups as the postprandial distress and epigastric pain syndrome. The rationale for the proposed new classification was based on the inadequacy of prior approaches such as the predominant symptom, the results of factor analyses in tertiary care and in the general population, clinical experience and new observations in the peer-reviewed literature. Epidemiologic data suggest that dyspeptic symptoms date back to the 1730s and their prevalence increased markedly subsequently, remaining the commonest diagnosis even in the endoscopic era. The current worldwide prevalence of functional dyspepsia is 7-45%, with large geographic variations. The role of Helicobacter pylori and Salmonella infection as etiologic factors is discussed. Amongst the pathophysiological features, the recent data on the role of phenotypic changes of acid secretion, alterations of fundic accommodation and antro-duodenal motility and gastric emptying, gastric hypersensitivity and hormonal disturbances are presented, but all these abnormalities are present only in a small part of the patients. The possible role of the polymorphism of alpha-adrenoceptor gene was also raised. The treatment of functional dyspepsia led to equivocal results and the high rate of placebo response makes difficult any interpretation. According to the recent meta-analyses, proton pump inhibitors and H 2 -histamine receptor blockers are superior to placebo. In spite of good results, cisapride was withdrawn in 2004. Eradication of Helicobacter pylori can induce sustained remission in a small but significant minority of

  15. Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

    Preciosa M Coloma

    Full Text Available BACKGROUND: Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings. OBJECTIVE: To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI from a large international healthcare data network. METHODS: Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. RESULTS: Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects': azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. LIMITATIONS: Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. CONCLUSION: A strategy to identify potentially drug-induced AMI from electronic healthcare

  16. 加味四逆散对身心应激模型大鼠胃粘膜超微结构及胃肠功能的影响%Effects of Jia-Wei-Si-Ni-San on Gastrointestinal Function and Gastric Mucosal Ultrastructure of Chronic Psychological Stress Rats Models

    谢慧臣; 刘芬; 杨强


    目的:研究加味四逆散(JWSNS)对模型大鼠胃粘膜超微结构、胃排空率及小肠推进比的影响,探讨JWSNS干预应激性胃肠功能障碍的机制.方法:大鼠随机分为正常组,模型组,加味四逆散大、中、小剂量组,西沙比利组,采用慢性心理性应激方法建立应激性胃溃疡大鼠模型,经JWSNS等干预后,采用透射电镜法观察腺胃区胃粘膜组织细胞及细胞间连接的超微结构改变,并检测胃肠动力变化.结果:电镜观察显示正常组大鼠胃粘膜上皮细胞间连接紧凑,胞膜完整,细胞器均匀分布,且形态正常,胞核形态及大小正常,核膜完整,无染色质浓缩、边集等异常;模型组大鼠胃粘膜上皮细胞间连接松解,胞膜结构部分缺失,胞质中细胞器崩解,基质透明,内质网扩张,线粒体肿胀,胞核形态极不规则,大量畸形核,部分核溶解,染色质明显边集、浓缩或均一化分布;其余治疗组均较模型组不同程度好转.与模型组比较,各治疗组及正常组胃排空率及小肠推进比均明显升高(P<0.05~0.01);与西沙比利组比较,加味四逆散大剂量组胃排空率升高不明显(P>0.05),而小肠推进比升高明显(P<0.05);与加味四逆散小剂量组比较,加味四逆散中、大剂量组胃排空率及小肠推进比升高明显(P<0.05~0.01).结论:JWSNS可显著改善慢性心理应激胃溃疡模型大鼠胃粘膜组织细胞的微观病理形态,并可改善胃肠功能.%This study was aimed to establish a chronic rat model of acute stress ulcer, and observe effect of Jia-Wei-Si-Ni-San (JWSNS) on gastric emptying rate and small intestinal propulsion ratio, gastric mucosal ultra-structure of rat model. The mechanism of JWSNS on the treatment of stress-induced gastrointestinal dysfunction was studied. Rats were randomly divided into the normal group, model group, JWSNS large dosage, medium dosage and small dosage group, Cisapride group. Stress gastric ulcer

  17. Enteral nutrition in the critically ill-an overview%重症病人的肠内营养支持



    blood flow and providing a source of energy locally for the enterocytes themselves.These effects maintain a healthy gastrointestinal mucosa thereby reducing the incidence of bacterial overgrowth and translocation.Nevertheless,hypo-caloric nutritional support is often the result of emphasising the enteral route.This is the case because even when using well designed feeding protocols,it may be difficult to achieve target rates of enteral feeding using nasogastric access;gastric stasis with large nasogastric aspirates(>2-3mL/kg) may delay feeding but this problem can sometimes be overcome by the prescription of prokinetics(cisapride or erythromycin).Needle jejunostomy is unpopular outside the setting of surgery for abdominal trauma or upper gastrointestinal malignancies.However,it is possible to pass a naso-jejunal tube blindly at the bedside in the majority of patients.Jejunal feeding is thought to be associated with a higher daily intake of protein and energy and a lower risk of aspiration but there are no randomised studies compating nasogastric with jejunal feeding in the critically ill.Others have suggested that a combination of parenteral and enteral nutrition should be used initially for the first few days of support so as to guarantee an adequate intake of energy and protein.As enteral feeding is established with an increasing hourly rate of administration,the parenteral nutrition is titrated downwards and withdrawn once full enteral nutritional support has been established.The disadvantages of this latter approach are firstly,it exposes the patient to the fisks of parenteral nutrition.Secondly,there is the additional cost of the parenteral nutrition and perhaps most importantly,there is no evidence to suggest that this combination feeding is any better than simple enteral nutrition on its own.Hypo-caloeic feeding may not necessarily be such a bad thing in the severely stressed,critically ill patient.Finally,there is the issue of the constituents of the feed

  18. 多潘立酮儿童安全性的系统评价%Safety of domperidone in children:a systematic review

    黄亮; 张伶俐; 汪志凌; 梁毅; 王梦雅; 胡志强; 全淑燕; 张智慧


    床用量。同年9月,MHRA宣布多潘立酮不再作为非处方药物。结论现有证据不足以证明儿童使用多潘立酮不良反应发生率高于安慰剂和其他促动力药物以及其他常规治疗。儿童使用多潘立酮存在发生严重不良反应的风险。%Objective To evaluate the safetY of domperidone in children. Methods Clinical studies involving domperidone used in children were searched from PubMed,Embase,Cochrane LibrarY, Chinese BiologY Medical disc,CnKI,vIP,and Wanfang Database. Adverse drug reaction information bulletins which were reported bY WHO Pharmaceuticals newsletter and national Center for adverse drug reaction monitoring were searched and adverse drug reactions( ADR)/adverse drug events( ADE)related to domperidone were collected. Websites of European Medicines AgencY,Food and Drug Administration of united states,Medicines and Healthcare Products RegulatorY AgencY( MHRA ),Health Canada,and Therapeutic Goods Administration were searched and information of risKs and benefits related to domperidone treatment were collected. Randomized controlled trails( RCTs ) were Meta-analYzed using RevMan 5. 2 software and other data were descriptivelY analYzed. Correlation analYsis of domperidone and adverse drug reactions was performed using evaluation criteria of WHO. severitY of ADR/ADE was evaluated using criteria CTCAE 4. 03 of united states Department of Health and Human services. Results A total of 9 RCTs,1 cohort studY,4 self-controlled studies,and 24 case reports were entered in this studY. Meta-analYsis of 9 RCTs showed the following results. There were no statistical significance in the incidence of ADR in children between the domperidone group and the control groups of placebo, cisapride, and mosapride. The incidence of ADR in children in the domperidone group was lower than that in the metoclopramide(RR=0. 44,95%CI:0. 23-0. 86,P =0. 02),and higher than that in the Traditional Chinese Medicine group(RR=16. 09,95%CI:2. 01-129. 04,P=0. 01