Objective To evaluate the effect of csomeprazole with different dosage and usage regimes on intragastric pH of healthy volunteers. Methods It was a randomized, open-label, three-way crossover study. Fifteen healthy volunteers received esomeprazole with 3 different dosages (20 mg or 40 mg once daily or 20 mg twice daily) with 5 days each. Twenty-four continuous ambulatory intragastric pH was recorded at day 5 of each regime. Results The mean time of intragastric pH above 4 was higher in regime of 20 mg twice daily [(21.16 ±2.45) hours ] than that in regimes of 20 mg once daily [(18. 70±4.19) hours] and 40 mg once daily [(19.27±2.68 ) hours] (P<0.05). The percentages of the sleeping and active period that pH remained above 3,4,5 were significantly higher in regime of 20 mg twice daily(day time:95.0%±7.5% ,92.0%±10.6% ,86.7% ± 14.5% ;night time:93.2%± 13.1% ,87.8%±20.3% ,78.6%±28. 9 % )compared with regimes of 40 mg once daily(day time:87.9%±9.5% ,83.5%±11.7%,75.6%±15.50%, night time:75. 7%±20. 8%,66. 9%±23. 8%,53. 3%±30. 3%) and 20 mg once daily(day time: 85.1 % ± 16.3 %, 81.1 %± 18. 1%, 71.5 % ± 20.3 % ; night time: 72.9 % ± 30.5 %,67.2 % ± 31.9 %, 55.7 % ± 31.8 % ) (P< 0.05 ). Esomeprazole maintained intragastric pH above these pH thresholds for a similar propotion of sleeping and active periods with 40 mg once daily and 20 mg once daily.Conclusions Esomeprazole has strong inhibitory effect on intragastric acid. The regime of 20 mg twice daily is superior to 40 mg once daily and 20 mg once daily in both day and night time acid inhibition.There is no difference between esomeprazole 40 mg once daily and 20 mg once daily.

Objective To evaluate the value of endoscopic profile in an adult population with typical heartburn. Methods Clinical and endoscopic data were collected from 5042 consecutive outpatients who underwent routine upper endoscopy without any alarm features between March 2006 and Feb. 2007. Results Three hundred and thirteen (6.2%) patients were diagnosed as having typical heartburn. Of these, erosive esophagitis (EE) was found in 99 (31.6%) patients, Barrett's esophagus (BE) in 10 (3. 2%) patients, peptic ulcer disease (PUD) in 21 (6. 7%) patients and carcinoma in three (0.9 %) patients (1 with esophageal carcinoma and 2 with gastric adenocarcinoma).Multivariate analysis revealed that age＞50, male, overweight and alcohol use were independent risk factors for positive endoscopy findings (P＜0.05) and EE (P＜0.05) in heartburn patients. Male and Helicobacter pylori infection were independent risk factors for PUD (P＜ 0.05). Conclusions In China, patients with typical heartburn but without alarm features, early endoscopic examination may be helpful in avoiding missing diagnosis of tumor.

Objective To assess the predictive value of thiopurine methyltransferase genotyping and enzyme activity in relation to side effects in patients with inflammatory bowel disease (IBD) who were treated with azathioprine (AZA). Methods One hundred and eleven IBD patients (26 with ulcerative colitis and 86 with Cronh's disease) with indication of AZA administration between April 2004 and Dec. 2009 were enrolled. All patients received 2 mg/kg of AZA daily. Polymerase chain reaction and high performance liquid chromatography were used to genotype the TPMT * 2, * 3A, * 3B, * 3C and to detect TPMT activity, respectively. The association of TPMT genotype and activity with side effects was analyzed in patients treated with AZA for 24 weeks or more, or in those discontinued AZA because of adverse effects. Results Adverse effects were reported in 38(33. 9%) patients, the most frequent being myelosuppression (20. 5%). The frequency of TPMT * 3C heterozygous mutation was 0. 9% (1/112). The TPMT activity was (12. 9±4. 8) U/ml RBC with unimodal distribution. One patient with TPMT * 3C heterozygous mutation developed myelosuppression at the 4th week after AZA treatment. The TPMP genotype myelosuppression patients. Conclusions TPMT genotype mutation and low enzyme activity can be used to predict myelosuppression with high specifically and low sensitivity. In patients treated with AZA, co-administration of 5-ASA results in a high frequency of myelosuppression with no effect on TPMT activity.

Objective To evaluate the diagnostic value of esomeprazole test in patients with gastroesophageal reflux disease.Methods Consecutive patients with heartburn and/or acid regurgitation in three medical centers were enrolled in a prospective,randomized,double-blind study with a placebo-control design.After upper endoscopy examination,patients were divided into non-erosive reflux diseases and erosive esophagitis.All patients underwent 24-hour ambulatory esophageal pH monitoring.Those who were diagnosed as gastroesophageal reflux diseases had either esophagitis under endoscopy or abnormal esophageal acid exposure in 24-hour ambulatory esophageal pH monitoring.The patients were randomly divided into treatment group and control group.The patients in treatment group were received 40 mg of esomeprazole daily while the patients in control group were given placebo once daily for 14 days.The severity and frequency of heartburn were recorded both by doctors and patients before and during treatment.Results Two hundred and seventeen patients were completed the study(105 patients in treatment group and 112 patients in control group).If the symptom of heartburn which disappeared in the sixth and seventh day of the first week,it was defined as positive for esomeprazole test,the sensitivity and specificity in treatment group were 87.7% and 42.5%,respectively If the symptom of heartburn disap peared in the second week,it was defined as positive for esomeprazole test.The corresponding sensitivity and specificity in treatment group were 84.6% and 45%,respectively.The Youden index was 0.362 and 0.296 for criteria of one and two weeks,respectively.If the heartburn score improved by more than 50%,75% or 100% from the baseline score after treatment,it was defined as positive for esomeprazole test,the sensitivity and specificity were 95.4% and 32.5%,87.7% and 32.5%,84.6% and 45%,respectively.Conclusions The esomeprazole test has high value in diagnosis of GERD with sensitivity of 87.7% and specificity of 42.5%.Positive definition of heartburn disappeared in the sixth and seventh day is superior in cost-effective.

ObjectiveTo compare the efficacy of step-up and top-down infliximab therapy on patients with Crohn's disease (CD).MethodsA prospective and open-label study was performed by the First Affiliated Hospital of SUN Yat-sen University during September 2007 to December 2010.Active CD patients who were refractory to steroid/immunomodulator or who were steroid-dependent were enrolled into step-up group.Active CD patients who had no steroid or immunomodulator therapy before were enrolled into top-down group. All patients were intravenously infused with infliximab of 5 mg/kg body weight in an induction regimen of 3 doses at week 0,2 and 6,followed by maintenance dosing every 8 weeks beginning at week 14.The clinical and endoscopic follow up lasted 30 weeks.Clinical symptoms and mucosal healing status under endoscopy were evaluated by follow-up at week 10 and 30.Results Forty-one CD patients were enrolled,with 24 in step-up group and 17 in top-down group. There were significant differences in disease duration (P =0.006),combination therapy (P ＜ 0.001 ) and severity of disease ( P =0.011 ) in baseline between step-up and top-down groups.At week 10 and 30 during treatment,the clinical remission rates in step-up group were 45.8％ (11/24) and 58.3％ (14/24) respectively; the mucosal healing rates in step-up group were 33.3％ (8/24) and 54.2％ (13/24) respectively; the clinical remission rates in topdown group were 70.6％ ( 12/17)and 82.4％ (14/17) respectively; and the mucosal healing rates in topdown group were 35.3％ (6/17) and 52.9％ (9/17) respectively.No significant differences in clinical remission and mucosal healing rates at both week 10 and 30 were observed between the two groups.The prevalences of adverse events in step-up and top-down group were 41.7％ (10/24) and 29.4％ (5/17)respectively ( P =0.422).ConclusionBoth step-up and top-down infliximab therapy can induce remission in more than half of CD patients,while top-down therapy might be more benefitiary to symptom and endoscopic remission.

Objective To investigate the evaluation standard and proper time point of anti-tuberculosis trial for differential diagnosis between intestinal tuberculosis (ITB) and Crohn's disease (CD). Methods Clinical data and endoscopic changes of 28 patients with confirmed ITB and 11 with confirmed CD,who underwent anti-tuberculosis trail, were retrospectively analyzed. Results No significant difference could be found in clinical characteristics of ITB and CD patients on baseline, such as active pulmonary tuberculosis, strong positive skin test and anal fistula/perianal abscess. Clinical symptoms were relieved in both groups right after anti-tuberculosis treatment. After 3 months of treatment, the no-improvement rate in ITB group was 0, whereas that of CD group was 27.3% (P =0. 004). The disappearance rate plus improvement rate of ulcer in ITB group was 90. 9% (20/22) plus 9. 1% (2/22) and 100% ( 28/28 ) plus 0 at 3 and 6 months of treatment, respectively. The disappearance rate plus improvement rate of nodular lesion was 58. 8% (10/17) plus 41.2% (7/17) and 76. 5% (13/17) plus 23.5% (4/17), respectively. There was no obvious improvement of active ulcer or nodular transformation in CD group at any time point ( P ＜ 0. 01 ).Conclusion With deficiency of special index for differential diagnosis of ITB and CD, some cases hard to differentiate still have to accept anti-tuberculosis treatment. Three months of anti-tuberculosis treatment is a proper time point to evaluate the efficacy. Disappearance of active ulcer and nodular transformation, together with cure or obvious improvement in clinic are taken as effective for treatment trail.

Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.MethodsThe clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.ConclusionsThe incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression.

Objective To observe the efficacy and safety of thalidomide in refractory Crohn's disease (CD).Methods A total of 21 moderate or severe active CD patients were enrolled,who had no response to glucocorticoid and azathioprine treatment or steroid-dependent.The patients were administrated with thalidomide 100 mg/d before sleep and followed up for one year.The clinical efficacy,endoscopic findings and safety were evaluated.Results Among 21 refractory CD patients,six patients stopped medication due to adverse effect and two because of ineffectiveness,three patients continued medication not completed one year follow-up,10 patients completed one year follow-up.The clinical remission,effective and ineffective rates were 23.8％(5/21),19.0％(4/21) and 57.1％(12/21) respectively.Under endoscope,the mucosal healing,improvement and no improvement rates were 9.5％(2/21),14.3％(3/21) and 76.2％ (16/21) respectively.The adverse effect rate was 71.4％ (15/21) including rash,conspitation,sommolence,numbness of hands and feet,leucopenia and muscular soreness.The mean time of the adverse effects onset was 3.4 weeks.Conclusions Thalidomide is effective in refractory CD treatment and could be used in patients unwilling to use biological medication or receive surgery.But the adverse effects should be noted.

Objective To evaluate the clinical and manometric characteristics of achalasia.Meth-ods Patients diagnosed as having achalasia from July 2010 to July 2014 at our hospital were enrolled.High resolution manometry(HRM)results were analyzed.Data of Eckardt scale,MDADI and SF-36 were ana-lyzed.Results All subjects had dysphagia,35.6% (37 /104)accompanied with regurgitation,26.9%(28 /104)with heartburn and 17.3%(18 /104)with weight loss.According to HRM results and Chicago classification criteria,16.35%(17 /104)of the subjects were classified as type Ⅰ,76.92%(80 /104)as type Ⅱ and 6.73%(7 /104)as type Ⅲ.27.9%(29 /104),19.2%(20 /104)and 24.0%(25 /104)of the subjects finished Eckardt scale,MDADI and SF-36,respectively.Eckardt score was positively correlated with integrated relaxation pressure(IRP)(r =0.421,P <0.05)and MDADI physical score was negatively with IRP(r =-0.530,P <0.05).Conclusion Dysphagia often occurs as the chief complaint among acha-lasia patients.And type Ⅱ is the most common.IRP is an indicator of the severity of clinical symptoms and impairment of quality of life.

Objective To investigate the changes of esophageal intraluminal baseline impedance in patients with refluxesophagitis.Methods From December 2013 to August 2014,47 patients with reflux esophagitis and 17 healthy controls were enrolled.The patients with reflux esophagitis were graded according to Los Angeles classification (LA) grading standards.All subjects accepted 24 h multichannel intraluminal impedance (MII) pH examination,and the baseline value of impedance were measured.Independent sample t test was used to compare the difference in impedance between the two groups.Spearman rank correlation coefficient was performed to analyze the correlation between acid exposure time (AET) and the baseline impedance of patients with reflux esophagitis.Kruskal-Wallis test was used to compare the differences in baseline impedance of patients with different grades of reflux esophagitis.Results The impedance baseline value of reflux esophagitis group was (1 676.72±644.41) Ω,which was lower than that of healthy control group ((2 151.27± 322.05) Ω),and the difference was statistically significant (t =-3.883,P＜0.01).The AET of esophagus was negatively correlated with the baseline impedance of the patients with reflux esophagitis (r=-0.530,P＜0.01).The baseline impedance of patients with grade LA-A and grade LA-B reflux esophagitis were 1 823.62 Ω (1 515.38 52 Ω,2 208.38 Ω) and 1 771.81 Ω(1 304.75 52 Ω,2 080.50 Ω),respectively,and the difference was not statistically significant (Z=-0.630,P=0.529).The baseline impedance of patients with grade LA C/D reflux esophagitis was 300 Ω (300 Ω,500 Ω),which was obviously lower than those of patients with grade LA-A or grade LA-B (Z=-2.647 and-2.818,both P＜0.017).Conclusion The baseline impedance of patients with reflux esophagitis is low and correlated with AET.