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 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 evaluate the efficacy and safety of azathioprine (AZA) in long term treatment of patients with active Crohn's disease (CD) in China. Methods Sixty patients with active CD,who needed to be treated with systemic steroids, were recruited. All patients initially received AZA combined with steroids therapy and AZA was maintained for treatment after withdrawal of steroids. Clinical efficacy, endoscopic healing of mucosa and adverse events were assessed at the end of the 12th, 24th, 48th, 72th and 96th weeks. Results The complete remission (CR) of the patients at the 12th, 24th, 48th, 72th and 96th weeks was 55.0%, 66. 7%, 61. 7%, 53. 3% and 53. 3%,respectively. Endoscopic examination was performed in 25 patients before treatment and at the end of the 48th week. Eight of them achieved mucosal healing that was kept to the end of 96th week (8/8).Whereas only 9 out of 17 patients without mucosal healing achieved CR at the end of 96th week (9/17,P=0. 026). The clinical features were compared between CR group and non-CR group at the end of 48th week. Logistic regression analysis showed that regaining of hs-CRP was the only independent factor for maintaining remission by AZA treatment ( P= 0. 009,OR 10.1,95 % CI 1.8 ～ 57.9). Sixteen patients (26.7 % ) had adverse events. Ten (16.7 % ) of them had to halt treatment because of serious adverse events. Leucopenia was the most common adverse event and could be occurred at any time during the treatment. Conclusion AZA combined with steroid therapy can effectively induce remission of active CD. Long term steroid-free remission is also effectively maintained by AZA treatment. The most common adverse event is leucopenia and some patients can get mucosal healing. Those who get mucosal healing may have longer duration of remission.

Objective To inspect the efficacy and mucosa healing condition of infliximab with azathioprine combination therapy in Crohn's disease (CD) and its correlation with prognosis.Methods A total of 20 active CD patients who received infliximab and azathioprine combination therapy at The First Affiliated Hospital of Sun Yat-sen University were objects of this study.The clinical efficacy was evaluated at 10 weeks,30 weeks,54 weeks and 2 years respectively according to CD activity index.The efficacy was evaluated under endoscopy at 10 weeks,30 weeks,54 weeks and 2 years respectively according to mucosal response situation under endoscopy.The data were analyzed by analysis of variance or Fisher's exact test between two groups.The factor affecred mucosal healing was analyzed by Logistic regression analysis.Results The clinical remission rate of patients without steroid at week 10,30,54 and 2 year were 12/20,16/20,15/20 and 15/20 respectively.Mucosal healing rate at week 10,30 and 54 weeks were 8/20,12/20 and 10/20 respectively.Logistic regression analysis indicated that age was the only factor affected mucosal healing at 30 weeks (OR =0.774,95％ CI:0.630 to 0.950).There was significant differences in clinical remission between mucosa response patients and invalid under endoscopy at 30 weeks and 2 years without steroid (at 30 weeks:14/14 vs 2/6; at 2 years:14/14 vs 1/6; all P＜0.01).Infliximab were withdrawn in 4 of 16 patients who was in non-steroid clinical remission at 30 weeks,and the other 12 patients were continued with infliximab therapy.There was no significant difference in non-steroid clinical remission rate (4/4 vs 11/12) and mucosa healing rate (2/4 vs 7/12) between withdrawal and continue of infliximab therapy (all P＞0.05).Conclusions Infliximab with azathioprine combination therapy can effectively promote and maintain mucosa healing in CD.The mucosa response patients can maintain long time non-steroid clinical remission.

Objective To investigate the role of combined multichannel intralumminal impedanee-pH (MII-pH) monitoring in the diagnosis of gastroesophageal reflux disease (GERD). Methods Forty-four consecutive patients, who had heartburn symptom and without esophageal mucosal lesion, underwent combined MII-pH monitoring. Then rabeprazole test was performed for 14 days with 10 mg twice daily. Rabeprazole test was defined as positive if patients were totally heartburn symptom free in the second week. The normal values from 70 healthy volunteers who underwent MII-pH monitoring were served as controls. Results Conventional esophageal pH monitoring showed that 20 patients (45.5%) had pathologic esophageal acid exposure or positive acid reflux associated symptom index. MII-pH monitoring revealed that 2 patients were positive for weakly acidic reflux related to symptom index, thus increased the diagnostic yield to 50% (22/44). Furthermore, rabeprazole test demonstrated that 4 patients were positive which increased the diagnostic yield to 54.5%(24/44). Conclusion The detective rate of GERD will be elevated if combined with MII-pH monitoring in diagnosis.

Objective To investigate the efficacy and safety of a novel biologies-infliximab in the treatment of patients with Crohn's disease (CD). Methods A prospective study was conducted in 10 patients with CD(8 with active refractory CD and 2 with severe lower gastrointestinal bleeding caused by CD). 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 efficacy of infliximab were evaluated by follow-up of 30 weeks. Results ① Five out of 8 patients with active CD had initial clinical response at week 2. Clinical remission was found in 4 patients at week 30, (3 of them in symptomatic remission without corticosteroids). ② Two patients with severe lower gastrointestinal bleeding caused by CD were in control of bleeding and absence of further recurrence by 30 weeks follow-up. ③ Endoscopy was performed in 6 patients at week 30 to evaluate the healing of mucosal ulceration. Four patients were evaluated for complete or almost mucosal healing. ④ Adverse events were seen in 7 out of 10 patients with infliximab treatment, among whom 2 cases had severe side effect including pneumonia in one and delayed hypersensitirity reaction in the other. Conclusion Infliximab has efficacy for the induction and maintenance of remission in part of patients with active CD. Some patients achieved mucosal healing with infliximab therapy and low incidence of serious adverse events.

Objective To investigate the prevalence of non-acidic reflux in patients with gastroesophageal reflux disease and its correlation extent with heartburn symptom by 24-hour combined multichannel intraluminal impedance-pH (MII-pH) monitoring. Methods Consecutive patients with chief complain of heartburn in gastrointestinal specialty clinic were enrolled. Patients were divided into erosive esophagitis (EE) group, non-erosive reflux disease (NERD) group after upper gastrointestinal endoscope, further diagnosed with 24-hour combined MII-pH monitoring and rabeprazole test. The MII-pH parameters were compared in these two groups. Results 36 cases of EE and 62 of NERD were enrolled. There was significant difference in acidic reflux frequency and acidic reflux time percentage between these two groups (P=0. 001 and 0. 002). The frequency of non-acidic reflux in EE and NERD groups was 37.3% (663/1777) and 44.3% (1220/2754) respectively (x2 =21. 723,P = 0. 000). The percentage of heartburn symptom positive index in patients with acidic reflux, non-acidic reflux , and total reflux in EE group was 36.1 % (13/36), 19.4 % (7/36) and 55.6%(20/36) respectively, while in NERD group was 27. 4% (17/62), 6.4 % (4/62) and 33.8% (21/62).Conclusion The percentage of non-acidic reflux in EE and NERD groups was 37.3% and 44.3%respectively, and the non-acidic reflux was highly related to heartburn symptom.

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.