Search

Treatments of vision-threatening retinal diseases are often hampered by drug delivery difficulties. Polyelectrolytically-coated alginate encapsulated-cell therapy (ECT) systems have shown therapeutic efficacy through prolonged in vivo drug delivery but still face various biocompatibility, viability, drug delivery and mechanical stability issues in clinical trials. Here, novel, injectable alginate-poly-l-lysine (AP)-coated composite alginate-collagen (CAC) ECT gels were developed for sustained ocular drug delivery, and their long-term performance was compared with non-coated CAC ECT gels. All optimised AP-coated gels (AP1- and AP5.5-CAC ECT: 2 mg/ml collagen, 1.5% high molecular weight alginate, 50,000 cells/gel, with 0.01% or 0.05% poly-l-lysine coating for 5 min, followed by 0.15% alginate coating) and non-coated gels showed effective cell proliferation control, cell viability support and continuous delivery of bioactive glial cell-derived neurotrophic factor (GDNF) with no significant gel degradation in vitro and in rat vitreous. Most importantly, intravitreally injected gels demonstrated therapeutic efficacy in Royal College of Surgeons rats with retinal degeneration, resulting in reduced photoreceptor apoptosis and retinal function loss. At 6 months post-implantation, no host-tissue attachment or ingrowth was detected on the retrieved gels. Non-coated gels were mechanically more stable than AP5.5-coated ones under the current cell loading. This study demonstrated that both coated and non-coated ECT gels can serve as well-controlled, sustained drug delivery platforms for treating posterior eye diseases without immunosuppression.

This study aimed to investigate whether use of a selective-blue-filtering (S-BF) lens can protect cultured primary porcine RPE cells against photo-irradiation. Transmittance of S-BF and UV-filtering (UVF) lenses was characterised spectrophotometrically. RPE cells were exposed to 1700 lux of white (peak λ at 443 and 533 nm; 0.44 mW/cm2) or blue (peak λ at 448 and 523 nm; 0.85 mW/cm2) LED light for 16 h to evaluate the influence of light source on the culture. The effect of the S-BF and UVF ophthalmic lenses on RPE cell cultures under blue light irradiation was then investigated. Cell viability was compared using trypan blue and MTT assays. Intracellular ROS production was detected by a fluorescein probe CM-H2DCFDA. Expression levels of catalase and Prdx3 were analysed by western blot. Trypan blue staining showed blue light caused more cell death than no light (p = 0.001) or white light (p = 0.005). MTT assay supported the hypothesis that exposure to blue light damaged RPE cells more severely than no light (p = 0.002) or white light (p = 0.014). Under blue light, use of the S-BF lens, which blocked 17% more blue light than the UVF lens, resulted in higher cellular viability (S-BF: 93.4±1.4% vs UVF: 90.6±1.4%; p = 0.022; MTT: 1.2-fold; p = 0.029). Blue and white light both significantly increased ROS production. The S-BF lens protected cells, resulting in lower levels of ROS and higher expression of catalase and Prdx3. To conclude, blue LED light exposure resulted in significant cytotoxicity to RPE cells. Partial blockage of blue light by an S-BF lens led to protective effects against retinal phototoxicity, which were mediated by reduction of ROS and increased levels of antioxidant enzymes.

To characterise longitudinal structural and functional changes in albino Sprague-Dawley rats following circumlimbal suture ocular hypertension (OHT) induction. Ten-week-old rats (n = 24) underwent suture implantation around the limbal region in both eyes. On the next day, the suture was removed from one eye (control eyes) and left intact in the other eye (OHT eyes) of each animal. Intraocular pressure (IOP) was monitored weekly twice for the next 15 weeks. Optical coherence tomography (OCT) and electroretinogram (ERG) were measured at baseline and weeks 4, 8, 12, and 15, and eyes were then collected for histological assessment. Sutured eyes (n = 12) developed IOP elevation of ~ 50% in the first 2 weeks that was sustained at ~ 25% above the control eye up to week 15 (p = 0.001). Animals with insufficient IOP elevation (n = 6), corneal changes (n = 3), and attrition (n = 3) were excluded from the analysis. OHT eyes developed significant retinal nerve fibre layer (RNFL) thinning (week 4: − 19 ± 14%, p = 0.10; week 8: − 17 ± 12%, p = 0.04; week 12: − 16 ± 10%, p = 0.04, relative to baseline) and reduction in retinal ganglion cell (RGC) density (− 32 ± 26%, p = 0.02). At week 15, both inner (9 ± 7%, p = 0.01) and outer retinal layer thicknesses (6.0 ± 5%, p = 0.001) showed a mild increase in thicknesses. The positive scotopic threshold response (− 28 ± 25%, p = 0.04) and a-wave were significantly reduced at week 12 (− 35 ± 21%; p = 0.04), whereas b-wave was not significantly affected (week 12: − 18 ± 27%, p = 0.24). The circumlimbal suture model produced a chronic, moderate IOP elevation in an albino strain that led to RNFL thinning and reduced RGC density along with the reductions in ganglion and photoreceptoral cell functions. There was a small thickening in both outer and inner retinal layers.

Objective Post-endoscopic sphincterotomy (EST) bleeding is one of the most frequent complications of endoscopic retrograde cholangiopancreatography (ERCP). Although the use of proton pump inhibitors (PPIs) reduces the risk of peptic ulcer bleeding, their role in preventing EST bleeding has not been evaluated. This study aimed to assess the use of pre-emptive PPIs in patients undergoing EST. Methods This was an investigator-initiated, open-label, randomized study. Consecutive patients scheduled to undergo ERCP and EST were enrolled after excluding those who had previous EST or used acid-suppression agents. Eligible patients were randomized to receive either PPI or standard care. The PPI group received intravenous esomeprazole 4 h before the EST and then every 12 h for 1 day, followed by high-dose oral esomeprazole for 10 days. All patients were followed up for 30 days. The primary outcome was the proportion of patients with combined immediate and delayed overt post-EST bleeding. Results Altogether 125 patients (60 in the PPI arm and 65 in the standard care arm) who had undergone EST were analyzed. Immediate bleeding was noted in nine (15.0%) patients in the PPI group and four (6.2%) in the standard care group (P = 0.14). Overt delayed post-EST bleeding was seen in two (3.3%) and five (7.7%) patients in PPI and standard care arms, respectively (P = 0.44). There were no significant differences in other outcomes, including a decrease in hemoglobin of >20 g/L, the need for blood transfusion, length of hospital stay and 30-day mortality. Conclusion Pre-emptive PPI did not reduce the risk of post-EST bleeding.

Purpose People in Hong Kong generally live in a densely populated area and their homes are smaller compared with most other cities worldwide. Interestingly, East Asian cities with high population densities seem to have higher myopia prevalence, but the association between them has not been established. This study investigated whether the crowded habitat in Hong Kong is associated with refractive error among children. Methods In total, 1075 subjects [Mean age (S.D.): 9.95 years (0.97), 586 boys] were recruited. Information such as demographics, living environment, parental education and ocular status were collected using parental questionnaires. The ocular axial length and refractive status of all subjects were measured by qualified personnel. Results Ocular axial length was found to be significantly longer among those living in districts with a higher population density (F2,1072 = 6.15, p = 0.002) and those living in a smaller home (F2,1072 = 3.16, p = 0.04). Axial lengths were the same among different types of housing (F3,1071 = 1.24, p = 0.29). Non-cycloplegic autorefraction suggested a more negative refractive error in those living in districts with a higher population density (F2,1072 = 7.88, p

Purpose To investigate the neuroprotective effects of Lycium barbarum polysaccharides (LBP) against chronic ocular hypertension (OHT) in rats and to consider if effects differed when treatment was applied before (pretreatment) or during (posttreatment) chronic IOP elevation. Methods Sprague-Dawley rats (10-weeks old) underwent suture implantation around the limbus for 15 weeks (OHT) or 1 day (sham). Four experimental groups were studied, three OHT groups (n = 8 each) treated either with vehicle (PBS), LBP pretreatment or posttreatment, and a sham control (n = 5) received no treatment. LBP (1 mg/kg) pre- and posttreatment were commenced at 1 week before and 4 weeks after OHT induction, respectively. Treatments continued up through week 15. IOP was monitored twice weekly for 15 weeks. Optical coherence tomography and ERG were measured at baseline, week 4, 8, 12, and 15. Eyes were collected for ganglion cell layer (GCL) histologic analysis at week 15. Results Suture implantation successfully induced approximately 50% IOP elevation and the cumulative IOP was similar between the three OHT groups. When compared with vehicle control (week 4: -23 ± 5%, P = 0.03), LBP pretreatment delayed the onset of retinal nerve fiber layer (RNFL) thinning (week 4, 8: -2 ± 7%, -11 ± 3%, P > 0.05) and arrested further reduction up through week 15 (-10 ± 4%, P > 0.05). LBP posttreatment intervention showed no significant change in rate of loss (week 4, 15: -25 ± 4.1%, -28 ± 3%). However, both LBP treatments preserved the retinal ganglion cells (RGC) and retinal functions up to week 15, which were significantly reduced in vehicle control. Conclusions LBP posttreatment arrested the subsequent neuronal degeneration after treatment commencement and preserved RGC density and retinal functions in a chronic OHT model, which was comparable with pretreatment outcomes.

To investigate the posttreatment neuronal rescue effects of Lycium barbarum polysaccharides (LBP) in an acute ocular hypertensive (AOH) model.Intraocular pressure (IOP) was elevated manometrically to 80 mm Hg (AOH) or 15 mm Hg (sham) for 120 minutes in adult Sprague-Dawley rats. Five experimental groups were considered: Three AOH groups were pretreated with PBS (vehicle) (n = 9), LBP 1 mg/kg (n = 8), or 10 mg/kg (n = 13), and one AOH group was posttreated with LBP 10 mg/kg (n = 8), once daily. The sham cannulation group (n = 5) received no treatment. Pretreatments commenced 7 days before and posttreatment 6 hours after AOH, and continued up through postcannulation day 28. All the animals underwent optical coherence tomography and electroretinogram measurements at baseline and postcannulation days 10 and 28. The ganglion cell layer (GCL) densities were quantified at day 28.Both inner retinal layer thickness (IRLT) and positive scotopic threshold response (pSTR) underwent significant reduction (≥50% of thickness and amplitude) in the vehicle group (P0.05). Pretreatment with LBP 1 and 10 mg/kg retained 77 ± 11% and 89 ± 8% of baseline IRLT, respectively, and preserved pSTR functions. The posttreatment group showed a significant reduction in IRLT (-35 ± 8%, P0.001) and pSTR (∼48% of baseline, P0.001) on day 10. By day 28, there was an improvement in functional pSTR (∼72% of baseline, P0.05) with no significant further thinning (-40 ± 8%, P = 0.15) relative to day 10. GCL density was reduced in vehicle control (P = 0.0001), but did not differ between sham and pre- and posttreated AOH groups.The rescue effect of LBP posttreatment was observed later, which arrested the secondary degeneration and improved the retinal function.

Meta-analysis shows that up to 26% of adenomas could be missed during colonoscopy. We investigated whether the use of artificial intelligence (AI)-assisted real-time detection could provide new insights into mechanisms underlying missed lesions during colonoscopy.A validated real-time deep-learning AI model for the detection of colonic polyps was first tested in videos of tandem colonoscopy of the proximal colon for missed lesions. The real-time AI model was then prospectively validated in a total colonoscopy in which the endoscopist was blinded to real-time AI findings. Segmental unblinding of the AI findings were provided, and the colonic segment was then re-examined when missed lesions were detected by AI but not the endoscopist. All polyps were removed for histologic examination as the criterion standard.Sixty-five videos of tandem examination of the proximal colon were reviewed by AI. AI detected 79.1% (19/24) of missed proximal adenomas in the video of the first-pass examination. In 52 prospective colonoscopies, real-time AI detection detected at least 1 missed adenoma in 14 patients (26.9%) and increased the total number of adenomas detected by 23.6%. Multivariable analysis showed that a missed adenoma(s) was more likely when there were multiple polyps (adjusted odds ratio, 1.05; 95% confidence interval, 1.02-1.09; P .0001) or colonoscopy was performed by less-experienced endoscopists (adjusted odds ratio, 1.30; 95% confidence interval, 1.05-1.62; P = .02).Our findings provide new insights on the prominent role of human factors, including inexperience and distraction, on missed colonic lesions. With the use of real-time AI assistance, up to 80% of missed adenomas could be prevented. (Clinical trial registration number: NCT04227795.).

Background and Aims Linked color imaging (LCI) is a newly available image-enhanced endoscopy (IEE) system that emphasizes the red mucosal color. No study has yet compared LCI with other available IEE systems. Our aim was to investigate polyp detection rates using LCI compared with narrow-band imaging (NBI). Methods This is a prospective randomized tandem colonoscopy study. Eligible patients who underwent colonoscopy for symptoms or screening/surveillance were randomized in a 1:1 ratio to receive tandem colonoscopy with both colonoscope withdrawals using LCI or NBI. The primary outcome was the polyp detection rate. Results Two hundred seventy-two patients were randomized (mean age, 62 years; 48.2% male; colonoscopy for symptoms, 72.8%) with 136 in each arm. During the first colonoscopy, the polyp detection rate (71.3% vs 55.9%; P = .008), serrated lesion detection rate (34.6% vs 22.1%; P = .02), and mean number of polyps detected (2.04 vs 1.35; P = .02) were significantly higher in the NBI group than in the LCI group. There was also a trend of higher adenoma detection rate in the NBI group compared with the LCI group (51.5% vs 39.7%, respectively; P = .05). Multivariable analysis confirmed that use of NBI (adjusted odds ratio, 1.99; 95% confidence interval, 1.09-3.68) and withdrawal time >8 minutes (adjusted odds ratio, 5.11; 95% confidence interval, 2.79-9.67) were associated with polyp detection. Overall, 20.5% of polyps and 18.1% of adenomas were missed by the first colonoscopy, but there was no significant difference in the miss rates between the 2 groups. Conclusion NBI was significantly better than LCI for colorectal polyp detection. However, both LCI and NBI missed 20.5% of polyps. (Clinical trial registration number: NCT03336359.)

Post-endoscopic sphincterotomy (EST) bleeding is one of the most frequent complications of endoscopic retrograde cholangiopancreatography (ERCP). Although the use of proton pump inhibitors (PPIs) reduces the risk of peptic ulcer bleeding, their role in preventing EST bleeding has not been evaluated. This study aimed to assess the use of pre-emptive PPIs in patients undergoing EST.This was an investigator-initiated, open-label, randomized study. Consecutive patients scheduled to undergo ERCP and EST were enrolled after excluding those who had previous EST or used acid-suppression agents. Eligible patients were randomized to receive either PPI or standard care. The PPI group received intravenous esomeprazole 4 h before the EST and then every 12 h for 1 day, followed by high-dose oral esomeprazole for 10 days. All patients were followed up for 30 days. The primary outcome was the proportion of patients with combined immediate and delayed overt post-EST bleeding.Altogether 125 patients (60 in the PPI arm and 65 in the standard care arm) who had undergone EST were analyzed. Immediate bleeding was noted in nine (15.0%) patients in the PPI group and four (6.2%) in the standard care group (P = 0.14). Overt delayed post-EST bleeding was seen in two (3.3%) and five (7.7%) patients in PPI and standard care arms, respectively (P = 0.44). There were no significant differences in other outcomes, including a decrease in hemoglobin of20 g/L, the need for blood transfusion, length of hospital stay and 30-day mortality.Pre-emptive PPI did not reduce the risk of post-EST bleeding.

Background: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin–clarithromycin-containing triple therapy as first-line treatment have fallen below 80%. Levofloxacin-containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7-day clarithromycin-containing triple therapy against the 7-day levofloxacin-containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first-line treatment for H. pylori infection in Hong Kong. Methods: Three hundred consecutive H. pylori-positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by 13C-urea breath test 6 weeks after treatment. Patients who failed either of the first-line eradication therapy were invited to undergo H. pylori susceptibility testing. Results: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention-to-treat and per-protocol analysis. More patients in the clarithromycin- than the levofloxacin-containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 μg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 μg/mL). Conclusions: The standard 7-day clarithromycin-containing triple therapy is still valid as the most effective empirical first-line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first-line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment.

This multicenter retrospective study investigated the management and outcome of patients with peptic ulcer/erosion-related aspirin and clopidogrel (A + C) cotherapy.From January 2002 to September 2006, patients with endoscopically proven peptic ulcers/erosions after receiving A + C cotherapy were analyzed.This group consisted of 106 patients (age, 69.3 +/- 11.7 years). Ulcers/erosions developed in 27 patients during hospitalization for cardiac events and in 79 patients after hospital discharge. Of 27 patients hospitalized for acute cardiac events, gastrointestinal (GI) bleeding and dyspepsia occurred in 24 and three, respectively. The most common lesion was gastric ulcer. Of 79 discharged patients, GI bleeding and dyspepsia occurred in 64 and 15, respectively. The most common bleeding and dyspeptic lesions were gastric ulcer and gastritis, respectively. Overall, 17 patients underwent endoscopic hemostasis all successfully. A + C cotherapy was continued in 57 patients for a median (interquartile range) of 3.0 (6.2) months. Most were coprescribed a proton pump inhibitor (PPI) (53, 93%). No recurrent GI bleeding was observed.After A + C cotherapy, gastric ulcer or gastritis were the most common endoscopic lesions. The combination of a PPI and endoscopic treatment for ulcer bleeding was highly successful. After patient stabilization, continuation of A + C cotherapy with a PPI appears to be safe.

Introduction: The major complication of aspirin and clopidogrel (A+C) co-therapy is upper gastrointestinal bleeding (UGIB). However, data are unavailable for real-life situations. Furthermore, the treatment effect of antisecretory agents is unknown. Aim: This cohort study aimed to determine the occurrence of UGIB. The treatment effect of H2-receptor antagonist (H2RA) and proton pump inhibitor (PPI) was also analyzed. Method: The records of 987 consecutive patients on A+C co-therapy between January 2001 and September 2006 were analyzed. The follow-up ended on the dates of a first occurrence of UGIB, stopping A+C co-therapy, a change in the antisecretory class, death, or March 2007. Results: After a follow-up of 5.8 ± 6.5 months, UGIB occurred in 39 (4.0%) patients. PPI, H2RA and control were prescribed in 213, 287 and 487 patients respectively. After adjustment for age, dose of aspirin, previous UGIB and duration of treatment, the risk was marginally reduced by H2RA (OR = 0.43, 95% CI 0.18–0.91, p = 0.04) and significantly reduced by PPI (OR = 0.04, 95% CI 0.002–0.21, p = 0.002), as compared to control. Conclusion: The occurrence of UGIB associated with A+C co-therapy for a median of 5.8 months was 4.0%. Co-prescription with PPI was associated with a lower risk.

Summary Background : Clopidogrel causes significantly less symptomatic peptic ulcer disease and gastrointestinal bleeding than low-dose aspirin in average-risk patients. The gastrotoxicity of clopidogrel in patients with active peptic ulcer disease is unknown. Aim : To compare the incidence of unhealed ulcers in patients receiving clopidogrel or aspirin. Methods : Patients with aspirin-induced peptic ulcer disease treated with omeprazole (20 mg/day) were randomized to receive clopidogrel (75 mg/day) or to continue with low-dose aspirin. Success was defined as ulcer/erosion healing at the eighth week. Results : One hundred and twenty-nine patients were recruited (69 received clopidogrel and 60 continued with aspirin). Thirty-one (45%) in the clopidogrel group and 25 (42%) in the aspirin group had a minor gastrointestinal bleed. No ulcer showed an adherent clot or visible vessel. The distributions of peptic ulcer disease were similar in the clopidogrel and aspirin groups (gastric ulcer: 41% vs. 40%; duodenal ulcer: 10% vs. 12%; gastric ulcer + duodenal ulcer: 6% vs. 3%; gastritis: 32% vs. 37%; duodenitis: 4% vs. 7%; gastritis + duodenitis: 0% vs. 2%). Clopidogrel and aspirin were re-started after 0.86 ± 1.79 and 0.44 ± 1.60 days, respectively (P = 0.170). Three (4%) patients stopped clopidogrel due to drug rash. Using per protocol analysis, the treatment success rates of clopidogrel and aspirin were 94% (62/66) and 95% (57/60), respectively. Conclusions : In patients with aspirin-associated peptic ulcer disease of low to moderate grade, both early conversion from aspirin to clopidogrel and continuation of aspirin are safe.

Background and Aim: The stool antigen test, the HpSA test, has been validated mainly in Western countries, but not properly in the Chinese population. Recently, another stool antigen test, the Apollo test, was developed, but its accuracy has rarely been validated. The aim of this study is to compare the accuracy of these two tests in the diagnosis of Helicobacter pylori infection in the Chinese population. Methods: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, biopsies were taken for the rapid urease test and histological examination as the gold standard. Stool specimens were collected and used for the HpSA and Apollo tests. Results: Overall, 86 patients (39 males and 47 females, with a mean age of 55.8 years) were recruited. Helicobacter pylori infection was present in 44 (51%) patients as determined by the gold standard. The sensitivity, specificity and accuracy were 86.4, 100, and 93.0%, respectively, for the HpSA, and 90.9, 97.6, and 94.2%, respectively, for the Apollo test when cases with equivocal results were considered as positive. In addition, agreement was achieved in 81 (94.2%) cases between the two tests, with a Kappa value of 0.887. Conclusion: Both the HpSA and Apollo tests achieve acceptable sensitivity and excellent specificity, with accuracies of over 90% for the detection of H. pylori infection in the Chinese population. © 2003 Blackwell Publishing Asia Pty Ltd

Background and Aim: Conventional [13C]-urea breath test ([13C]-UBT) requires prior fasting and a test meal, which theoretically improves the accuracy of the test. However, recent studies have suggested that prior fasting and test meal may not be essential. We aimed to determine the accuracy of a new [13C]-UBT protocol without fasting in Chinese. Methods: Dyspeptic patients referred for upper endoscopy were recruited. The gold standard for Helicobacter pylori infection was the combination of Campylobacter-like organism (CLO) test and histology. Group I (n = 213) patients underwent [13C]-UBT with prior fasting and with citrate acid test meal. Group II (n = 123) patients underwent [13C]-UBT without prior fasting but with test meal. Group III (n = 90) patients underwent [13C]-UBT without prior fasting and without test meal. Results: The highest accuracy for groups I, II and III was 96.7, 95.1 and 95.5% using a cut-off value of 5.0, 5.5 and 3.5, respectively. The sensitivities and specificities were 97.4 and 95.8% in group I, 93.3 and 96.8% in group II, and 96.5 and 93.9% in group III, respectively. Conclusion: The [13C]-UBT protocols without prior fasting and either with or without test meal produce highly accurate and reliable results in the Chinese population.

Purpose To investigate the characteristics of retinal electrophysiological activity in relation to early myopia development in children. Methods Fifty-six children aged 6 to 9 years with emmetropic refractive error (defined as ≥ -0.5 diopter [D] and ≤ +0.5 D) were recruited. Cycloplegic refraction, axial length, and global flash multifocal electroretinogram (MOFO mfERG) at 49% and 96% contrast levels were recorded in all children at their first visit. The refraction and axial length measurements were repeated after 1 year. The amplitudes and implicit times of the direct component (DC) and the induced component (IC) of the MOFO mfERG obtained at the initial visit were analyzed. Correlations between the MOFO mfERG parameters and changes in refractive error and axial length were investigated. Results The mean spherical equivalent refractive error and axial length of the eyes of the children at the first visit were +0.19 ± 0.33 D and 23.14 ± 0.6 mm, respectively. After 1 year, the mean refractive error increased by -0.55 ± 0.53 D, whereas axial length increased by 0.37 ± 0.22 mm. The changes in refractive error and axial length were significantly correlated with the central IC amplitudes at 49% contrast level measured at the initial visit (ρ = 0.46, P < 0.001 and ρ = -0.34, P = 0.01, respectively). Conclusions The prospective changes we have shown are believed to derive from central inner retina. These changes appear to precede myopia and could be a potential reference for juvenile myopia development.

Background: The proportion of duodenal ulcers not associated with Helicobacter pylori infection or the use of non-steroidal anti-inflammatory drugs (NSAIDs) is increasing. Aim: To identify the clinical and endoscopic characteristics of non-H. pylori, non-NSAID duodenal ulcers. Methods: Clinical and endoscopic data and H. pylori status were prospectively collected from consecutive patients who underwent upper endoscopy from 1997 to 1999. Patients with duodenal ulcers were identified, and those with non-H. pylori, non-NSAID duodenal ulcers were analysed further. Results: A total of 11 717 upper endoscopies were performed in 8344 patients. Of these, 1153 (14%) had duodenal ulcers. Of 599 patients with active ulcers and known H. pylori status, 104 (17%) had ulcers not associated with H. pylori or the use of NSAIDs, 393 (66%) had ulcers associated with H. pylori alone, 51 (8.5%) had ulcers associated with the use of NSAIDs alone and 51 (8.5%) had ulcers associated with both. Multivariate logistic regression analysis revealed that the presence of concomitant diseases (odds ratio=15.0; 95% confidence interval, 8.64–25.9; P

Behçet's disease, as initially described, is a triad of recurrent oral and genital ulcers and relapsing uveitis. The incomplete form, in which there is no ocular involvement, has been described in Japan and Korea, but this is not commonly recognized in the southern Chinese. We reported herein a rare case of repeated intestinal perforations caused by an incomplete form of Behçet's syndrome in a southern Chinese man.

Cytomegalovirus infection is usually reported inimmunocompromised patients. In this study, apparentlyimmunocompetent patients with cytomegaloviral colitiswere reviewed. Records with a diagnosis ofcytomegaloviral colitis from January 1989 to June 1996 wereretrieved for analysis. Ten patients were included(median age 70 yr). The major presenting symptoms werediarrhea and hematochezia. Ulceration was the mainmacroscopic finding. Rectal bleeding was mostlyself-limiting. Three patients developed localcomplications (rectovaginal fistula in two; rectalstricture in one). In the two patients with rectovaginalfistula, lymphocytes subsets and proliferative response wereentirely normal. In the other patient, low B lymphocytecount and low response to mitogen were demonstrated.However, the immunoglobulins were not suppressed and rectal biopsies revealed noncaseatinggranulomas, suggesting activated cell-mediated immunity.In conclusion, a high index of suspicion is crucial forearly diagnosis of cytomegaloviral colitis in patients with bloody diarrhea, even though obviousevidence of immunodeficiency is lacking.

Objective Simethicone, which is a principal ingredient in the defoaming agent used during gastroscopy, can inhibit the growth of Helicobacter pylori (MIC, 64-128 mg/l). This prospective study was designed to evaluate the in vivo and in vitro effects of simethicone on the accuracy of the rapid urease test (RUT). Methods In the in vivo study, three sets of gastric biopsies (two from the antrum, and one from the corpus) were taken from 75 patients. The first set was examined histologically, and the second set was used for the RUT (pre-simethicone RUT). Then, 25 ml simethicone (1200 mg/l) was introduced into the stomach for a contact time of 1 min. A third set of gastric biopsies was taken for the RUT (post-simethicone RUT). In the in vitro clinical study, 41 patients were recruited. The first set of gastric biopsies was used for the RUT (pre-incubation RUT). The second set was incubated in 1 ml of simethicone for 5 min before being used for the RUT (post-incubation RUT). In the spectrophotometric study, urease activity before and after incubation in simethicone for 5 min was quantified in 12 patients by measuring the absorbance at 560 nm. Results Reading at 15 min, the concordance rate between the pre-simethicone and post-simethicone RUT was 98%. In the in vitro clinical study, the concordance rate between the pre-incubation and post-incubation RUT was 97%. The spectophotometric study showed a significant reduction of 43% in urease activity after incubation in simethicone. Conclusion The application of a defoaming agent containing simethicone does not affect the accuracy of the RUT. However, simethicone modestly suppresses urea hydrolysis.

Little is known about the efficacy of H(2)-receptor antagonists in preventing recurrence of aspirin-related peptic ulcers. We compared the efficacy of high-dose famotidine with that of pantoprazole in preventing recurrent symptomatic ulcers/erosions.We performed a randomized, double-blind, controlled trial of 160 patients with aspirin-related peptic ulcers/erosions, with or without a history of bleeding. Patients were given either famotidine (40 mg, morning and evening) or pantoprazole (20 mg in the morning and placebo in the evening). All patients continued to receive aspirin (80 mg daily). The primary end point was recurrent dyspeptic or bleeding ulcers/erosions within 48 weeks.A total of 130 patients (81.1%) completed the study; 13 of 65 patients in the famotidine group reached the primary end point (20.0%; 95% one-sided confidence interval [CI] for the risk difference, 0.1184-1.0) compared with 0 of 65 patients in the pantoprazole group (P.0001, 95% one-sided CI for the risk difference, 0.1184-1.0). Gastrointestinal bleeding was significantly more common in the famotidine group than the pantoprazole group (7.7% [5/65] vs 0% [0/65]; 95% one-sided CI for the risk difference, 0.0226-1.0; P = .0289), as was recurrent dyspepsia caused by ulcers/erosions (12.3% [8/65] vs 0% [0/65]; 95% one-sided CI for the risk difference, 0.0560-1.0; P = .0031). No patients had ulcer perforation or obstruction.In patients with aspirin-related peptic ulcers/erosions, high-dose famotidine therapy is inferior to pantoprazole in preventing recurrent dyspeptic or bleeding ulcers/erosions.

The combination of aspirin, clopidogrel, and enoxaparin (combination therapy) is the standard treatment for acute coronary syndrome but is associated with gastrointestinal bleeding. However, information in this area is scarce.This retrospective study aimed to determine the incidence of upper gastrointestinal bleeding in a real-life situation. The effect of proton pump inhibitor (PPI) treatment was also analyzed.From January 2002 to December 2006, all patients receiving combination therapy were analyzed. The end point was the occurrence of upper gastrointestinal bleeding during combination therapy or within 7 days of stopping enoxaparin.The patient group consisted of 666 patients (age 72.1 +/- 12.6 yr). Gastrointestinal bleeding occurred in 18 (2.7%) patients. The overall hospital mortality was 4.1% (27 patients). A cardiac event was the major cause (N = 24, 3.6%). Only one patient died of massive gastrointestinal bleeding (0.15%). Multiple logistic regression analysis demonstrated that previous peptic ulcer, cardiogenic shock, and the lack of PPI coprescription were significant risk factors for gastrointestinal bleeding. The age-adjusted odds ratio (95% confidence interval) for gastrointestinal bleeding was 5.07 (1.31-16.58) for previous peptic ulcer, 21.41 (2.56-146.68) for cardiogenic shock, and 0.068 (0.010-0.272) for the coprescription with a PPI.In real life, the incidence of gastrointestinal bleeding associated with the combination of aspirin, clopidogrel, and enoxaparin therapy was estimated to be 2.7%. Previous peptic ulcer disease or cardiogenic shock were significant independent risk factors. Coprescription with a PPI can significantly reduce the risk.

We compared the clinical and laboratory features of human immunodeficiency virus (HIV)- and non-HIV-infected patients with penicilliosis marneffei. HIV-infected patients had a higher incidence of fungemia. A total of 85.7% of the HIV-negative patients had underlying diseases including hematologic malignancies or had received therapy with corticosteroids or cytotoxic agents. By a Penicillium marneffei-specific mannoprotein Mp1p enzyme-linked immunosorbent assay, serum antigen titers were found to be higher in HIV-positive patients, whereas serum antibody levels were found to be higher in HIV-negative patients., published_or_final_version

Unbuffered rapid urease test (RUT) is an accurate, rapid, and inexpensive method of detecting Helicobacter pylori. However, it is generally recommended to prepare the reagent daily. This prospective study was undertaken to evaluate the shelf-life of our unbuffered RUT at -20 degrees C. Two sets of antral biopsies (X2) and body biopsies (X1) were taken from all patients. They were subjected to histologic examination and RUT stored at -20 degrees C. We studied 303 patients. One hundred seventy-nine (59%) were infected as defined by histologic examination. The reagent was classified according to the storage time (group I, 0-30 days [n = 109]; group II, 31-60 days [n = 63]; group III, 61-90 days [n = 80]; and group IV, tau91 days [n = 51]). There was an excellent agreement between the histologic examination and the RUT of the four groups (kappa coefficient: group I, 0.88; group III, 0.80; group III, 0.87; group IV, 0.88). The sensitivity of our RUT in groups I, II, III, and IV were 92%, 92%, 91%, and 89%, respectively. The corresponding specificity were 97%, 88%, 97%, and 100%. Our RUT remains highly sensitive and specific when it is stored at -20 degrees C for 4 months.

Background: All patients with liver cirrhosis are recommended for evaluation of oesophagogastric varices (EGV) regularly. This prospective study was designed to develop a predictive model for EGV in cirrhotic patients. Methods: Ninety-two patients were recruited. From all patients studied, the size of palpable spleen, liver chemistry value, platelet count, prothrombin time, diameter of main portal vein and splenic length as assessed by ultrasonography were determined. Upper endoscopy was performed. Oesophageal varices (EV) and gastric varices (GV) were graded (EV, grade 1-4; GV, grade 1-3). In the predictive model, the EGV was classified into two grades (low, grade 1-2 EV or grade 1 GV; high, grade 3-4 EV or grade 2-3 GV). Results: There were 53 patients with EGV and 39 patients without EGV as determined by endoscopy. Patients with EGV had a significantly higher degree of ascites and hepatic encephalopathy, lower platelet count and longer splenic length than those without EGV. Low platelet count and presence of ascites were the significant independent predictors for high-grade EGV (concordance rate 0.83). The optimal critical value for the platelet count was 150 x 10 9 /L. Of patients without thrombocytopenia and ascites, 37% had low-grade EGV but none had high-grade EGV, whereas 38 and 35% of patients with thrombocytopenia or ascites had low and high-grade EGV, respectively. Therefore, this predictive model for high-grade varices had a positive and negative predictive value of 35 and 100%, respectively. Conclusion: Endoscopic screening for EGV was not necessary until thrombocytopenia or ascites occurred.

The overtube is the major cause for severe complications during endoscopic variceal ligation with a single-shot ligator. This retrospective study was designed to examine the necessity of the placement of an overtube during elective endoscopic variceal ligation. Thirty-one sessions in 18 patients were analyzed. An overtube was inserted using an over-the-scope technique in 11 sessions (group 1) but was omitted in 20 sessions (group II). The complications, technical difficulties, and operating time were analyzed. Child's grading, the size of the esophageal varices, and the number of rubber bands deployed were comparable in both groups. There was a significantly longer operating time (p < 0.01) and more oropharyngeal injury (p = 0.03) in group I than in group II. Mid esophageal injury, which was associated with resistance in withdrawing the gastroscope from the overtube, occurred in 55% of sessions in group I but in 0% of session in group II. In conclusion, the use of an overtube is associated with more complications, and it can be omitted during elective endoscopic variceal ligation.

Colonic skip lesions are typically described in Crohn's colitis, but this phenomenon has been recognized in ulcerative colitis (skipped appendiceal involvement), Behcet's colitis, cytomegaloviral colitis, and even in Aeromonas hydrophilia and Histoplasma capsulatum infection. However, skip lesions in typhoid ileo-colitis have not been reported in the English-language literature. We report herein a patient with skip ulcers due to typhoid fever.

ContextColorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated.ObjectivesTo investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases.Design, Setting, and ParticipantsPatients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years.Main Outcome MeasuresThe prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex.ResultsThe prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P

The membrane sector (F0) of the purified mitochondrial ATP synthetase complex (Complex V) was prepared by extracting Complex V with (a) 4 m NaBr and (b) 4 m urea. NaBr extraction resulted in nearly complete removal of the β, δ, and ϵ subunits of F1-ATPase and approximately 50% of the γ subunit. The extracted Complex V so obtained had no ATP-Pi exchange or ATPase activity, but the latter activity and rutamycin sensitivity could be partially restored by addition of F1-ATPase. ATPase activity of the reconstituted complex was 30 to 50% of that of the untreated Complex V, rutamycin sensitivity was only about 70–75%, and F1-ATPase binding to the extracted complex was associated with 70% loss of its activity. Additions of other coupling factors ± phospholipids did not improve these results. Urea (4 m ) extraction of Complex V resulted in a preparation depleted almost completely of δ, ϵ, oligomycin sensitivity-conferring protein (OSCP), and the ATPase inhibitor protein, and largely of α, β, and γ. This preparation (urea-F0) combined with added F1-ATPase without loss of F1 activity, and when supplemented with OSCP it resulted in a reconstituted complex with ATPase activity (15–17 μmol/min/mg) and rutamycin sensitivity (>90%) comparable to those of unresolved Complex V. The preparation also exhibited uncoupler and rutamycin-sensitive ATP-Pi exchange activity (115 nmol/min/mg). F1 binding to urea-F0 did not require added OSCP, but rutamycin sensitivity depended on OSCP addition. The above results suggest that NaBr extraction, which has been used by several other laboratories, results in an F0 with altered properties, as indicated by partial loss of rutamycin sensitivity and extensive loss of ATPase activity of the reconstituted system. By contrast, F0 prepared by urea extraction of Complex V exhibits upon reconstitution with F1 and OSCP undiminished ATPase activity and rutamycin sensitivity as well as uncoupler-sensitive ATP-Pi exchange activity.

The methyl 4-azidobenzimidate derivative of the naturally occurring ATPase inhibitor protein (IF1) of mitochondria binds to the beta subunits of soluble F1-ATPase upon photoactivation [Klein, G., Satre, M., Dianoux, A.-C., & Vignais, P. V. (1981) Biochemistry 20, 1339--1344]. A number of specific ATPase inhibitors, namely, 4-chloro-7-nitrobenzofurazan (NBF-Cl), efrapeptin, 5'-[p-(fluorosulfonyl)benzoyl]adenosine (FSBA), phenylglyoxal, aurovertin, tridentate ferrous bathophenanthroline, and octylguanidine (referred to hereafter as "artificial" inhibitors), are also considered to bind to the beta subunit, and there is strong evidence that the first three bind at the active site. Since the inhibition by IF1 of complex V ATPase activity can be reversed by incubation of the inhibited complex at pH 8.0, this system was used to investigate whether the inhibitions brought about by IF1 and the artificial inhibitors were independent, mutually interfering, or mutually exclusive. The experiments were carried out in two ways. (a) Complex V was first maximally inhibited by IF1. Then an artificial inhibitor was added and allowed to react. Excess artificial inhibitor was removed by precipitation of the doubly inhibited complex V with ammonium sulfate and resuspension in inhibitor-free buffer at pH 8.0. Incubation at pH 8.0 released the inhibition due to IF1. However, it was found that the factor that controlled reemergence of ATPase activity was the degree of inhibition exerted by the artificial inhibitor. When the artificial inhibitor was removed first (which was done by addition of dithiothreitol when the artificial inhibitor was NBF-Cl), then reemergence of activity depended on incubation at pH 8.0 to reverse the inhibition due to IF1. These results indicated that IF1-inhibited complex V could be independently inhibited by various artificial inhibitors. The artificial inhibitors used in this type of study were NBF-Cl, efrapeptin, aurovertin, FSBA, and phenylglyoxal. (b) Complex V was first treated with the artificial inhibitor (ferrous bathophenanthroline or octylguanidine) and then with IF1. Results showed that prior treatment of complex V with these inhibitors did not interfere with IF1 subsequently exerting maximal and reversible inhibition. The above results have been discussed in view of the recent finding that F1-ATPase contains two functional and interacting hydrolytic sites [Grubmeyer, C., & Penefsky, H.S. (1981) J. Biol. Chem. 256, 3718--3727].

Antibody raised in rabbits against Complex V (miochondrial ATP synthetase complex) purified from beef heart mitochondria cross-reacted with Complex V and submitochondrial particles from beef heart, beef adrenals, and rat liver as shown by double-diffusion and rocket immunoelectrophoresis analysis. Of the various isolated and purified components of Complex V, only the oligomycin sensitivity-conferring protein showed strong reactivity with the anti-Complex V antibody, soluble F 1 -ATPase reacted very faintly, while F 6 and ATPase inhibitor protein showed no precipitin lines. Crossed immunoelectrophoresis indicated that antigenic determinants recognized by the antibody were present on OSCP and possibly on the dicyclohexylcarbodiimide-binding protein. The components of Complex V could be precipitated from beef heart submitochondrial particles dissolved in Triton X-100 and pretreated with control IgG. When the composition of the immunoprecipitate was compared to that of purified Complex V, all the constituent polypeptides of the latter were present in the immunoprecipitate, except for one polypeptide in the low-molecular-weight region. Incubation of Complex V or submitochondrial particles with the anti-Complex V antibody in the absence of Triton X-100 caused inhibition of ATP- P i exchange but not of ATPase activity. In the presence of Triton X-100, oligomycin sensitivity of Complex V was lost and the antibody was able to inhibit also the ATPase activity. The enzymic activity of soluble F 1 -ATPase was unaffected by the antibody in the absence or presence of Triton X-100. These results suggest that the anti-Complex V antibody might be a useful tool for identifying and probing the role of Complex V components involved in energy transduction.