Meta-analysis of the Use of ACEI for Inhibiting Albuminuria in Diabetic Patients

Aim To examine whether AER(albumin excretion rate) in normotensive diabeticpatients can be effectively inhibited by ACEI. Methods Literature on randomized controlled trials ofACEI for inhibiting AER in normotensive diabetic patients was searched. The electronic databasesretrieved were Medline (1980 ― 2003), Embase database (1980 ― 2000), Cochrane Library, CL( 1980 ―2004), CBMdisc( 1980 ― 2002), and IPA( 1980 ― 2002). Seven studies were chosen. Data werecombined by Revman 4.2. Results: The pooled effect of change in AER is - 56.31 μg·min^(-1)) [ -81.96, -30.66] (P<0.0001). According to the analysis of subgroups, the pooled effects of 1 - 5 yearsare - 11.97 μg·min^(-1)[-22.04, -1.89] (P = 0.02), -28.01 μg·min^(-1)[-34.50, -21.52](P<0.00001), -43.24 μg·min^(-1) [ -57.15, -29.32] (P< 0.00001), -61.65 μg·min^(-1)[77.77,-45.54] (P< 0.00001), and -98.41 μg·min^(-1)[-162.02,-34.79] (P = 0.002). Regarding progression toclinincal proteinuria as end-point, the pooled Peto OR =0.27 [0.18,0.40] (95% CI), P < 0.00001.According to the analysis of subgroups, the pooled effects of 2 and 5 years are Peto OR = 0.30[0.18,0.51] (P<0.00001) and Peto OR=0.25 [0.13, 0.50](P<0.0001). Publication bias is small.Conclusion In normotensive diabetic patients, ACEI inhibits AER effectively and reduces theprobability of progression of microalbuminuria to clinical proteinuria.

Effect of L158,809 and Cilazapril on the Expression of TGF-β_1 and Secretion of Extracellular Matrix Proteins in Cultured Human Mesangial Cells

Objective: To explore the effect of L158, 809 (angiatensin Ⅱ receptorMockers, ARBs) and Cilazapril (Angiotensin converting enzyme inhibitor, ACEI) on the expression oftransforming growth factor-β_1 (TGF-β_1) and secretion of fibronectin, laminin and type Ⅳcollagen from the cultured human mesangial cells . Methods: Human mesangial cells were cultured indifferent glucose (5.6 mmol/L and 30 mmol/L) and agents (1, 10, 100 and 500 μmol/L) concentrations. The proliferation of mesangial cells were detected at 24, 48 and 72 h . Then the mesangial cellsare divided into four groups, low glucose (5.6 mmol/L) control group, high glucose (30 mmol/L)control group , L158, 809 (10 μmol/L) group and cilazapril (10 μmol/L) group. Forty- eight hourslater, the expression of TGF-β_1 were detected by RT-PCR. Concentrations of TGF-β_1 ,fibronection, laminin and type Ⅳ collagen in the su-pematants of the, mesangial cells weredetermined by EUSA and radioimmunoassay methods. Results: Compared with low glucose control group,the mesangial cells under high glucose medium show excessive proliferation and more TGF-β_1,fibronectin, laminin and type Ⅳ collagen in the supernatant. The expression of TGF-β_1 mRNA wasalso significantly increased under high glucose. The levels of TGF-β_1 and ECM (extracellularmatrix) proteins in the L158, 809 group and cilazapril group are obviously lower than that of thehigh glucose control group. The expression of TGF-β_1 mRNA was markedly decreased in the L158, 809group and cilazapril group compared with that of high glucose control group . Conclusion: Highglucose stimulated the cultured human mesangial cells to excessively proliferate, express TGF-β_1and secrete ECM proteins, and the high glucose-indeced changes were suppressed by either L158, 809and cilazapril.

POLYMORPHISM OF ANGIOTENSIN CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Angiotensin converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness. Methods. A case control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0 05; odd ratio 4 98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P<0 05; odd ratio 3 8). Accordingly, the mean values of FEV 1% and FEV 1/FVC were higher in asthmatics carrying non DD alleles than patients with DD genotype (73 78% vs 56 56%, P<0 05; 79 19% vs 69 29%, P<0 05, respectively). Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.

Is NEDD4-1 a negative regulator of phosphatase and tensin homolog in gastric carcinogenesis?

The expression of phosphatase and tensin homolog (PTEN ), a tumor suppressor gene, is frequently downregulated in gastric carcinomas due to mutation, loss of heterozygosity, and promoter hypermethylation. However, it is unknown if additional mechanisms may account for the down-regulation of PTEN expression. While neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) is believed to be a potential dual regulator of PTEN, there are conflicting reports regarding their interaction. To gain further insight into the role of NEDD4-1 and its association with PTEN in gastric carcinoma development, we measured the protein expression of NEDD4-1 and PTEN in gastric mucosae with various pathological lesions and found that NEDD4-1 increased from normal gastric mucosa to intestinal metaplasia and decreased from dysplasia to gastric carcinoma. These changes did not correlate with PTEN expression changes during gastric carcinogenesis. Moreover, we found similar results in protein levels in the primary tumors and adjacent non-tumorous tissues. These results differ from a previous report showing that expression of NEDD4-1 is up-regulated in gastric carcinomas, and show a more complex pattern of NEDD4-1 gene expression during gastric carcinogenesis.

Management of non-variceal upper gastrointestinal tract hemorrhage:Controversies and areas of uncertainty

Upper gastrointestinal tract hemorrhage （UGIH） remains a common presentation requiring urgent evaluation and treatment. Accurate assessment, appropriate intervention and apt clinical skills are needed for proper management from time of presentation to discharge. The advent of pharmacologic acid suppression, endoscopic hemostatic techniques, and recognition of Helicobacter pylori as an etiologic agent in peptic ulcer disease （PUD） has revolutionized the treatment of UGIH. Despite this, acute UGIH still carries considerable rates of morbidity and mortality. This review aims to discuss current areas of uncertainty and controversy in the management of UGIH. Neoadjuvant proton pump inhibitor （PPI） therapy has become standard empiric treatment for UGIH given that PUD is the leading cause of non variceal UGIH, and PPIs are extremely effective at promoting ulcer healing. Howeve, neoadjuvant PPI administration has not been shown to affect hard clinical outcomes such as rebleeding or mortality. The optimal timing of upper endoscopy in UGIH is often debated. Upon completion of volume resuscitation and hemodynamic stabilization, upper endoscopy should be performed within 24 h in all patientswith evidence of UGIH for both diagnostic and therapeutic purposes. With rising healthcare cost paramount in today＇s medical landscape, the ability to appropriately triage UGIH patients is of increasing value. Upper en- doscopy in conjunction with the clinical scenario allows for accurate decision making concerning early discharge home in low risk lesions or admission for further moni toring and treatment in higher risk lesions. Concomitant pharmacotherapy with non steroidal antiinflammatory drugs （NSAIDs） and antiplatelet agents, such as clopidogrel, has a major impact on the etiology, severib/, and potential treatment of UGIH. Long term PPI use in patients taking chronic NSAIDs or clopidogrel is discussed thoroughly in this review.

Management of acute nonvariceal upper gastrointestinal bleeding:Current policies and future perspectives

Acute upper gastrointestinal bleeding(UGIB) is a gastroenterological emergency with a mortality of 6%-13%.The vast majority of these bleeds are due to peptic ulcers.Nonsteroidal anti-inflammatory drugs and Helicobacter pylori are the main risk factors for peptic ulcer disease.Endoscopy has become the mainstay for diagnosis and treatment of acute UGIB,and is recommended within 24 h of presentation.Proton pump inhibitor(PPI) administration before endoscopy can downstage the bleeding lesion and reduce the need for endoscopic therapy,but has no effect on rebleeding,mortality and need for surgery.Endoscopic therapy should be undertaken for ulcers with high-risk stigmata,to reduce the risk of rebleeding.This can be done with a variety of modalities.High-dose PPI administration after endoscopy can prevent rebleeding and reduce the need for further intervention and mortality,particularly in patients with high-risk stigmata.

Cardiovascular and cerebrovascular outcomes in elderly hypertensive patients treated with either ARB or ACEI

Background Although angiotensin converting enzyme inhibitors （ACEI） and angiotensin receptor blockers （ARB） are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue. Methods This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack. Results The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios （HR）： 2.124, 95% confidence interval （95% CI）： 1.048-4.306]. The Kaplan-Meier method also suggests that the rate of primary endpoint occurrence was higher in the ARB group than the ACEI group （P = 0.04）. In regard to the secondary endpoints, there were no significant differences between the two treatment arms （P = 0.137, HR： 1.454, 95% CI： 0.888-2.380）. Patient age and coronary heart disease history were independent predictors of the secondary endpoint. Conclusion ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension.

Depression discrimination using fMRI and DTI data by wavelet based fusion scheme

Both functional magnetic resonance imaging （fMRI） and diffusion tensor imaging （DTI） can provide different information of the human brain, so using the wavelet transform method can achieve a fusion of these two types of image data and can effectively improve the depression recognition accuracy. Multi-resolution wavelet decomposition is used to transform each type of images to the frequency domain in order to obtain the frequency components of the images. To each subject, decomposition components of two images are then added up separately according to their frequencies. The inverse discrete wavelet transform is used to reconstruct the fused images. After that, principal component analysis （PCA） is applied to reduce the dimension and obtain the features of the fusion data before classification. Based on the features of the fused images, an accuracy rate of 80. 95 % for depression recognition is achieved using a leave-one-out cross-validation test. It can be concluded that this wavelet fusion scheme has the ability to improve the current diagnosis of depression.

Inappropriate use of digoxin in patients presenting with digoxin toxicity

Background Digoxin remains widely used today despite its narrow therapeutic index and toxicity. The objective of this study was to investigate the percentage of inappropriate use of digoxin and long-term outcomes of elderly patients hospitalized for digoxin toxicity. Methods The study included 99 consecutive patients hospitalized for digoxin toxicity. The other study criteria for the inappropriate use of digoxin was regarded if participants having depressed left ventricular systolic function （ejection fraction 〈 45%） who were not on optimal medical therapy including beta-blocker and angiotensin-converting-enzyme inhibitor therapy or if participants having permanent AF who were not on optimal beta-blocker therapy. Results Appropriate digoxin usage was confirmed in 33 of patients in spite of its narrow therapeutic index. A total of 16 of 99 patients died, with a mean follow-up time of 22.1 ± 10.3 months. Conclusions Contrary to popular belief, the rate of inappropriate digoxin usage remains high. On account of its narrow therapeutic index and toxicity, digoxin should be used more carefully according to the current evidence and guidelines.

Purification and Characterization of Angiotensin I Converting Enzyme Inhibition Peptides from Sandworm Sipunculus nudus

Three angiotensin I converting enzyme(ACE) inhibition peptides were isolated from sandworm Sipunculus nudus protein hydrolysate prepared using protamex. Consecutive purification methods, including size exclusion chromatography and reverse-phase high performance liquid chromatography(RP-HPLC), were used to isolate the ACE inhibition peptides. The amino acid sequences of the peptides were identified as Ile-Asn-Asp, Val-Glu-Pro-Gly and Leu-Ala-Asp-Glu-Phe. The IC_(50) values of the purified peptides for ACE inhibition activity were 34.72 μmol L^(-1), 20.55 μmol L^(-1) and 22.77 μmol L^(-1), respectively. These results suggested that S. nudus proteins contain specific peptides that can be released by enzymatic hydrolysis. This study may provide an experimental basis for further systematic research, rational development and clinical utilization of sandworm resources.

A Meta-analysis of angitensin-converting enzyme inhibitors on normotensive early diabetic renal diseases

Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.

The impact of optimal medical therapy at discharge on mortality in patients with coronary artery disease

Objective To analyze the current usage of optimal medical therapy （OMT）, influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease （CAD） patients with different subgroups. Methods A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Results Out of 3176 patients, only 39.8% （n = 1265） were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% （n = 217） of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality （HR： 0.65, 95% CI： 0.45~0.95; P = 0.025）. Sub-group analyses indicate that male acute coronary syndrome （ACS） patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. Conclusions OMT was asso- ciated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.

CLINICAL OUTCOMES OF FIVE-YEAR FOLLOW-UP OF EARLY AND LONG-TERM TREATMENT WITH CAPTOPRIL ON THE PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Objective To investigate clinical outcomes of early and long-term treatment with captopril on patients with acute myocardial infarction (AMI) during a five-year follow-up. Methods In a randomi- zed trial, 822 patients (623 males, 199 females) with a first AMI with less 72h of symptoms were treated with captopril (treatment group, n=478, dosage from a first 6.25mg to 25mg t.i.d ) and conventional treatment (control group, n=344). Multivariable Cox’ regression were used to analyze relative risk of independent variables. Cumulative survival of both groups were calculated with Kaplan-Meier analysis and analyzed by using log-rank comparison. Results During the five-year follow-up, the age, Killip class (≥Ⅱ), anterior infarction, diabetes mellitus, and peak CPK increased relative risk of death after AML, but the effects of captopril, beta-blocker, antiplatelet drug, and thrombolytic therapy on the relative risk of death were contrary. The cumulative survival in different time during follow-up was higher in patients with captopril than controls (P< 0.001). Conclusion Early and long-term treatment with captopril was related to a beneficial outcome during the five-year follow-up after AMI.

Dynamic Positioning System Based on Active Disturbance Rejection Technology

A dynamically positioned vessel, by the International Maritime Organization （IMO） and the certifying class societies （DNV, ABS, LR, etc.）, is defined as a vessel that maintains its position and heading （fixed location or pre-determined track） exclu- sively by means of active thrusters. The development of control technology promotes the upgrading of dynamic positioning （DP） systems. Today there are two different DP systems solutions available on the market： DP system based on PID regulator and that based on model-based control. Both systems have limited disturbance rejection capability due to their design principle. In this paper, a new DP system solution is proposed based on Active Dis^n＇bance Rejection Control （ADRC） technology. This technology is com- posed of Tracking-Differentiator （TD）, Extended State Observer （ESO） and Nonlinear Feedback Combination. On one hand, both TD and ESO can act as filters and can be used in place of conventional filters; on the other hand, the total disturbance of the system can be estimated and compensated by ESO, which therefore enhances the system＇s disturbance rejection capability. This technology＇s advantages over other methods lie in two aspects： 1） This method itself can not only achieve control objectives but also filter noisy measurements without other specialized filters; 2） This method offers a new useful approach to suppress the ocean disturbance. The simulation results demonstrate the effectiveness of the proposed method.

Meeting the ADA Guidelines of Diabetic Care at King Fahd Hospital of University, Khobar, Eastern Province, Saudi Arabia in 2012

The main purpose of this study is determining the extent of achieving American Diabetes Association （ADA） targets in diabetes type I and II at KFUH （King Fahd Hospital of University） in the year of 2012. Observational, cross sectional, retrospective study was conducted on 479 patients; the informations were reviewed using Quadramed CPR system. All the data obtainedwere analyzed by medical statistician using SPSS program. The results show that only 19.0% was achieved the target of HbA~; and the targets of LDL, HDL and TG were achieved in 38.4%, 35.9%, and 48.2% respectively. The routine ophthalmology and dietitian review were found to be in only 32.1% and 27.3%, respectively. The use of medications recommended by ADA was 51.4% for aspirin and 54.7 % for both statin and ACE inhibitor. The present study indicated that most of the ADA guidelines were not achieved in our diabetic patients being followed in our center, which is almost similar to other studies in most of the parameters. The achievement of diabetes targets is a difficult task but may not be impossible. It requires a multidisciplinary approach. So, further studies are needed to determine the reasons behind the gap between practice and guidelines.

Changing the treatment of heart failure with reduced ejection fraction： clinical use of sacubitril-valsartan combination

Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor （ARNI） since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides （NPs）, bradykinin, endothelin and angiotensin II （Ang-II）. Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ （with opposite biological actions）. So, a combined inhibition of these both systems （Sacubitril / valsartan） may enhance the benefits of NPs effects in HF （natriuresis, diuresis, etc） while Ang-Ⅱ receptor is inhibited （reducing vasoconstriction and aldosterone release）. In a large clinical trial （PARADIGM-HF with 8442 patients）, this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF （compared to enalapril）. This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.

Somatostatin adjunctive therapy for non-variceal upper gastrointestinal rebleeding after endoscopic therapy

AIM:To evaluate the effect of pantoprazole with a somatostatin adjunct in patients with acute non-variceal upper gastrointestinal bleeding(NVUGIB).METHODS:We performed a retrospective analysis of a prospective database in a tertiary care university hospital.From October 2006 to October 2008,we enrolled 101 patients with NVUGIB that had a high-risk stigma on endoscopy.Within 24 h of hospital admission,all patients underwent endoscopic therapy.After successful endoscopic hemostasis,all patients received an 80-mg bolus of pantoprazole followed by continuous intravenous infusion(8 mg/h for 72 h).The somatostatin adjunct group(n=49)also received a 250-μg bolus of somatostatin,followed by continuous infusion (250μg/h for 72 h).Early rebleeding rates,disappearance of endoscopic stigma and risk factors associated with early rebleeding were examined.RESULTS:Early rebleeding rates were not significantly different between treatment groups(12.2%vs 14.3%,P=0.766).Disappearance of endoscopic stigma on the second endoscopy was not significantly different between treatment groups(94.2%vs 95.9%,P=0.696).Multivariate analysis showed that the complete Rockall score was a significant risk factor for early rebleeding(P =0.044,OR:9.080,95%CI:1.062-77.595).CONCLUSION:The adjunctive use of somatostatin was not superior to pantoprazole monotherapy after successful endoscopic hemostasis in patients with NVUGIB.

Effect of captopril or verapamil on intracellular sodium in cultured vascular smooth muscle cells

The effects of captopril (Cap) and verapamil (Ver)alone and in combination on intracellular Na+ concentration ([Na+]i) in cultured aortic smooth muscle cells (ASMC) of rabbits was evaluated by a direct measurement of [Na+]i with fluorescent dye sodium-binding benzofuran isophthalate (SBFI) combined with digital image. [Na+]i in resting cells was found to be 11.9 ± 0. 7 mmol/L. Angiotensin II (Ang-II, 0.1-10μmol/L) induced an increase of [Na+]i in concentration-dependent manner. Ver (0.1-10μmol/L) inhibited Ang-II (1 μmol/L)-induced increase in [Na+]i, while Cap enhanced Ang-II-induced increase in [Na+]i at 10μmol/L but not at 0.1-1μmol/L. Ver (0.1-1μmol/L)abolished enhancement of Ang-II-induced increase in [Na+]i by Cap. Thus, the inhibition of Capenhanced [Na+]i by Ver may provide a new hypothesis for the underlying molecular mechanism of synergistic effect of the combination of Ca2+ antagonists and angiotensinconverting enzyme inhibitors in controlling blood pressure.

A population-based case-crossover study of polyethylene glycol use and acute renal failure risk in the elderly

AIM:To evaluate the possibility of an association between polyethylene glycol(PEG) and acute renal failure(ARF) in elderly patients using a health insurance claims database.METHODS:We conducted a population-based casecrossover study using information obtained from Korean Health Insurance Review and Assessment Service(HIRA) claims from January 1,2005 to December 31,2005(Seoul,Korea).The study population consisted of elderly patients who received PEG prior to experiencing their first ARF-related hospitalization from April 1,2005 to December 31,2005.For each patient,one case and two control periods were matched.PEG use in a 2-or 4-wk window period prior to hospitalization for ARF was compared with PEG use in two earlier 2-or 4-wk control window periods.Conditional logistic regression analysis was used to estimate odds ratios(ORs) and 95% CI,adjusting for concomitant uses of diuretics,angiotensin converting enzyme inhibitors,non-steroidal anti-inflammatory drugs,antibiotics,anti-cancer drugs,and contrast media.RESULTS:Within the HIRA database which contained 1 093 262 elderly patients,1156 hospitalized ARF cases were identified.Among these cases,PEG was prescribed to 17(1.5%) patients before hospitalization.The adjusted ORs when applying the 2-and 4-wk window periods were 0.4(95% CI:0.03-5.24) and 2.1(95% CI:0.16-27.78),respectively.CONCLUSION:No increased risk of ARF was found in elderly PEG users.However,based on the limited number of study subjects,further analysis should be performed to confirm these results.

In vitro effect of pantoprazole on lower esophageal sphincter tone in rats

AIM:To investigate the in vitro effects of pantoprazole on rat lower esophageal sphincter(LES)tone.METHODS:Rats weighing 250-300 g,provided by the Yeditepe University Experimental Research Center(Yü-DETAM),were used throughout the study.They were anesthetized before decapitation.LES tissues whose mucosal lining were removed were placed in a stan-dard 30-mL organ bath with a modif ied Krebs solution and continuously aerated with 95% oxygen-5% carbon dioxide gas mixture and kept at room temperature.The tissues were allowed to stabilize for 60 min.Sub-sequently,the contractile response to 10-6 mol/L carba-chol was obtained.Different concentrations of freshly prepared pantoprazole were added directly to the tis-sue bath to generate cumulative concentrations of 5×10-6 mol/L,5×10-5 mol/L,and 1.5×10-4 mol/L.Activi-ties were recorded on an online computer via a 4-channeltransducer data acquisition system using the software BSL PRO v 3.7,which also analyzed the data.RESULTS:Pantoprazole at 5×10-6 mol/L caused a small,but statistically insignif icant,relaxation in the car-bachol-contracted LES(2.23% vs 3.95%).The 5×10-5 mol/L concentration,however,caused a signif icant relax-ation of 10.47% compared with the control.1.5×10-4 mol/L concentration of pantoprazol caused a 19.89% relaxation in the carbachol contracted LES(P<0.001).CONCLUSION:This is the fi rst study to demonstrate that pantoprazole has a relaxing effect in isolated LESs.These results might have signif icant clinical implications for the subset of patients using proton pump inhibitors who do not receive full symptomatic alleviation from gastroesophageal reflux disease.