Proton Pump Inhibitors Intake Research Articles

Analysis of Possible Correlation with Associated Conditions of Patients with Gastric Fundic Gland Polyp

Gastric polyps are lesions that are often evaluated by the endoscopist. Among them incidence of Fundic gland polyp (FGP) showing an increasing pattern these days due to various associated conditions like long-term proton pump inhibitor (PPI) therapy. This study was designed to evaluate the conditions that were associated with the presentation of FGP including PPI therapy of ≥ 6 month. Our study concluded with a high incidence of 14% longterm PPI intake of ≥ 6 month among the patients presented with FGP. Beside that a high female predominance, potent association with gastritis and negative Helicobacter Pylori status, Personal habits like Smoking and alcohol intake also appeared as an important factor associated with FGP. Our current findings can serve as an assistance to evaluate associated conditions like FGP in patients with PPI intake of 6 month or more presenting with features of gastritis irrespective of HP status and give a high concentration on personal habit modification like alcohol and smoking in the treatment of FGP patients.

Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort)

ObjectiveTo assess incidence and prognostic significance of bacterial infections (BIs) occurring in compensated viral cirrhosis.DesignThis prospective study involved 35 French centres. Inclusion criteria were biopsy-proven HCV or HBV cirrhosis, Child–Pugh...

Low Prevalence of Hypomagnesemia in Long-term Recipients of Proton Pump Inhibitors in a Managed Care Cohort.

Chronic intake of proton pump inhibitors (PPI) has been associated with hypomagnesemia, but prevalence of PPI-associated hypomagnesemia is not known. We examined the prevalence of hypomagnesemia among long-term PPI recipients by using a large health maintenance organization database. We collected data on 10,167 participants eligible for chronic drug prescriptions from 2008 through 2013. Adult subjects receiving continuous PPI therapy for ≥ 6 months between 2008 and 2013 and ≥ 1 serum magnesium determination(s) were identified. Patients with any magnesium levels less than 1.6 mg/dL were selected for analysis; those with recognizable causes of altered magnesium homeostasis were excluded. Five hundred ninety participants received long-term PPIs, and 414 (70.2%) met the inclusion criteria for a total exposure of 2293 PPI-years (average, 5.7 years/subject). Of these patients, 57 (13.8%) had ≥ 1 low serum magnesium; 5 were no longer on PPIs, and 44 had other recognizable causes for hypomagnesemia (25 receiving diuretics, 8 with chronic diarrhea, 8 with chronic kidney disease, and 3 with malignancies). Of the 8 remaining patients (7 female; mean age, 71.2 ± 13.4 years; mean daily medications, 5.4 ± 1.1), mild hypomagnesemia (range, 1.2-1.5 mg/dL) was noted in 13.9% of 289 measurements. All 8 patients had normal serum levels of magnesium at their final measurement. In the absence of known precipitating factors, chronic PPI use does not appear to be associated with hypomagnesemia.

Diagnostic methods for H. pylori infection: Choices, opportunities and pitfalls.

Diagnostic methods for H. pylori infection: Choices, opportunities and pitfalls.

Gastric neuroendocrine neoplasms and proton pump inhibitors: fact or coincidence?

Objective. Reporting on three cases of gastric neuroendocrine tumors (g-NETs) in patients taking long-term proton pump inhibitors (PPIs). These tumors are not classifiable considering current criteria. g-NETs are currently grouped as: types 1 and 2, related to hypergastrinemia due to chronic atrophic gastritis and Zollinger-Ellison syndrome respectively, and type 3, normogastrinemic and more aggressive. Although the g-NETs onset in patients taking PPIs is biologically plausible, only a few cases have been reported so far. Materials and methods. From January 2005 to July 2014, 31 g-NETs were referred to our Unit: 24 (77%), one (3%) and three (10%) resulted types 1, 2 and 3, respectively. Three cases (10%) did not meet the current classification criteria. Results. The three patients were administered long-term PPIs for gastro-esophageal reflux disease. Patient 1: a 78-year-old man, with a 4-mm well-differentiated g-NET (Ki-67<1%) and marked hypergastrinemia. Patient 2: a 58-year-old man affected by a 6-mm well-differentiated (Ki-67 = 4%) g-NET, with normal gastrin levels. Patients 3: a 67-year-old woman with an 18-mm well-differentiated g-NET (Ki-67 <2%), with mild hypergastrinemia. In the three patients, histology and pertinent blood tests excluded chronic atrophic gastritis, Helicobacter pylori infection or Zollinger-Ellison syndrome. The first two patients underwent endoscopic polypectomy; in the third case total gastrectomy was performed. Further clinical, endoscopic and imaging follow-up did not show any g-NET recurrence. Conclusions.The present data point to the existence and epidemiological relevance of g-NETs associated with PPIs intake. These neoplasms are not included in the current classification, thus their treatment and follow-up have not been established.

The influence of lidocaine topical anesthesia during transesophageal echocardiography on blood methemoglobin level and risk of methemoglobinemia.

Methemoglobinemia is a relatively rare, but potentially life-threating medical condition, which may be induced by application of topical anaesthetic agents commonly used during endoscopic procedure. The aim of our study was to assess the influence of lidocaine used prior to transesophageal echocardiography (TEE) on the blood level of methemoglobin in vivo. Additionally we attempted to establish the occurrence rate of clinically evident lidocaine-induced methemoglobinemia on the basis of data collected in our institution. We retrospectively analyzed patient records from 3,354 TEEs performed in our echocardiographic laboratory over the course of 13 years in search for clinically evident methemoglobinemia cases. Additionally, 18 consecutive patients referred for TEE were included in the prospective part of our analysis. Blood samples were tested before and 60 min after pre-TEE lidocaine anesthesia application. Information concerning concomitant conditions and pharmacotherapy were also obtained. In 3,354 patients who underwent TEE in our institution no cases of clinically evident methemoglobinemia occurred. In the prospective part of the study, none of 18 patients [16 (89 %) men, mean age 63 ± 13] was diagnosed with either clinical symptoms of methemoglobinemia or exceeded normal blood concentration of methemoglobin. Initial mean methemoglobin level was 0.5 ± 0.1 % with mild, statistically (but not clinically) significant rise to 0.6 ± 0.1 % after 60 min (p = 0.02). Among the analyzed factors only the relation between the proton pump inhibitors intake and methemoglobin blood level rise was identified as statistically relevant (p = 0.03). In adults, pre-TEE lidocaine anesthesia with recommended dosage results in significant increase in methemoglobin blood level, which however does not exceed normal values and does not result in clinically evident methemoglobinemia.

Opportunistic Screening of Vitamin B12 Deficiency in IT Professionals Presenting for Routine Health Check-up.

Vitamin B12 deficiency is mainly diagnosed in symptomatic patients. However, the deficiency may also be prevalent in asymptomatic patients. Our aim was to study the prevalence of Vit B12 deficiency in IT professionals (Information Technology Professionals from Software industry) who presented for routine health screening and to correlate the deficiency to various parameters. This was single centre, observational study comprising of 84 IT professionals. The data was collected in structured format. The study was designed to identify prevalence of Vit B12 deficiency and correlate to other factors such as type of diet, income level & regular use of medication (such as Antacid & Metformin). Total 28 individuals were found to be deficient (33.34%). Prevalence of Vit B12 deficiency amongst Vegetarian and non vegetarian diet adhering subjects was 47.5% and 20.45% respectively. B12 deficiency was also prevalent in high income age group. Further chronic intake of PPI (Proton pump inhibitor) and Metformin was associated with prevalence of 37.5% and 33.34% in the present study. During health screening of IT Professionals, significant prevalence of Vit B12 deficiency was noted across all income groups & non vegetarian diet consuming subjects also. There is significant correlation between Vit B12 deficiency with chronic use of PPI and Metformin.

Elevated Serum anti-Helicobacter pylori IgG Levels is a Predictor of Successful Eradication Therapy

AIM : To identify a predictor of successful primary Helicobacter pylori ( H. pylori ) eradication assessed in routine clinical practice. METHODS : From February 2013 to January 2015, 186 patients underwent primary eradication therapy. We retrospectively reviewed the medical records. All patients underwent EGD before eradication therapy and H. pylori infection was diagnosed by ≥10 U/ml serum anti- H. pylori IgG. We used standard triple therapy including a proton pump inhibitor (PPI) (rabeprazole 10 mg or lansoprazole 30 mg), clarithromycin 200 mg and amoxicillin 750 mg twice daily for seven days. To determine if eradication succeeded, a 13 C-urea breath test was performed on all patients more than eight weeks after primary eradication. RESULTS : The overall success rate of H. pylori eradication therapy was 62% (116/186). We assessed potential predictors of successful primary H. pylori eradication therapy including gender, age, smoking habits, prior PPI intake, kind of PPI, serum IgG value and degree of atrophy. Univariate analysis showed that high serum IgG significantly predicts successful eradication (odds ratio (OR) 2.583, 95% confidence interval (CI) 1.285-5.191, p = 0.008). The eradication rate was 77% (43/56) in the ≥45 U/ml group and 56% (73/130) in the <45 U/ml group, and significance was confirmed by multivariate analysis (OR 2.626, 95% CI 1.269-5.436, p = 0.009). Multivariate analysis showed a trend that advanced age (≥70 year-old) increased the rate of successful eradication (OR 1.669, 95% CI 0.857-3.252, p = 0.132). CONCLUSION : Elevated serum IgG significantly predicts successful primary H. pylori eradication.

Proton pump inhibitor intake neither predisposes to spontaneous bacterial peritonitis or other infections nor increases mortality in patients with cirrhosis and ascites.

Background and AimThe aim of this study was to assess the impact of proton pump inhibitor (PPI) intake on the development of spontaneous bacterial peritonitis (SBP) or other infections, as well as on mortality, in a thoroughly documented cohort of patients with cirrhosis and ascites.Patients and MethodsWe performed a retrospective analysis of follow-up data from 607 consecutive patients with cirrhosis undergoing their first paracentesis at a tertiary center. A binary logistic regression model investigating the association between PPI intake and SBP at the first paracentesis was calculated. Competing risk analyses and Cox models were used to investigate the effect of PPIs on the cumulative incidence of SBP or other infections and transplant-free survival, respectively. Adjustments were made for age, hepatocellular carcinoma, history of variceal bleeding, varices and model of end-stage liver disease score.ResultsEighty-six percent of patients were receiving PPIs. After adjusting for potential confounding factors, PPI intake was neither associated with increased SBP prevalence at the first paracentesis (odds ratio (OR):1.11,95% confidence interval (95%CI):0.6–2.06; P = 0.731) nor cumulative incidence of SBP (subdistribution hazard ratio (SHR): 1.38; 95%CI:0.63–3.01; P = 0.42) and SBP or other infections (SHR:1.71; 95%CI:0.85–3.44; P = 0.13) during follow-up. Moreover, PPI intake had no impact on transplant-free survival in both the overall cohort (hazard ratio (HR):0.973,95%CI:0.719–1.317; P = 0.859) as well as in the subgroups of patients without SBP (HR:1.01,95%CI:0.72–1.42; P = 0.971) and without SBP or other infections at the first paracentesis (HR:0.944,95%CI:0.668–1.334; P = 0.742).ConclusionsThe proportion of cirrhotic patients with PPI intake was higher than in previous reports, suggesting that PPI indications were interpreted liberally. In our cohort with a particularly high prevalence of PPI intake, we observed no association between PPIs and SBP or other infections, as well as mortality. Thus, the severity of liver disease and other factors, rather than PPI treatment per se may predispose for infectious complications.

Patient-reported adherence to coprescribed proton pump inhibitor gastroprotection in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis patients using nonsteroidal anti-inflammatory drugs.

BackgroundPatients with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) are commonly treated with nonsteroidal anti-inflammatory drugs (NSAIDs), sometimes with a concomitant gastroprotective proton pump inhibitor (PPI). The present study examines real-life patient adherence to PPIs when coprescribed with NSAIDs.MethodsThis retrospective medical record survey identified patients diagnosed with OA, RA, or AS who had PPIs coprescribed with NSAIDs for prevention of NSAID-associated gastrointestinal ulcers. Actual NSAID and PPI intake was retrospectively recorded using a self-reported questionnaire. Adherence to PPI treatment was assessed using descriptive statistics.ResultsIn total, 96 patients (69% female, mean age 67 years, 72% OA, 16% RA, 12% AS) were included. The mean patient-reported adherence to coprescribed PPIs was 73%–81%. The percentage of patients with a self-reported adherence of ≤80% was 26%. No predictive factors for low adherence could be identified.ConclusionDespite doctors’ instructions to use PPIs concomitantly with NSAIDs, the mean patient-reported adherence to coprescribed PPIs in this population indicates a risk of a “gastroprotective treatment gap”. The patients’ adherence to gastroprotective PPIs for the prevention of NSAID-associated upper gastrointestinal ulcers can be improved.

Relative risk factors associated with the development of fundic gland polyps.

The prevalence of fundic gland polyps (FGPs) is increasing. Some researchers consider this increase to be associated strongly with the long-term use of proton-pump inhibitors (PPIs); however, not all researchers share this belief. There are minimal data on the development of FGPs in China. Therefore, we aimed to investigate the prevalence of FGPs and risk factors associated with the development of this disease. We studied 10 904 consecutive patients who underwent gastroduodenal endoscopies at our digestive endoscopy center between February 2011 and January 2013. Information on sex, age, Helicobacter pylori infection, PPIs intake, and the pathological results of the polyps were collected in the FGPs group and in the control group. The use of PPIs, sex, and H. pylori infection were statistically evaluated as dichotomous variables using a χ-test; age was evaluated as a continuous variable using a t-test. Finally, these factors were evaluated using a multiple logistic regression analysis. Gastric polyps were found in 759 (7.0%) patients, and 213 (2.0%) of these patients had FGPs. FGPs accounted for 28.1% of the gastric polyps. In the FGPs group, the percentage of H. pylori infection was 66.8% and the percentage of PPIs intake for at least 12 months was 23.1%. In the control group, the percentage of H. pylori infection was 77.4% and the percentage of PPIs intake for at least 12 months was 2.3%. The difference in the long-term use of PPIs was statistically significant between these two groups [χ=33.98, P<0.05, odds ratio (OR)=12.83, 95% confidence interval (CI): 4.47-36.80]. The results of the logistic regression were as follows: long-term use of PPIs (P<0.01, OR=14.11, 95% CI: 4.15-47.93); age (P<0.01, OR=1.69, 95% CI: 1.31-2.18). The P-values for sex and H. pylori infection were higher than 0.05. Age and the long-term use of PPIs were risk factors for the presence of FGPs; the long-term use of PPIs was a particularly strong risk factor.

Indirect evidence for proton pump inhibitor failure in patients taking them independent of meals.

We investigated the association between conditions of proton pump inhibitor (PPI) treatment failure and food intake in an elderly ambulatory population. Our data originate from a large population-based cohort study. During a home visit done by a trained study physician, patients were asked for each medication to state whether it was taken in relation to a meal (before, concurrently with, and after) or independent of a meal. This information was analyzed for all patients taking a PPI daily and correlated to markers of PPI failure. Out of 2717 patients participating in a home visit and taking at least one medication, 383 took a PPI daily (14.1%). A PPI intake independent of meals was defined as incorrect and was observed in 64 patients, whereas 319 patients took their PPI in relation to a meal, which was defined as the correct intake. Treatment failure was observed in 10 out of 64 (15.6%) PPI users with incorrect intake and in 18 out of 319 (5.6%) PPI users with correct intake. The risk of treatment failure was threefold higher in patients taking their PPI independent of meals (OR 3.35; 95%CI 1.44-7.76). The higher risk for PPI failure in patients taking PPIs independent of meals suggests that synchronized PPI administration with meals is indeed essential, and better counseling of patients is needed.

Proton pump inhibitors for reflux therapy in infants: effectiveness determined by impedance pH monitoring

To evaluate the influence of proton pump inhibitors (PPI) in predominantly milk-fed infants with symptoms of GERD by 24-h pH-multichannel intraluminal impedance (24-h pH-MII). Ten infants (8 males and 2 females) with a mean gestational age of 39 weeks (28-40) were included. 24-h pH-MII was performed before prescription and during intake of PPI. Total acid exposure time, bolus exposure time (acidic/non-acidic/total) and the number of refluxes (acidic/non-acidic/total) were determined. Clinical symptoms were recorded and used to calculate the Reflux Symptom Index (RSI) and the Symptom Severity Index (SSI). There was a significant decrease in the number of acidic refluxes, total acid exposure and acidic bolus exposure time. However, this went along with a significant increase in non-acidic bolus exposure time. The total number of refluxes and the total bolus exposure time remained unchanged. Under PPI, a decrease of SSI and RSI for pain-related symptoms could be observed. For respiratory symptoms and vomiting however no significant changes could be demonstrated. Under PPI, an improvement of pain-related symptoms could be shown. The decrease of acid exposure went along with an increase of non-acidic refluxes resulting in almost constant total reflux numbers. This finding is interpreted as main reason for some persisting symptoms despite adequate PPI dosage. Concluding from our data PPI therapy should only be indicated in case of pain, but has no effect in case of vomiting or recurrent respiratory symptoms.

The risks of long-term proton pump inhibitors use

To explore the risks of long-term proton pump inhibitors (PPI) use. A total of 79 study subjects were selected from patients seeking health care at outpatient gastroenterology clinic at Peking University People's Hospital during January 2011 to June 2013. Long-term PPI use was defined as taking PPI for at least one year. They were divided into study (n = 79) and control (n = 47) groups after matching for age and gender. The study group had 43 females and 36 males with an average age of (63 ± 10) years. And the control group had 28 females and 19 males with an average age of (63 ± 9) years. Data collected were demographic characteristics, clinical diagnosis, detailed dosing information of PPI. serum hemochrome, serum gastrin, vitamin B(12), serum iron, magnesium, calcium, copper, zinc, bone density of hip joint and lumbar vertebra L(1-4). Statistic analysis was performed with SPSS software (t and χ(2) test). The medium duration of PPI use was 3.07(1-15) years. Daily usage was a full or half amount of pharmaceutical directed dosage. Questionnaires regarding appetite, defecation, infection, otalgia change in long-term PPI use indicated:among them, 77(97.5%) cases had no appetite change and 2 (2.5%) improved. And 73 cases (92.4%) had no change or 2 cases improved (2.5%) in bowel movements habits while another 4 cases (5.1%) changed into loose stools. Lung or intestinal infection was not found. No case had an onset of otalgia related with PPI intake. Among PPI users, 14 cases (17.7%) appeared to have gastric polyps. T value of total bone density of hip and inter-hip was -0.93 ± 1.04 and -0.61 ± 0.91 respectively in the study group. And both were lower than those in the control group (-0.44 ± 1.12, -0.19 ± 0.94; t = -2.49, -2.35; P = 0.014, 0.021). No statistical differences existed in T value of neck of hip, as well as total T value and T value of each L(1-4) between study and control groups (all P > 0.05). Higher serum Mg compared to control group ((1.03 ± 0.08) vs (0.97 ± 0.07) mmol/L, t = 4.13, P = 0.000). No difference of serum calcium, copper, iron, zinc, vitamin B(12), folic acid and Hb,MCV,MCH between study and control groups (all P > 0.05). Higher serum gastrin versus normal range and controls were found in the study group ((108 ± 28) vs 100 vs (79 ± 26) ng/L, t = 2.56, 5.78; both P < 0.05). Taking manual routine dosage have higher hip and lumbar osteoporosis than half-dosage, and bone density decreased and normal bone density ratios are lower(all P < 0.05). Long-term use of PPI with small or average dosage may slightly decrease hip density and increase serum gastrin. However, there is little effect on vitamin B(12) and minerals.

Validation study of the Esohisto consensus guidelines for the recognition of microscopic esophagitis (histoGERD Trial).

In patients with gastroesophageal reflux disease (GERD), histology is generally believed to be a tool of limited diagnostic value. Our study aimed to assess the prevalence of microscopic esophageal lesions as defined by the Esohisto consensus guidelines, which have proven high interobserver agreement in previous studies. In the prospective Central European multicenter histoGERD trial, we recruited 1071 individuals (576 females and 495 males; median age, 53 years; range, 15-93 years) undergoing gastroscopy for nonselected reasons. Biopsy material was systematically sampled from above and below the gastroesophageal junction. Overall, histologic diagnosis of mild and severe esophagitis was made in 423 (39.5%) and 296 (27.6%) individuals, respectively, whereas the squamous mucosa of 352 individuals (32.9%) was normal upon histology or showed only insignificant findings. Proliferative changes of the squamous epithelium, in particular basal cell layer hyperplasia, papillary elongation, and intercellular space dilation, were more common than inflammatory cell infiltration. The presence of microscopic esophagitis was associated with male sex (P = .009), patients' symptoms (P = .003), history of proton pump inhibitor intake (P < .001), and the endoscopic diagnosis of esophagitis (P < .001). Notably, among the 450 patients with no endoscopic signs of esophagitis (Los Angeles Category N), 41.8% and 17.1% were identified with mild and severe (microscopic) esophagitis, respectively, indicating higher sensitivity of histologic diagnosis. In conclusion, our data illustrate the value of histology in the workup of patients with reflux disease. We suggest that biopsies should routinely be obtained when patients undergo upper gastrointestinal endoscopy for evaluation of GERD and may particularly be beneficial in patients with nonerosive reflux disease.

Correlation between Specific Bacterial Groups in the Oral Cavity and the Severity of Halitosis: Any Possible Beneficial Role for Selected Lactobacilli?

Objective: Halitosis is a widespread problem, normally attributable to specific volatile sulphur compounds (VSC) in the breath. The aim of this study was to first relate halitosis with possible gastric infection by Helicobacter pylori and secondly to quantify specific bacterial groups in the oral cavity flora, thus correlating them with VSC concentrations and Proton Pump Inhibitors (PPIs) intake. Four selected lactobacilli were then assessed in the possible reduction of halitosis in subjects with a total salivary bacterial concentration higher than 105 CFU/ml. Methods: Specific bacterial groups, namely total bacteria, total coliforms, sulphite-reducing bacteria (SRB) and lactobacilli, were quantified in samples of saliva from 29 subjects taking PPIs compared with 36 control subjects. The amount of the three VSC hydrogen sulfide (H2S), methyl mercaptan (CH3SH) and dimethyl sulfide (CH3)2S in the breath and the presence of H. pylori were determined. Results: No significant correlation was found between H. pylori and halitosis as well as with PPIs intake. The baseline bacterial groups quantification (log10 CFU/ml of saliva, PPI group vs. control) showed: total bacteria 8.44 vs. 4.47 (p=0.001); total coliforms 4.95 vs. 2.82 (p=0.001); sulfite-reducing bacteria 5.47 vs. 2.58 (p=0.052); total lactobacilli 4.00 vs. 2.36 (p=0.016). After 15 days of lactobacilli supplementation, the same parameters (d15 vs baseline) gave: total bacteria 7.92 vs. 8.44 (p=0.019); total coliforms 3.13 vs. 4.95 (p=0.001); sulfite-reducing bacteria 4.69 vs. 5.47 (p=0.047); total lactobacilli 7.86 vs. 4.00 (p=0.048). No statistically significant differences were noted in VSC concentrations at any time. Conclusions: The intake of PPIs directly correlated with the overgrowth of specific bacterial groups in the oral cavity, but there was no correlation with H. pylori or with VSC concentration. The significant reduction in all the bacterial groups analysed after two weeks suggested the improvement of the overall oral flora in subjects chronically treated with PPIs.

Eosinophilic esophagitis in Egyptian adult patients presenting with upper gastrointestinal symptoms

Background and Study Aim: Eosinophilic esophagitis (EoE) is a clinicopathological disease characterized by esophageal dysfunction and marked esophageal eosinophilic infiltration. It shows a marked increase in incidence and prevalence and has been associated with gastroesophageal reflux disease (GERD). The aim of this work was to detect the prevalence of EoE in Egyptian adult patients presenting with upper gastrointestinal symptoms and to clarify its clinical pattern and the possibility of its overlap with GERD. Patients and Methods: The study included 91 adult patients presenting with various upper gastrointestinal symptoms. Upper gastrointestinal endoscopy was done and esophageal biopsies were taken. The presence of >15 eosinophils per high power field together with a history of intake of proton pump inhibitors for at least 3 weeks without improvement was used as prerequisite diagnostic criteria for EoE. Results: Classification of the patients was based on both endoscopic and histo-pathological findings. Accordingly, out of the 91 patients, 70 had GERD (76.9%); 58 of them had erosive reflux disease (ERD) and 12 had endoscopically normal esophagus but with histopathological changes compatible with reflux esophagitis and were classified as non erosive reflux disease (NERD). Eighteen patients had normal endoscopic and histopathological esophagus (19.8%), and 3 patients had EoE (3.3%), with an overlap between ERD and EoE in one patient. The mean age of EoE patients was 41.6 ± 11.7 years. Two of them were males and one was a female. All of the 3 patients complained of dysphagia and none complained of heartburn. The endoscopists did not report any endoscopic findings characteristic of EoE. Conclusion: The prevalence of EoE is low in adult Egyptian patients presenting with upper gastrointestinal symptoms. Dysphagia is the main presenting symptom of EoE while heartburn is not characteristic of the disease. Normal esophagus endoscopically does not exclude EoE.

Gut neuroendocrine tumor blood qPCR fingerprint assay: characteristics and reproducibility

We have developed a PCR-based tool that measures a 51-gene panel for identification of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) in peripheral blood. This manuscript assesses the robustness (performance metrics) of this tool with a specific focus on the effects of individual parameters including collection, storage, acid suppressive medication [proton pump inhibitor (PPI)], age, sex, race and food on accuracy. Performance metrics were evaluated using a gold standard (mRNA derived from three individual human neuroendocrine tumor cell lines) and clinical samples using qPCR. One hundred percent of the 51 transcripts were amplified in the gold standard (NEN cell line-derived mRNA) (CQ<35, average efficiency 1.94). The inter- and intra-assay variations were 1%-2%. In clinical samples, 50 of 51 targets (98%) were amplified. The inter- and intra-assay reproducibility ranged between 0.4% and 1.2%. The coefficient of variation (CV) was 5.3%. Expression of the reference gene, ALG9, was robust [low variation, low M-value, high (99.5%) PCR efficiency] and unaffected by sample processing. Test meals, long-term PPI use (>1 year), age, sex and ethnicity had no effect on the signature. Expression of two genes, ALP2 and CD59 correlated strongly with RNA integrity (R=0.72, p<0.001) and could be used to assess storage and processing. The 51 marker gene signature was robust and reproducible, exhibiting acceptable inter- and intra-assay metrics (<5%). Feeding, PPI intake, age, sex and ethnicity do not affect the signature. Expression levels of APLP2 and CD59 are effective surrogate markers of proper sample collection and processing.

Impact of the proton pump inhibitors and CYP2C19*2 polymorphism on platelet response to clopidogrel as assessed by four platelet function assays

Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel's antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome. We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period. Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p=0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events. PPI co-administration did not influence clopidogrel's antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay.

The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats

Recent studies revealed that long-term intake of proton pump inhibitor (PPI) increases the risk of vertebral or hip fracture; however, the exact mechanism for this is not known. To evaluate the effect of long-term PPI therapy on bone turnover, we analyzed the signaling pathway involved in osteoclast differentiation and bone resorption/formation markers using ovariectomized rats. Six-week-old Sprague-Dawley (S-D) rats were ovariectomized, and two weeks later they were divided into four groups (group A, normal diet + placebo; group B, low calcium diet + placebo; group C, normal diet + PPI; and group D, low calcium diet + PPI). Omeprazole, at a concentration of 30 mg/kg, was administered orally for eight weeks and the rats were sacrificed when they were 16 weeks old. The relative expression levels of the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio, c-Fos, nuclear factor of activated T cells c1 (NFATc1) and osteocalcin in femoral bone marrow cells were compared, and serum C-terminal cross-linking telopeptide of type I (CTX-1) levels were determined. The relative ratio of RANKL/OPG was increased in group D, and gene expression levels of c-Fos and NFATc1 were upregulated in groups B and D, which are involved in differentiation and activation of osteoclasts. Furthermore, expression levels of osteocalcin, a bone formation marker, were decreased and levels of serum CTX-1, a bone resorption marker, were increased in group D. Taken together, a low calcium diet and PPI administration are thought to collaborate in order to alter osteoclast activity and bone resorption signaling.