Prolonged Proton Pump Inhibitor Therapy Research Articles

Proton pump inhibitor (PPI) administration and Clostridioides difficile infection - is this a real clinical problem? A critical review of the literature

Background: Proton pump inhibitors (PPIs) are widely used drugs that reduce gastric acid secretion. In recent years, there has been a gradual increase in their use. The safety of prolonged PPI therapy and the potential for cumulative side effects of these drugs raise legitimate concerns. An association between PPI administration and the risk of Clostridioides difficile infection has been suggested. The findings regarding this phenomenon require further unequivocal verification.
 Material and methods: A review of publications obtained from the PubMed database and published between 2016-2023. Based on the keywords "proton pump inhibitor", "PPI" and "Clostridium", 132 articles were selected. Finally, 6 meta-analyses were included in the analysis.
 Results: Studies conducted in recent years have shown a statistically significant increase in the risk of C. difficile infection in patients taking PPIs compared to those who avoid this therapy. The aforementioned relationship was observed in both adults and pediatric patients. One study proved that the risk remained high even up to 1 year after the end of treatment. The described relationship is still a matter of debate due to the fact that patients using antacids are usually elderly, have several comorbidities and a higher risk of developing C. difficile infection regardless of PPI use.
 Conclusions: The relationship between the use of PPIs and the risk of developing C. difficile infection is still controversial, which justifies the need for continued clinical trials to objectively resolve this issue. PPIs exert high efficacy in the treatment of acid-dependent diseases, but due to the many ambiguities surrounding possible side effects, caution in their administration seems warranted, especially for long-term therapy in elderly patients with polypharmacy.

Effects of prolonged proton pump inhibitor treatment on nutritional status and respiratory infection risk in cystic fibrosis: A matched cohort study.

Evidence on the effectiveness of proton pump inhibitors (PPI) as adjuvant therapy to improve maldigestion in people with cystic fibrosis (pwCF) is limited and there is increasing concern on possible side effects. We conducted a matched cohort study based on paediatric and adult pwCF who received PPI for ≥3 months. Treated patients were matched to a group of patients who never received PPI using a nearest neighbour propensity score matching based on sex, year of birth, CFTR genotype and pancreatic insufficiency. The study included 160 pwCF: 80 treated and 80 untreated patients. Over a median follow-up of 2 years, no significant differences in changes in BMI z-score were detected between groups (adjusted mean difference: 0.06, 95% CI: -0.17-0.30). At baseline 25% (n=20) of the treated patients and 22.5% (n=18) of the untreated patients had a positive culture for P. aeruginosa (Pa). At follow-up percentages of Pa positive cultures increased to 47.5% (n=38) in the treated group and to 26.3% (n=21) in the untreated group (adjusted mean difference: 23.1%, 95% CI: 10.8-35.3). Prolonged PPI therapy should be used cautiously in pwCF since it may increase the risk of respiratory infection by Pa. In addition, such treatment does not seem to improve nutritional status.

Drawbacks of the Current Algorithm for Patients With Symptoms of Gastroesophageal Reflux Disease and the Impact of Adding Wireless pH Study to the Initial Diagnostic Endoscopy: Data From High-Volume Rural Antireflux Center.

Patients with symptoms of gastroesophageal reflux disease (GERD) are often given a trial of proton pump inhibitors (PPIs). When they respond, patients usually continue PPI therapy. If this empiric treatment fails, esophagogastroduodenoscopy (EGD) is recommended. When EGD findings are equivocal, pH study is warranted. We hypothesize that this algorithm results in prolonged PPI therapy, repetition of EGDs and patient dissatisfaction. This study evaluates the impact of placing a pH probe at the time of the initial EGD. IRB approval was obtained for retrospective chart review of patients who presented with GERD symptoms between August 2015 and March 2019. Patients were included if they underwent EGD with placement of wireless pH probe. A total of 379 patients (260 females, 119 males) with average age was 56.7±14.2 years. There were 253/379 (66.7%) patients who had previous EGDs (1-10). Health Satisfaction Survey was completed by 357/379 (94.2%) patients and 250/357 (70%) reported dissatisfaction with GERD control. PPI use was noted in 299/379 (78.8%) patients with average duration of 10.9±9.1 years. Testing off antisecretory medication was performed in 360/379 (94.9%). The average time interval between the clinic visit and performing EGD and pH study was 22±25 days. The current GERD algorithm results in prolonged PPI therapy, repeated endoscopies and patient dissatisfaction. Placing a pH probe at the time of initial endoscopy is safe and expedient in a rural setting. Positive pH studies avoid repeating EGDs and negative pH studies warrant a search for potential alternative diagnosis.

Effect of proton pump inhibitors on mortality of cirrhotic patients with pneumonia.

ObjectivePneumonia is life-threatening in patients with liver cirrhosis. Proton pump inhibitors (PPIs) may increase the risk of these patients developing pneumonia. However, whether PPIs increase mortality in patients with cirrhosis and pneumonia remain unknown.MethodsWe used the Taiwan National Health Insurance Database to enroll 1,201 cirrhotic patients with pneumonia without active gastrointestinal bleeding who were receiving PPIs and were hospitalized between January 1, 2010 and December 31, 2013. A one-to-three propensity score match was performed to select a comparison group based on age, gender, and comorbid disorders.ResultsThe overall 30-day and 90-day all-cause mortality rates were 13.7% and 26.9% in the PPI group, and 14.3% and 25.1% in the non-PPI group, respectively. After Cox regression model adjusting for age, gender, and comorbid disorders, the hazard ratios of the effect of PPIs on 30-day and 30 to 90-day mortality were 0.94 (95% Confidence Interval [CI], 0.79–1.12, P = 0.468) and 1.26 (95% CI, 1.05–1.52; P = 0.013), respectively.ConclusionsPPIs were not associated with 30-day mortality among cirrhotic patients with pneumonia but not active gastrointestinal bleeding. However, prolonged PPI therapy may be associated with higher mortality.

GASTRIC FUNDIC GLAND POLYPS: CAN HISTOLOGY BE USEFUL TO PREDICT PROTON PUMP INHIBITORS USE?

Fundic gland polyps allegedly increased in frequency in recent decades, and had attracted great attention due to possible association with prolonged proton pump inhibitor therapy. Prolonged use of this drug could cause parietal cell hyperplasia, obstruction of glandular lumen and cystic dilation of the gland. This study aims to analyze clinical and pathological features of fundic gland polyps in patients with and without proton pump inhibitor therapy in a selected population from Brazil. It was selected a sample of 101 Brazilian patients (78 females and 23 males), from a five years retrospective search of the files from a private pathology laboratory. The patients had an average age of 57 years and we included patients with a histological diagnosis of fundic gland polyp. The clinical data were obtained from their files and all histological slides were reviewed and examined with hematoxylin and eosin (HE) and Giemsa. Information about the use or non-use of proton pump inhibitors (PPI) was obtained in 84 patient files. In 17 cases we could not determine if PPI were used or not. Among those in which the information was available, a positive history of anti-acid therapy was observed in 63 (75.0%) patients. Parietal cell hypertrophy/hyperplasia and parietal cell protrusions were detected in most slides. Histological findings were identical in PPI users and PPI negative patients. Helicobacter pylori infection was detected in just two samples. Epithelial dysplasia or adenocarcinoma were not observed in our cases. Histopathological analysis of fundic gland polyps could not distinguish between PPI and non-PPI related cases. Parietal cell cytoplasmic protrusions, an alleged marker of prolonged acid suppression therapy, was detected in both groups. Histological features could not discriminate anti-acid therapy related fundic glands polyps in our patients.

Proton Pump Inhibitors and Bone Health: What the Orthopaedic Surgeon Needs to Know.

* Proton pump inhibitors (PPIs) are widely prescribed medications that are utilized for the treatment of gastroesophageal reflux and similar gastrointestinal disorders in all patient populations.* There is evidence that prolonged use of PPIs can lead to osteoporosis and altered bone metabolism and can even affect developing bone in pediatric patients.* There is evidence that the use of these medications increases the risk of fractures in pediatric and adult patients, including fragility fractures of the hip and spine in elderly patients.* There is preclinical evidence that the use of PPIs can affect bone-healing after fracture, delaying callus formation and altering the biomechanics of healing bone.* Orthopaedic surgeons, primary-care managers, and gastroenterologists should consider these risks when their patients are receiving prolonged PPI therapy, and the risks and benefits of PPI use should be taken into account when tailoring PPI use to each individual patient.

A case of postkidney transplant patient with gastric tuberculosis mimicking gastric malignancy

A 60-year-old male patient, who is a known case of end-stage kidney disease postliving donor renal transplantation on triple maintenance immunosuppression, presented with persistent dyspeptic symptoms 8 months posttransplant, not relieved with prolonged proton-pump inhibitor therapy. On endoscopy, found to have large ulcerated nodular lesion in the body of stomach suggestive of malignancy. On biopsy, it was diagnosed with primary gastric tuberculosis (TB). Complete clinical and endoscopic resolution was achieved following anti-TB treatment.

The relationship between proton pump inhibitors and renal disease.

ABSTRACTProton pump inhibitors (PPIs) bind to enzyme H+/K+-ATPase and inhibit its activity in the stomach, thus decreasing the secretion of gastric acid. PPIs may trigger acute interstitial nephritis, a potentially severe adverse event commonly associated with acute kidney injury. Studies have found that prolonged use of PPIs may increase the risk of chronic kidney disease (CKD). The increase in prescription and inadequate use of this class of medication calls for studies on the effects of prolonged PPI therapy on renal function. Therefore, this review aimed to analyze recent studies on the matter and discuss the possible consequences of the long-term use of PPIs on renal function.

Proton-Pump Inhibitor Treatment in Eosinophilic Esophagitis is Associated with Decreased Eosinophil Degranulation

Eosinophilic esophagitis (EoE) is an increasingly recognized disorder whose diagnosis is based on histologic demonstration of eosinophilic inflammation. We previously reported improvement of symptoms in children with EoE on long-term proton-pump inhibitor (PPI) monotherapy despite persistent eosinophilic inflammation. We sought to determine whether PPI monotherapy in children with EoE is associated with decreased eosinophil degranulation. Ten children with EoE had esophageal biopsies assessed for eosinophil, mast cell and Langerhans cell concentration and eosinophil degranulation at diagnosis and following PPI treatment. There was no significant difference in cell concentrations between initial and one-year follow-up. A significant decrease in number of free lying granules was observed at the one-year follow-up biopsies. Prolonged PPI therapy in EoE is associated with decreased eosinophil degranulation.

Thickened Gastric Folds Secondary to Prolonged Proton Pump Inhibitor Use: Clinically Relevant?

Purpose: A 60-year-old Caucasian woman was referred for an endoscopic ultrasound after a thorough evaluation for intermittent epigastric and right hypochondriac abdominal pains revealed markedly thickened gastric folds. Of note, she had been on a proton pump inhibitor (PPI) on a daily basis for many years. Her work-up included ultrasonography of the abdomen, biliary scintigraphy, upper GI scintigraphy, CT and MRI of the abdomen, a colonoscopy, and an EGD at another facility. The only abnormal findings were those of thickened gastric folds in the body and fundus on radiological and endoscopic imaging (Image 1). Helicobacter pylori infection was ruled out on antral biopsies. Due to a concern for an infiltrative or inflammatory gastric disorder, she underwent an endoscopic ultrasound at our tertiary referral center for further evaluation. There was thickening of the mucosa and submucosa but not the muscularis layer (Image 2), with a 2.1-cm wall thickness and no perigastric lymphadenopathy. A cold snare biopsy was obtained revealing benign oxyntic mucosa with focal cystic dilatation and cytoplasmic vacuolization, consistent with PPI therapy and no other abnormality. It has been well described that long-term PPI use can result in reversible, duration dependent, parietal cell hypertrophy and hyperplasia secondary to the resultant hypergastrinemia and its trophic effects. However, macroscopic findings suggestive of hypertrophied gastric folds have not been well described in this setting. Hence, we postulate, that the trophic effect of excessive gastrin in the setting of prolonged PPI therapy could potentially lead to gastric hypertrophy, the long term effects and malignant potential of which are yet unknown and merit further investigation.FigureFigure

Omental patch repair effectively treats perforated marginal ulcer following Roux-en-Y gastric bypass

Marginal ulcer formation remains a significant complication of Roux-en-Y gastric bypass (RYGB). Up to 1 % of all RYGB patients will develop free perforation of a marginal ulcer. Classically, this complication has required anastomotic revision; however, this approach is associated with significant morbidity. Several small series have suggested that omental patch repair may be effective. The aim of this study was to examine the management of perforated marginal ulcers following RYGB. All patients who underwent operative intervention for perforated ulcers between 2003 and 2011 were reviewed. Those with a history of RYGB with perforation of a marginal ulcer were included in the analysis. Data collected included operative approach, operative time, blood loss, length of hospital stay, complications, smoking history, and steroid or NSAID use. From January 2003 to December 2011, a total of 1,760 patients underwent RYGB at our institution. Eighteen (0.85 %) developed perforation of a marginal ulcer. Three patients' original procedure was performed at another institution. Eight patients (44 %) had at least one risk factor for ulcer formation. Treatment included omental patch repair (laparoscopic, n = 7; open, n = 9) or anastomotic revision (n = 2). Compared to anastomotic revision, omental patch repair had shorter OR time (101 ± 57 vs. 138 ± 2 min), decreased estimated blood loss (70 ± 72 vs. 250 ± 71 mL), and shorter total length of stay (5.6 ± 1.4 vs. 11.0 ± 5.7 days). Perforated marginal ulcer represents a significant complication of RYGB. Patients should be educated to reduce risk factors for perforation, as prolonged proton pump inhibitor therapy may not prevent this complication in a patient with even just one risk factor. In our sample population we found laparoscopic or open omental patch repair to be a safe and effective treatment for this condition and it was associated with decreased operative time, blood loss, and length of stay.

Overutilization of proton-pump inhibitors: what the clinician needs to know.

Proton-pump inhibitors (PPIs) remain the leading evidence-based therapy for upper gastrointestinal disorders, including gastroesophageal reflux disease, dyspepsia, and peptic ulcer disease. The effectiveness of PPIs has led to overutilization in multiple treatment arenas, exposing patients to an increasing number of potential risks. The overutilization of PPIs in ambulatory care settings is often a result of failure to re-evaluate the need for continuation of therapy, or insufficient use of on-demand and step-down therapy. PPI overutilization in the inpatient setting is often a result of inappropriate stress ulcer prophylaxis (SUP) in nonintensive care unit patients, and failure to discontinue SUP prior to hospital discharge. Potential consequences of prolonged PPI therapy include hypergastrinemia, enterochromaffin-like cell hyperplasia, and parietal cell hypertrophy, leading to rebound acid hypersecretion. PPIs have been linked via retrospective studies to increased risk of enteric infections including Clostridium difficile-associated diarrhea, community-acquired pneumonia, bone fracture, nutritional deficiencies, and interference with metabolism of antiplatelet agents. Reducing inappropriate prescribing of PPIs in the inpatient and outpatient settings can minimize potential for adverse events, and foster controllable cost expenditure.

Effect of Proton Pump Inhibitors and H2 Antagonists on the Stomach Wall in 99mTc-Sestamibi Cardiac Imaging

On the basis of previously unpublished observations, we hypothesized that prolonged use of proton pump inhibitors (PPIs) causes an increase in (99m)Tc-sestamibi uptake in the stomach wall, manifested as curvilinear activity surrounding the photopenic fundus of the stomach cavity. We prospectively evaluated the frequency of stomach wall uptake in patients undergoing myocardial perfusion SPECT who were taking PPIs or H(2) antagonists. Patients (n = 138) who were scheduled for single-day rest/stress (99m)Tc-sestamibi SPECT were randomly selected. Poststress SPECT was performed 30 min after treadmill exercise or 45 min after dipyridamole infusion. The rest scan was obtained 45 min after tracer injection. All patients drank 473 mL of water 5-10 min after both the rest and the stress radiotracer injections. Patients were questioned regarding their use of PPIs and H(2) antagonists. The significant use of either was defined as more than 2 wk of continuous therapy before cardiac SPECT. Masked observers assessed poststress planar projection images in endless-loop cinematic format for the following 3 patterns: stomach cavity uptake, attributable to duodenogastric reflux of tracer; stomach wall uptake; and no stomach uptake. A 2-tailed chi(2) test with Yates correction was used to calculate statistically significant associations among variables. Only patients with observed patterns of stomach wall uptake (n = 30) and no stomach wall uptake (n = 91) were included. Patients with stomach cavity uptake (n = 17) were excluded because the assessment of the adjacent stomach wall uptake was not possible. Of the patients included (n = 121), 30 were men and 91 were women. Sixty-seven patients were older than 60 y; 26 patients were taking PPIs. Of the 95 patients not taking PPIs, 14 were taking H(2) antagonists. No patients were taking both medications. Stomach wall uptake was strongly associated with prolonged use of PPIs (chi(2) = 51.9, P < 0.0001). No statistically significant association was noted among age, sex, or use of H(2) antagonists (P = NS). Prolonged PPI therapy, but not H(2) antagonist therapy, contributes to a significant increase in stomach wall activity, potentially resulting in Compton scatter or ramp filter artifacts affecting the inferior wall of the left ventricle. Stomach wall activity, unlike the stomach cavity activity, cannot be prevented by the ingestion of water before imaging. Therefore, it is important to elicit a history of prolonged PPI use to better anticipate the possibility of increased stomach wall activity, which can confound the image quality and interpretation.

Long-term proton pump induced hypergastrinaemia does induce lineage-specific restitution but not clonal expansion in benign Barrett's oesophagus in vivo

BackgroundBarrett's oesophagus is a common premalignant lesion caused partly by acid reflux. Although the requisite therapy, proton pump inhibitors (PPIs), have been implicated in the progression of Barrett's oesophagus in...

No Association Between Gastric Fundic Gland Polyps and Gastrointestinal Neoplasia in a Study of Over 100,000 Patients

Fundic gland polyps (FGPs), the most common type of gastric polyps, have been associated with prolonged proton pump inhibitor therapy and an increased risk of colon cancer. The presence of FGPs has been inversely correlated with Helicobacter pylori infection. We evaluated the prevalence of H pylori-associated gastritis, colonic polyps, and carcinomas in subjects with and without FGPs. We analyzed data collected from community-based endoscopy centers in 36 states (plus Washington DC and Puerto Rico) on patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy between April 2007 and March 2008. Of the 103,385 patients who underwent EGD during this time period, gastric biopsy samples were collected from 78,801 and colonic biopsies from 26,017. Slides of samples from Helicobacter-infected FGPs and FGPs with dysplasia were reviewed. FGPs were detected in 6081 patients (67.8% women). Helicobacter infection was present in less than 0.5% patients with FGPs and 13.0% of those without FGPs (odds ratio [OR], 29.05; 95% confidence interval [CI], 20.4-41.4; P < .0001). Colonic adenomas were detected in 42.3% of women with FGPs and 33.8% of those without (OR, 1.43; 95% CI, 1.26-1.63; P < .001); there was no significant difference in colonic adenomas between men with and without FGPs. Women had a higher prevalence of FGPs. FGPs were associated with gastroesophageal reflux disease symptoms, gastric heterotopia, hyperplastic colonic polyps (only in men), and colonic adenomas (only in women, especially those over 60 years of age). The presence of FGPs was inversely correlated with H pylori infection, active gastritis, and gastric neoplasia.

A case of hypereosinophilic syndrome presenting withintractable gastric ulcers

We report a rare case of hypereosinophilic syndrome (HES) presenting with intractable gastric ulcers. A 71-year-old man was admitted with epigastric pain. Initial endoscopic findings revealed multiple, active gastric ulcers in the gastric antrum. He underwent Helicobacter pylori (H pylori) eradication therapy followed by proton pump inhibitor (PPI) therapy. However, follow-up endoscopy at 4, 6, 10 and 14 mo revealed persistent multiple gastric ulcers without significant improvement. The proportion of his eosinophil count increased to 43% (total count: 7903/mm(3)). Abdominal-pelvic and chest computed tomography scans showed multiple small nodules in the liver and both lungs. The endoscopic biopsy specimen taken from the gastric antrum revealed prominent eosinophilic infiltration, and the liver biopsy specimen also showed eosinophilic infiltration in the portal tract and sinusoid. A bone marrow biopsy disclosed eosinophilic hyperplasia as well as increased cellularity of 70%. The patient was finally diagnosed with HES involving the stomach, liver, lung, and bone marrow. When gastric ulcers do not improve despite H pylori eradication and prolonged PPI therapy, infiltrative gastric disorders such as HES should be considered.

Laryngopharyngeal Reflux: Beauty is in The Eye of The Beholder

Laryngopharyngeal Reflux: Beauty is in The Eye of The Beholder

P-5: TCAP-1 administration in rats modulates the anxiogenic effects of CRF in three tests of anxiety

s / Neuropeptides 40 (2006) 417–445 443 are known to correlate negatively with body mass index (BMI) so that ghrelin is elevated in anorexia nervosa and decreased in obesity. In patients with cancer cachexia, it has been postulated that lack of appetite and weight loss, despite elevated ghrelin levels, results from partial ghrelin resistance. Exogenous ghrelin administered to these patients has been shown to increase caloric intake by 31%. In this study, we have shown that increased endogenous release of ghrelin from neuroendocrine tumors (NETs) can overcome the partial ghrelin resistance seen in cancer cachexia. Methods: The study was conducted as a single-center, prospective trial enrolling 35 patients with NETs. Total ghrelin levels and chromogranin A (CgA) values were measured and analyzed for differences by t test (p < 0.05). Subgroups examined included patients with and without hepatic metastases, carcinoid versus pancreatic NETs, and patients with and without hypergastrinemia due either to prolonged proton pump inhibitor use or due to Zollinger-Ellison Syndrome (ZES). Results: Mean total ghrelin levels in patients with NET and hepatic metastases (589 pg/ml) were significantly elevated compared to the group of NET patients without hepatic metastases (411 pg/ml). The former had a mean BMI of 27.2 compared to a mean of 26.3 for the latter. These higher ghrelin levels correlated with higher serum chromogranin A levels. Mean total ghrelin in patients with hypergastrinemia due to prolonged proton pump inhibitor therapy (591 pg/ml) differed significantly from untreated patients (418 pg/ml). No significant differences in ghrelin levels were seen in patients with carcinoid tumors compared to those with pancreatic neuroendocrine tumors nor between patients with Zollinger-Ellison syndrome versus those without. All patients with neuroendocrine tumors had elevated levels of ghrelin compared to the standard reference range. Conclusions: We report that in all subgroups analyzed, patients with NETs had levels of ghrelin that positively correlated with BMI suggesting that any partial ghrelin resistance may be overcome with increased endogenous ghrelin. This data supports the possibility that ghrelin is co-released from NETs and exerts an orexigenic effect in these patients, helping to maintain weight preservation despite widely disseminated disease. doi:10.1016/j.npep.2006.09.044 P-8: INVOLVEMENT OF PROTEOGLYCANCONTAINING CELLS AND/OR THE PROTEOGLYCAN EXTRACELLULAR MATRIX IN SYNAPTIC TRANSMISSION Yu.S. Garkun , A.A. Denisov , P.G. Molchanov , N.V. Yakubovich , V.A. Kulchitsky ; a Institute of Physiology, National Academy of Sciences, 28 Akademicheskaya Str., 220072, Minsk, Belarus; b Belarus State University, 4 Nezavisemosty Ave., 220050, Minsk, Belarus In many respects cell-to-cell communications are determined by interaction between cells and extracellular matrix. We attempted to change the functional state of the extracellular matrix by applying chondroitin sulfate to test the hypothesis that proteoglycans can influence synaptic transmission in brain slices by transforming extracellular matrix. Experimental series were performed on 400 lm-thick hippocampal slices from 3–4-week old rats. Population spikes (PS) and field excitatory postsynaptic potentials (fEPSPs) in the CA1 area were recorded under electrical stimulation of the Schaffer collaterals in a series of 48 hippocampal slices taken from 16 young rats under perfusion with 0.001– 1.0% chondroitin sulfate. Beginning at 60s after application of 0.01% chondroitin sulfate, an increase in the amplitude of the fEPSPs in response to both paired pulse stimuli was induced and persisted until 90s. Following this, the fEPSPs in response to both pulses declined rapidly over 60s, to an extent whereby fEPSPs were almost abolished. The initial facilitation of fEPSPs and PSs amplitudes following chondroitin sulfate may result from either an increase in net excitatory post-synaptic current or an increase in post-synaptic impedance. Similarly, the subsequent impairment of fEPSPs and PSs amplitude in the period 90 to 150s after chondroitin application presumably reflects a reduction in excitatory post-synaptic current or a large fall in postsynaptic impedance. All these processes can be initiated by structural shifts in perineuronal nets including changes of a configuration of active zones and receptor ratio. Thus, proteoglycans may influence interneuronal communications in the CA1 region of the hippocampus. doi:10.1016/j.npep.2006.09.045 P-9: VASOACTIVE INTESTINAL PEPTIDE MODULATES PLASMACYTOID DENDRITIC CELL FUNCTION BY ALTERATION OF THE IMMUNE PHENOTYPE AND INHIBITION OF IFNA SECRETION D. Fabricius , M. Sue O’Dorisio , Sue Blackwell , Bernd Jahrsdoerfer ; a Department of Pediatrics, University of Iowa, Iowa City, IA, USA; b Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; c Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA Plasmacytoid dendritic cells (pDC) are thought to be the main sentinels for viral infections, to which they

P-8: Involvement of proteoglycan-containing cells and/or the proteoglycan extracellular matrix in synaptic transmission

s / Neuropeptides 40 (2006) 417–445 443 are known to correlate negatively with body mass index (BMI) so that ghrelin is elevated in anorexia nervosa and decreased in obesity. In patients with cancer cachexia, it has been postulated that lack of appetite and weight loss, despite elevated ghrelin levels, results from partial ghrelin resistance. Exogenous ghrelin administered to these patients has been shown to increase caloric intake by 31%. In this study, we have shown that increased endogenous release of ghrelin from neuroendocrine tumors (NETs) can overcome the partial ghrelin resistance seen in cancer cachexia. Methods: The study was conducted as a single-center, prospective trial enrolling 35 patients with NETs. Total ghrelin levels and chromogranin A (CgA) values were measured and analyzed for differences by t test (p < 0.05). Subgroups examined included patients with and without hepatic metastases, carcinoid versus pancreatic NETs, and patients with and without hypergastrinemia due either to prolonged proton pump inhibitor use or due to Zollinger-Ellison Syndrome (ZES). Results: Mean total ghrelin levels in patients with NET and hepatic metastases (589 pg/ml) were significantly elevated compared to the group of NET patients without hepatic metastases (411 pg/ml). The former had a mean BMI of 27.2 compared to a mean of 26.3 for the latter. These higher ghrelin levels correlated with higher serum chromogranin A levels. Mean total ghrelin in patients with hypergastrinemia due to prolonged proton pump inhibitor therapy (591 pg/ml) differed significantly from untreated patients (418 pg/ml). No significant differences in ghrelin levels were seen in patients with carcinoid tumors compared to those with pancreatic neuroendocrine tumors nor between patients with Zollinger-Ellison syndrome versus those without. All patients with neuroendocrine tumors had elevated levels of ghrelin compared to the standard reference range. Conclusions: We report that in all subgroups analyzed, patients with NETs had levels of ghrelin that positively correlated with BMI suggesting that any partial ghrelin resistance may be overcome with increased endogenous ghrelin. This data supports the possibility that ghrelin is co-released from NETs and exerts an orexigenic effect in these patients, helping to maintain weight preservation despite widely disseminated disease. doi:10.1016/j.npep.2006.09.044 P-8: INVOLVEMENT OF PROTEOGLYCANCONTAINING CELLS AND/OR THE PROTEOGLYCAN EXTRACELLULAR MATRIX IN SYNAPTIC TRANSMISSION Yu.S. Garkun , A.A. Denisov , P.G. Molchanov , N.V. Yakubovich , V.A. Kulchitsky ; a Institute of Physiology, National Academy of Sciences, 28 Akademicheskaya Str., 220072, Minsk, Belarus; b Belarus State University, 4 Nezavisemosty Ave., 220050, Minsk, Belarus In many respects cell-to-cell communications are determined by interaction between cells and extracellular matrix. We attempted to change the functional state of the extracellular matrix by applying chondroitin sulfate to test the hypothesis that proteoglycans can influence synaptic transmission in brain slices by transforming extracellular matrix. Experimental series were performed on 400 lm-thick hippocampal slices from 3–4-week old rats. Population spikes (PS) and field excitatory postsynaptic potentials (fEPSPs) in the CA1 area were recorded under electrical stimulation of the Schaffer collaterals in a series of 48 hippocampal slices taken from 16 young rats under perfusion with 0.001– 1.0% chondroitin sulfate. Beginning at 60s after application of 0.01% chondroitin sulfate, an increase in the amplitude of the fEPSPs in response to both paired pulse stimuli was induced and persisted until 90s. Following this, the fEPSPs in response to both pulses declined rapidly over 60s, to an extent whereby fEPSPs were almost abolished. The initial facilitation of fEPSPs and PSs amplitudes following chondroitin sulfate may result from either an increase in net excitatory post-synaptic current or an increase in post-synaptic impedance. Similarly, the subsequent impairment of fEPSPs and PSs amplitude in the period 90 to 150s after chondroitin application presumably reflects a reduction in excitatory post-synaptic current or a large fall in postsynaptic impedance. All these processes can be initiated by structural shifts in perineuronal nets including changes of a configuration of active zones and receptor ratio. Thus, proteoglycans may influence interneuronal communications in the CA1 region of the hippocampus. doi:10.1016/j.npep.2006.09.045 P-9: VASOACTIVE INTESTINAL PEPTIDE MODULATES PLASMACYTOID DENDRITIC CELL FUNCTION BY ALTERATION OF THE IMMUNE PHENOTYPE AND INHIBITION OF IFNA SECRETION D. Fabricius , M. Sue O’Dorisio , Sue Blackwell , Bernd Jahrsdoerfer ; a Department of Pediatrics, University of Iowa, Iowa City, IA, USA; b Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; c Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA Plasmacytoid dendritic cells (pDC) are thought to be the main sentinels for viral infections, to which they

Improvement of laryngopharyngeal reflux symptoms after laparoscopic Hill repair

Background People with proven gastroesophageal reflux disease may also experience symptoms such as voice loss, chronic cough, globus, and sore throat. These laryngopharyngeal reflux symptoms have been reported to respond to prolonged proton pump inhibitor therapy, but the Hill approach to resolving these specific individual symptoms has not been widely reported in surgical literature. Methods This clinical outcome study is an analysis of symptom improvement in 145 patients who underwent laparoscopic Hill hiatal hernia repair. A standardized questionnaire was used to score eight gastroesophageal reflux disease symptoms and four laryngopharyngeal reflux symptoms. Also, each patient’s primary chief complaints were analyzed. Results Gastroesophageal reflux and laryngopharyngeal reflux symptoms significantly improved ( P < 0.01) compared with preoperative symptoms. Each patient’s primary chief complaints improved as well. Conclusions This clinical outcome analysis documents symptomatic improvement of laryngopharyngeal reflux and gastroesophageal reflux. Likewise, when these laryngopharyngeal reflux symptoms are chief complaints, with proven gastroesophageal reflux disease, the Hill approach to symptom resolution is likely to be successful.