reflux Tag

[caption id="attachment_74872" align="alignleft" width="150"]Dr. Johnston, Ph.D. Dr. Johnston, Ph.D.[/caption]

MedicalResearch.com Interview with:

Nikki Johnston, Ph.D.

Professor of Otolaryngology and Communication Sciences & Microbiology and Immunology

Medical College of Wisconsin

Co-founder and Chief Scientific Officer, N-Zyme Biomedical Inc.

MedicalResearch.com: Please provide a summary of your findings in your Modulation of Pepsin-Mediated Inflammatory Responses in Vocal Cord Epithelial Cells by Amprenavir and how that is impacting your future research studies.

Dr. Johnston: In this study, we wanted to know whether pepsin — the key nonacid component of reflux — could trigger inflammatory signaling in vocal cord epithelial cells, and whether a pepsin inhibitor could reverse that response. We found that exposing human vocal cord cells to pepsin at neutral pH, mimicking the nonacidic conditions typical of laryngopharyngeal reflux (LPR), significantly increased the transcription factor HIF-2α along with the downstream inflammatory genes IL8, IL1B, and ICAM1. Co-treatment with amprenavir, a pepsin inhibitor and the active metabolite of fosamprenavir, reduced HIF-2α levels and significantly suppressed IL8, ICAM1, and TNF expression.

Interestingly, when we blocked HIF-2α's transcriptional activity directly, only IL1B expression was reduced; IL8 and ICAM1 were unaffected or even further increased. This tells us that HIF-2α is one contributor to pepsin-driven inflammation in the vocal cords, but not the whole story — pepsin is very likely activating several parallel stress pathways (NF-κB and MAPK signaling, among others) at the same time. For our future work, this reinforces that a single downstream pathway inhibitor is unlikely to fully quiet pepsin-induced inflammation, whereas a pepsin inhibitor acting further upstream, like amprenavir, has the potential to blunt several of these pathways at once. We are now examining whether similar mechanisms extend to pepsin's emerging role in pulmonary fibrotic disease and gastro-esophageal reflux disease (GERD).

[caption id="attachment_53500" align="alignleft" width="150"]Yun-Han Wang PhD Student Karolinska Institute Yun-Han Wang[/caption] MedicalResearch.com Interview with: Yun-Han Wang, PhD Student Karolinska Institute MedicalResearch.com: What is the background for this study? Response: Proton pump inhibitor (PPI) use has been linked to increased risk of fracture in adults. Despite an increasing trend in prescription of PPIs in children, there is scarce evidence regarding this safety concern in pediatric patients.

MedicalResearch.com Interview with: Drs. R.P.J. Willems  |  Arts-onderzoeker Medische Microbiologie en Infectiepreventie Amsterdam MedicalResearch.com: What is the background for this study? Does your study refer to both PPIs and H2-blockers?  Response: There is mixed evidence on the associated risk of colonization and infection with multidrug-resistant microorganisms with acid suppressive therapy. We therefore aimed to investigate current literature in order to determine whether acid suppressants facilitate intestinal colonization with multidrug-resistant microorganisms. We included studies on PPIs, H2 blockers and antacids.

MedicalResearch.com Interview with: [caption id="attachment_39050" align="alignleft" width="184"]Dr. Edward D. McCoul, MD, MPH Ochsner Medical Center Dr. McCoul[/caption] Dr. Edward D. McCoul, MD, MPH Ochsner Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Population-level data suggests a link between gastroesophageal reflux disease and cancer of the throat and sinuses in adults over 65 years of age.  T he strength of association between reflux and cancer is strongest for anatomic sites closest to the esophagus, where acid and other stomach contents may have the greatest exposure.

MedicalResearch.com Interview with: Charat Thongprayoon, MD Bassett Medical Center Cooperstown, NY 13326 MedicalResearch.com: What is the background for this study? What are the main findings? Response: We conducted a meta-analysis including 5 observational studies with 536,902 patients to assess the risks of chronic kidney disease (CKD) and/or end-stage kidney disease (ESRD) in patients who are taking proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs). We found a statistically significant association between the use of PPI and 1.3-fold increased risk of CKD or ESRD development. Compared with H2Ras, the use of proton pump inhibitors was significantly associated with 1.3-fold higher risk for CKD development. Conversely, there was no significant association between the use of H2RAs and chronic kidney disease.

MedicalResearch.com Interview with: [caption id="attachment_31334" align="alignleft" width="126"]Dr. Mark Noar Director of The Heartburn and Reflux Study Center Towson, MD Dr. Mark Noar[/caption] Dr. Mark Noar Director of The Heartburn and Reflux Study Center Towson, MD  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background for this study was developed out of a need to know whether the Stretta procedure was effective in both the short and long-term in all forms of reflux. This included standard refluxing patients who had never had surgery but also in the subpopulation of patients who had recurring reflux after having had reflux corrective surgery. The question to be answered was whether the Stretta procedure would be less effective, more effective, or just as effective in the patient who had had prior surgery compared to patients who did not have surgery. The main findings were that independent of whether a patient had had surgery for the correction of reflux or just had standard reflux without prior surgery, the Stretta procedure was equally effective in all patient subgroups both in the short-term and the long-term.

John Maret-Ouda  MD,  PhD candidateMedicalResearch.com Interview with: John Maret-Ouda  MD,  PhD candidate Upper Gastrointestinal Surgery Department of Molecular medicine and Surgery Karolinska Institutet Stockholm, Sweden MedicalResearch: What is the background for this study? What are the main findings? Dr. Maret-Ouda : This review is part of the BMJ series “Uncertainties pages”, where clinically relevant, but debated, medical questions are highlighted and discussed. The present study is assessing treatment of severe gastro-oesophageal reflux disease, where the current treatment options are medical (proton-pump inhibitors) or surgical (laparoscopic antireflux surgery). The clinical decision-making is often left to the clinician and local guidelines. We evaluated the existing literature to compare the two treatment options regarding reflux control, complications, future risk of oesophageal adenocarcinoma, health related quality of life, and cost effectiveness. The main findings were that surgery might provide slightly better reflux control and health related quality of life, but is associated with higher risks of complications compared to medication. A possible preventive effect regarding oesophageal adenocarcinoma remains uncertain. Regarding cost effectiveness, medication seems more cost effective in the short term, but surgery might be more cost effective in the longer term. Since medication provides good treatment of severe gastro-oesophageal reflux disease, but with lower risks of complications, this remains the first line treatment option.

Ronnie Fass, M.D., FACG, Professor of Medicine Case Western Reserve University Director, Division of Gastroenterology and Hepatology, Head, Esophageal and Swallowing Center, Metro Health Medical Center Cleveland, OHMedicalResearch.com Interview with: Ronnie Fass, M.D., FACG, Professor of Medicine Case Western Reserve University Director, Division of Gastroenterology and Hepatology, Head, Esophageal and Swallowing Center, Metro Health Medical Center Cleveland, OH MedicalResearch: What are the main findings of the study? Dr. Fass: This is the first study to compare the extent of acid reflux between nighttime sleep and daytime naps in patients with Gastroesophageal reflux disease. The results of our study show that naps are associated with significantly greater esophageal acid exposure compared to sleep. Acid reflux events were more frequent and their total duration was longer during naps when compared with acid reflux events during nighttime sleep. Additionally, the fraction of time that the subjects were experiencing acid reflux with pH < 4 was significantly higher during naps than nighttime sleep and subjects experienced more symptoms due to acid reflux during their nap than their sleep.