No description available.

Introduction: Impairment of cytosolic calcium ([Ca2+]i) signaling and in particular calcium overload has emerged as a possible unifying mechanism for precipitating acute pancreatitis (AP.) In the L-arginine (L-arg) experimental model of AP, nitric oxide (NO) has been implicated however the disease progression is largely unaffected by nitric oxide synthase (NOS) inhibitors (8). Additionally, L-ornithine (L-orn), a NOS-independent metabolite of L-arg, has been shown to be potent at inducing AP (28). Both L-arg and L-orn activate calcium-sensing like receptors (CaSR) (31) such as the GPRC6a which may be responsible for initiating the [Ca2+]i overload. The aim of this study is to investigate the effects of L-arg and L-orn on pancreatic acinar cells that maybe linked to the pathophysiology of AP. Furthermore to provide an alternative theory to the NO mediated ones, in particular that L-arg induces toxic changes in [Ca2+]i via a GPRC6a like receptor. Methods: Whole pancreata were harvested from male Sprague Dawley rats. Pancreatic acinar cells were isolated by collagenase digestion. [Ca2+]i was measured using fura-2 imaging, and cell viability assessed using physiological CCK. Oxidative stress was measured using dichlorofluorescein (DCF) and cell death was quantified using trypan blue exclusion. Results: L-arg and L-orn (100mM) induced spike-like, reversible increases in [Ca2+]i in 46% and 74% of cells and Ca2+ overload in 11% and 26% respectively. At 500 mM both induced Ca2+ overload in all cells however this was also seen with the osmotic control, mannitol. Isosmotic L-arg and L-orn (100mM) induced only reversible increases in [Ca2+]i. Neither L-arg nor L-orn had significant effects on CCK-evoked [Ca2+]i oscillations. Both L-arg and L-orn induced significant oxidative stress responses (22% and 37% of a maximum response seen with 3mM H202, respectively). Both L-arg and L-orn caused cell death in 76% +/- 4 and 89% +/- 7 at 3 hours respectively, compared to 35% +/- 4 and 40% +/- 3 with controls (Hepes, Glycine). Conclusion: The data suggests that the L-arg and L-orn causes significant increase in oxidative stress and cell death. The data suggests that although changes in [Ca2+]i were induced by both L-arg and L-orn the large concentrations used experimentally are likely to induce significant osmotic effects.

No description available.

Since their introduction in the late 1980s, proton pump inhibitors (PPI) have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. This class of drugs has improved the treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal anti-inflammatory drug-induced gastropathy. PPIs have minimal side effects and few significant drug interactions. They are generally considered safe for long-term treatment. We present a rare side effect, acute pancreatitis, occurring in a patient who was treated with the proton pump inhibitor omeprazole.

Treatment of severe acute pancreatitis is considered to be conservative. The only generally accepted indication for surgery in severe acute pancreatitis patients is an established infection of the necrotic tissue and persisting or progressing symptoms of multiorgan failure despite the maximal intensive treatment. For surgical treatment are also indicated patients with complications of severe acute pancreatitis (erosive hemorrhage, perforation of GIT etc.). In the proposed work, attention is drawn to those cases, where the general condition of the patient deteriorates combined with a progression of ACS and where a decompressive laparotomy can improve the prognosis of the disease. In our group of 214 patients with severe acute pancreatitis, who were treated over the last six years, 70 patients were indicated for surgery. Out of this count, in 17 cases the indication for decompressive laparotomy was a raise of intraabdominal pressure up to the values of ACS together with the symptoms of organ dysfunction, 6 patients died and 11 younger patients survived.

BACKGROUND: Acute pancreatitis (AP) is a sterile initiator of systemic inflammation that can trigger multiple organ dysfunction syndrome (MODS). In the acute phase of AP, the kynurenine pathway of tryptophan metabolism plays an important role in the genesis of AP-MODS in experimental animal models, but it is unknown whether the pathway is activated in human AP. Human data are required to support the rationale for kynurenine 3- monooxygenase (KMO) inhibition as a treatment for AP-MODS and reinforce the translational potential. Additionally, as respiratory dysfunction is frequent in severe AP, the role of lung ultrasonography in severity stratification deserves investigation. Furthermore, the effect of AP-MODS on long-term survival is unknown. OBJECTIVES: My objectives were to: 1) Define the temporal and quantitative relationship of kynurenine metabolites with the onset and severity of APMODS, 2) Investigate the value of lung ultrasonography in the early diagnosis of respiratory dysfunction in human AP-MODS, and 3) Examine whether early AP-MODS impacts on long-term survival. METHODS: 1) A prospective, observational, clinical experimental medicine study titled “Inflammation, Metabolism, and Organ Failure in Acute Pancreatitis” (IMOFAP) was performed. For 90 days, consecutive patients with a potential diagnosis of AP were recruited and venous blood was sampled at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. Kynurenine metabolite concentrations were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and analysed in the context of clinical data, disease severity indices, and cytokine profiles. 2) In a nested cohort within IMOFAP, 41 participants underwent lung ultrasonography to evaluate whether this imaging modality can detect respiratory dysfunction in AP. 3) Survival data for a prospectively maintained database of patients with AP was analysed after accounting for in-hospital deaths. RESULTS: 1) During the IMOFAP study, 79 patients were recruited with an elevated serum amylase, of which 57 patients met the diagnostic criteria for AP; 9 had severe disease. Temporal profiling revealed early tryptophan depletion and contemporaneous elevation of plasma concentrations of 3- hydroxykynurenine, which paralleled systemic inflammation and AP severity. 2) Lung ultrasonography findings correlated with respiratory dysfunction. 3) 694 patients were followed up for a median of 8.8 years. AP-MODS conferred a deleterious effect on overall survival which persisted after the exclusion of inhospital deaths (10.0 years, 95% C.I. = 9.4-10.6 years) compared to AP without MODS (11.6 years, 95% C.I. = 11.2-11.9 years; P = 0.001). This effect was independent of age. CONCLUSIONS: In the acute phase of AP, metabolic flux through KMO is elevated and proportionate to AP severity. Lung ultrasonography may be a useful technique for evaluating AP-MODS. AP-MODS is an independent predictor of long-term mortality. Together, this work reinforces the rationale for investigating early phase KMO inhibition as a therapeutic strategy in humans.

Class of 2005 Abstract / Objectives: To develop a decision analytic model to compare the clinical and economic outcomes of enteral nutrition (EN) and total parenteral nutritional (TPN) support in acute pancreatitis patients. Methods: All randomized clinical trials comparing EN and TPN in acute pancreatitis patients published in the medical and pharmacy literature were identified. Six trials were identified by searching MEDLINE, Web of Science, Cochrane Controlled Trials Register, International Pharmaceutical Abstracts, HealthStar, Cumulative Index to Nursing & Allied Health Literature, and citation review of applicable literature. The costs used for the decision tree were from the perspective of a hospital. A literature based decision tree was formed based from these costs and the probabilities of events from the six identified clinical trials. The TreeAge Pro computer program (TreeAge Software, Inc.; Williamstown, MA) was used to conduct the cost effectiveness analysis. Therapeutic success was considered, for the purposes of the trial, as having no complications. Results: EN was associated with a lower risk of infections, a reduced length of hospital stay, and fewer surgical interventions. There was no statistical difference in the risk of mortality, adult respiratory distress syndrome or multiple organ failure between groups treated with EN or TPN. The results found that EN dominated TPN by being both less costly and more effective. The average costs for EN and TPN were $46,345 and $73,878, respectively. The success rates were 0.652 and 0.358 for EN and TPN, respectively. Conclusion: Enteral nutrition was the dominant route of administration for nutritional support, when compared to total parenteral nutrition both clinically and economically for acute pancreatitis patients.

The spectrum of acute pancreatitis (AP) affects between 4.9 and 73.4 patients out of 100,000 worldwide annually (Tenner, Baillie, DeWitt, & Vege, 2013). AP uses the Atlanta classification system to establish a diagnosis of mild, moderate, or severe. The American College of Gastroenterology (ACG) has established comprehensive clinical practice guidelines (CPG) for the management of AP, the most recent version published in 2013 (Tenner et al., 2013). There have been similar CPGs published internationally that integrate current evidence-based research into recommendations for practice. These guidelines along with the ACG's guidelines recommend initiating a diet for mild acute pancreatitis patients due to research findings of improved patient outcomes (i.e. reduced length of hospital stay, decreased rate of infections, and reduced mortality) (Horibe et al., 2015; Lariño-Noia et al., 2014). There is an international awareness of the need for increased CPG nutrition recommendation compliance in the practice setting as many studies have found providers prefer to keep patients nil per os (NPO) and do not adhere to CPGs (Andersson, Andrén-Sandberg, Nilsson, & Andersson, 2012; Greenberg et al., 2016; Sun et al., 2013). The purpose of this doctor of nursing practice (DNP) project is to assess providers' current nutrition therapy practice and knowledge of the ACG’s CPG nutrition recommendations for mild AP patients. The researcher conducted the assessment with a hospitalist practice at Banner University Medical Center in Phoenix, Arizona. The results of the project contribute to the current body of research on national adherence to CPGs for AP and act as a needs assessment for future projects where a nutrition protocol order set may be established. The investigation of nutrition therapy for AP patients seeks to improve and standardize the care this patient population receives while in the acute care setting.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21632号 / 医博第4438号 / 新制||医||1034(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 生田 宏一, 教授 上本 伸二, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) resulting in significant morbidity and occasional mortality. Post-ERCP pancreatitis (PEP) has been recognized since ERCP was first performed, and many studies have shown a consistent risk that must be balanced against the many benefits of this procedure. This review will discuss the pathogenesis, epidemiology, potential risk factors, and clinical presentation of PEP. Moreover, it will discuss in detail the most recent updates of PEP prevention and management.