Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS):study protocol for a nationwide prospective cohort study

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

Contains fulltext : 69534.pdf (publisher's version ) (Open Access)BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150

Fluid hydration to prevent post-ERCP pancreatitis in average- to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial): Study protocol for a randomized controlled trial

Background: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP. Methods: The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness. Discussion: The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study

Introduction Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. Methods and analysis PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. Ethics and dissemination PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Sustainable urban development: An ethic challenge, continious change

The speed and complexity of worldwide change are taxing every institution and complicating processes and functions. We need to understand cities as complex adaptive systems and question how to manage change. 1) The complexity of social cultural-, ecological and economic systems, science and technology as the driving forces for urban development makes it necessary to abandon the perception of a global steady state. Instead, managing these complex coevolving systems and interdependencies for sustainability, requires the ability to cope with, adapt to and shape cities without losing options for future development. 2) Value is mostly defined narrowly in terms of financial calculus. Successful urban development requires a new ethical value based economy. It will imply behavior change to meet value-based goals. Combining social and ethical values with economic accounting defines our future cities. Opposite and challenging the conservatism of the past ("checks and balances" cerebral, cognitive, rational, the sum of market forces, etc). For sustainable urban development there is one goal (telos), which does not result in a static state of goal achievement. That goal is change itself. Therefore the city is an interconnected multifaceted continuous changing entity: an economic structure \u96a society, an artifact, an ecosystem, a polis, a culture defined as the things we find important, beliefs and habits. Long term effects can only be secured if city making is adapting changeability, ethical founded, and becoming places of solidarity, of passion and compassion. Adding value economically and reinforce ethical values simultaneously

Ty-1, a universal resistance gene against geminiviruses that is compromised by co-replication of a betasatellite

Tomato yellow leaf curl virus (TYLCV), a begomovirus, causes large yield losses and breeding for resistance is an effective way to combat this viral disease. The resistance gene Ty-1 codes for an RNA-dependent RNA polymerase and has recently been shown to enhance transcriptional gene silencing of TYLCV. Whereas Ty-1 was earlier shown to also confer resistance to a bipartite begomovirus, here it is shown that Ty-1 is probably generic to all geminiviruses. A tomato Ty-1 introgression line, but also stable transformants of susceptible tomato cv. Moneymaker and Nicotiana benthamiana (N. benthamiana) expressing the Ty-1 gene, exhibited resistance to begomoviruses as well as to the distinct, leafhopper-transmitted beet curly top virus, a curtovirus. Stable Ty-1 transformants of N. benthamiana and tomato showed fewer symptoms and reduced viral titres on infection compared to wild-type plants. TYLCV infections in wild-type N. benthamiana plants in the additional presence of a betasatellite led to increased symptom severity and a consistent, slightly lowered virus titre relative to the high averaged levels seen in the absence of the betasatellite. On the contrary, in Ty-1 transformed N. benthamiana viral titres increased in the presence of the betasatellite. The same was observed when these Ty-1-encoding plants were challenged with TYLCV and a potato virus X construct expressing the RNA interference suppressor protein βC1 encoded by the betasatellite. The resistance spectrum of Ty-1 and the durability of the resistance are discussed in light of antiviral RNA interference and viral counter defence strategies.</p

Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects

1. The renal effects of insulin may play a central role in the association between insulin resistance, hypertension and hyperuricaemia. After a 2-h baseline period, we investigated the effects of exogenous insulin for 4 h (50 m-units h-1 kg-1) on fractional renal sodium and urate excretion in 13 healthy subjects, using the euglycaemic clamp and lithium clearance technique, and performed a control experiment in eight of the subjects. 2. Insulin caused a decline in both fractional renal sodium excretion, from 1.13 +/- 0.41% to 0.88 +/- 0.58% (control study: 0.81 +/- 0.35 to 1.35 +/- 0.49%; P < 0.001, insulin versus control), and fractional renal urate excretion, from 6.72 +/- 1.87% to 5.71 +/- 2.02% (control study: 7.03 +/- 2.06 to 7.05 +/- 1.94%; P = 0.085, insulin versus control). The changes in fractional renal sodium and urate excretion were positively correlated (r = 0.71, P < 0.01). Estimated fractional distal sodium reabsorption increased during insulin infusion from 93.7 +/- 2.8% to 96.7 +/- 1.9% (control study: 95.7 +/- 1.5% to 93.6 +/- 1.1%; P < 0.001, insulin versus control). Estimated fractional proximal tubular sodium reabsorption fell from 81.0 +/- 0.5% to 73.7 +/- 4.7% during insulin infusion, but less in the control study (81.5 +/- 4.3% to 79.3 +/- 4.8%; P = 0.056, insulin versus control). The changes in fractional proximal tubular sodium reabsorption and fractional distal sodium reabsorption during insulin infusion were inversely correlated (r = -0.59, P = 0.03). 3. During the course of the insulin infusion experiment an inverse correlation between the changes in fractional sodium and urate excretion, and the insulin-mediated glucose disposal, became gradually evident (r = -0.73, P < 0.01, and r = -0.71, P < 0.01, respectively; fourth hour of the insulin infusion period). 4. We conclude that exogenous insulin acutely decreases renal sodium and urate excretion, and that this effect is probably exerted at a site beyond the proximal tubule

Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects

1. The renal effects of insulin may play a central role in the association between insulin resistance, hypertension and hyperuricaemia. After a 2-h baseline period, we investigated the effects of exogenous insulin for 4 h (50 m-units h-1 kg-1) on fractional renal sodium and urate excretion in 13 healthy subjects, using the euglycaemic clamp and lithium clearance technique, and performed a control experiment in eight of the subjects. 2. Insulin caused a decline in both fractional renal sodium excretion, from 1.13 +/- 0.41% to 0.88 +/- 0.58% (control study: 0.81 +/- 0.35 to 1.35 +/- 0.49%; P < 0.001, insulin versus control), and fractional renal urate excretion, from 6.72 +/- 1.87% to 5.71 +/- 2.02% (control study: 7.03 +/- 2.06 to 7.05 +/- 1.94%; P = 0.085, insulin versus control). The changes in fractional renal sodium and urate excretion were positively correlated (r = 0.71, P < 0.01). Estimated fractional distal sodium reabsorption increased during insulin infusion from 93.7 +/- 2.8% to 96.7 +/- 1.9% (control study: 95.7 +/- 1.5% to 93.6 +/- 1.1%; P < 0.001, insulin versus control). Estimated fractional proximal tubular sodium reabsorption fell from 81.0 +/- 0.5% to 73.7 +/- 4.7% during insulin infusion, but less in the control study (81.5 +/- 4.3% to 79.3 +/- 4.8%; P = 0.056, insulin versus control). The changes in fractional proximal tubular sodium reabsorption and fractional distal sodium reabsorption during insulin infusion were inversely correlated (r = -0.59, P = 0.03). 3. During the course of the insulin infusion experiment an inverse correlation between the changes in fractional sodium and urate excretion, and the insulin-mediated glucose disposal, became gradually evident (r = -0.73, P < 0.01, and r = -0.71, P < 0.01, respectively; fourth hour of the insulin infusion period). 4. We conclude that exogenous insulin acutely decreases renal sodium and urate excretion, and that this effect is probably exerted at a site beyond the proximal tubule

Relationship between insulin's haemodynamic effects and insulin-mediated glucose uptake

BACKGROUND: Insulin resistance and hyperinsulinaemia are associated with hypertension. The relationship between insulin's metabolic and haemodynamic actions has not been fully elucidated however. METHODS: We investigated, using the euglycaemic clamp technique, the relationship between insulin-mediated glucose uptake and insulin-induced changes in leg blood flow and cardiac index in 13 healthy subjects. As insulin's effects on blood flow are time dependent, studies were performed during a 4-h insulin (50 mU kg-1 h-1) infusion period. RESULTS: Mean arterial pressure during insulin infusion increased (82.9 +/- 6.7 to 89.8 +/- 7.7 mmHg; P < 0.001), whereas heart rate was unaltered. Leg blood flow gradually increased from 1.09 +/- 0.57 to 1.47 +/- 0.67 mL min-1 dL-1 during the second hour, and to 1.65 +/- 0.68 mL min-1 dL-1 during the fourth hour of the clamp (P = 0.01). Stroke volume index increased from 56.5 +/- 13.3 to 63.7 +/- 16.3 mL m-2 (P = 0.004) and cardiac index from 3.42 +/- 1.02 to 3.73 +/- 1.05 L min-1 m-2 (P = 0.04). The insulin-mediated glucose disposal and the increases in leg blood flow were not correlated during the second hour (r = 0.21, P = 0.51) but showed a strong correlation during the fourth hour of the clamp (r = 0.88, P < 0.001). Insulin-mediated glucose disposal was not correlated with the increases in cardiac index. CONCLUSION: Thus, insulin-mediated muscle blood flow may be an important contributor to glucose uptake during sustained exogenous hyperinsulinaemia aiming at physiological insulin levels