Dissecting Kawasaki disease: a state-of-the-art review.

Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. The diagnosis is based on the presence of persistent fever and clinical features including exanthema, lymphadenopathy, conjunctival injection, and changes to the mucosae and extremities. Although the etiology remains unknown, the current consensus is that it is likely caused by an (infectious) trigger initiating an abnormal immune response in genetically predisposed children. Treatment consists of high dose intravenous immunoglobulin (IVIG) and is directed at preventing the development of CAA. Unfortunately, 10-20% of all patients fail to respond to IVIG and these children need additional anti-inflammatory treatment. Coronary artery lesions are diagnosed by echocardiography in the acute and subacute phases. Both absolute arterial diameters and z-scores, adjusted for height and weight, are used as criteria for CAA. Close monitoring of CAA is important as ischemic symptoms or myocardial infarction due to thrombosis or stenosis can occur. These complications are most likely to arise in the largest, so-called giant CAA. Apart from the presence of CAA, it is unclear whether KD causes an increased cardiovascular risk due to the vasculitis itself. CONCLUSION: Many aspects of KD remain unknown, although there is growing knowledge on the etiology, treatment, and development and classification of CAA. Since children with previous KD are entering adulthood, long-term follow-up is increasingly important. What is known: • Kawasaki disease (KD) is a pediatric vasculitis with coronary artery damage as its main complication. • Although KD approaches its 50th birthday since its first description, many aspects of the disease remain poorly understood. What is new: • In recent years, multiple genetic candidate pathways involved in KD have been identified, with recently promising information about the ITPKC pathway. • As increasing numbers of KD patients are reaching adulthood, increasing information is available about the long-term consequences of coronary artery damage and broader cardiovascular risk.

Regression and Complications of z-score-Based Giant Aneurysms in a Dutch Cohort of Kawasaki Disease Patients.

Kawasaki disease (KD) is a pediatric vasculitis. Its main complication is the development of coronary artery aneurysms (CAA), with giant CAA at the end of the spectrum. We evaluated regression and event-free rates in a non-Asian cohort of patients with giant CAA using the current z-scores adjusted for body surface area instead of absolute diameters. KD patients with giant CAA (z-score ≥10) visiting our outpatient clinic between January 1999 and September 2015 were included. Patient characteristics and clinical details were extracted from medical records. Regression was defined as all coronary arteries having a z-score of ≤3. A major adverse event was defined as cardiac death, myocardial infarction, cardiogenic shock, or any coronary intervention. Regression-free and event-free rates were calculated using the Kaplan-Meier method. We included 52 patients with giant CAA of which 45 had been monitored since the acute phase. The 1-, 2-, and 5-year regression-free rates were 0.86, 0.78, and 0.65, respectively. The 5-year, 10-year, and 15-year event-free rates were 0.79, 0.75, and 0.65, respectively. Four children, whose CAA would not have been classified as 'giant' based on absolute diameters instead of z-scores, had experienced an event during follow-up. CONCLUSION: We found a high percentage of children in whom the lumen of giant CAA completely normalized. Four children not classified as 'giant' based on absolute diameters with z-scores of ≥10 experienced a cardiac event. Hence, the use of z-scores seems to be justified.

Cardiovascular imaging in children and adults following Kawasaki disease.

Kawasaki disease (KD) is a paediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. Two guidelines exist regarding the follow-up of patients after KD, by the American Heart Association and the Japanese Circulation Society. After the acute phase, CAA-negative patients are checked for cardiovascular risk assessment or with ECG and echocardiography until 5 years after the disease. In CAA-positive patients, monitoring includes myocardial perfusion imaging, conventional angiography and CT-angiography. However, the invasive nature and high radiation exposure do not reflect technical advances in cardiovascular imaging. Newer techniques, such as cardiac MRI, are mentioned but not directly implemented in the follow-up. Cardiac MRI can be performed to identify CAA, but also evaluate functional abnormalities, ischemia and previous myocardial infarction including adenosine stress-testing. Low-dose CT angiography can be implemented at a young age when MRI without anaesthesia is not feasible. CT calcium scoring with a very low radiation dose can be useful in risk stratification years after the disease. By incorporating newer imaging techniques, detection of CAA will be improved while reducing radiation burden and potential complications of invasive imaging modalities. Based on the current knowledge, a possible pathway to follow-up patients after KD is introduced. Key Points • Kawasaki disease is a paediatric vasculitis with coronary aneurysms as major complication. • Current guidelines include invasive, high-radiation modalities not reflecting new technical advances. • Cardiac MRI can provide information on coronary anatomy as well as cardiac function. • (Low-dose) CT-angiography and CT calcium score can also provide important information. • Current guidelines for follow-up of patients with KD need to be revised.

Fast-scan cyclic voltammetry of 5-hydroxytryptamine.

Fast-scan cyclic voltammetry, a demonstrated analytical method for the in vivo detection of dopamine, is extended to the detection of in vitro and in vivo 5-hydroxytryptamine (5-HT) with the use of a specific potential wave form applied at 1000 V/s. The wave form, 0.2 to 1.0 to -0.1 to 0.2 V, is employed to accelerate electrode response times which are significantly slower with other wave forms due to the adsorption of 5-HT. The scan rate of 1000 V/s enables follow-up reactions which lead to the formation of strongly adsorptive products to be outrun. The peak current at a carbon fiber disk microelectrode exposed to 1 microM 5-HT in flow injection experiments is 1 nA, with a half-rise time of less than 200 ms. The peak current of Nafion-coated electrodes exposed to the same concentration of 5-HT is 5 nA, with a half-rise time on the order of 400 ms. The rate of adsorption of 5-HT was determined to be 4.22 +/- 0.33 s-1. Several compounds present in brain tissue as well as the pharmacological agents used to elicit 5-HT release in the caudate of the rat were evaluated. Those which gave a response could be differentiated from 5-HT on the basis of respective oxidative and reductive peak potentials. Nafion-coated electrodes were used to monitor transient increases in both dopamine and exogenous 5-HT in the caudate of the anesthetized rat in response to electrical stimulation. The rate of cellular uptake of 5-HT was shown to be 3-fold slower than dopamine uptake. NS-15841

Decreasing classroom misbehavior through the use of DRL schedules of reinforcement.

In three studies, reinforcing low rates of responding reduced inappropriate behaviors. In the first study, the talking-out behavior of one TMR student was reduced when the teacher allowed 5 min of free time for a talk-out rate less than 0.06 per minute. In a second study, the talking-out behavior of an entire TMR class was reduced when reinforcement was delivered for a response rate less than 0.10 per minute. In a third study, successively decreasing DRL limits were used to reduce off-task verbalizations of an entire high school business class. In each case, the DRL procedure proved manageable for the teacher and successful in reducing misbehavior.