Kawasaki disease in siblings and a review of drug treatment.

We have managed two anonymized siblings with Kawasaki disease (KD). The occurrence of KD in the elder brother alerted us to the occurrence of incomplete KD in the younger brother. Both siblings were treated with intravenous immunoglobulin and a high dose of dipyridamole with resolution of the coronary artery aneurysm. Dipyridamole was used instead of aspirin because both siblings were glucose-6-phosphate dehydrogenase deficient for which aspirin was contraindicated. To prevent damage to the coronary arteries, treatment should be started as soon as the diagnosis is made. There have been a lot of advances in medical therapy in recent years, which are reviewed together with conventional proven therapy for KD. Early diagnosis and prompt treatment are important to achieve optimal treatment outcome in KD. Family history of KD among siblings enables clinicians for an earlier diagnosis so as to prevent the disease complications particularly in patients with incomplete features.

Pencil beam scanning versus passively scattered proton therapy for unresectable pancreatic cancer.

BACKGROUND: With an increasing number of proton centers capable of delivering pencil beam scanning (PBS), understanding the dosimetric differences in PBS compared to passively scattered proton therapy (PSPT) for pancreatic cancer is of interest. METHODS: Optimized PBS plans were retrospectively generated for 11 patients with locally advanced pancreatic cancer previously treated with PSPT to 59.4 Gy on a prospective trial. The primary tumor was targeted without elective nodal coverage. The same treatment couch, target coverage and normal tissue dose objectives were used for all plans. A Wilcoxon t-test was performed to compare various dosimetric points between the two plans for each patient. RESULTS: All target volume coverage goals were met in all PBS and passive scattering (PS) plans, except for the planning target volume (PTV) coverage goal (V100% >95%) which was not met in one PS plan (range, 81.8-98.9%). PBS was associated with a lower median relative dose (102.4% vs. 103.8%) to 10% of the PTV (P=0.001). PBS plans had a lower median duodenal V59.4 Gy (37.4% vs. 40.4%; P=0.014), lower small bowel median V59.4 Gy (0.11% vs. 0.37%; P=0.012), lower stomach median V59.4 Gy (0.01% vs. 0.1%; P=0.023), and lower median dose to 0.1 cc of the spinal cord {35.0 vs. 38.7 Gy [relative biological effectiveness (RBE)]; P=0.001}. Liver dose was higher in PBS plans for median V5 Gy (24.1% vs. 20.2%; P=0.032), V20 Gy (3.2% vs. 2.8%; P=0.010), and V25 Gy (2.6% vs. 2.2%; P=0.019). There was no difference in kidney dose between PBS and PS plans. CONCLUSIONS: Proton therapy for locally advanced pancreatic cancer using PBS was not clearly associated with clinically meaningful reductions in normal tissue dose compared to PS. Some statistically significant improvements in PTV coverage were achieved using PBS. PBS may offer improved conformality for the treatment of irregular targets, and further evaluation of PBS and PS incorporating elective nodal irradiation should be considered.

Does Masked Hypertension Cause Early Left Ventricular Impairment in Youth?

Objectives: Masked hypertension (MH) is not uncommon in the youth and may increase risks of long-term cardiovascular impairment. However, little is known about the subclinical heart damage in this group of patients. Currently, 3-layer speckle tracking imaging based on two-dimensional echocardiography is feasible to detect the early signs of myocardial damage. We therefore aimed to investigate whether subtle changes of cardiac function occurred in the young MH patients by using advanced quantification with layer-specific speckle tracking. Methods: A total of 40 adolescents with MH (age 18 ± 3 years, 73% males) and 40 age-, gender-, race-, and height-matched normotensive volunteers were enrolled in our study. MH was defined as one or more of the ambulatory blood pressure (BP) parameters (24-h, daytime and night-time average BPs) higher than ≥ 95th percentile for gender and height according to the local reference. Both comprehensive two-dimensional echocardiography with layer-specific strain analysis and 24-h ambulatory BP monitoring were performed. Longitudinal strain and circumferential strain in endocardial, mid-myocardial, and epicardial layers were determined accordingly with the dedicated software (EchoPAC software version 201, GE Healthcare, Horten, Norway). Results: Compared with normotensive controls, youths with MH had higher ambulatory pulse rate and left ventricular mass index, and were more obese. Interestingly, similar ventricular volumes and ejection fraction were observed in the study groups, but further analysis with layer-specific strains revealed that endocardial and mid-myocardial longitudinal and circumferential mechanical function were decreased in the young MH subjects when compared to normotensive individuals (all p < 0.05). However, there were no difference regarding radial strain and apical rotation derived from traditional speckle tracking analysis. Conclusion: Subclinical change of LV mechanic function assessed by layer-specific speckle tracking is present in youth with MH despite considered as normal with conventional ways.Thus, MH in youth should be monitored closely instead of labeling as an entirely benign entity.

Left ventricular mass of persistent masked hypertension in Hong Kong Chinese adolescents: a 4-year follow-up study.

OBJECTIVE: In our previous study, the prevalence of childhood masked hypertension was 11%. This study aims to assess the left ventricular mass index of persistent masked hypertension and determine the factors of elevated left ventricular mass index in Hong Kong Chinese adolescents from a community cohort. DESIGN: Community prospective cohort study, follow-up of a case-control study in community. SUBJECTS: Patients with masked hypertension at baseline were invited to recheck ambulatory blood pressure for the persistence of masked hypertension. RESULTS: A total of 144 out of 165 patients with masked hypertension in the 2011/2012 ambulatory blood pressure survey consented to participate in the study. In all, 48 patients were found to have persistent masked hypertension by ambulatory blood pressure rechecking and were matched with normotensive controls by sex, age, and body height. The left ventricular mass (117.3±39.9 g versus 87.0±28.2 g versus 102.0±28.2 g) and left ventricular mass index (30.1±8.4 g/m2.7 versus 23.9±6.3 g/m2.7 versus 25.1±5.7 g/m2.7) were significantly higher in the persistent masked hypertension group (p<0.0001) compared with the patients without persistent masked hypertension and controls. In multivariate linear regression analysis, left ventricular mass index was found to be higher in male gender (ß=4.874, p<0.0001) and the patients with persistent masked hypertension (ß=2.796, p=0.003). In addition, left ventricular mass index was positively associated with body mass index z-score (ß=3.045, p<0.0001) and low-density lipoprotein cholesterol concentration (ß=1.634, p=0.015). CONCLUSIONS: Persistent masked hypertension in adolescents is associated with elevated left ventricular mass index.

Automated left heart chamber volumetric assessment using three-dimensional echocardiography in Chinese adolescents.

BACKGROUND: Several studies have reported the accuracy and reproducibility of HeartModel for automated determination of three-dimensional echocardiography (3DE)-derived left heart volumes and left ventricular (LV) ejection fraction (LVEF) in adult patients. However, it remains unclear whether this automated adaptive analytics algorithm, derived from a 'training' population, can encompass adequate echo images in Chinese adolescents. OBJECTIVES: The aim of our study was to explore the accuracy of HeartModel in adolescents compared with expert manual three-dimensional (3D) echocardiography. METHODS: Fifty-three Chinese adolescent subjects with or without heart disease underwent 3D echocardiographic imaging with an EPIQ system (Philips). 3D cardiac volumes and LVEF obtained with the automated HeartModel program were compared with manual 3D echocardiographic measurements by an experienced echocardiographer. RESULTS: There was strong correlation between HeartModel and expert manual 3DE measurements (r = 0.875-0.965, all P < 0.001). Automated LV and left atrial (LA) volumes were slightly overestimated when compared to expert manual measurements, while LVEF showed no significant differences from the manual method. Importantly, the intra- and inter-observer variability of automated 3D echocardiographic model was relatively low (<1%), surpassing the manual approach (3.5-17.4%), yet requiring significantly less analyzing time (20 ± 7 vs 177 ± 30 s, P < 0.001). CONCLUSION: Simultaneous quantification of left heart volumes and LVEF with the automated HeartModel program is rapid, accurate and reproducible in Chinese adolescent cohort. Therefore, it has a potential to bring 3D echocardiographic assessment of left heart chamber volumes and function into busy pediatric practice.

Variants of cardiomyopathy and hypertension in neuroblastoma.

Catecholamine-associated cardiomyopathies caused by neuroblastoma have rarely been reported. We are reporting 2 cases of neuroblastoma associated with hypertension and severe cardiomyopathic changes in different extremes. One case was dilated cardiomyopathy with heart failure, and the other showed echocardiographic features simulating hypertrophic obstructive cardiomyopathy. Both girls had high levels of urine catecholamines on presentation. Anthracycline group of chemotherapy was avoided. Chemotherapy and tumor resection resulted in successful normalization of blood pressure and regression of cardiomyopathic changes. Blood pressure and cardiomyopathic changes should be monitored not only at presentation, but also during the treatment for neuroblastoma.

The Figure-of-Eight Walk test: reliability and associations with stroke-specific impairments.

OBJECTIVES: To investigate (1) the intra-rater, inter-rater and test-retest reliabilities of the Figure-of-Eight Walk (F8W) test times; (2) its correlation with other stroke-specific impairments; and (3) the cut-off scores best discriminating patients with stroke from the healthy elderly. DESIGN: Cross-sectional study. SETTING: University-based rehabilitation centre. PARTICIPANTS: A convenience sample of 64 subjects: 35 subjects with chronic stroke and 29 healthy elderly. MAIN OUTCOME MEASURES: F8W test times, Fugl-Meyer Motor Assessment for the lower extremities (FMA-LE), hand-held dynamometer measurements of bilateral hip abductor and knee extensor isometric muscle strength, Five times Sit to Stand Test (FTSTST) times, 10-Meter Walk Test (10MWT), Timed Up and Go Test (TUGT) times, Berg Balance Scale (BBS) and Activities-specific Balance Confidence Scale (ABC) scores. RESULTS: Excellent intra-rater, inter-rater and test-retest reliabilities (intra-class correlation coefficient (ICC) range 0.944-0.999) of F8W test times were found. The F8W test times were also found to be significantly associated with FMA-LE, BBS, FTSTST, TUG scores and 10MWT. No significant correlation was found between F8W test times and either leg strength or ABC results. A F8W test time of 8.2 s was found to be the most representative for discriminating between healthy elderly and stroke subjects, with a sensitivity of 100% and a specificity of 89.7%. CONCLUSIONS: The F8W test time is a reliable measurement tool, which is able to differentiate the patients with stroke and healthy elderly subjects and correlated well with stroke-specific impairments and walking tests. The F8W is a reliable measurement tool for assessing the advanced walking performance of subjects with chronic stroke. Implication for Rehabilitation The F8W test times have excellent intra-rater, inter-rater and test-retest reliabilities in patients with chronic stroke. The F8W test times were also found to be significantly associated with FMA-LE, BBS, FTSTST, TUG scores and 10MWT. A F8W test time of 8.2 s was found to be the most representative for discriminating between healthy elderly and stroke subjects, with a sensitivity of 100% and a specificity of 89.7%. The F8W test time is a reliable and valid measure in assessing the advanced walking skill in patients with stroke.

Prevalence and risk factors for hypertension in Hong Kong Chinese adolescents: waist circumference predicts hypertension, exercise decreases risk.

PURPOSE: To determine the prevalence, risk factors for and patterns of hypertension in Chinese adolescents based on a territory-wide school based screening programme in Hong Kong. METHODS: Cross-sectional anthropometric and oscillometric blood pressure (BP) measurements and lifestyle information were obtained as part of a growth survey of students from randomly selected secondary schools in Hong Kong. Those with blood pressure ≥ 95th centile were screened a second or third time. Hypertension is defined as elevated blood pressure on three separate occasions. The independent effects of age, sex, body mass index, high waist circumference (≥ 85th centile), sleep duration, family history of hypertension and frequency of exercise on hypertension were explored by multivariate analysis. RESULTS: Among the 6193 students screened, the prevalence of elevated blood pressure on the first, second and third screens was 9.54%, 2.77% and 1.44% respectively. Hypertension was more likely to be systolic. High waist circumference (≥ 85th centile) was independently associated with a higher risk of hypertension (adjusted OR 2.4), while exercising twice or more per week was protective (adjusted OR 0.28). CONCLUSIONS: The prevalence of hypertension in Hong Kong Chinese adolescents is 1.44%. The current study shows high waist circumference is a predictor of hypertension in adolescents, while increased physical activity is a protective factor. Incorporating waist circumference into screening protocols may increase the sensitivity of cardiovascular risk stratification. Healthcare providers should be strong advocates helping to prevent obesity and promote physical activity in adolescents and children.

Assessment of coronary artery aneurysms in paediatric patients with Kawasaki disease by multidetector row CT angiography: feasibility and comparison with 2D echocardiography.

BACKGROUND: Transthoracic ECHO is the locally accepted method for coronary surveillance of patients with Kawasaki disease but it may have limited visualization in the older child. OBJECTIVE: To assess the feasibility of multidetector CT (MDCT) angiography in the follow-up of coronary artery aneurysms in children with previous Kawasaki disease. MATERIALS AND METHODS: Six children (5 boys, 1 girl; mean age 11.5 years) with known Kawasaki disease and coronary artery involvement underwent CT coronary angiography using 16-detector MDCT. The visualized lengths and diameter of all coronary segments were measured. The number, size and location of coronary artery aneurysms were recorded and compared with recent ECHO. RESULTS: Twelve coronary artery aneurysms (seven saccular, five fusiform) were identified by MDCT angiography. One saccular aneurysm at the junction of the distal right coronary artery and posterior descending artery was not detected by ECHO while the remaining six in proximal segments were detected by both modalities. Two of five fusiform aneurysms were not detected by ECHO due to their small sizes. Excellent agreement was found between CT and ECHO for maximal diameter and length of the visualized aneurysms. CONCLUSIONS: MDCT angiography accurately defines coronary artery aneurysms. It is more sensitive for detecting aneurysms at distal coronary segments and fusiform aneurysms of small size.

Secreted PDZD2 exerts concentration-dependent effects on the proliferation of INS-1E cells.

PDZD2 (PDZ domain containing 2) is a multi-PDZ protein expressed in pancreas and many other tissues. PDZD2 shows extensive homology to pro-interleukin-16 (pro-IL-16) and is localized mainly to the endoplasmic reticulum. We have recently demonstrated that PDZD2, like pro-IL-16, is proteolytically cleaved at its C-terminus to generate a secreted protein, sPDZD2 (for secreted PDZD2). To understand the possible functional role of PDZD2 in pancreas, we investigated the cellular distribution of PDZD2 in adult pancreas using an antiserum that recognizes both the full-length and secreted forms of PDZD2. Immunohistochemical analysis revealed a strong expression of PDZD2 in pancreatic islet beta cells but not alpha cells. Consistent with the beta-cell-enriched expression of PDZD2, immunoblot analysis indicated expression of both full-length PDZD2 and sPDZD2 in the insulinoma cell line INS-1E. A recombinant sPDZD2 protein was synthesized for study of its functional effect on INS-1E cells. In culture media with limiting serum, co-incubation with sPDZD2 stimulated the proliferation of INS-1E cells. The mitogenic effect of sPDZD2 was concentration-dependent, and was associated with a slight inhibition of the insulin promoter activity at high sPDZD2 concentrations. As a potential mitogen of beta-like cells, sPDZD2 may be useful for the optimization of beta-cell growth and differentiation in vitro.

Oral sildenafil for treatment of severe pulmonary hypertension in an infant.

We report the use of oral sildenafil in a 5-month-old preterm infant with severe bronchopulmonary dysplasia and pulmonary arterial hypertension refractory to inhaled nitric oxide treatment, maximal ventilatory support and conventional vasodilator therapy. Sildenafil was prepared as a liquid suspension by the method of trituration and administered via an orogastric tube to the patient. Forty-eight hours after sildenafil treatment, echocardiography revealed that the tricuspid incompetence was substantially diminished and the contractility of both ventricles improved, indicating a marked reduction in pulmonary arterial pressure. Oral sildenafil treatment was continued for 6 months until complete resolution of pulmonary arterial hypertension, and oxygen supplement was weaned off. There was no adverse effect during the treatment period. Oral sildenafil may be useful in reducing pulmonary vascular resistance and can be considered for treatment of severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia.