Takaomi Minami

Development of a new point-of-care testing system for measuring white blood cell and C-reactive protein levels in whole blood samples.

BACKGROUND White blood cell (WBC) count and C-reactive protein (CRP) level are the most common markers of inflammation. There is a growing need for point-of-care testing (POCT) of WBC and CRP, and more advances in convenient devices are required. We developed an analyzer-free POCT system for measuring WBC and CRP using a low volume blood sample. METHODS The POCT-WBC is based on the granulocyte esterase assay, while the POCT-CRP is based on the immunochromatographic assay. These kits were examined for precision as well as correlation with currently used popular commercial automated assays. The correlations were clinically analyzed in children with acute infection (n=62; mean age 4.2y). The correlations regarding the monitoring of values were further examined in several follow-up subjects. RESULTS The POCT-WBC and POCT-CRP kits demonstrated good precision. POCT-WBC exhibited a significantly close correlation with those of the control assay (r=0.94, p<0.05). The results of POCT-CRP also exhibited a significantly close correlation with those of the control assay (r=0.94, p<0.05). In the follow-up study, the results of the respective kits were similar to those of the control assays. CONCLUSIONS The POCT-WBC and POCT-CRP are promising tools for assessing infection in clinical practice.

Arrhythmia risk and β-blocker therapy in pregnant women with long QT syndrome

Background Pregnancy is one of the biggest concerns for women with long QT syndrome (LQTS). Objectives This study investigated pregnancy-related arrhythmic risk and the efficacy and safety of β-blocker therapy for lethal ventricular arrhythmias in pregnant women with LQTS (LQT-P) and their babies. Methods 136 pregnancies in 76 LQT-P (29±5 years old; 22 LQT1, 36 LQT2, one LQT3, and 17 genotype-unknown) were enrolled. We retrospectively analysed their clinical and electrophysiological characteristics and pregnancy outcomes in the presence (BB group: n=42) or absence of β-blocker therapy (non-BB group: n=94). Results All of the BB group had been diagnosed with LQTS with previous events, whereas 65% of the non-BB group had not been diagnosed at pregnancy. Pregnancy increased heart rate in the non-BB group; however, no significant difference was observed in QT and Tpeak–Tend intervals between the two groups. In the BB group, only two events occurred at postpartum, whereas 12 events occurred in the non-BB group during pregnancy (n=6) or postpartum period (n=6). The frequency of spontaneous abortion did not differ between the two groups. Fetal growth rate and proportion of infants with congenital malformation were similar between the two groups, but premature delivery and low birthweight infants were more common in those taking BB (OR 4.79, 95% CI 1.51 to 15.21 and OR 3.25, 95% CI 1.17 to 9.09, respectively). Conclusions Early diagnosis and β-blocker therapy for high-risk patients with LQTS are important for prevention of cardiac events during pregnancy and the postpartum period, and β-blocker therapy may be tolerated for babies in LQT-P cases.

The serum concentration of soluble interleukin-2 receptor in patients with Kawasaki disease

Kawasaki disease is a febrile disease of childhood that is associated with increased inflammatory cytokines and immunoregulatory abnormalities. While the serum concentrations of soluble IL-2 receptor can change under such pathologies, the relevance of the soluble IL-2 receptor concentration in patients with Kawasaki disease has not been specified. We aimed to summarize the existing studies that reported the soluble IL-2 receptor concentrations in patients with Kawasaki disease. Original articles that were published up to July 2016 were collected using a PubMed/Medline-based search engine. A total of nine articles that reported the serum soluble IL-2 receptor concentrations in acute-phase Kawasaki disease were eligible. All of the articles described a high soluble IL-2 receptor concentration in patients with Kawasaki disease relative to the level of controls or the reference range. Two of five articles on patients with coronary artery aneurysms described a significantly higher soluble IL-2 receptor concentration in patients with coronary artery aneurysms than patients without. Two articles on patients with intravenous immunoglobulin therapy described a significant decrease of the soluble IL-2 receptor concentration after the therapy. Accordingly, the serum soluble IL-2 receptor can be a potent marker of disease activity and therapeutic effects in patients with Kawasaki disease; further studies are thus warranted for its use in the clinical setting.

Pulse Wave Velocity in Kawasaki Disease

Kawasaki disease (KD) is an acute childhood febrile disease of unknown etiology. It exhibits not only coronary artery aneurysms in some cases but also systemic vasculitis. Whether KD is associated with accelerated atherosclerosis remains debatable. The measurement of pulse wave velocity (PWV) is useful as a simple, noninvasive measurement of arterial stiffness, an atherosclerotic manifestation. We herein present a systematic review of clinical studies that focused on PWV in patients with KD. A PubMed-based search identified 8 eligible studies published until June 2015. The PWV of patients with KD, regardless of antecedent coronary artery lesions, was high relative to controls, even though their blood pressure appeared to be similar. Although definitive conclusions cannot be made with the limited information, patients with KD may be at risk of systemic atherosclerosis in association with arterial stiffness. Further research, including longitudinal and outcome studies, is needed to determine the clinical significance of a potential increase in PWV in patients with KD.

6q21–22 deletion syndrome with interrupted aortic arch

Interstitial deletion of 6q21–22 has been previously reported in 11 individuals, who presented with intellectual disability, facial dysmorphism, cardiac abnormality, cerebellar hypoplasia and dysplasia of the corpus callosum. Here, we report the first instance of a patient with 6q21–22 deletion presenting with interrupted aortic arch in addition to the previously described clinical signs. Array analysis using Agilent Human genome CGH 180K identified a 13.3-Mb deletion at 6q21–q22.31 (nt. 109885195–123209593).

Infantile incomplete Kawasaki disease mimicking cervical purulent lymphadenitis with coronary artery aneurysm

1 Zimprich A, Grabowski M, Asmus F et al. Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome. Nat. Genet. 2001; 29: 66–9. 2 Grabowski M, Zimprich A, Lorenz-Depiereux B et al. The epsilon-sarcoglycan gene (SGCE), mutated in myoclonusdystonia syndrome, is maternally imprinted. Eur. J. Hum. Genet. 2003; 11: 138–44. 3 Baker KE, Parker R. Nonsense-mediated mRNA decay: terminating erroneous gene expression. Curr. Opin. Cell Biol. 2004; 16: 293–9. 4 Lohmann K, Klein C. Update on the genetics of dystonia. Curr. Neurol. Neurosci. Rep. 2017; 17: 26. 5 Peall KJ, Kurian MA, Wardle M et al. SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype. J. Neurol. 2014; 261: 2296–304.

Xq26.1-26.3 duplication including MOSPD1 and GPC3 identified in boy with short stature and double outlet right ventricle

Xq25q26 duplication syndrome has been reported in individuals with clinical features such as short stature, intellectual disability, syndromic facial appearance, small hands and feet, and genital abnormalities. The symptoms are related to critical chromosome regions including Xq26.1‐26.3. In this particular syndrome, no patient with congenital heart disease was previously reported. Here, we report a 6‐year‐old boy with typical symptoms of Xq25q26 duplication syndrome and double outlet right ventricle (DORV) with pulmonary atresia (PA). He had the common duplicated region of Xq25q26 duplication syndrome extending to the distal region including the MOSPD1 locus. MOSPD1 regulates transforming growth factor beta (TGFβ) 2,3 and may be responsible for cardiac development including DORV. In the patients lymphocytes, mRNA expression of TGFβ2 was lower than control, and might cause DORV as it does in TGFβ2‐deficient mice. Therefore, MOSPD1 is a possible candidate gene for DORV, probably in combination with GPC3. Further studies of the combined functions of MOSPD1 and GPC3 are needed, and identification of additional patients with MOSPD1 and GPC3 duplication should be pursued.

Treatment of a patient with kawasaki disease associated with selective iga deficiency by continuous infusion of cyclosporine a without intravenous immunoglobulin

Intravenous immunoglobulin therapy is standard for Kawasaki disease (KD) treatment; however, anaphylactic reactions to immunoglobulins are a risk in KD patients with selective IgA deficiency (sIgAD). The therapy for KD associated with sIgAD has not been established. The IgA immune response is believed to play an important role in KD vasculitis. We report the case of a 5-year-old boy with KD and sIgAD treated with intravenous cyclosporine A (CsA, 3.0 mg/kg/day) instead of intravenous immunoglobulin (IVIG). The fever and inflammation immediately resolved without a coronary artery lesion. In KD patients with sIgAD, we believe that an IgA immune response is lacking, which is the reason for milder KD symptoms than in those without sIgAD. This case report aids in clarifying the role of IgA antibodies in KD and provides evidence that CsA is a potential candidate for first-line therapy for patients with KD with contraindications to IVIG.