Ei Ikegami

Possible Synergic Effect of Angiotensin-I Converting Enzyme Gene Insertion/Deletion Polymorphism and Angiotensin-II Type-1 Receptor 1166A/C Gene Polymorphism on Ischemic Heart Disease in Patients with Kawasaki Disease

ACE I/D and AT1R 1166A/C polymorphisms are considered to comprise individual risk factors for the development of coronary disease. We sought to demonstrate that the ACE I/D and AT1R 1166A/C polymorphisms affect coronary artery stenosis in patients with Kawasaki disease (KD). We examined 147 healthy controls and 281 Japanese children with KD. The patients were further divided into group N (n = 246, no ischemia) and group I (n = 35, severe coronary artery stenosis with myocardial ischemia), and we studied the genotype of ACE I/D and AT1R 1166A/C polymorphisms. We also examined ACE activity in patients with acute KD. We did not detect any prevalent genotypes of the ACE and AT1R polymorphisms between controls and KD patients. However, the prevalence of the D allele in the ACE polymorphism and of the C allele in the AT1R polymorphism tended to be higher in group I than in group N (odds ratios, 2.00 and 2.32, respectively). In addition, the presence of the D and/or C alleles significantly increased the relative risk of developing myocardial ischemia (odds ratio, 2.71; p = 0.038). During the convalescent phase of KD, ACE activity was increased despite significant attenuation during the acute phase. These results suggested that the renin-angiotensin system is associated with the formation of severe coronary artery stenosis and myocardial ischemia.

Reduced shear stress and disturbed flow may lead to coronary aneurysm and thrombus formations

Background: With Kawasaki disease it is important to clarify the mechanisms of coronary artery aneurysm and thrombus to avoid acute myocardial infarction. The authors tested the hypothesis that shear stress is reduced at coronary branching sites and in coronary artery aneurysms, and that this reduction of shear stress can promote formation of coronary artery aneurysms and thrombus.

A Deep Intronic Mutation in the SLC12A3 Gene Leads to Gitelman Syndrome

Many mutations have been detected in the SLC12A3 gene of Gitelman syndrome (GS, OMIM 263800) patients. In previous studies, only one mutant allele was detected in ∼20 to 41% of patients with GS; however, the exact reason for the nonidentification has not been established. In this study, we used RT-PCR using mRNA to investigate for the first time transcript abnormalities caused by deep intronic mutation. Direct sequencing analysis of leukocyte DNA identified one base insertion in exon 6 (c.818_819insG), but no mutation was detected in another allele. We analyzed RNA extracted from leukocytes and urine sediments and detected unknown sequence containing 238bp between exons 13 and 14. The genomic DNA analysis of intron 13 revealed a single-base substitution (c.1670–191C>T) that creates a new donor splice site within the intron resulting in the inclusion of a novel cryptic exon in mRNA. This is the first report of creation of a splice site by a deep intronic single-nucleotide change in GS and the first report to detect the onset mechanism in a patient with GS and missing mutation in one allele. This molecular onset mechanism may partly explain the poor success rate of mutation detection in both alleles of patients with GS.

Multiple fungal splenic abscesses in a patient with T‐acute lymphoblastic leukemia undergoing chemotherapy

Of the various infections associated with therapy for cancer, invasive fungal infection poses a serious threat. However, with the practice of administering fluconazole (FLCZ) to immunocompromised patients following hematopoietic stem cell transplantation or chemotherapy, the incidence of invasive fungal infection has become lower. 1,2 However, the incidence of FLCZ-resistant candidiasis and aspergillosis has been increasing in recent years. 3,4 Here, we report a patient with T-acute lymphoblastic leukemia (ALL) after receiving chemotherapy, developed multiple splenic abscesses caused by Candida krusei .

Bifid scrotum and anocutaneous fistula associated with a perineal lipomatous tumor complicated by temporary bilateral cryptorchidism in utero mimicking ambiguous genitalia: 2-D/3-D fetal ultrasonography.

Ambiguous genitalia (AG) is a morphological diagnosis defined as genitalia not typical of a male or female. Findings mimicking AG, such as penoscrotal anomalies, anorectal malformations, and perineal lipomatous tumors, may prevent accurate identification of the fetal sex. We report a case of bifid scrotum and anocutaneous fistula associated with a perineal lipomatous tumor complicated by temporary bilateral cryptorchidism in utero, which were findings mimicking AG. Several perineal anomalies are associated developmental occurrences. In the present case, the combination of bifid scrotum and temporary bilateral cryptorchidism in the male fetus mimicked the combination of clitoromegaly and prominent labia, which are commonly observed in female fetuses. However, serial systemic assessments using prenatal 2‐D/3‐D ultrasonography and magnetic resonance imaging were unable to detect the anocutaneous fistula and differentiate the perineal lipomatous tumor. This case report suggests that the prenatal detection of perineal abnormalities may warn obstetricians of potentially undetected congenital perineal anomalies.

Criteria of Myocardial Fractional Flow Reserve and Coronary Flow Ratio for Detection of Myocardial Ischemia in Patients with Kawasaki Disease

Purpose of this study is to estimate the criteria of myocardial fractional flow reserve (FFRmyo) and coronary flow ratio (CFR) for detection of silent myocardial ischemia. 112 patients (1y-15y) were divided into three groups; normal coronary or coronary dilation without stenosis (N) group (n=61), coronary stenosis without ischemia (n-IS) group (n=30), myocardial ischemia (IS) group (n=21) by 2-D echo, and rest and exercised myocardial scintigraphy. FFRmyo is defined as the ratio of maximal achievable flow in myocardium subtended by a stenosed coronary artery to the maximal achievable myocardial flow induced by papaverine. CFR was calculated as a ratio of averaged peak velocity before and after papaverine. FFRmyo and CFR were calculated and compared among three groups. Sensitivity and specificity for detection of myocardial ischemia were calculated by abnormal values of FFRmyo and CFR. Moreover, FFRmyo and CFR tests estimated effectiveness of PTCA and CABG. Results: Criteria for detection of myocardial ischemia were defined the mean±2sds for values of FFRmyo and CFR in N group; <0.75 in FFRmyo and <2.0 in CFR. FFRmyo and CFR in IS group (0.64±0.3#, 1.2±0.4#) were significantly decrease (# p<0.05). Sensitivity and specificity for detection of myocardial ischemia were very high by FFRmyo and CFR. Moreover, FFRmyo and CFR were very useful index for analysis of coronary blood flow velocity and pressure dynamics before and after PTCA and CABG. Conclusions: The values of <0.75 in FFRmyo and <2.0 in CFR can be useful to estimate myocardial ischemia and to evaluate the effectiveness of PTCA and CABG.

ACE I/D and AT1 1166A/C Polymorphism as a Risk Factor for Coronary Artery Stenosis in Kawasaki Disease

Gene polymorphism is considered to become the individual risk factors for the disease developments. We studied the gene polymorphism of Angiotensin Converting Enzyme(ACE) I/D, and Angiotensin II Receptor1 (AT1) 1166A/C polymorphism in Kawasaki disease patients and examined whether these polymorphism associate with coronary artery stenosis. (Subjects and Methods) 195 Kawasaki disease patients were enrolled in this study. Written informed consents were acquired from all patients. We divided the patients into three groups. Group N (n=122); no coronary artery changes, Group C (n=40); coronary artery dilation and/or stenosis without myocardial ischemia, Group S (n=33); coronary artery stenosis with myocardial ischemia. Genomic DNA specific primers were designed and Polymerase Chain Reaction (PCR) were performed. PCR products were separated on the agarose gel directly (ACE I/D polymorphism), or after the sequence specific restriction enzymes digestion (AT1 1166A/C polymorphism). (Results) We could not detect any significant differences in specific genotypes between the groups. However, when we evaluated the patients whether they possess D allele of ACE I/D polymorphism and/or C allele of AT1 1166A/C polymorphism, the patients who own both ACE polymorphism D allele and AT1 polymorphism C allele were significantly higher in Group S (χ2 test; p<0.05). We concluded the Kawasaki disease patients who have both D allele in ACE I/D polymorphism and C allele in AT1 1166A/C polymorphism are exposed to the higher risk for coronary artery stenosis.