Hirotaro Ogino

Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan.

Background: Some Kawasaki disease (KD) patients do not respond to initial treatment with intravenous immunoglobulin (IVIG). The purpose of this study was to determine potential risk factors associated with IVIG nonresponse among KD patients in Japan. Methods: Data were obtained from questionnaires used for the 18th nationwide KD survey of patients who visited hospitals in Japan from 2003 through 2004. Data for patients who met the case definition for KD and received 2 g/kg single infusion IVIG as the initial treatment within 10 days of illness were analyzed. IVIG nonresponders were defined as patients who needed secondary treatment after initial IVIG administration. Results: Among 15,940 KD patients in Japan during 2003–2004, 6330 patients received 2 g/kg single infusion IVIG within 10 days of illness onset. IVIG nonresponders accounted for 20.3% of them (n = 1286). Male sex [odds ratio (OR), 1.21, 95% confidence interval (CI), 1.06–1.37], receipt of the initial IVIG before the fifth day of illness (OR: 1.89, 95% CI: 1.66–2.15), and having recurrent KD (OR: 1.38, 95% CI: 1.00–1.90) were significantly associated with IVIG nonresponse. In addition, IVIG nonresponders had significantly higher risks for coronary artery aneurysms (OR: 10.38, 95% CI: 6.98–15.45) or giant coronary artery aneurysms (OR: 54.06, 95% CI: 12.84–227.65). Conclusions: Physicians should consider potential IVIG nonresponse among recurrent KD patients or KD patients diagnosed and treated before the fifth day of illness, particularly if they are boys and have laboratory values associated with nonresponse such as low platelet count, and elevated alanine aminotransferase and C-reactive protein. Some of these patients may benefit from administration of the alternative secondary treatment early during the illness along with the initial IVIG treatment.

Evaluation of Preclinical Atherosclerosis by Flow-Mediated Dilatation of the Brachial Artery and Carotid Artery Analysis in Patients with a History of Kawasaki Disease

Cardiac sequelae of Kawasaki disease are an important cause of ischemic heart disease in young adults. The possibility of early progression of atherosclerosis following Kawasaki disease is therefore of great concern. We examined whether preclinical atherosclerotic changes are seen in patients with a history of Kawasaki disease, and whether these changes appear in all or in only a proportion of patients. Sixty-five patients with a history of Kawasaki disease, aged 13.1 ± 2.1 years, and 20 aged-matched controls participated in the study. All subjects underwent flow-mediated dilatation (FMD) of the brachial artery and analysis of carotid artery size and pulse-wave transmission. Patients were classified into four groups depending on the severity of the maximum coronary artery lesion: group 0 (normal), group 1 (mild), group 2 (moderate), and group 3 (severe). There was no statistical difference in the carotid artery analyses between the four groups. FMD (mean ± SD) was significantly lower in groups 2 and 3 than in groups 0 and 1 and the control group (group 0, 19.4 ± 3.9%; group 1, 19.5 ±4.1%; group 2, 8.9 ± 2.8%; group 3, 4.2 ± 1.5%; control group, 18.8 ± 2.8%; p < 0.0001). There was a significantly negative correlation between the severity of the coronary artery lesion and FMD (p < 0.0001 for both). Endothelial dysfunction was revealed by FMD in patients with persistent coronary artery lesions subsequent to Kawasaki disease. Preclinical atherosclerosis may be present only in patients with coronary aneurysms.

Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease

Over 35 years have elapsed since the first case of Kawasaki disease was described in 1967. 1 As they grow older, many patients with a history of Kawasaki disease are treated in departments of internal medicine rather than in pediatric departments. This disease has been extensively studied throughout the world, and many reports have been published on its etiology and cardiovascular sequelae. While the causes of Kawasaki disease unfortunately remain unknown, its cardiovascular sequelae have been intensively studied, contributing to the establishment of their pathology, natural history, diagnosis, and treatment. This provided the impetus for the Japanese Circulation Society to prepare a set of guidelines. The latest guidelines for the diagnosis of Kawasaki disease, as revised in 2002, are shown in Table 1. These are used to diagnose the disease in its acute phase. The diagnostic guidelines may be useful in adults with an unknown history of Kawasaki disease when the illness is suspected from the morphology of any coronary artery aneurysms. In preparing the present guidelines for the cardiovascular sequelae of Kawasaki disease, the first issue addressed was the classification of the size and severity of coronary artery aneurysms using standardized criteria. The consensus criteria shown in Table 2 were prepared according to the conventional classification and the opinions of specialists.

Multiple Hepatoblastomas Associated with Trisomy 18 in a 3-Year-Old Girl

A very rare case of full trisomy 18 associated with multiple hepatoblastomas is reported. The patient also had ventricular septal defect and patent ductus arteriosus, which were repaired at 6 months of age. After the cardiac surgery, she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein level. A partial hepatic lobectomy was performed at 7 months of age, and the resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4 months of age, a chest radiography disclosed an elevated left diaphragm, and abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor cell obtained on two occasions were both 47,XX, +18. She has no evidence of recurrence at 3 years of age without specific therapy.

Chapter 12 GC/MS of Molecular Species of Glycerophospholipids

Publisher Summary This chapter provides an overview of the mass chromatographic procedures for the analysis of the molecular species of choline and ethanolamine phosphatides from rat brain. The chapter discusses the relationship between the composition of the molecular species localized at different subcellular fractions of brain and the physiological function of the cerebral nervous system. The chapter describes the quantitative analysis of platelet activating factor— particularly by selected ion monitoring (SIM) technique and its application to biological materials, and describes the chronological changes in composition of the molecular species of choline phosphatides during the pre- and post-natal periods of rat cerebra. Identification of the individual molecular species by this technique is achieved without difficulty and monitoring m/z 117 indicates the presence of acetyl moiety, m/z [R+130] + indicates the presence of fatty alcohol, while m/z [M-57] + confirms the occurrence of both acetic and fatty alcohol residues in the same molecule. After comparing the retention times of the unknowns with those of standard AGEPC, an unequivocal identification is obtained. This system is successfully applied to PAF from rat skin and muscle stimulated by moxibustion and to PAF in normal rat uterus.

Successful trimethoprim-sulfamethoxazole therapy in a patient with hyperimmunoglobulin E syndrome

A male patient with hyperimmunoglobulin E syndrome is described. Recurrent lymphadenitis and cutaneous staphylococcal abscesses were resistant to various antibiotics, and chemotaxis and hydrogen peroxide production of polymorphonuclear leukocytes were impaired. Following trimethoprim‐sulfamethoxazole therapy, he was free from the above infections, and impaired polymorphonuclear leukocyte functions recovered and serum IgE decreased to approximately one‐fifth of its initial level. Subsequent irregular medications, however, resulted in impairment of polymorphonuclear leukocyte functions and an increased serum IgE concentration, which recovered after regular resumption of trimethoprim‐sulfamethoxazole treatment. From these results, the beneficial effects of trimethoprim‐sulfomethoxazole in hyperimmunoglobulin E syndromgak clinically apparent, but in vitro studies failed to demonstrate the positive effect of trkethoprim‐sulfamethoxazole on polymorphonuclear leukocytes and their mechanism still remains to be elucidated.

Determination of Molecular Species of Glycerophospholipids by a GC-MS Selected Ion Monitoring Technique

Four types of glycerophospholipids, i.e., 1,2-dalkyl, 1-alkenyl-2-acyl, 1-alkyl-2-acyl and 1,2-diacyl glycerols as TMS or TBDMS derivatives were separated and identified by monitoring three kinds of fragment ions, 1) M-15 or M-57 for determining molecular weight; 2) RCO + 74, R + 130 and RCH=CH + 56 for acyl, alkyl and alkenyl residues, respectively, and 3) base peaks corresponding to TMS-glycerol (m/e 129, 130) or O-TBDMS (m/e 131).