Background: Carvedilol is a beta-adrenergic receptor antagonist primarily metabolized by cytochromes P450 (CYP) 2D6. This study established a carvedilol population pharmacokinetic (PK)–pharmacodynamic (PD) model to describe the effects of CYP2D6 genetic polymorphisms on the inter-individual variability of PK and PD. Methods: The PK–PD model was developed from a clinical study conducted on 21 healthy subjects divided into three CYP2D6 phenotype groups, with six subjects in the extensive metabolizer (EM, *1/*1, *1/*2), seven in the intermediate metabolizer-1 (IM-1, *1/*10, *2/*10), and eight in the intermediate metabolizer-2 (IM-2, *10/*10) groups. The PK–PD model was sequentially developed, and the isoproterenol-induced heart rate changes were used to establish the PD model. A direct effect response and inhibitory E max model were used to develop a carvedilol PK–PD model. Results: The carvedilol PK was well described by a two-compartment model with zeroorder absorption, lag time, and first-order elimination. The carvedilol clearance in the CYP2D6*10/*10 group decreased by 32.8% compared with the other groups. The inhibitory concentration of carvedilol estimated from the final PK–PD model was 16.5 ng/mL regardless of the CYP2D6 phenotype. Conclusion The PK–PD model revealed that the CYP2D6 genetic polymorphisms were contributed to the inter-individual variability of carvedilol PK, but not PD.

PURPOSE: We undertook this study to investigate discrepancies in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values, and variations following intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). METHODS: A total of 123 KD patients were retrospectively enrolled. Patients were treated with IVIG 2 g/kg at 2 to 9 days after disease onset. We obtained white blood cell (WBC) count, percentage of neutrophils (% neutrophils), CRP, ESR, and N-terminal pro-brain natriuretic peptide (NT-proBNP) values before and 48 to 72 hours after IVIG treatment. Discrepancy was defined as CRP ≥10 mg/dL and ESR <50 mm/hr (Group 1), or CRP <10 mg/dL and ESR ≥50 mm/hr (Group 2). RESULTS: Thirty-six of 123 subjects (29.2%) had a discrepancy: 25 (20.3%) in Group 1 and 11 (8.9%) in Group 2. In Group 1, 15 patients (60%) had fever for <5 days (early presenter) and 10 (40%) had fever for ≥5 days (late presenter). There were six early presenters (55%) and five late presenters (45%) in Group 2. Late presenters had higher ESR than early presenters (34.3±21.0 mm/hr vs. 26.3±19.3 mm/hr, P=0.029). After IVIG treatment, elevated WBC count, % neutrophils, CRP, and NT-proBNP levels normalized. In contrast, ESR increased from 37.4±21.9 mm/hr to 48.0±22.7 mm/hr (n=36, P=0.051). CONCLUSIONS: A discrepancy may be related to the duration of fever. Due to discrepancies in CRP and ESR values in acute KD, both should be measured to assess the degree of inflammatory activity before IVIG treatment. After IVIG treatment, the ESR should not be used as a marker of response to therapy in KD.
Blood Sedimentation* ; C-Reactive Protein* ; Erythrocytes* ; Fever ; Humans ; Immunization, Passive* ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Leukocytes ; Mucocutaneous Lymph Node Syndrome* ; Neutrophils ; Retrospective Studies

Polymorphism of angiotensin converting enzyme (ACE) gene is reported to be associated with ischemic heart disease, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy. In this study, we investigated the relationship between Kawasaki disease and insertion/deletion polymorphism of ACE gene. Fifty five Kawasaki disease patients and 43 healthy children were enrolled. ACE genotype was evaluated from each of the subjects' DNA fragments through polymerase chain reaction (PCR). Frequencies of ACE genotypes (DD, ID, II) were 12.7%, 60.0%, 27.3% in Kawasaki group, and 41.9%, 30.2%, 27.9% in control group respectively, indicating low rate of DD and high rate of ID genotype among Kawasaki patients (p<0.01). Comparing allelic (I, D) frequencies, I allele was more prevalent in Kawasaki group than in control group (57.3% vs. 43.0%, p<0.05). In Kawasaki group, both genotype and allelic frequencies were not statistically different between those with coronary dilatations and those without. ACE gene I/D polymorphism is thought to be associated with Kawasaki disease but not with the development of coronary dilatations.
*Polymorphism, Genetic ; Peptidyl-Dipeptidase A/*genetics ; Mucocutaneous Lymph Node Syndrome/*enzymology/*genetics/pathology ; Male ; Infant ; Humans ; Genotype ; Gene Frequency ; Female ; Dilatation, Pathologic ; Coronary Vessels/pathology ; Child, Preschool ; Case-Control Studies ; Alleles

Foreign body aspiration (FBA) is a common accident in young children. Undiagnosed and retained foreign bodies may result in severe early and late complications such as asphyxia, pneumonia, atelectasis and bronchiectasis. Moreover, because it can mimic bronchiolitis, croup or asthma, an accurate history and a high index of suspicion are of paramount importance for early diagnosis. With our experience on bronchial FBA initially misdiagnosed as acute bronchiolitis, we emphasize that a minute radiological finding should not be neglected and a repeat chest radiograph may be helpful when the initial study shows normal findings. Multidetector computed tomography is a very useful noninvasive diagnostic modality for FBA.
Asphyxia ; Asthma ; Bronchi ; Bronchiectasis ; Bronchiolitis ; Child ; Croup ; Early Diagnosis ; Foreign Bodies* ; Humans ; Multidetector Computed Tomography ; Pneumonia ; Pulmonary Atelectasis ; Radiography, Thoracic

A group of patients with Kawasaki disease (KD) initially present with cervical lymphadenitis or deep neck infection. These unusual KD presentations lead to unnecessary antibiotic therapy or surgical intervention, thereby delaying intravenous immunoglobulin treatment and increasing the risk of coronary artery damage. We present four KD patients whose initial presentations mimicked a retropharyngeal abscess. Nonsuppurative cervical lymphadenitis or suspected neck abscess unresponsive to intravenous antibiotics could signal the possibility of KD.
Abscess ; Anti-Bacterial Agents ; Coronary Vessels ; Humans ; Immunoglobulins ; Lymphadenitis ; Mucocutaneous Lymph Node Syndrome ; Neck ; Retropharyngeal Abscess

Kawasaki disease (KD) is the self-limited and multisystem vasculitis which accompanies many complications. Ophthalmic findings in KD are bilateral conjunctival injection, iridocyclitis, superficial keratitis, vitreous opacities and subconjunctival hemorrhage. Optic disc swelling is a rare ophthalmic complication in KD. We describe a 3-year-old boy who presented with 7 days of fever, both conjunctival injection without discharge, and right cervical lymph node enlargement of more than 1.5 cm. He was diagnosed as incomplete KD. He had no ocular symptom except bilateral conjunctival injection. On ophthalmic examination, he was diagnosed by anterior uveitis with optic disc swelling. The brain magnetic resonance imaging was performed and revealed no evidence of increased intracranial pressure. Echocardiography revealed the dilated right coronary artery up to 3.4 mm. Fever subsided and optic disc swelling was completely improved after intravenous immunoglobulin (2 g/kg) treatment. Optic disc swelling is a rare ophthalmic complication in KD.
Brain ; Child, Preschool ; Coronary Vessels ; Echocardiography ; Fever ; Hemorrhage ; Humans ; Immunoglobulins ; Intracranial Pressure ; Iridocyclitis ; Keratitis ; Lymph Nodes ; Magnetic Resonance Imaging ; Male ; Mucocutaneous Lymph Node Syndrome* ; Papilledema ; Uveitis* ; Uveitis, Anterior ; Vasculitis

PURPOSE: To evaluate the postoperative CT appearance, complications and potential pitfalls of radical cystectomy with orthotopic neobladder reconstruction. MATERIALS AND METHODS: We examined 46 patients [43 men and 3 women aged 34-72 (mean, 56.7) years] who had undergone neobladder reconstruction (ileocolic neobladder in 25 patients and ileal-W neobladder in 21). The CT scans were assessed in terms of their depiction of normal anatomy, namely the shape, location and internal architecture of the neobladder, the location of bladder bases, and the ureteral course. Early and late complications were also assessed. RESULTS: The characteristics of ileocolic neobadder were a right-side location, a lobulated outer margin, internal projections due to haustra or plication, a base in the retropubis, and right-side insertion of both ureters. In contrast, the characteristics of an ileal-W neobladder were a central location, an ovoid shape, nodular thickening at the ureteral insertion site, internal projections due to plication, and a retropubic bladder base. Early complications included hematoma with abscess formation (n=2), and postoperative peritonitis (n=1), while late complications were hydronephrosis due to stricture at the ureteral anastomotic site (n=16), tumor recurrence at this site (n=1), distal ureteral stone (n=1), mucus urinary retention (n=1), incisional hernia (n=2), tumor recurrence in the pelvic side wall (n=1), carcinomatosis peritonei (n=1), and liver metastasis (n=2). CONCLUSION: A knowledge of normal anatomic changes is essential for the accurate interpretation of CT scans. CT is a useful modality for the evaluation of postoperative change and the complications occurring in patients who have undergone radical cystectomy with othotopic neobladder reconstruction.
Abscess ; Carcinoma ; Constriction, Pathologic ; Cystectomy ; Female ; Hematoma ; Hernia ; Humans ; Hydronephrosis ; Liver ; Male ; Mucus ; Neoplasm Metastasis ; Peritonitis ; Recurrence ; Tomography, X-Ray Computed ; Ureter ; Urinary Bladder ; Urinary Retention

Aneurysms of the left main coronary artery are very rare in patients with acute coronary syndrome. The increased accuracy of computed tomography permits the detection of coronary artery anatomic structures after one peripheral injection of contrast agent. We report a 42-year-old man with a left main coronary aneurysm, with a thrombus presenting as non-ST elevation myocardial infarction, detected by coronary computed tomographic angiography.
Acute Coronary Syndrome ; Adult ; Aneurysm ; Angiography* ; Coronary Aneurysm* ; Coronary Angiography ; Coronary Vessels ; Humans ; Myocardial Infarction* ; Thrombosis*

Aneurysms of the left main coronary artery are very rare in patients with acute coronary syndrome. The increased accuracy of computed tomography permits the detection of coronary artery anatomic structures after one peripheral injection of contrast agent. We report a 42-year-old man with a left main coronary aneurysm, with a thrombus presenting as non-ST elevation myocardial infarction, detected by coronary computed tomographic angiography.
Acute Coronary Syndrome ; Adult ; Aneurysm ; Angiography* ; Coronary Aneurysm* ; Coronary Angiography ; Coronary Vessels ; Humans ; Myocardial Infarction* ; Thrombosis*

BACKGROUND AND OBJECTIVES: This was a multicenter study to evaluate the usefulness of the tumor necrosis factor-alpha (TNF-alpha) blocker infliximab for treatment of Korean pediatric patients with refractory Kawasaki disease (KD). SUBJECTS AND METHODS: Data from 16 patients throughout Korea who were diagnosed with refractory KD and received infliximab were collected retrospectively. RESULTS: Complete response to therapy with cessation of fever occurred in 13 of 16 patients. C-reactive protein (CRP) concentrations decreased following infliximab infusion in all 14 patients in whom it was measured before and after treatment. There were no infusion reactions or complications associated with infliximab except in 1 case with acute hepatitis occurring during treatment followed by calculous cholecystitis 4 months later. Fifteen patients had coronary artery (CA) abnormalities before infliximab therapy. Three had transient mild dilatation and 9 had CA aneurysms, with subsequent normalization in 4 patients, persistent mild dilatation in 3, persistent aneurysm in 2, and there were 3 cases (2 with CA aneurysm, 1 with mild CA dilatation) without follow-up echocardiography. CONCLUSION: The results of this study suggest that infliximab may be useful in the treatment of refractory KD, and it appears that there is no significant further progression of CA lesions developing after infliximab treatment. Multicenter trials with larger numbers of patients and long-term follow-up are necessary to assess the clinical efficacy and safety of infliximab in refractory KD.
Aneurysm ; Antibodies, Monoclonal ; C-Reactive Protein ; Child ; Cholecystitis ; Coronary Vessels ; Dilatation ; Echocardiography ; Fever ; Follow-Up Studies ; Hepatitis ; Humans ; Korea ; Mucocutaneous Lymph Node Syndrome ; Retrospective Studies ; Tumor Necrosis Factor-alpha ; Infliximab