Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease that is often associated with genetic defects. Mutations of complement factor H (CFH) are the most common genetic defects that cause aHUS and often result in end-stage renal disease. Since CFH is mainly produced in the liver, liver transplantation (LT) has been performed in patients with defective CFH. METHODS: The clinical courses of four kidney allograft recipients who lost their native kidney functions due to aHUS associated with a CFH mutation were reviewed. RESULTS: Subject A underwent kidney transplantation (KT) twice, aHUS recurred and the allograft kidney failed within a few years. Subject B received a KT and soon experienced a recurrence of aHUS coinciding with infection. Her allograft kidney function has worsened, and she remains on plasma infusion therapy. Subject C underwent LT followed by KT. She is doing well without plasma infusion therapy after combined LT-KT for 3 years. Subject D received KT following LT and is now recurrence-free from aHUS. CONCLUSION: In patients with aHUS associated with a CFH mutation, KT without LT was complicated with a recurrence of aHUS, which might lead to allograft loss. Conversely, LT was successful in preventing the recurrence of aHUS and thus might be another option for a recurrence-free life for aHUS patients associated with CFH mutation.
Allografts ; Atypical Hemolytic Uremic Syndrome ; Complement Factor H ; Complement System Proteins ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney ; Liver Transplantation ; Liver ; Plasma ; Rare Diseases ; Recurrence

PURPOSE: To evaluate the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) in children. METHODS: We retrospectively reviewed the medical records of 18 patients with PTLD who underwent liver (LT) or kidney transplantation (KT) between January 1995 and December 2014 in Seoul National University Children's Hospital. RESULTS: Eighteen patients (3.9% of pediatric SOTs; LT:KT, 11:7; male to female, 9:9) were diagnosed as having PTLD over the last 2 decades (4.8% for LT and 2.9% for KT). PTLD usually presented with fever or gastrointestinal symptoms in a median period of 7 months after SOT. Eight cases had malignant lesions, and all the patients except one had evidence of Epstein-Barr virus (EBV) involvement, assessed by using in situ hybridization of tumor tissue or EBV viral load quantitation of blood. Remission was achieved in all patients with reduction of immunosuppression and/or rituximab therapy or chemotherapy, although 1 patient had allograft kidney loss and another died from complications of chemotherapy. The first case of PTLD was encountered after the introduction of tacrolimus for pediatric SOT in 2003. The recent increase in PTLD incidence in KT coincided with modification of clinical practice since 2012 to increase the tacrolimus trough level. CONCLUSION: While the outcome was favorable in that all patients achieved complete remission, some patients still had allograft loss or mortality. To prevent PTLD and improve its outcome, monitoring for EBV infection is essential, which would lead to appropriate modification of immunosuppression and enhanced surveillance for PTLD.
Allografts ; Child ; Drug Therapy ; Epstein-Barr Virus Infections ; Female ; Fever ; Herpesvirus 4, Human ; Humans ; Immunosuppression ; In Situ Hybridization ; Incidence ; Kidney ; Kidney Transplantation ; Liver ; Lymphoproliferative Disorders* ; Male ; Medical Records ; Mortality ; Organ Transplantation* ; Retrospective Studies ; Rituximab ; Seoul ; Tacrolimus ; Transplants* ; Viral Load

BACKGROUND: Argyria is a rare irreversible cutaneous pigmentation disorder caused by prolonged exposure to silver. Herein, we report a case of generalized argyria that developed after chronic ingestion of soluble silver-nano particles and presented with muscle weakness. CASE PRESENTATION: A 74-year-old woman visited our emergency room, complaining of fever and mental deterioration. She was diagnosed with acute pyelonephritis and recovered after antibiotic therapy. At presentation, diffuse slate gray-bluish pigmented patches were noticed on her face and nails. Two months prior to visiting our hospital, she was diagnosed with inflammatory myopathy and given steroid therapy at another hospital. We performed a nerve conduction study that revealed polyneuropathy. In skin biopsies from pigmented areas of the forehead and nose, the histopathologic results showed brown-black granules in basement membranes of sweat gland epithelia, which are diagnostic findings of argyria. We reviewed pathology slides obtained from the left thigh muscles and found markedly degenerated myofibers with disorganization of myofibrils without inflammatory reactions, consistent with unspecified myopathy, rather than inflammatory myopathy. The patient was diagnosed with generalized argyria with polyneuropathy and myopathy and transferred to a rehabilitation institution after being tapered off of steroids. CONCLUSIONS: Clinicians should be aware of clinical manifestations of argyria and consider it in differential diagnosis when they examine patients who present with skin pigmentation and muscle weakness.
Aged ; Argyria* ; Basement Membrane ; Biopsy ; Diagnosis, Differential ; Eating ; Emergency Service, Hospital ; Female ; Fever ; Forehead ; Humans ; Muscle Weakness* ; Muscles ; Muscular Diseases ; Myofibrils ; Myositis ; Neural Conduction ; Nose ; Pathology ; Pigmentation Disorders ; Polyneuropathies ; Pyelonephritis ; Rehabilitation ; Silver ; Skin ; Skin Pigmentation ; Steroids ; Sweat Glands ; Thigh

Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients. Known pathogenic mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1 in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior–Løken syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In the remaining undiagnosed patients, we applied targeted exome sequencing of 34 ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43 patients. Another 18 likely damaging heterozygous variants were identified in 13 NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic and candidate mutations identified in 55 patients with NPHP-RC in Korea using a step-wise application of two genetic tests. These results support the clinical utility of targeted exome sequencing to resolve the issue of allelic and genetic heterogeneity in NPHP-RC.
Adolescent ; Diagnosis* ; Exome* ; Genetic Heterogeneity* ; Humans ; Kidney Failure, Chronic ; Korea ; Liver ; Mass Screening ; Wills

The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF < or = 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age > or = 75 yr, Killip class > or = III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein > or = 2.59 mg/L, LVEF < or = 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF < or = 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR.
Aged ; Coronary Angiography ; Coronary Artery Disease/mortality/*pathology/surgery ; Echocardiography ; Female ; Heart/radiography ; Humans ; Male ; Middle Aged ; Mitral Valve Insufficiency/*pathology ; Myocardial Infarction/mortality/*pathology/surgery ; Myocardium/pathology ; Percutaneous Coronary Intervention ; Prospective Studies ; Stroke Volume/*physiology ; Treatment Outcome ; Ventricular Dysfunction, Left/*surgery ; Ventricular Function, Left/physiology

BACKGROUND: Aortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH. METHODS: Minimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding. RESULTS: Banding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 +/- 0.8 vs. 33.2 +/- 2.0 vs. 26.6 +/- 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 +/- 0.20% vs. 5.26 +/- 3.12% vs. 4.03 +/- 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028). CONCLUSION: In this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.
Animals ; Aorta* ; Echocardiography ; Fibrosis ; Hypertrophy, Left Ventricular ; Mechanics* ; Models, Animal* ; Rats ; Rats, Sprague-Dawley

Cytomegalovirus (CMV) infection has been described in immunosuppressed individuals such as patients with AIDS, those receiving chemotherapy, and post-transplantation. CMV can cause severe disease either via reactivation of latent virus or via primary infection. In immunocompetent patients, CMV infection is usually transient and does not exhibit many symptoms. The colon is the site most frequently affected by severe CMV disease in immunocompetent patients. Clinically, CMV colitis commonly presents with diarrhea, fever, and abdominal pain. Although some patients recover spontaneously, others suffer from severe complications, such as bowel perforation, severe gastrointestinal bleeding and, rarely, stricture, and surgery is the choice of treatment in these patients. We report a case of stricture of the proximal transverse colon, presenting as a complication of CMV colitis, in an immunocompetent man with acute respiratory distress syndrome. We performed laparoscopic segmental resection of the proximal transverse colon.
Abdominal Pain ; Colitis ; Colon ; Colon, Transverse ; Constriction, Pathologic ; Cytomegalovirus ; Diarrhea ; Fever ; Hemorrhage ; Humans ; Immunocompetence ; Laparoscopy ; Respiratory Distress Syndrome, Adult ; Viruses

Clopidogrel, a thienopyridine derivative, is an anti-platelet agent that acts as an antagonist of the platelet adenosine diphosphate receptor and considered for essential prophylaxis for intracoronary stent thrombosis in the treatment of ischemic heart disease. Clopidogrel is considered as safe as aspirin but a few cases of severe hematologic adverse reactions associated with clopidogrel had been reported such as neutropenia, aplastic anemia, thrombocytopenic purpura, and thrombocytopenia. We report a rare case of neutropenia induced by clopidogrel in chronic renal failure in a patient who underwent percutaneous coronary intervention.
Adenosine Diphosphate ; Anemia, Aplastic ; Aspirin ; Blood Platelets ; Humans ; Kidney Failure, Chronic ; Myocardial Ischemia ; Neutropenia ; Purpura, Thrombocytopenic ; Pyridines ; Stents ; Thrombocytopenia ; Thrombosis ; Ticlopidine