PURPOSE: Although many strides have been made in the radiological and laboratory diagnosis, the liver biopsy is still considered an important tool for the diagnosis of liver disease. We report our experience that histologic investigation of the liver was essential searching for the etiologic diagnosis in eight children with fever of unknowm origin and hepatosplenomegaly, who's diagnosis were not documented by other diagnostic studies. METHODS: Histologic investigation of the liver including Percutanous liver biopsy, open surgical biopsy, necropsy or autopsy was taken at Seoul national university of children's hospital between 1985 and 1995 in twelve children with fever of unknown origin and hepatosplenomegaly. We performed light and electron microscopic examination, culture and PCR of the tissue obtained by liver biopsy. RESULTS: 1) The etiologic diagnoses were possible by histologic investigation of the liver in 9 of 12 Cases; Nine cases were congenital tuberculosis, cryptococcosis, hepatic capillariasis, candidiasis, amoebiasis, neonatal herpes hepatitis, Escherichia. coli abscess and two cases of cytomegalovirus hepatitis. Three cases in which organisms could not be found in tissue obtained from biopsy were suspected clinically as liver abscess and parasite infestation. 2) Three cases were males and 6 were females, ranging in age from 1 days to 6 years; mean age 23.6 months. 3) Clinical manifestations were fever of unknown origin(9 Cases), hepatomegaly(9 Cases), splenomegaly(5 Cases), skin lesions(2 Cases) and jaundice(3 Cases). 4) Laboratory findings were increased AST/ALT(7 Cases), hyperbilirubinemia(3 Cases), leukocytosis(5 Cases), eosinophilia(2 Cases), increased CRP(9 Cases) and increased ESR(5 Cases). 5) In four children, there were underlying diseases which were acute lymphoblastic leukemia, acute myeloid leukemia and two cases of prematures. CONCLUSIONS: In children with fever of unknown origin and hepatosplenomegaly, we recommend liver biopsy for early diagnosis and apropriate management.
Abscess ; Amebiasis ; Autopsy ; Biopsy* ; Candidiasis ; Child* ; Clinical Laboratory Techniques ; Cryptococcosis ; Cytomegalovirus ; Diagnosis ; Early Diagnosis ; Escherichia ; Female ; Fever of Unknown Origin* ; Fever* ; Hepatitis ; Humans ; Leukemia, Myeloid, Acute ; Liver Abscess ; Liver Diseases ; Liver* ; Male ; Parasites ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Seoul ; Skin ; Tuberculosis

PURPOSE: Recent reports suggest that many professionals, including emergency physicians, suffer from job stress and psychosocial stress. Emergency physicians also report a high premature attrition rate. Our goal was to investigate the levels of job and psychosocial stress and the relationship between these stresses and abandonment of their own specialty. METHODS: Data was collected using a cross-sectional mail survey with a self-administered questionnaire. The questionnaire included 49 questions in scales relating to job stress, job satisfaction and plans for their remaining years in their specialty. Three hundred and forty-two emergency physicians participated in this study and completed the questionnaire RESULTS: Among the 342 questionnaires, 132(48.4%) were returned. Multivariate analysis of variance revealed statistically significant differences in job stress and psychosocial stress between academic emergency physicians and clinical emergency physicians. The average scores for job stress, job satisfaction and psychosocial stress among emergency physicians were, respectively, 3.35+/-0.57, 2.93+/-0.50 and 2.33+/-0.78. Mean levels of job stress and psychosocial stress were higher among academic emergency physicians. Job satisfaction and occupational commitment were also higher among academic emergency physicians. Variables such as patient load, working hours per week, and night shifts proved unimportant. Of clinical emergency physicians, 54% planned on leaving their specialty within ten years. CONCLUSION: Job stress and psycosocial stress of academic emergency physicians were higher, but job satisfaction and occupational commitment were higher. Job stress and psycosocial stress of clinical emergency physicians were lower, but premature attrition rate were higher.
Emergencies ; Humans ; Job Satisfaction ; Multivariate Analysis ; Postal Service ; Surveys and Questionnaires ; Weights and Measures

It has been well known that long-term immune suppression in renal transplant patients increases the possibility of complications. Infectious disease is one of the representative complications. We experienced a case of nocardiosis with cytomegalovirus infection after third renal transplantation in China. Nocardiosis is an important opportunistic infection in immunosuppressed patients, lymphoma, sarcoidosis, and organ transplant patients. CMV can cause severe hepatitis, pneumonitis, enteritis, endometritis, and encephalitis. It can depress bone marrow, and impair the immune system so as to increase other bacterial infection and trigger rejections. Third renal transplantation causes long-term immune suppression or over-immune suppression on transplant patients. Very few cases of third renal transplantation have been reported in Korea. We reduced the dose of immune- suppressants, and treated it successfully with ganciclovir and Trimethoprim/Sulfamethoxazole (Bactrim(R)).
Bacterial Infections ; Bone Marrow ; China* ; Communicable Diseases ; Cytomegalovirus ; Cytomegalovirus Infections ; Encephalitis ; Endometritis ; Enteritis ; Female ; Ganciclovir ; Hepatitis ; Humans ; Immune System ; Kidney Transplantation* ; Korea ; Lymphoma ; Nocardia Infections* ; Opportunistic Infections ; Pneumonia ; Sarcoidosis ; Transplants

Polyoma virus (PV) nephropathy is a known cause of graft loss after renal transplantation. In a renal transplant patient suspected of graft rejection, it is important to discriminate between PV induced interstitial nephritis and acute cellular rejection, because of similar pathologic findings. After the loss of the first allograft secondary to PV nephropathy, transplant graft nephroureterectomy before retransplantaton may have an influence in the recurrence of PV nephropathy. However, this question has not been completely resolved. Case: A 23-year-old male underwent first renal transplantation from his HLA haploidentical 25 year-old-sister. His renal function had been good with cyclosporine, steroid and azathioprine until 9 months after transplantation, when his serum creatinine level rose to 2.2 mg/dL. A renal biopsy revealed features of tubulitis and we confirmed PV nephropathy through a positive PV monoclonal antibody reaction to inclusion body. After gradual loss of graft function, he underwent hemodialysis. After 48 months of hemodialysis, the patient underwent cadaveric renal retransplantation without transplant graft nephroureterectomy. Thrombocytopenia and suspected delayed graft function occurred after 2 days of transplantation. A graft biopsy revealed thrombotic microangiopathy. Improved graft function was attained after a temporary stop of tacrolimus and ATGAM(R) bridging therapy. The patient is maintaining satisfactory graft function 33 months after retransplantation without clinical and serological evidence of recurrent PV infection.
Allografts ; Azathioprine ; Biopsy ; Cadaver ; Creatinine ; Cyclosporine ; Delayed Graft Function ; Graft Rejection ; Humans ; Inclusion Bodies ; Kidney Transplantation ; Male ; Nephritis, Interstitial ; Polyomavirus* ; Recurrence ; Renal Dialysis ; Tacrolimus ; Thrombocytopenia ; Thrombotic Microangiopathies ; Transplants* ; Young Adult

BACKGROUND: This study aimed to evaluate the current overall preventable trauma death rate (PTDR) in Korea and identify factors associated with preventable trauma death (PTD). METHODS: The target sample size for review was designed to be 1,131 deaths in 60 emergency medical institutions nationwide. The panels for the review comprised trauma specialists working at the regional trauma centers (RTCs); a total of 10 teams were formed. The PTDR and factors associated with PTD were analyzed statistically. RESULTS: Of the target cases, 943 were able to undergo panel review and be analyzed statistically. The PTDR was 30.5% (6.1% preventable and 24.4% possibly preventable). Those treated at a RTC showed a significantly lower PTDR than did those who were not (21.9% vs. 33.9%; P = 0.002). The PTDR was higher when patients were transferred from other hospitals than when they directly visited the last hospital (58.9% vs. 28.4%; P = 0.058; borderline significant). The PTDR increased gradually as the time from accident to death increased; a time of more than one day had a PTDR 14.99 times higher than when transferred within one hour (95% confidence interval, 4.68 to 47.98). CONCLUSION: Although the PTDR in Korea is still high compared to that in developed countries, it was lower when the time spent from the accident to the death was shorter and the final destined institution was the RTC. To reduce PTDR, it is necessary to make an effort to transfer trauma patients to RTCs directly within an appropriate time.
Developed Countries ; Emergencies ; Humans ; Korea ; Mortality ; Sample Size ; Specialization ; Trauma Centers ; Wounds and Injuries

In brain death state, bilateral pupil light reflexes are disappeared, and pupils are fixed with dilated. However, spontaneous movements such as ocular microtremor or bilateral cyclical constriction-dilatation of pupils have been rarely reported in brain death patients. We present a brain death patient whose right pupil displayed spontaneously repetitive constriction and dilatation regardless of external stimuli such as light and pain. Early recognition of this phenomenon may prohibit the delay in the diagnosis of brain death and organ transplantation.
Brain Death ; Brain ; Coma ; Constriction ; Diagnosis ; Dilatation ; Humans ; Organ Transplantation ; Pupil ; Reflex ; Transplants

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21(Cip/WAF1) activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21(Cip/WAF1) short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.
Animals ; Arginine ; Cell Dedifferentiation ; Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism ; Elongation Factor 2 Kinase/*metabolism ; Fibroblast Growth Factor 2/*metabolism ; Fibroblasts/*metabolism/pathology ; Flavonoids/pharmacology ; MAP Kinase Signaling System/drug effects/genetics ; Methylation ; Mice ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Myofibroblasts/pathology ; NIH 3T3 Cells ; Protein Methyltransferases/*metabolism ; Protein-Arginine N-Methyltransferases/*metabolism ; RNA, Small Interfering/genetics

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21(Cip/WAF1) activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21(Cip/WAF1) short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.
Animals ; Arginine ; Cell Dedifferentiation ; Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism ; Elongation Factor 2 Kinase/*metabolism ; Fibroblast Growth Factor 2/*metabolism ; Fibroblasts/*metabolism/pathology ; Flavonoids/pharmacology ; MAP Kinase Signaling System/drug effects/genetics ; Methylation ; Mice ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Myofibroblasts/pathology ; NIH 3T3 Cells ; Protein Methyltransferases/*metabolism ; Protein-Arginine N-Methyltransferases/*metabolism ; RNA, Small Interfering/genetics

Objective: : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods: : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1–3 and 3–5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results: : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0–17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150–0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5–11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

Background: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. Methods: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. Results: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3–4 months. Conclusion We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media.Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.