Bosentan and Rifampin Interactions Modulate Influx Transporter and Cytochrome P450 Expression and Activities in Primary Human Hepatocytes

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with 20 μM bosentan+200 μM rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

Sarcomatoid Intrahepatic Cholangiocarcinoma: A Rare Case of Primary Liver Cancer

Sarcomatoid carcinoma arising from intrahepatic cholangiocyte, an extremely rare primary liver cancer, has highly invasive and metastatic potential. The pathogenesis of this tumor is unclear, although histogenetic mechanisms, such as transdifferentiation/dedifferentiation (epithelial-mesenchymal transition or metaplastic transformation), biphasic differentiation (combination and collision), and redifferentiation, might be suggested to explain the simultaneous co-existence of carcinoma and sarcoma components in the same tumor. Immunohistochemical staining might be necessary to differentiate whether sarcomatous component is originated from hepatocyte or cholangiocyte. We report a case of sarcomatoid intrahepatic cholangiocarcinoma in a 58 year-old man presenting as an incidentally detected liver mass on regular health examination, which was diagnosed by an application of immunohistochemical methods after surgical resection, with a review of the literature based on 9 cases reported in Korea.

Gastric Endoscopic Submucosal Dissection Is Safe for Day Patients

BACKGROUND/AIMS: Although the advantages of endoscopic submucosal dissection (ESD) are well established, there are important limitations that relate to its higher cost and higher rate of complications compared with endoscopic mucosal resection. This study assessed the therapeutic safety and efficacy of ESD in the treatment of small gastric dysplasia and early gastric cancer (EGC) located within the antrum in an outpatient setting, and it compared the results with those from patients admitted to hospital for ESD treatment. METHODS: This study was a retrospective analysis of a prospectively maintained database. We reviewed consecutive patients with EGC or gastric dysplasia who underwent ESD between October 2007 and May 2008. The lesions were smaller than 2 cm and were located in the antrum. We analyzed 105 lesions in 105 patients. The patients were assigned to two groups according to each patient's preference. RESULTS: The overall rates of complete resection were 98.1% in the inpatients group and 94.3% in the outpatients group. Immediate bleeding occurred in four inpatients, which included one patient in the outpatient group. Delayed bleeding occurred in one inpatient within 24 hours of the procedure. Macroperforations did not occur in either group. A microperforation was found in one outpatient. CONCLUSIONS: The safety and efficacy of ESD used to treat small gastric tumors in the antrum in an outpatient setting appeared to be similar to the safety and efficacy of ESD used to treat patients who were admitted to the hospital.

A Case of Portal Vein and Splenic Vein Occlusion after Endoscopic Variceal Occlusion Therapy in Gastric Variceal Bleeding / 계명의대학술지

Acute gastric variceal bleeding is one of the most serious complications in portal hypertension, and is associated with high mortality and morbidity. Endoscopic variceal obturation (EVO) using Histoacryl(R) (n-butyl-2-cyanoacrylate) has been accepted as an effective hemostatic procedure in acute gastric variceal bleeding. However, EVO is not a widely performed because of technical difficulties and complications such as mucosal ulceration, perforation, and systemic embolism. Herein, we report a patient who developed hepatic failure caused by portal vein occlusion by Histoacryl(R) injection for management of gastric variceal bleeding.

Endoscopic Management of Rectal Dieulafoy's Lesion: A Case Series and Optimal Treatment

Rectal Dieulafoy's lesion (DL) is rare cause of lower gastrointestinal bleeding. Because of its rarity, there is no consensus on the optimal endoscopic hemostasis technique for rectal DL. We analyzed six patients who underwent endoscopic management for rectal DL after presenting with hematochezia at a single institute over 10 years. Of the six patients, three underwent endoscopic band ligation (EBL) and three underwent endoscopic hemoclip placement (EHP). Only one patient was treated with thermocoagulation. There were no immediate complications in any of the patients. None of the patients required a procedure or surgery for the treatment of rebleeding. Mean procedure times of EBL and EHP were 5.25 minutes and 7 minutes, respectively. Both EHP and EBL are shown to be effective in the treatment of bleeding rectal DL. We suggest that EBL may have potential as the preferred therapy owing to its superiority in technical and economic aspects, especially in elderly and high-risk patients.

A Case of Early Gastric Cancer with Synchronous Multiple Bone Metastases

The prognosis of an early gastric cancer (EGC) is generally excellent, with a 5-year survival rate of 90% in most reports; however, there have been few reports of EGC with distant metastases. Recently we encountered a rare case of EGC with synchronous multiple bone metastases. A 43-year-old woman visited a local clinic due to back pain. Lumbar spine metastases were suspected by MRI. She was transferred to our hospital and underwent bone marrow biopsy which revealed an adenocarinoma. After endoscopic evaluation for primary cancer work-up, we found a suspicious EGC lesion. The results of endoscopic biopsy was signet ring cell carcinoma. Our pathologist additionally reviewed the bone marrow biopsy slides and found signet ring cells in it. PET CT showed disseminated multiple bone metastases but, there wasn't any other malignant lesion. Here we report a rare case of EGC with synchronous multiple bone metastases.

A Case of Early Gastric Cancer with Synchronous Multiple Bone Metastases

The prognosis of an early gastric cancer (EGC) is generally excellent, with a 5-year survival rate of 90% in most reports; however, there have been few reports of EGC with distant metastases. Recently we encountered a rare case of EGC with synchronous multiple bone metastases. A 43-year-old woman visited a local clinic due to back pain. Lumbar spine metastases were suspected by MRI. She was transferred to our hospital and underwent bone marrow biopsy which revealed an adenocarinoma. After endoscopic evaluation for primary cancer work-up, we found a suspicious EGC lesion. The results of endoscopic biopsy was signet ring cell carcinoma. Our pathologist additionally reviewed the bone marrow biopsy slides and found signet ring cells in it. PET CT showed disseminated multiple bone metastases but, there wasn't any other malignant lesion. Here we report a rare case of EGC with synchronous multiple bone metastases.

A Diagnostic Approach to Abnormal Liver Function Tests in Asymptomatic Patients / 대한내과학회지

Interpretation of abnormalities in liver function tests is valuable because they provide clues for various hepatobiliary disease. Because liver function tests have become a routine checkup in screening tests, isolated alterations of biochemical markers of liver damage in a seemingly healthy patient often represent a challenge for a clinician. Detailed history taking and physical examination are often helpful in interpretation of abnormal liver function tests and differential diagnosis. Proper diagnosis and management can be made with further laboratory tests and understanding of the laboratory results.

A Case of Percutaneous Catheter Thrombectomy in a Patient With Massive Pulmonary Thromboembolism

Acute massive pulmonary thromboembolism (PTE) is a life threatening medical condition. Therefore, prompt diagnosis and rapid recovery of the pulmonary flow is essential for decreasing the associated morbidity and mortality. We report here on a case of a 68-year old woman for whom we attempted percutaneous catheter thrombectomy in the treatment of an acute massive PTE.

Outcome and Prognosis in Critically Ill Children Receiving Continuous Renal Replacement Therapy

PURPOSE: Continuous renal replacement therapy(CRRT) has been the first choice for the treatment of acute renal failure in critically ill children not only in western countries but also in Korea. However, there are very few studies that have analyzed the outcome and prognosis of this modality in Korean children. We performed this study to evaluate the factors associated with the outcome and prognosis of patients treated with CRRT. METHODS: We retrospectively reviewed the medical records of 32 children who had received CRRT at Severance hospital from 2003 to 2006. The mean age was 7.5 years(range 4 days- 16 years) and the mean body weight was 25.8 kg (range 3.2-63 kg). RESULTS: Eleven(34.4%) of the 32 patients survived. Bone marrow transplantation and malignancy were the most common causes of death and underlying disease leading to the need for CRRT. Mean patient weight, age, duration of CRRT, number of organ failures, urine output, estimated glomerular filtration rate(eGFR), C-reactive protein, and blood urea level did not differ significantly between survivors and nonsurvivors. (1) Pediatric risk of mortality(PRISM) III score at CRRT initiation(9.8+/-5.3 vs. 26.7+/-7.6, P<0.0001), (2) maximum pressor number (2.1+/-1.2 vs. 3.0+/-1.0, P=0.038), and (3) the degree of fluid overload(5.2+/-6.0 vs. 15.0+/-8.9, P=0.002) were significantly lower in survivors than in nonsurvivors. Multivariate analysis revealed that fluid overload was the only independent factor reducing survival rate. CONCLUSION: CRRT was successfully applied to the treatment of acute renal failure in a wide range of critically ill children. To improve survival, we suggest the early initiation of CRRT to prevent the systemic worsening and progression of fluid overload in critically ill children with acute renal failure.

Plasmodium falciparum Cultivation Using the Petri Dish: Revisiting the Effect of the 'Age' of Erythrocytes and the Interval of Medium Change

Differences in the characteristics of the culture conditions can influence the multiplication rate of Plasmodium falciparum. The Petri dish method is one of the most popular methods of cultivating this parasite. In many previous studies, ideal culture conditions of the Petri dish method were achieved by using erythrocytes collected from blood that had been stored for at least 2 weeks, with daily changes of the medium. In the present study, we studied the multiplication rate of P. falciparum in cultures containing erythrocytes of various ages together with changing the medium at various intervals of time. Our results strongly suggest that the rate of in vitro multiplication of P. falciparum was higher in freshly collected erythrocytes than in aged erythrocytes regardless of the anticoagulant and that when the parasitemia is lower than 8% with a hematocrit of 5%, the medium change interval can be as long as 48 hr without a great reduction in the rate of multiplication.

Urachal Anomalies in Children: A Single Center Experience

The objective of this study is to define optimal diagnosis and treatment strategies for patients with urachal anomalies in the pediatric age group. The medical records of 21 children who had undergone surgery for urachal anomalies at Severance Hospital, Yonsei University College of Medicine from January 1990 to April 2005 were reviewed. The subjects included 14 males and 7 females (M:F 2:1). The four types of urachal anomalies confirmed were a urachal cyst in 10 patients (47.6%), a patent urachus in 6 (28.6%), a urachal sinus in 4 (19.0%) and a urachal diverticulum in 1 (4.8%) patient. The most common presenting complaint was umbilical discharge (n = 10, 40.0%), followed by abdominal mass (n = 9, 36.0%). Urachal anomalies were diagnosed by ultrasonography in 18 patients, and 7 of them were additionally examined by computed tomography. The remaining patients were diagnosed solely by surgical exploration. Excision was performed in all patients and was supplemented by partial cystectomy in three. Umbilical discharge was the most common clinical manifestation in our patients, suggesting that ultrasonography should be performed in patients with umbilical discharge to differentiate urachal anomalies. We found the most common anomaly to be the urachal cyst, and all patients were successfully treated by surgical excision.

Clinical Outcome of Multicystic Dysplastic Kidney in 46 Children

PURPOSE: Conservative management of multicystic dysplastic kidney(MCDK) without nephrectomy has recently been advocated. The purpose of this study was to determine the clinical course of conservatively managed MCDK and to find out possible predictive factors for involution of MCDK by ultrasonography(US). METHODS: A retrospective analysis was made on 46 patients(26 boys and 20 girls) in whom MCDK was detected and had been traced by US between Dec. 1993 and Aug. 2005 at Severance Hospital. RESULTS: Median follow-up time was 30 months(range 2-102 months). All patients underwent radionuclide scans and voiding cystourethrograms. The serial follow-up US showed complete involution in 11(24%), partial involution in 19(41%), and no interval change or increased in cyst size in 13(28%) patients. Nephrectomy was done in 3 patients(7%) due to relapsing urinary tract infection(UTI) and severe abdominal distension. The mean age of complete involution of MCDK was 37 months(range 12-84 months). Episodes of UTI were present in 17 patients(37%) and additional genitourinary(GU) abnormalities were found in 22 patients(44%). Hypertension and renal insufficiency was complicated in one patient. No child developed malignant tumor. Univariate analysis showed that five variables were associated with complete involution of the MCDK; gender, site, UTI episode, additional GU abnormalities, and renal length on initial US. After adjusting using the Pearson model, the presence of additional GU abnormalities was exclusively associated with complete involution among the 5 variables(P=0.034). CONCLUSION: In our review of 46 cases of MCDK, non-surgical approach for patients with MCDK was advisable and we could predict poor prognosis when MCDK is associated with other GU anomalies.

A Case of ANCA-associated Pauci-immune Crescentic Glomerulonephritis in Juvenile Rheumatoid Arthritis

Juvenile rheumatoid arthritis(JRA) is the most common major connective tissue disease in children. Renal involvement in JRA is rare. Among the renal lesions that have been reported in JRA, amyloidosis and drug-induced nephropathy are the most common. Crescentic glomerulonephritis in JRA has rarely been reported. We report a case of ANCA-associated pauci-immune crescentic glomerulonephritis in JRA. The patient was a 15-year old boy with a 3-year history of JRA. He presented with gross hematuria, proteinuria, positive p-ANCA and elevation of BUN and creatinine. Pathologic findings revealed focal necrotizing and crescentic glomerulonephritis. There were no significant immunoglobulin or complement deposits. His renal function recovered after intravenous methylprednisolone pulse therapy and oral steroid use. In Korea, this is the first reported case of pauci-immune crescentic glomerulonephritis in JRA.

A Clinical Study of Renal Abscesses in Children

PURPOSE: Renal abscess is very rare in children and its diagnosis is difficult because symptoms are often nonspecific. In previous studies, only 15% to 25% of patients were reported to be diagnosed at the time of admission. Early diagnosis and treatment are important because mortality rate correlates positively with the time of diagnosis. The purpose of this study is to clarify the clinical features of children with renal abscess and to investigate the possible indicators of this disease for early diagnosis and proper treatment. METHODS: Twelve children diagnosed with renal abscess from Jan. 1996 to Jul. 2004 were included. The age of patients ranged from 5 months to 15 years. We retrospectively analyzed the demographics of patients, their symptoms, predisposing factors, diagnostic methods and causative organisms and the treatment modalities. RESULTS: Fever was the most common manifestation. Five children(42%) had vesicoureteral reflux. Renal ultrasonography and computerized tomography were the most frequently used imaging tools to detect renal abscess. Gram negative bacteria were isolated in 7 patients and Staphylococcus aureus grew in 2 patients. All patients received intravenous antibiotics and 4 patients underwent aspiration or drainage of renal abscess. The average admission duration was 30 days. CONCLUSION: Renal abscess should be included in the differential diagnosis of prolonged fever in children, especially when flank pain is combined. For early diagnosis and a better prognosis, patients should be promptly investigated with ultrasonography or computerized tomography.

Evaluation of Anti-Malarial Effects of Mass Chemoprophylaxis in the Republic of Korea Army

Vivax malaria was endemic on the Korean peninsula for many centuries until the late 1970's when the Republic of Korea (ROK) was declared "malaria free". Since its re-emergence in 1993, the number of malaria cases in the military increased exponentially through 2000 near the demilitarized zone. Chemoprophylaxis with chloroquine and primaquine has been used in the ROK Army since 1997 in an attempt to reduce the number of the malaria cases throughout the ROK. Data show that chemoprophylaxis contributed, in part, to the decrease in the number of malaria cases among military personnel. However, mass chemoprophylaxis on a large scale in the ROK Army is unprecedented and extensive supervision and monitoring is warranted to determine its effectiveness and to monitor the appearance of chloroquine tolerant/resistant strains of Plasmodium vivax.

A Case of Hemolytic Uremic Syndrome in a Child with Ischemic Colitis

Hemolytic uremic syndrome(HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia and the most common pathogen is Escherichia coli (E. coli) O157:H7. Ischemic colitis, which rarely occurs in children, is due to the reduced local blood flow to the intestine, tissue necrosis and secondary bacterial infection. We describe a patient who was admitted with abdominal pain, vomiting and hematochezia, and diagnosed as ischemic colitis by barium enema. This patient showed hemolytic anemia, thrombocytopenia and progressive renal failure and was subsequently diagnosed as hemolytic uremic syndrome. After hemodialysis, the patient showed improvement of symptoms and resolution of renal failure and ischemic colitis.

A Systemic Lupus Erythematosus Patient with Protein Losing Enteropathy

Protein-losing enteropathy (PLE) is a rare manifestation of systemic lupus erythematosus (SLE), and it is an uncommon cause of hypoalbuminemia without proteinuria. We describe a case of an 11 year-old girl who had diarrhea and periorbital edema as the initial symptoms of SLE. PLE was diagnosed by 24-hour stool alpha-1 antitrypsin clearance and 99mTc-human serum albumin scintigraphy.

Status of Vivax Malaria in the Republic of Korea in 2002

BACKGROUND: Since 1997, the annual case occurrence of vivax malaria in the Republic of Korea (ROK) has exceeded 1,000 cases. The military has been an important source of the current outbreak. We collected informations about malaria cases (soldiers, veterans and civilians) that occurred in 2002, and analyzed the characteristics of the current outbreak. METHODS: Informations about the day of onset, region, and occupation of malaria cases of soldiers, veterans and civilians were collected through the National Institute of Health. RESULTS: Out of a total of 1,757 cases, 425 cases (24.2%) occurred in the military, 468 cases (26.6 %) among the veterans, and 864 cases (49.2%) among the civilians. Ten-day incidence reached its peak in the late July to the mid August. Areas such as Paju, Ganghwa, Yeoncheon and Cheolwon showed the highest prevalence. CONCLUSION: Presently, the current malaria outbreak appears to be in decreasing phase, however, attention should continuously be paid to prevent further spreading of malaria.

Status of Vivax Malaria in the Republic of Korea in 2002

BACKGROUND: Since 1997, the annual case occurrence of vivax malaria in the Republic of Korea (ROK) has exceeded 1,000 cases. The military has been an important source of the current outbreak. We collected informations about malaria cases (soldiers, veterans and civilians) that occurred in 2002, and analyzed the characteristics of the current outbreak. METHODS: Informations about the day of onset, region, and occupation of malaria cases of soldiers, veterans and civilians were collected through the National Institute of Health. RESULTS: Out of a total of 1,757 cases, 425 cases (24.2%) occurred in the military, 468 cases (26.6 %) among the veterans, and 864 cases (49.2%) among the civilians. Ten-day incidence reached its peak in the late July to the mid August. Areas such as Paju, Ganghwa, Yeoncheon and Cheolwon showed the highest prevalence. CONCLUSION: Presently, the current malaria outbreak appears to be in decreasing phase, however, attention should continuously be paid to prevent further spreading of malaria.