BACKGROUND: Alpha-interferon achieves HBeAg seroconversion in about 30 to 40% of patients with chronic hepatitis B, and recently discovered lamivudine, an oral nucleoside analogue, inhibits hepatitis B virus replication and reduces hepatic necroinflammation in patients with chronic hepatitis B effectively. In this study, we compared the efficacy and safety of alpha-interferon, lamivudine and their combination regimen. METHODS: Fourty chronic hepatitis B patients, who were diagnosed through HBV DNA, HBeAg positivity, alanine aminotransferase elevation, and liver biopsy were enrolled in this study. Twelve patients were treated with 500 MU of alpha-interferon subcutaneously 3 times a week for 6 months, 9 patients were treated with 150 mg of lamivudine and alpha-interferon, and 19 patients were treated with 150 lamivudine daily for 6 months. RESULTS: After treatment, all of the three groups showed rapid decline in HBV DNA level, but lamivudine group showed more clearance of HBV DNA than interferon group (alpha-interferon: 75%, combination group: 89%, lamivudine group: 100%, respectively) (p=0.04). HBeAg seroconversion rate was 25% for interferon group, 11% for combination group, 26% for lamivudine group, showing no difference between three groups (p=0.705). Mean serum ALT level and rate of ALT normalization during therapy showed no differnece (83% for interferon group, 78% for combination group, 84% for lamivudine group). CONCLUSION: It is suggested that the efficacy of combination interferon/lamivudine therapy appears disappointing and further study should be done for appropriate combination or monotherapy of lamivudine for patients with chronic hepatitis B.
Alanine Transaminase ; Biopsy ; DNA ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Interferon-alpha* ; Interferons ; Lamivudine* ; Liver

BACKGROUND: Increased body fat, abdominal obesity and insulin resistance are important clinical features in hypogonadal men. Several studies have demonstrated that a low testosterone concentration in men is associated with coronary heart disease, visceral obesity and insulin resistance. In this study, the effects of testosterone replacement therapy on the abdominal visceral fat and cardiovascular risk factors in hypogonadal men were investigated. METHODS: We selected 26 men with secondary hypogonadism (mean serum testosterone+/-SD 0.39+/- 0.57ng/mL), who were then treated with testosterone for 12 months. We measured the body composition, including the abdominal visceral fat area by abdominal CT at the L4 level, both before and 12 months after treatment, and the lipid profile, fasting plasma insulin, HOMA-IR and the serum homocysteine, CRP and IL-6 before and 6, 12 months after treatment. RESULTS: With respect to the body composition, the lean body mass had significantly increased 12 months after treatment(P= 0.002), but there were no significant changes in the body fat mass and abdominal visceral fat area. There was a trend toward a decreased fasting plasma insulin and HOMA-IR, but this did not reach statistical significance. The total cholesterol had decreased significantly at 12 months(P=0.04) and the HDL cholesterol decreased significantly over the course of study(P=0.02). There were no significant changes in the serum homocysteine, CRP and IL-6 after treatment. CONCLUSIONS: After 12 months testosterone replacement therapy in the 26 men with hypogonadism, the lean body mass had increased significantly, but there was no significant change on the abdominal visceral fat during the treatment period. Testosterone replacement had deleterious effect on HDL cholesterol, but not significant effects on insulin resistance and the serum homocysteine, CRP and IL-6. These results suggest that testosterone replacement therapy may have a few adverse effects on cardiovascular diseases in hypogonadal men. However, it will be necessary to examine the long-term effects of testosterone replacement on the incidence of cardiovascular events as well as the cardiovascular risk factors in men with hypogonadism
Adipose Tissue ; Body Composition ; Cardiovascular Diseases ; Cholesterol ; Cholesterol, HDL ; Coronary Disease ; Fasting ; Homocysteine ; Humans ; Hypogonadism ; Incidence ; Insulin ; Insulin Resistance ; Interleukin-6 ; Intra-Abdominal Fat* ; Male ; Multiple Endocrine Neoplasia Type 1 ; Obesity, Abdominal ; Plasma ; Risk Factors* ; Testosterone* ; Tomography, X-Ray Computed

BACKGROUND: Increased body fat, abdominal obesity and insulin resistance are important clinical features in hypogonadal men. Several studies have demonstrated that a low testosterone concentration in men is associated with coronary heart disease, visceral obesity and insulin resistance. In this study, the effects of testosterone replacement therapy on the abdominal visceral fat and cardiovascular risk factors in hypogonadal men were investigated. METHODS: We selected 26 men with secondary hypogonadism (mean serum testosterone+/-SD 0.39+/- 0.57ng/mL), who were then treated with testosterone for 12 months. We measured the body composition, including the abdominal visceral fat area by abdominal CT at the L4 level, both before and 12 months after treatment, and the lipid profile, fasting plasma insulin, HOMA-IR and the serum homocysteine, CRP and IL-6 before and 6, 12 months after treatment. RESULTS: With respect to the body composition, the lean body mass had significantly increased 12 months after treatment(P= 0.002), but there were no significant changes in the body fat mass and abdominal visceral fat area. There was a trend toward a decreased fasting plasma insulin and HOMA-IR, but this did not reach statistical significance. The total cholesterol had decreased significantly at 12 months(P=0.04) and the HDL cholesterol decreased significantly over the course of study(P=0.02). There were no significant changes in the serum homocysteine, CRP and IL-6 after treatment. CONCLUSIONS: After 12 months testosterone replacement therapy in the 26 men with hypogonadism, the lean body mass had increased significantly, but there was no significant change on the abdominal visceral fat during the treatment period. Testosterone replacement had deleterious effect on HDL cholesterol, but not significant effects on insulin resistance and the serum homocysteine, CRP and IL-6. These results suggest that testosterone replacement therapy may have a few adverse effects on cardiovascular diseases in hypogonadal men. However, it will be necessary to examine the long-term effects of testosterone replacement on the incidence of cardiovascular events as well as the cardiovascular risk factors in men with hypogonadism
Adipose Tissue ; Body Composition ; Cardiovascular Diseases ; Cholesterol ; Cholesterol, HDL ; Coronary Disease ; Fasting ; Homocysteine ; Humans ; Hypogonadism ; Incidence ; Insulin ; Insulin Resistance ; Interleukin-6 ; Intra-Abdominal Fat* ; Male ; Multiple Endocrine Neoplasia Type 1 ; Obesity, Abdominal ; Plasma ; Risk Factors* ; Testosterone* ; Tomography, X-Ray Computed

Repeated administration of amphetamine (AMPH) produces behavioral sensitization, a proposed model for the escalation of drug use characteristic of human addicts. beta-Phenylethylamine (PEA) is an endogenous trace amine found in mammalian brain and resembles AMPH both structurally and behaviorally. Previously, it has been reported that chronic PEA administration produces behavioral sensitization to the challenges of AMPH. However, these data were obtained with very high amount of PEA for a relatively long period of time. Further, the effect of PEA challenge on the expression of behavioral sensitization developed by AMPH pre-exposures has not been tested yet. Thus, we examined in the present experiment the expression of behavioral sensitization with AMPH challenge after a mild chronic PEA treatment. Rats were repeatedly administered with systemic injections of saline, beta-phenylethylamine (PEA) (10 or 50 mg/kg), or amphetamine (AMPH) (1.5 mg/kg). When challenged a week after the last pre-injection, rats pre-exposed to either PEA or AMPH showed behavioral sensitization to AMPH (1.0 mg/kg), while these effects were not observed to PEA (50 mg/kg) itself. These results demonstrate that repeated exposure to PEA produces behavioral sensitization to AMPH challenge, while PEA challenge has no effect on the expression of behavioral sensitization developed by AMPH pre-exposures, suggesting that PEA may play a role in the development of locomotor sensitization to AMPH, but not in the expression of it.
Amphetamine ; Animals ; Brain ; Humans ; Peas ; Phenethylamines ; Rats ; Schizophrenia

The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.
Amphetamine ; Animals ; Glycogen Synthase Kinases ; Humans ; Membrane Proteins ; Microinjections ; Negotiating ; Neurons ; Nucleus Accumbens ; Phosphorylation ; Phosphotransferases ; Plastics ; Proto-Oncogene Proteins c-akt ; Rats ; Reward ; Signal Transduction ; Street Drugs ; Substance-Related Disorders

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the term applied to arginine vasopressin (AVP) excess associated with hyponatremia without edema in the absence of physiologic or pharmacologic stimuli to AVP secretion. SIADH is associated with various conditions such as malignant tumors, infection, central nervous system disorders, and different pharmacological agents. The patient was 73-year-old female. She was admitted to the hospital because of persistent cough, dizziness, general weakness and confusion. On admission, her serum osmolality was 253 mOsm/kg, urine osmolality was 416 mOm/kg, and urine Na concentration was 159 mEq/L. Her Chest X-ray and CT scan of lung showed about 4x3.5 cm sized mass at posterior basal segment of left lower lobe of the lung, and CT-guided percutaneous needle aspiration revealed small round cell with clusters of malignant squamous cells. She was treated by salt restriction, hypertonic saline infusion and demeclocycline. We planned chemotherapy for advanced combined lung cancer, but she was discharged because of poor general condition and associated pneumonia without cancer chemotherapy. We report a rare case of SIADH in small cell cancer of lung combined with squamous cell cancer of lung.
Aged ; Arginine Vasopressin ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Central Nervous System Diseases ; Cough ; Demeclocycline ; Dizziness ; Drug Therapy ; Edema ; Female ; Humans ; Hyponatremia ; Inappropriate ADH Syndrome ; Lung Neoplasms* ; Lung* ; Needles ; Neoplasms, Squamous Cell* ; Osmolar Concentration ; Pneumonia ; Thorax ; Tomography, X-Ray Computed

BACKGROUND: Autofluorescence bronchoscopy (AFB), when used as an adjunct to conventional white light bronchoscopy (WLB) improves the bronchoscopist's ability to localized small intraepithelial lesions. Current study was undertaken to evaluate prevalence of preinvasive intraepithelial lesions (dysplasia II-III and CIS) and efficacy of additional AFB system to WLB in comparison with WLB alone. METHODS: In patients with suspicion of lung cancer or follow-up ones with known lung cancer, WLB (Pentax; BP 3500, Japan) and AFB (Richard Wolf, Germany) were done and all subjects with endoscopic abnormalities underwent biopsies from January 2005 to December 2005. RESULTS: 169 patients (134 suspected to have lung cancer radiologically, 18 with known lung cancer, and 17 with initial abnormal WLB visual findings) were enrolled. Overall preinvasive intraepithelial lesions were detected in 6.5% (11 persons). Biopsy based sensitivity of WLB+AFB and WLB alone for detecting preinvasive intraepithelial lesions was 77.8% compared with 22.2% (relative ratio 3.5, 95% CI 0.93-13.24). Corresponding specificity was 56.9% compared with 89.2% (relative ratio 0.64, 95% CI 0.54-0.75). The positive predicitve value was 6% and 3%, and the negative predictive value was 94% and 87%, respectively, for WLB+AFB and WLB alone. CONCLUSIONS: WLB+AFB was superior to WLB alone in detecting preinvasive intraepithelial lesions, but general use of AFB as a screening tool seems to be limited in suspected or known lung cancer group because of low prevalence. It is necessary of further study for precise indication for AFB among the lung cancer risk groups.
Biopsy ; Bronchoscopy* ; Follow-Up Studies ; Humans ; Lung Neoplasms ; Mass Screening ; Prevalence ; Sensitivity and Specificity ; Wolves

Ethnically specific data on genetic variation are crucial for understanding human biology and for clinical interpretation of variant pathogenicity. We analyzed data obtained by deep sequencing 1303 Korean whole exomes; the data were generated by three independent whole exome sequencing projects (named the KOEX study). The primary focus of this study was to comprehensively analyze the variant statistics, investigate secondary findings that may have clinical actionability, and identify loci that should be cautiously interpreted for pathogenicity. A total of 495 729 unique variants were identified at exonic regions, including 169 380 nonsynonymous variants and 4356 frameshift insertion/deletions. Among these, 76 607 were novel coding variants. On average, each individual had 7136 nonsynonymous single-nucleotide variants and 74 frameshift insertion/deletions. We classified 13 pathogenic and 13 likely pathogenic variants in 56 genes that may have clinical actionability according to the guidelines of the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology. The carrier frequency of these 26 variants was 2.46% (95% confidence interval 1.73–3.46). To identify loci that require cautious interpretation in clinical sequencing, we identified 18 genes that are prone to sequencing errors, and 671 genes that are highly polymorphic and carry excess nonsynonymous variants. The catalog of identified variants, its annotation and frequency information are publicly available (https://koex.snu.ac.kr). These findings should be useful resources for investigating ethnically specific characteristics in human health and disease.
Biology ; Clinical Coding ; Exome ; Exons ; Genetic Variation ; Genetics, Medical ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Pathology, Molecular ; Virulence

OBJECTIVE: Patients with lung cancer have a relative high risk of developing secondary primary lung cancers. This study examined the additional value of autofluorescence bronchoscopy (AFB) for diagnosing synchronous lung cancers and premalignant lesions. METHODS: Patients diagnosed with lung cancer from January 2005 to December 2005 were enrolled in this study. The patients underwent a lung cancer evaluation, which included white light bronchoscopy (WLB), followed by AFB. In addition to the primary lesions, any abnormal or suspicious lesions detected during WLB and AFB were biopsied. RESULTS: Seventy-six patients had non-small cell lung cancer (NSCLC) and 23 had small cell lung cancer (SCLC). In addition to the primary lesions, 84 endobronchial biopsies were performed in 46 patients. Five definite synchronous cancerous lesions were detected in three patients with initial unresectable NSCLC and in one with SCLC. The secondary malignant lesions found in two patients were considered metastatic because of the presence of mediastinal nodes or systemic involvement. One patient with an unresectable NSCLC, two with a resectable NSCLC, and one with SCLC had severe dysplasia. The detection rate for cancerous lesions by the clinician was 6.0% (6/99) including AFB compared with 3.0% (3/99) with WLB alone. The prevalence of definite synchronized cancer was 4.0% (4/99) after using AFB compared with 2.0% (2/99) before, and the staging-up effect was 1.0% (1/99) after AFB. Since the majority of patients were diagnosed with advanced disease, the subjects with newly detected cancerous lesions did not have their treatment plans altered, except for one patient with a stage-up IV NSCLC who did not undergo radiotherapy. CONCLUSIONS: Additional AFB is effective in detecting early secondary cancerous lesions and is a more precise tool in the staging workup of patients with primary lung cancer than with WLB alone.
Biopsy ; Bronchoscopy* ; Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms* ; Lung* ; Prevalence ; Radiotherapy ; Small Cell Lung Carcinoma

BACKGROUND: The lack of medical personnel has led to the employment of hospitalists in Korean hospitals to provide high-quality medical care. However, whether hospitalists' care can improve patients' outcomes remains unclear. We aimed to analyze the outcome in patients cared for by hospitalists. METHODS: A retrospective review was conducted in 1,015 patients diagnosed with pneumonia or urinary tract infection from March 2017 to July 2018. After excluding 306 patients, 709 in the general ward who were admitted via the emergency department were enrolled, including 169 and 540 who were cared for by hospitalists (HGs) and non-hospitalists (NHGs), respectively. We compared the length of hospital stay (LOS), in-hospital mortality, readmission rate, comorbidity, and disease severity between the two groups. Comorbidities were analyzed using Charlson comorbidity index (CCI). RESULTS: HG LOS (median, interquartile range [IQR], 8 [5–12] days) was lower than NHG LOS (median [IQR], 10 [7–15] days), (P < 0.001). Of the 30 (4.2%) patients who died during their hospital stay, a lower percentage of HG patients (2.4%) than that of NHG patients (4.8%) died, but the difference between the two groups was not significant (P = 0.170). In a subgroup analysis, HG LOS was shorter than NHG LOS (median [IQR], 8 [5–12] vs. 10 [7–16] days, respectively, P < 0.001) with CCI of ≥ 5 points. CONCLUSION: Hospitalist care can improve the LOS of patients, especially those with multiple comorbidities. Further studies are warranted to evaluate the impact of hospitalist care in Korea.
Comorbidity ; Emergency Service, Hospital ; Employment ; Hospital Mortality ; Hospitalists ; Humans ; Korea ; Length of Stay ; Patients' Rooms ; Pneumonia ; Retrospective Studies ; Urinary Tract Infections