BACKGROUND/AIMS: The effect of entecavir (ETV) in treatment-naive chronic hepatitis B (CHB) is well established. This study aimed to assess the efficacy of ETV treatment at 0.5 mg/day in ETV-switch and ETV-retreatment groups of CHB patients without lamivudine (LMV)-resistance from LMV monotherapy. METHODS: Study subjects included 350 CHB patients who had been treated with 0.5 mg/day of ETV for at least 6 months. Patients were divided into two groups: an LMV-naive group (n = 263) and an LMV-experienced group (n = 87). The LMV-experienced group was further subdivided into an ETV-switch group (n = 43) and an ETV-retreatment group (n = 44) defined by the period between stopping LMV and restarting ETV. RESULTS: There were no significant differences in mean age, sex ratio, prevalence of liver cirrhosis and hepatitis B e antigen (HBeAg) positivity between the LMV-naive and -experienced groups. However, the LMV-naive group had higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and a shorter ETV treatment duration than the LMV-experienced group. There were also distributional differences in the hepatitis B virus (HBV) DNA levels of LMV-naive and -experienced patients prior to ETV treatment. After ETV treatment, there were no significant differences between the two groups in the rates of undetectable HBV DNA at 6, 12 and 18 months; HBeAg loss and seroconversion; normalization of ALT; virologic breakthrough; and ETV-genotypic resistance. Lastly, the effect of ETV did not differ between the ETV-switch and -retreatment groups. CONCLUSIONS: The effect of ETV in the LMV-experienced group without LMV-resistance did not differ from that in the LMV-naive group. Furthermore, there was no difference in the effect of ETV between the ETV-switch and -retreatment groups.
Alanine Transaminase ; Aspartate Aminotransferases ; DNA ; Guanine ; Hepatitis B ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Lamivudine ; Liver Cirrhosis ; Prevalence ; Sex Ratio

BACKGROUND: The associations of apolipoprotein E (ApoE) genotypes and cholesterol levels with cognitive decline in Alzheimer's disease (AD) are controversial. The aim of this study is to investigate the individual and combined effects of ApoE epsilon 4 allele (Epsilon4) and cholesterol levels on the progression of AD. METHODS: ApoE genotypes and fasting serum total cholesterol levels were measured in 79 patients with AD. The associations were investigated between Epsilon4, cholesterol level and decline in cognitive function (Korean version of Mini-Mental State Examination) over one year. RESULTS: No prospective individual and combined associations were found between Epsilon4, cholesterol level and decline of cognitive function. Adjustment for age, gender, education, and functional activities of daily living made little difference to the associations. CONCLUSIONS: The cognitive decline of AD might be determined by other factors rather than the impact of Epsilon4 or cholesterol levels.
Activities of Daily Living ; Alleles ; Alzheimer Disease* ; Apolipoproteins E ; Apolipoproteins* ; Cholesterol* ; Education ; Fasting ; Genotype ; Humans

Puromycin aminonucleoside (PAN) -induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. To investigate whether proteinuria in the PAN model is associated with an alteration of zonula occludens-1 (ZO-1) expression within the glomeruli, and whether cyclosporin A (CsA) has an effect on proteinuria and ZO-1 expression in this model, eighteen Sprague Dawley (SD) rats were assigned into three groups. Twelve rats received a single intraperitoneal injection of PAN (15 mg/100 g). The other six rats received an equal volume of saline (normal control group; control). CsA solution was administered intraperitoneally once a day for 20 days after the PAN injection (n=6, PAN+CsA). The remaining six rats received PAN, but they didn't receive CsA (n=6, PAN). Compared to control rats (35.1 +/- 5.4 mg/day), the 24-hour urinary protein excretion on day 18 was significantly higher in the PAN rats (1021.9 +/- 128.9 mg/day, p< 0.01), and the CsA treatment partly reversed the increase in proteinuria in the PAN rats (556.4 +/- 102.3 mg/day, p< 0.05). Glomerular ZO-1 protein expressions were significantly increased in the PAN rats as compared to the control group on day 20 (176%, p< 0.01). CsA treatment for 20 days in the PAN rats inhibited the increase in ZO-1 protein expression by 71.1% (p< 0.05). CsA treatment significantly diminished the glomerular ZO-1 expression in the PAN rats as assessed by immunohistochemistry. CsA treatment significantly reduced proteinuria and the diminished glomerular ZO-1 expression in a PAN nephrosis rat model. These findings suggest the potential role of the slit diaphragm associated proteins in the development of the nephrotic syndrome, and CsA decreased the proteinuria probably by a direct action on the expression of these proteins in podocytes. Further investigations are needed to clarify the role of slit diaphragm associated proteins in the development of PAN nephrosis.
Animals ; Antimetabolites, Antineoplastic ; Cyclosporine/*pharmacology ; Immunosuppressive Agents/*pharmacology ; Kidney Glomerulus/*drug effects/metabolism ; Male ; Membrane Proteins/*metabolism ; Nephrosis/chemically induced/*drug therapy/*metabolism ; Phosphoproteins/*metabolism ; Puromycin Aminonucleoside ; Rats ; Rats, Sprague-Dawley ; Research Support, Non-U.S. Gov't

BACKGROUND: Urinary TGF-beta1 reflects intrarenal TGF-beta1 production and is increased in patients with progressive nephropathies. We studied the effects of angiotensin receptor blocker (ARB) on serum and urinary TGF-beta1 excretion in chronic glomerulonephritis patients with proteinuria. Also the role of urinary TGF-beta1 in ARB induced antiproteinuric responses was evaluated. METHODS: Patients with non-diabetic chronic renal disease with proteinuria of 1 g or more were enrolled in this open, prospective study. After four weeks of washout period, the patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12 weeks. Clinical parameters and urinary indices including proteinuria and urinary TGF-beta1 were measured at baseline and after each 12 week treatment period. RESULTS: Among the 42 patients who completed the study, 31 responded to ARB therapy determined as a decrease in proteinuria by 30% (responders), and 11 did not respond (non-responders). ARB treatment controlled blood pressure to a similar degree in both responders and non-responders. Renal function and other biochemical parameters did not change during the study period. Both doses of losartan significantly lowered proteinuria and urinary TGF-beta1 excretion in responders (50 mg: 33.4% and 29.0%, 100 mg: 64.1% and 45.8%, respectively, p<0.05). In contrast, non-responders showed no significant reduction in proteinuria and no further decrease in urinary TGF-beta1 after 100 mg treatment. Urinary TGF-beta1 excretion lacked any correlation between clinical parameters such as proteinuria or renal function. Responders were younger, showed lower baseline proteinuria and urinary TGF-beta1 excretion and greater reduction in urinary TGF-beta1 excretion after ARB treatment. However, lower baseline urinary TGF-beta1 excretion was the only significant predictor of response to ARB therapy. CONCIUSION: Our data suggest that ARB therapy in nondiabetic proteinuric chronic glomerulonephritis patients reduces proteinuria and urinary TGF-beta1 excretion and baseline urinary TGF-beta1 excretion may predict antiproteinuric response to ARB therapy.
Angiotensins ; Blood Pressure ; Glomerulonephritis* ; Humans* ; Losartan* ; Prospective Studies ; Proteinuria* ; Renal Insufficiency, Chronic ; Transforming Growth Factor beta1

BACKGROUND: Diabetic nephropathy (DN) is clinically characterized by persistent proteinuria. The underlying pathologic changes responsible for the nephropathy are the loss of size selective and/or charge selective properties of the glomerular filtration barrier. Size selectivity is maintained primarily by the slit diaphragm and ZO-1 is one of the basic components of it. However, the precise role of the ZO-1 in the pathogenesis of the glomerular diseases is not fully understood. We investigated the changes of ZO-1 expression in diabetic glomeruli in vivo, and by high glucose in cultured podocyte in vitro. We also evaluated the effect of angiotensin II type 1 receptor blocker (ARB) on the ZO-1 changes induced by diabetes or high glucose. METHODS: To determine the effect of ARB on podocytes ZO-1 protein and mRNA expression, immortalized mouse podocytes were incubated with RPMI medium containing normal glucose (NG, 5.6 mM) or high glucose (HG, 30 mM) with or without ARB (10-6 M, L-158, 809). For animal studies, rats were injected with diluent (Control, C, n=18) or streptozotocin. The latter were left untreated (DM, n=18) or treated with 1 mg/kg/day ARB (DM+ARB, n=18). Six rats from each group were sacrificed monthly, and Western blot and RT?PCR were performed for ZO-1 with sieved glomeruli. Renal sections were stained for ZO-1 by immunohistochemistry. RESULTS: The ZO-1 mRNA and protein expressions in podocytes exposed to HG conditions were significantly higher than those in podocytes exposed to NG media (p<0.05). ARB treatment inhibited the HG induced increase in ZO-1 mRNA and protein expression by 73% and 64%, respectively (p<0.05). Compared to the C rats (19.8+/-3.2 mg/day), 24 hour urinary protein excretion at 3 month was significantly higher in the DM rats (90.6+/-11.3 mg/day, p< 0.05), and ARB treatment partly reversed the increase in proteinuria in DM rats (51.6+/-6.6 mg/day, p<0.05). Glomerular ZO-1 mRNA and protein expressions were also significantly increased in DM than corresponding C at all duration (p<0.05). ARB treatment for 3 months in DM rats inhibited the increase in ZO-1 mRNA and protein expression by 57.5% and 70.6%, respectively (p<0.05). ARB treatment for 3 months significantly ameliorated increased glomerular ZO-1 expression in DM rats as assessed by immunohistochemistry. CONCLUSION: In conclusion, ZO-1 mRNA and protein expressions were increased in podocytes exposed to HG and in DM glomeruli, and this increment in ZO-1 expression was ameliorated with ARB. Taken together, these data suggest that change of ZO-1 expression in podocytes is implicated in the early changes of diabetic nephropathy and may contribute to the development of proteinuria.
Angiotensin II* ; Angiotensins* ; Animals ; Blotting, Western ; Diabetic Nephropathies ; Diaphragm ; Glomerular Filtration Barrier ; Glucose* ; Immunohistochemistry ; Mice* ; Podocytes* ; Proteinuria ; Rats* ; Receptor, Angiotensin, Type 1* ; RNA, Messenger ; Streptozocin

A 22-year-old woman visited our clinic with a history of radiofrequency volumetric reduction for bilateral masseter muscles at a local medical clinic. Six days after the radiofrequency procedure, she noticed a facial asymmetry during smiling. Physical examination revealed immobility of the mouth drawing upward and laterally on the left. Routine nerve conduction studies and needle electromyography (EMG) in facial muscles did not suggest electrodiagnostic abnormalities. We assumed that the cause of facial asymmetry could be due to an injury of zygomaticus muscles, however, since defining the muscles through surface anatomy was difficult and it was not possible to identify the muscles with conventional electromyographic methods. Sono-guided needle EMG for zygomaticus muscle revealed spontaneous activities at rest and small amplitude motor unit potentials with reduced recruitment patterns on volition. Sono-guided needle EMG may be an optimal approach in focal facial nerve branch injury for the specific localization of the injury lesion.
Electromyography ; Facial Asymmetry ; Facial Muscles ; Facial Nerve ; Female ; Humans ; Masseter Muscle ; Mouth ; Muscles ; Needles ; Neural Conduction ; Paralysis ; Physical Examination ; Smiling ; Volition

BACKGROUND/AIMS: Toxocariasis rarely causes a liver abscess. We assessed clinical and laboratory manifestations as well as therapeutic responses in patients with toxocariasis presenting as a liver abscess. METHODS: Fourteen patients with toxocariasis presenting as a liver abscess were analyzed retrospectively. Symptoms, occupational history, dietary habits, contact with pets, allergic disease, peripheral eosinophil count, serum immunoglobulin E (IgE) level, and invasion to other organs were evaluated. After treatment with albendazole, follow-up was conducted with abdominal computed tomography (CT) and the measurement of serum eosinophil and IgE levels. RESULTS: Among 568 patients with a liver abscess, 14 were diagnosed with active toxocariasis. The mean age of the patients was 48 years, and nine (64%) were men. Four (28.6%) patients had pain in the right upper quadrant of the abdomen or epigastric area, one had cough, and the others (64.3%) had no symptom. Pulmonary involvement was noted in five patients and colon involvement in one. Six (42.9%) patients had a recent history of eating raw meat. Initial laboratory findings showed increased eosinophil and IgE levels in all patients. The initial CT showed one or multiple ill-defined, hypodense lesions in the liver. After 1 month of albendazole treatment, eosinophil counts were normalized or had decreased in 13 (93%) patients. On follow-up CT, liver abscesses disappeared within 6 months after therapy in 92% of patients. CONCLUSIONS: Symptoms, laboratory findings, and treatment of a liver abscess caused by toxocariasis differ from those of a pyogenic liver abscess. Early serologic testing may increase diagnostic yield and efficacy of treatment in patients with a liver abscess and peripheral eosinophilia.
Abdomen ; Albendazole ; Colon ; Cough ; Eating ; Eosinophilia ; Eosinophils ; Follow-Up Studies ; Food Habits ; Humans ; Immunoglobulin E ; Immunoglobulins ; Liver ; Liver Abscess ; Liver Abscess, Pyogenic ; Male ; Meat ; Retrospective Studies ; Serologic Tests ; Toxocariasis

BACKGROUND: Angiotensin II, a potent vasoconstrictor, plays a key role in renal injury and in the progression of chronic renal disease of diverse causes. In every organ system, the biologic effects of angiotensin II are mediated through its interaction with specific receptors on cell membranes. Angiotensin II receptor antagonist specifically inhibits angiotensin II-mediated physiologic responses such as systemic and renal vasoconstriction, sodium reabsorption by renal proximal tubule, and stimulation of aldosterone and adrenergic hormone release by the adrenal gland. It has been reported that losartan, angiotensin II receptor antagonist, has a significant antiproteinuric effect in patients with diabetic and non-diabetic renal disease. This study was carried out to investigate the effect of angiotensin-converting enzyme (ACE) gene polymorphism on the renal response to angiotensin II receptor antagonist in non-diabetic proteinuric chronic renal patients. METHODS: Seventy patients with non-diabetic chronic renal disease with urinary protein excretion greater than 500 mg/day were enrolled in this prospective study. Subjects were given losartan 50 mg o.d. for the first 12 weeks, and then were given to 100 mg o.d. for another 12 weeks. RESULTS: Twelve weeks and twenty-four weeks later, blood pressure, urinary protein excretion, total cholesterol, and triglyceride decreased significantly compared with baseline values. There was a significant correlation between the levels of baseline urinary protein excretion and the magnitudes of the reduction of urinary protein excretion after treatment with losartan. Baseline blood pressure, BUN, serum creatinine, and urinary protein excretion were not different in the responder group (patients with more than 30% reduction of urinary protein excretion after losartan treatment) compared with the nonresponder group. Systolic blood pressure and mean arterial pressure in the responder group were significantly lower than the nonresponder group after twelve and twenty-four weeks. Urinary protein excretion in the responder group was significantly lower than the nonresponder group after twelve weeks. When the patients were divided into three groups according to ACE gene polymorphism, II, ID and DD, there were no significant differences in the blood pressure change, reduction of urinary protein excretion following losartan treatment and distributions of responder among three groups. CONCLUSION: Our results suggest that angiotensin II receptor antagonist, losartan, significantly reduced blood pressure and proteinuria in patients with non- diabetic chronic renal disease. The magnitude of antiproteinuric effect of losartan was not influenced by ACE gene polymorphism. However, further studies with large number of patients are required to confirm the issues regarding the ACE gene polymorphism and the antiproteinuric effects of angiotensin II receptor antagonist in non-diabetic chronic renal disease.
Adrenal Glands ; Aldosterone ; Angiotensin II* ; Angiotensins* ; Arterial Pressure ; Blood Pressure ; Cell Membrane ; Cholesterol ; Creatinine ; Humans ; Losartan ; Prospective Studies ; Proteinuria ; Receptors, Angiotensin* ; Renal Insufficiency, Chronic* ; Sodium ; Triglycerides ; Vasoconstriction

Sclerosing encapsulating peritonitis (SEP) is a rare but serious complication in patients with continuous ambulatory peritoneal dialysis (CAPD), and is characterized by a progressive, intra-abdominal, inflammatory process resulting in the formation of sheets of new fibrous tissue, which cover, bind, and constrict the viscera, thereby compromising the motility of the bowel. No satisfactory estimate is available on the comparative incidence of dialysis related SEP and the pathogenesis of SEP still remains uncertain. Although recent therapeutic approaches have reported varying degrees of success, an efficient measure to detect, at an early stage, patients at risk for SEP would be beneficial and a standardized treatment regimen to prevent the illness is urgently needed. This study aimed to evaluate the clinical features of SEP and to identify the possible risk factors for the development of SEP in CAPD patients. We retrospectively reviewed by questionnaire SEP cases among CAPD patients from 7 university hospital dialysis centers in Korea, including Yonsei University, Ajou University, Catholic University, Inha University, Kyungpook University, Seoul National University and Soonchunhyang University, from January 1981 to December 2002. Out of a total of 4, 290 CAPD patients in these centers, 34 cases developed SEP with an overall prevalence of 0.79%. The male to female ratio was 17: 17. The median age of these patients was 44.5 years (range 19 - 66). The median duration of CAPD before SEP was 64 months (9 - 144) and 68% of patients (23/34) had been on CAPD for more than 4 years. Peritonitis (including two fungal cases) was the main cause of catheter removal in SEP (27 cases, 79%). Seventy-five percent of the cases (15/ 20) were administered beta-blocker for a mean duration of 85 months (26 - 130). Among 10 cases with available peritoneal equilibration test (PET) data, 8 showed high transporter characteristics, and the remaining 2 were high average. Eighteen cases were diagnosed by clinical and radiologic methods, and 16 were surgically diagnosed. Eleven cases were surgically treated and the others were treated conservatively with intermittent total parenteral nutrition (TPN). The overall mortality rate was 24%. SEP is a serious, life threatening complication of CAPD. Most cases had a PD duration of more than 4 years, a history of severe peritonitis, and high transporter characteristics in PET. Therefore, to reduce the incidence of SEP, careful monitoring and treatment, including early catheter removal in patients with severe peritonitis, should be considered for long-term CAPD patients with the above characteristics.
Adult ; Aged ; Female ; Humans ; Incidence ; Korea/epidemiology ; Male ; Middle Aged ; Peritoneal Dialysis, Continuous Ambulatory/*adverse effects/*statistics & numerical data ; Peritonitis/*epidemiology/etiology/*pathology ; Prevalence ; Sclerosis

To evaluate the clinical efficacy and safety of newly developed recombinant human erythropoietin (Epokine(R)), a phase III clinical trial was performed in patients with end-stage renal disease undergoing maintenance hemodialysis. Epokine(R)was given initially at a dosage of 50unit/kg, intravenously, three times a week after each dialysis session and the dosage was adjusted according to the changes in hemoglobin level. Out of total 79 patients who were enrolled initially, data of 64 patients who have completed 12 weeks study period were analyzed. The results were as following: 1) Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine(R) administration. Hemoglobin increased significantly from 6.8+/-0.8 to 10.4+/-1.3 and hematocrit increased significantly from 20.9+/-2.2 to 31.1+/-5.2 after 12 weeks(P<0.05). Corrected reticulocyte count(%) increased significantly from 0.6+/-0.4 to 1.4+/-0.7 after 2 weeks and to 1.3+/-0.6 after 12 weeks(P<0.05). 2) A significant increase in platelet count was observed from 2 weeks after Epokine(R) administration (P<0.05). 3) Serum ferritin and serum iron decreased significantly and total iron binding capacity increased significantly after 2 weeks(P<0.05). 4) The mean of pre-hemodialysis systolic blood pressure(mmHg) increased significantly from 148+/-21 to 154+/-25 at 12 weeks(P<0.05). Also, post-hemodialysis blood pressure(systolic/diastolic) at 12 weeks increased significantly from baseline levels(146+/-28/ 82+/-15 vs. 153+/-25/87+/-14mmHg, P<0.05). 5) Anti-erythropoietin antibody was not detected in all subjects. 6) Side effects observed in this study were similar to those reported by earlier reports. Headache(9 cases), and flu-like syndrome(7 cases) were the most common side effects. These side effects were not severe and disappeared without discontinuation of Epokine(R) administration in most of the patients. In conclusion, Epokine(R) is safe and effective in treating anemia of hemodialysis patients with end stage renal disease.
Anemia ; Dialysis ; Erythropoietin ; Ferritins ; Hematocrit ; Humans* ; Iron ; Kidney Failure, Chronic ; Platelet Count ; Renal Dialysis* ; Reticulocytes