BACKGROUND: Thiazides have been used in nephrogenic diabetes insipidus (NDI) patients to decrease urine volume, but the mechanism of antidiuretic effect is not known yet. Recently, it has been demonstrated that abundance of aquaporin-2 (AQP2) was decreased in lithium induced NDI. We performed this study to investigate the effect of hydrochlorothiazide (HCTZ) in lithium induced NDI rats and the change of AQP2 expression. METHODS: NDI was induced in 7 male Spraque- Dawley rats by feeding lithium carbonate containing rat chow (40 mmol/kg) for 5 weeks. 4 rats were control group. HCTZ 3.75 mg/day (n=3 among lithium treated; Li+TZ) or vehicle (n=4 among lithium treated and control; Li and Control, respectively) was infused to the rats through osmotic minipump for the last 7 days. Urine volume and urine osmolality were measured. Kidneys were processed for immunohistochemistry and immunoblotting using antibody to AQP2. RESULTS: Li+TZ showed decreased urine volume (46+/-11 mL/day for Li+TZ vs. 127+/-1 mL/day for Li, p<0.05) and higher urine osmolality (557+/-139 mmol/kgH2O for Li+TZ vs. 207+/-9 mmol/kgH2O for Li, p<0.05) comparing to Li. In semi-quantitative immunoblotting using whole kidney homogenate, Li+TZ showed increase in AQP2 expression comparing to Li (39+/-2% for Li+TZ vs. 20+/-9% for Li, p<0.05, % of normal controls). In immunohistochemistry, AQP2 expression in cortex was markedly decreased after lithium treatment. But, AQP2 expression was slightly increased after HCTZ treatment. CONCLUSION: HCTZ treatment partially increased urine concentrating ability and AQP2 expression in rats with lithium induced NDI. We concluded that partial improvement in urine concentrating ability might be associated with upregulation of AQP2.
Animals ; Antidiuretic Agents ; Aquaporin 2* ; Diabetes Insipidus, Nephrogenic* ; Humans ; Hydrochlorothiazide* ; Immunoblotting ; Immunohistochemistry ; Kidney ; Kidney Concentrating Ability ; Lithium Carbonate ; Lithium* ; Male ; Osmolar Concentration ; Rats* ; Thiazides ; Up-Regulation

BACKGROUND: Diagnosis of RTA (renal tubular acidosis) is not easy due to its nonspecific and various manifestations. To find out the clues to diagnosis, we investigated initial manifestations, laboratory features and clinical course of RTA patients. METHODS: Thirty-seven patients with RTA type I or II, whose follow-up period was over 6 months were included in the study. We reviewed their medical records retrospectively. RESULTS: Male to female ratio was 5:32 and the average age at the time of diagnosis was 38.7 (15~60). Twenty-five patients had RTA type I, nine had type II, and three had both. The average follow-up period was 6.4 years. Initial manifestations were asthenia (54%), nausea (46%), urinary stone (24%), paresthesia (24%), lower extremity weakness (22%), and paralysis (11%). Underlying diseases at the time of diagnosis include Sjogren's syndrome (14%), SLE (8%), drug-induced nephropathy (11%), diabetic nephropathy (5.4%), Sjogren's syndrome combined with SLE (2.7%), and medullary sponge kidney (2.7%). Laboratory tests revealed acidosis with hypokalemia (59%), acidosis without hypokalemia (14%), and hypokalemia without acidosis (24%). The level of total CO2 was 22 mmol/L or lower in 27 patients. The Na:Cl ratio on the average was 1:1.26 and for 33 patients below 1:1.35. Renal function deteriorated in 8 patients and 7 of them had underlying diseases. Urinary stone developed in 2 patients with RTA type I. CONCLUSION: When patients with nonspecific symptoms show decreased levels of serum total CO2, potassium, or Na:Cl ratio, RTA should always be considered.
Acidosis ; Acidosis, Renal Tubular* ; Asthenia ; Diabetic Nephropathies ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Hypokalemia ; Lower Extremity ; Male ; Medical Records ; Medullary Sponge Kidney ; Nausea ; Paralysis ; Paresthesia ; Potassium ; Retrospective Studies ; Sjogren's Syndrome ; Urinary Calculi

BACKGROUND: Renovascular hypertension has variable etiologic diseases and therapeutic outcomes. We performed a retrospective analysis of the causes and treatment results of renovascular hypertension to elucidate long-term prognosis with respect to blood pressure and renal function. METHODS: We reviewed patients who were admitted to Seoul National University Hospital for evaluation of renovascular hypertension in period from January, 1983 to December, 2002. Diagnosis of renovascular hypertension was made by combination of positive functional studies such as captopril renal scintigraphy and/or captopril test and angiographic demonstration of significant stenoses in one or both of renal arteries. Patients who were followed up for more than six months were included and classified according to the etiologic disease and treatment modalities. Responses of blood pressure and renal function in each patient were periodically evaluated. RESULTS: Of 74 patients included, 37 were male and 37 were female. The median age of the patients was 40. Atherosclerotic renal artery stenosis was the most common diagnosis (31, 41.9%), followed by Takayasu's arteritis (21, 28.4%) and fibromuscular dysplasia (14, 18.9%). Control of blood pressure and preservation of renal function were significant in medical, radiological, and surgical therapy group. There was no significant difference in response of blood pressure and renal function to treatment among treatment groups. Poor response of blood pressure and deterioration of renal function were observed more frequently in patients with atherosclerotic renal artery stenosis than in those with Takayasu's arteritis or fibromuscular dysplasia. CONCLUSION: Atherosclerosis was the most common etiologic diagnosis of renovascular hypertension. Medical treatment showed satisfactory treatment results as compared to radiologic and surgical revascularization. Patients with atherosclerotic renal artery stenosis showed poorer control of blood pressure and preservation of renal function.
Atherosclerosis ; Blood Pressure ; Captopril ; Constriction, Pathologic ; Diagnosis ; Female ; Fibromuscular Dysplasia ; Humans ; Hypertension, Renovascular* ; Male ; Prognosis ; Radionuclide Imaging ; Renal Artery ; Renal Artery Obstruction ; Retrospective Studies ; Seoul ; Takayasu Arteritis

During inflammation of the colon, cells of the gut mucosa produce or express numerous inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), and intercellular adhesion molecule 1 (ICAM-1). These mediators have been implicated as contributory factors to the inflammatory process, which results in colitis during inflammatory bowel disease (IBD). Rebamipide is an anti-gastric ulcer drug with anti-inflammatory properties in vivo and in vitro. The effects of Rebamipide on IBD have not been largely evaluated. Therefore, this study investigated the potential of Rebamipide to regulate the production of inflammatory mediators such as TNF-alpha, IL-1beta, and ICAM-1. Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis (IBD animal model), were treated intrarectally with 2 mM Rebamipide. Body weight, macro- and micro-histological scores, and activity were evaluated. As an index of tissue edema, the thickness of the colonic wall was measured between the serosal surface and the luminal surface of the mucosa. TNF-alpha, IL-1 beta, and ICAM-1 were detected by immunohistochemical staining. Rebamipide treatment of mice exhibiting TNBS-induced colitis dramatically improved the clinical and histopathological findings of inflammation. In addition, Rebamipide suppressed TNF-alpha, IL-1 beta, and ICAM-1 expression in TNBS-treated animals. Taken together, these findings suggest that Rebamipide is a potential therapeutic agent for treating patients with IBD.
Animals ; Body Weight ; Colitis ; Colon* ; Down-Regulation* ; Edema ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Intercellular Adhesion Molecule-1* ; Interleukin-1beta ; Mice ; Mucous Membrane ; Phenobarbital ; Tumor Necrosis Factor-alpha* ; Ulcer

BACKGROUND: Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7 days. RESULTS: Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2Cl- cotransporter after furosemide infusion was increased in cortex (151+/-10 vs. 100+/-10%, p< 0.05) and outer medulla (122+/-5 vs. 100+/-3%, p< 0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (alpha: 187+/-25 vs. 100+/-17%, p< 0.05; beta: 155+/-8 vs. 100+/-15%, p< 0.05; gamma: 168+/-16 vs. 100+/-9%, p< 0.05) and outer medulla (alpha: 171+/-27 vs. 100+/-17%, p< 0.05; beta: 986+/-91 vs. 100+/-33%, p< 0.01; gamma: 242+/-24 vs. 100+/-22%, p< 0.01). Consistent with these results, ENaC beta-subuint immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. CONCLUSION: These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.
Absorption ; Aldosterone ; Animals ; Body Weight ; Creatinine ; Drinking Water ; Epithelial Sodium Channels ; Extremities ; Furosemide* ; Immunoblotting ; Immunohistochemistry ; Kidney* ; Nephrons ; Rats* ; Rats, Sprague-Dawley ; Sodium*

OBJECTIVE: To investigate the clinical usefulness of serial measurement of erythrocyte sediment rate(ESR) and C-reactive protein(CRP) for monitoring the radiological progression in early rheumatoid arthritis(RA). METHODS: Thirty one patients with RA according to the 1987 ACR criteria, with joint symptoms for less than one year, and who had not previously received disease modifying antirheumatic drugs(DMARDs) were assessed from Oct. 1994 to Aug. 1998 in retrospective study. Area under curve(AUC) of ESR and CRP were calculated in these patients. Joing damage in the hands was assessed by modified Sharp's method. RESULTS: Male to female ratio was 1: 3.4. Median age of this group was 45.8+/-13.2 years. Patients who had positive rheumatoid factor were 82%. Mean duration until first visit was 271.9+/-145.8 days. At the first clinic visit, mean ESR and CRP were 50mm/hr and 2.0mg/dL. Mean erosions and joint space narrowing score by modified Sharp's method were 55.2 and 12.4, respectively. Correlation analysis showed that ESR AUC and CRP AUC were significantly associated with radiologic progression. CONCLUSIONS: Elevated over-time ESR and CRP provide a convenient short term correlation with radiologic outcome(i.e. erosions). Elevated over-time ESR and CRP can be used as a guide for therapy.
Ambulatory Care ; Area Under Curve ; Arthritis, Rheumatoid* ; Erythrocytes ; Female ; Hand ; Humans ; Joints ; Male ; Retrospective Studies ; Rheumatoid Factor

Pulmonary alveolar hemorrhage (PAH) is a rare and often fetal presenting feature of systemic lupus erythematosus (SLE) and enters the differential diagnosis of diffuse lung disease in patients with SLE. Reported mortality rats are extremely high, between 70 and 90 percents. Because death frequently occurs within the first several days of the hemorrhage, the diagnosis needs to be established promptly and treatment should be initiated immediately. Treatment of alveolar hemorrhage has included various combinations of corticosteroids, cytotoxic agents, and plasmapheresis, but survival rates have been extremely low despite aggressive therapy. We experienced a case of diffuse alveolar hemorrhage in a 29 year-old SLE male patient. PAH was diagnosed by hemoptysis, anemia, infiltration on chest X-ray and hemosiderin-laden macrophages in bronchoalveolar lavage. After high dose intravenous steroid, cyclophosphamide intravenous therapy and plasmapheresis, the condition of patient was markedly improved. He was discharged and received monthly intravenous pulse cyclophosphamide. He has done well since, showing no further pulmonary hemorrhage with steroid tapering.
Adrenal Cortex Hormones ; Adult ; Anemia ; Animals ; Bronchoalveolar Lavage ; Cyclophosphamide ; Cytotoxins ; Diagnosis ; Diagnosis, Differential ; Hemoptysis ; Hemorrhage* ; Humans ; Lung Diseases ; Lupus Erythematosus, Systemic* ; Macrophages ; Male ; Mortality ; Plasmapheresis* ; Rats ; Survival Rate ; Thorax

OBJECTIVE: Cardiovascular disease is the most frequent cause of death in rheumatoid arthritis(RA) patients and hyperhomocysteinemia is an independent risk factor for cardiovascular disease. We evaluated the status of homocysteine, vitamin B12 and folate in RA patients and the influence of the drugs used in RA on homocysteine and vitamin levels. METHODS: Fifty-six RA patients and 22 controls were studied. Plasma total homocysteine was measured by HPLC method and serum folate and vitamin B12 were measured by chemiluminescence immunoassay. In RA patients, age, sex, disease duration, medications and laboratory findings were analyzed. RESULTS: Serum vitamin B12 level was significantly lower in RA patients compared to controls(p=0.033). No significant difference in serum folate level was found between RA patients and controls but plasma total homocysteine level was significantly higher in RA patients. There was no difference in plasma total homocysteine level between patients taking MTX with folate and controls, but plasma total homocysteine level was significantly higher in patients not taking MTX compared with controls(p=0.028). In RA patients taking only hydroxychloroquine(HCQ) as a DMARD, there was significantly lower serum folate level(p=0.033) and higher plasma total homocysteine level(p=0.043) compared with controls. There was a significant negative correlation between plasma total homocysteine level and serum folate level in RA patients(r=-0.319, p=0.017). CONCLUSION: Plasma total homocysteine level was increased in RA patients but not in patients taking MTX and folate. These findings suggested that folate supplementation may be effective to prevent hyperhomocysteinemia in RA patients.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Cardiovascular Diseases ; Cause of Death ; Chromatography, High Pressure Liquid ; Folic Acid* ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Immunoassay ; Luminescence ; Plasma* ; Risk Factors ; Vitamin B 12* ; Vitamins*

OBJECTIVE: The synovium in rheumatoid arthritis(RA) is characterized by an increase in the thickness of lining layer and infiltration of cells into the sublining area. Histomorphologic studies of RA have indicated that initial destruction is more closely related to the presence of transformed appearing proliferating synovial cells than to the presence of subsynovial or periarticular inflammation. Based on the fact that synovial lining cells have some properties of transformed appearing cells, we examined the expressions of Fos, Jun and Myc oncoproteins in the synovial tissue from patients with rheumatoid arthritis and osteoarthritis. METHODS: Synovial tissues from 15 patients with RA and 15 with osteoarthritis(OA) were studied by the immunohistochemical staining technique. Nine of 15 RA specimen were from arthroscopic synovectomy and the other 6 were from total knee replacement arthroplasty. RESULT: In all specimen studied, Myc and Fos were expressed in the synovial lining cells and Myc, Fos and Jun were expressed in the sublining cells, including lymphocytes, other inflammatory cells and blood vessels. Lymphocytes in the diffuse infiltrates showed increased expression of three oncoproteins compared to lymphocytes in the nodular aggregates. When oncoprotein expressions in RA were compared to OA, Fos and Myc expressions in the synovial lining cell layer were significantly higher in RA than in OA and Jun, Fos and Myc expressions in inflammatory cells were significantly higher in RA than in OA. The expressions of Fos and Myc were significantly correlated with the degree of synovial hypercellularity. In RA, the expressions of all three oncoproteins were increased in synovectomy group than joint replacement group. CONCLUSION: We observe that there are increased expressions of Myc, Fos and Jun in RA synovium than OA. These changes are more prominent in synovectomy group than joint replacement group, which suggest the differential expression of oncoproteins according to disease progression.
Arthritis, Rheumatoid ; Arthroplasty ; Arthroplasty, Replacement, Knee ; Blood Vessels ; Disease Progression ; Humans ; Inflammation ; Joints ; Lymphocytes ; Oncogene Proteins ; Oncogenes ; Osteoarthritis ; Synovial Membrane*

It has been emphasized that the treatment of choice for the trochanteric fracture of the femur is open reduction and rigid internal fixation. Regarding the stability of the fracture, most reports were focused on the comminution of the medial cortex, but few reports were paid attention to the additional fracture of the greater trochanter. This paper was aimed to evaluate the fragment of the greater trochanter on the maintenance of reduction. We treated 23 cases of unstable trochanteric fractures in which 16 cases were treated with Dynamic Hip Screw (DHS) alone, and 7 cases were treated with DHS and additional DHS Trochanter Stabilizing Plate (TSP). We compared the two groups and the results were as follows: 1. The average lag screw slipping distance was 17.1mm in DHS Group and 10.0mm in TSP Group. 2. The average distance of lateral displacement of greater trochanter over the trochantric fractures was 11.5mm in DHS Group and no change in TSP Group. The above results suggested that the comhined use of DHS Trochanter Stabilizing Plate with Dynamic Hip Screw provided good results in the treatment of uristable intertrochanteric fractures with completely detached greater trochanter and reverse oblique fracture.
Femur* ; Hip Fractures* ; Hip*