BACKGROUND: Herpes simplex virus thymidine kinase (HSVtk) phosphorylates the prodrug ganciclovir to a nucleoside analog that inhibits DNA synthesis, causing cell death. Neighbouring nontransfected cells may be affected through a 'bystander effect', thereby amplifying the antiproliferative actions. This study was carried out to determine whether retrovirus-mediated HSVtk gene therapy could reduce intimal hyperplasia and prevent stenosis following balloon injury of the rat carotid artery. METHODS: A replication-defective recombinant retroviral vector containing HSVtk cDNA (LtkSN) was constructed. Cultured primary rat smooth muscle cells (SMCs) infected with this vector (SMC/LtkSN) were transplanted to the balloon injured rat right carotid artery. One week after transplantation, HSVtk gene therapy group was administered a 2-week treatment of ganciclovir (30 mg/kg/d). Three weeks after balloon injury and SMC/LtkSN transplantation, carotid arteriography was performed and carotid arteries were perfusion-fixed for histologic examination. RESULTS: Carotid arteriographic evaluation comparing with the uninjured left carotid artery showed that the mean luminal diameter of HSVtk gene therapy group (n=5, 85+/-3%) was significantly larger than that of balloon injury only group (n=5, 65+/-5%). The neointimal mass of HSVtk gene therapy group was less than that of balloon injury only group. SMC/LtkSN transplantation without ganciclovir treatment group (n=3) showed asymmetric intimal proliferation probably because of gravitational pooling of seeding. There were inflammatory cell infiltrations at the gravity dependent portion of HSVtk gene therapy group. CONCLUSION: Retrovirus-mediated HSVtk gene therapy following balloon injury of the rat carotid artery reduced neointimal expansion and arteriographic stenosis.
Angiography ; Animals ; Carotid Arteries* ; Carotid Artery Injuries* ; Cell Death ; Constriction, Pathologic* ; DNA ; DNA, Complementary ; Ganciclovir ; Genetic Therapy* ; Gravitation ; Herpes Simplex* ; Hyperplasia ; Myocytes, Smooth Muscle ; Phenobarbital ; Phosphotransferases* ; Rats* ; Simplexvirus* ; Thymidine Kinase ; Zidovudine

PURPOSE: As a new strategy to modulate drug resistance in the treatment of relapsed or refractory non-Hodgkin's lymphoma(NHL), continuos infusion of drugs has been incorporated into the chemotherapy. We conducted a phase II study to determine the activity and safety of EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisolone) chemotherapy, in which the natursl products are administered as a continuous infusion, for previously treated NHL's of intermediate grade. MATERIALS AND METHODS: EPOCH chemotherapy (etoposide 50 mg/m2/day 24 hour- continuous infusion, days 1~4, vincristine 0.4 mg/m2/day 24 hour-continuous infusion, days 1~4, doxorubicin 10 mg/m2/day 24 hour-continuous infusion, days 1~4, cyclophosphamide 750 mg/m2 i.v., day 5, prednisolone 60 mg/m2/day p.o. days 1-5) was given to eligible patients every 3 weeks and we assessed response and toxicity of the regimen. RESULTS: Between June 1993 and December 1995, total 56 patients entered this trial and 49 were evaluable. The complete response rate was 41%(95% C.I.: 27-55%). After follow up of 9~50(median 38) months, progression free survival was 0~39+(median 7) months and the overall survival was 1~44+(median 14) months. The prognostic factor analyses showed that B symtoms and serum LDH level before treatment and response to previous treatment affected complete response rate, and patients' performance status and response to previous treatment affected progression free survival and overall survival. Toxicities of EPOCH regimen were leukopenia, stomatitis, nausea/vomiting and neurotoxicity, but they were tolerable. There was 1 case of treatment-related death due to sepsis. CONDUSION: EPOCH chemotherapy was safe and effective for the patients with relapsed NHL. However, the results of patients with NHL refractory to previous treatment were so poor that more intensive, novel treatment would be needed for this category of patients.
Cyclophosphamide ; Disease-Free Survival ; Doxorubicin* ; Drug Resistance ; Drug Therapy* ; Follow-Up Studies ; Hodgkin Disease* ; Humans ; Leukopenia ; Lymphoma, Non-Hodgkin ; Prednisolone ; Sepsis ; Stomatitis ; Vincristine*

BACKGROUND: Oxidative stress in primary aldosteronism (PA) is thought to worsen aldosterone-induced damage by activating proinflammatory processes. Therefore, we investigated whether inflammatory markers associated with oxidative stress is increased with negative impacts on heart function as evaluated by echocardiography in patients with PA. METHODS: Thirty-two subjects (mean age, 50.3±11.0 years; 14 males, 18 females) whose aldosterone-renin ratio was more than 30 among patients who visited Severance Hospital since 2010 were enrolled. Interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein 1, tumor necrosis factor α (TNF-α), and matrix metalloproteinase 2 (MMP-2), and MMP-9 were measured. All patients underwent adrenal venous sampling with complete access to both adrenal veins. RESULTS: Only MMP-2 level was significantly higher in the aldosterone-producing adenoma (APA) group than in the bilateral adrenal hyperplasia (BAH). Patients with APA had significantly higher left ventricular (LV) mass and A velocity, compared to those with BAH. IL-1β was positively correlated with left atrial volume index. Both TNF-α and MMP-2 also had positive linear correlation with A velocity. Furthermore, MMP-9 showed a positive correlation with LV mass, whereas it was negatively correlated with LV end-systolic diameter. CONCLUSION: These results suggest the possibility that some of inflammatory markers related to oxidative stress may be involved in developing diastolic dysfunction accompanied by LV hypertrophy in PA. Further investigations are needed to clarify the role of oxidative stress in the course of cardiac remodeling.
Adenoma ; Chemokine CCL2 ; Cytokines ; Echocardiography ; Heart ; Heart Diseases ; Humans ; Hyperaldosteronism* ; Hyperplasia ; Hypertrophy ; Interleukin-6 ; Interleukin-8 ; Male ; Matrix Metalloproteinase 2 ; Oxidative Stress ; Tumor Necrosis Factor-alpha ; Veins

No abstract available.
Autistic Disorder* ; Brain* ; Perfusion* ; Tomography, Emission-Computed, Single-Photon*

Acrometastasis is rare and accounts for 0.1% of all metastasis. Renal cell carcinoma accounts for only 10% of this infrequent site. It is usually the late manifestation of a disseminated tumor, but may also be the primary manifestation of an occult cancer. Clinically, it may mimic benign tumors or nonneoplastic osteoarthritic conditions, thus resulting in misdiagnosis and improper treatment. We reported a case of acrometastasis in a renal cell carcinoma in a 76-year-old man who had been diagnosed with a progressed renal cell carcinoma with metastasis of the lung and brain.
Aged ; Brain ; Carcinoma, Renal Cell* ; Diagnostic Errors ; Humans ; Lung ; Neoplasm Metastasis

Seborrheic keratoses (SK) are very common benign tumor arising in epidermis. Few malignant transformation of SK were reported. Inflammation, ulceration or atypical nature is the evidence of malignant transformation. Some melanoma can mimic SK. So, all SK need confirm histopathologic diagnosis. We reported a case of recurrent seborrheic keratosis with satellite lesions on the left groin in a linear pattern in a 46-year-old man.
Diagnosis ; Epidermis ; Groin* ; Humans ; Inflammation ; Keratosis, Seborrheic* ; Melanoma ; Middle Aged ; Ulcer

We report a case of intradermal nevus in a 43-year-old female patient, who presented with a tender, solitary papule on the periungual area, which seemed to be a periungual fibroma. The skin biopsy revealed the upper dermis and lower dermis containing nests and cords of nevus cells without junctional activity. It was totally removed by excisional biopsy.
Adult ; Biopsy ; Dermis ; Female ; Fibroma* ; Humans ; Nevus ; Nevus, Intradermal* ; Skin

Actinic keratoses (AK) are premalignant lesions, which can develop into invasive squamous cell carcinoma(SSC). Therapies for AK include cryotherapy, curettage, topical 5-fluorouracil, laser therapy and so forth. All therapies currently prescribed can be painful and may result in scarring and changes in skin pigmentation. A potential new treatment modality for AK is the imiquimod (Aldara(R)), which can be applied by patients themselves. We reported a case of AK which was very extensive on the scalp of the old man, who was treated with topical imiquimod.
Actins* ; Cicatrix ; Cryotherapy ; Curettage ; Fluorouracil ; Humans ; Keratosis, Actinic* ; Laser Therapy ; Scalp ; Skin Pigmentation

Urinary tract complications, manifesting as leakage or obstruction, generally occur in 3.0~13% of renal recipients. Most complications occur at the ureterovesical anastomosis and are secondary to technical causes and ureteric ischemia. Ultrasound and computed tomographic images are described in a recipient who underwent oversea deceased donor renal transplantation and presented with recurrent ureteral obstruction and hydronephrosis secondary to combination of unusually located transplant kidney, long-coiled ureter, ureteric compression and ischemia of the transplant ureter.
Humans ; Hydronephrosis ; Ischemia ; Kidney ; Kidney Transplantation ; Tissue Donors ; Ultrasonography ; Ureter* ; Ureteral Obstruction ; Urinary Tract*

PURPOSE: Drug resistance is one of the major obstacles to treatment of cancer. Multidrug resistance (MDR) caused by overexpression of p-glycoprotein (Pgp) in cancer cell membrane is a well-known mechanism of drug resistance in in vitro system and was reported to be a significant mechanism of resistance in non-Hodgkins lymphoma (NHL). Verapamil, a calcium channel blocker, is proven in vitro to overcome the MDR caused by Pgp. We performed a phase II trial of verapamil in patients with NHL refractory to EPOCH regimen (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) to overcome the MDR caused by Pgp. MATERIALS AND METHODS: Verapamil was administered via intravenous route from 1 hour before to 12 hour after the 96-hour infusion of etoposide, doxorubicin, and vincristine which were known to be substrates of Pgp in EPOCH regimen. The dose of verapamil was 0.15 mg/Kg in bolus and 0.2 mg/Kg/hr in infusion at the beginning and escalated by 0.05 mg/Kg/hr every 24 hours if there was no dose-limiting toxicities such as 2nd or 3rd degree AV block, hypotension, or congestive heart failure. Plasma verapamil concentrations were measured every 24 hour by gas chromatography. Mdrl expression level in tumor tissues was measured by RT-PCR. RESULTS: From Feb. to Nov. 1994, 14 patients were treated with this protocoL However, poor tolerability and no response in these patients led to early closure of the study at this 1st stage of patient accrual according to Gehans method. Among 14 patients, 12 experienced 2nd or 3rd degree AV block and/or hypotension and required temporary cessation of infusion and reduction of verapamil dose. However, there was no congestive heart failure or treatment-related death. The peak concentrations of verapamil were 0.29-1.94 pM (mean 0.93 pM) and mean concentrations during the 4-day infusion were 0.22-1.21 pM (mean 0.6 pM). Mdrl expression levels measured in 6 patients were 0.99-14.43 U (median 4.39). CONCLUSION: These results suggest that verapamil in this dose and schedule was neither tolerable nor effective for the reversal of drug resistance in NHL patients.
Appointments and Schedules ; Atrioventricular Block ; Calcium Channels ; Cell Membrane ; Chromatography, Gas ; Cyclophosphamide ; Doxorubicin ; Drug Resistance* ; Drug Resistance, Multiple ; Etoposide ; Heart Failure ; Hodgkin Disease* ; Humans ; Hypotension ; Lymphoma, Non-Hodgkin ; P-Glycoprotein ; Plasma ; Prednisolone ; Verapamil* ; Vincristine