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

BACKGROUND: Recent data suggest that the colonization rate of group B streptococci(GBS) in pregnant women and the incidence of neonatal infections by GBS is increasing trend in Korea, but the antimicrobial susceptibilities and serotypes in pregnant women have not been reported in Korea. So, we studied to define the antimicrobial susceptibility patterns and frequency of serotypes of GBS in pregnant women. METHODS: The susceptibility and serotyping of 60 GBS isolates from 27 pregnant women and four isolates from their two neonates were tested by an agar dilution method and agglutination test, respectively. The typing sera used in this study were Ia, Ib, II, III, IV, and V. RESULTS: Minimal inhibitory concentration range of 60 GBS from pregnant women were penicillin G 0.015-0.12 microgram/ml, vancomycin 0.5-2 microgram/ml, clindamycin 0.015-4.0 microgram/ml, chloramphenicol 2-4 microgram/ml, erythromycin 0.015-2 microgram/ml, tetracycline 0.5-256 microgram/ml, cephalothin 0.12-0.25 microgram/ml, ceftriaxone 0.03-0.12 microgram/ml, respectively. The resistance rate of GBS were 6.7% to clindamycin, 0% to erythromycin, and 98.3% to tetracycline. Most of GBS serotypes from pregnant women in decreasing order were Ib(48.3%), Ia(24.1%), III(20.7%). CONCLUSION: All GBS strains isolated from pregnant women are highly susceptible to commonly used antimicrobial agents with the exception of tetracycline. The low prevalence of severe neonatal GBS infections in Korea is not due to the absence of serotype III, but probably due to a low genital carriage rate of GBS by pregnant women.
Agar ; Agglutination Tests ; Anti-Infective Agents ; Ceftriaxone ; Cephalothin ; Chloramphenicol ; Clindamycin ; Colon ; Erythromycin ; Female ; Humans ; Incidence ; Infant, Newborn ; Korea ; Penicillin G ; Pregnant Women* ; Prevalence ; Serotyping ; Tetracycline ; Vancomycin

BACKGROUND: Since its introduction in 1987, the laparoscopic cholecystectomy has become the treatment of choice for most patients with symptomatic cholelithiasis. However, about 20% of the patients requiring a cholecystectomy present with acute cholecystitis, and the safety of a laparoscopic cholecystectomy in these patients has been questioned. With increasing experience, many studies have reported that a laparoscopic cholecystectomy in patients with acute cholecystitis is safe and cost effective. This study was to review retrospectively the results of laparoscopic cholecystectomies in patients with acute inflamed gallbladders. METHODS: From July 1993 through Fabruary 1997, laparoscopic cholecystectomies were attempted in 250 patients with or without symptomatic gallbladder disease. Acute cholecystitis, confirmed by clinical, laboratory, operative, and histological findings, was present in 61 patients. The preoperative factors that may be useful in predicting conversion to an open operation were analyzed. RESULTS: The frequency of conversion to an open operation was 19.7% for acute inflammation and 3.2% for chronic inflammation. Patients who had a laparoscopic cholecystectomy done within 72 hours of the onset of symptoms had a lower rate of conversion to open procedures. Patients who had a laparoscopic cholecystectomy done and who had a white blood cell count over 15 10(9)/L, persistant high fever (>38.0degrees C) over 3 days, and managed diabetes mellitus for over 3 years had a high rate of conversion to open procedures. There were no bile-duct injuries and no mortalites. CONCLUSIONS: Laparoscopic intervention appears to be a safe and beneficial option in the management of patients with acute cholecystitis. Surgeons should have extensive experience with both routine laparoscopic cholecystectomy and conventional open biliary tract surgery. A greater number of patients with inflammation require conversion to an open operation compared with the number of patients with no obvious inflammation who require conversion. Conversion to an open operation was frequent for patients with empyema, with symptoms that had lasted for longer than 72 hours prior to the operation, with white blood cell counts over 15 10(9)/L, with persistant high fever (>38.0degrees C) over 3 days and with managed diabetes mellitus for over 3 years, suggesting that once this diagnosis of acute cholecystitis is made, excessive time should not be spent in a laparoscopic trial dissection before conversion to an open operation.
Biliary Tract ; Cholecystectomy* ; Cholecystectomy, Laparoscopic ; Cholecystitis, Acute* ; Cholelithiasis ; Diabetes Mellitus ; Diagnosis ; Empyema ; Fever ; Gallbladder ; Gallbladder Diseases ; Humans ; Inflammation ; Leukocyte Count ; Retrospective Studies

BACKGROUND: It has been known that superselective local infusion of urokinase (UK) for an acute ischemic stroke in the carotid artery territories (CAT) is associated with a high incidence of complete recanalization (RCN) of the occluded arteries and good clinical outcomes without excess risk of hemorrhagic transformation. We intended to evaluate the clinical outcomes of patients who had experienced an acute ischemic stroke in CAT who underwent superselective local infusions of UK and to find clinical variables affecting complete RCN or clinical outcomes. METHODS: Consecutively, 18 patients with acute ischemic strokes in CAT (12 in MCA occlusion and 6 in ICA) were enrolled in this study. All patients underwent superselective local infusion of UK and were assessed degree of to the RCN with angiographic findings and clinical outcomes using a modified Barthel index and a modified NIH stroke scale score prospectively. RESULTS: A complete RCN was achieved in 12 patients (67%), partial RCN in 3 patients (17%) and no RCN in 3 other patients (17%). A complete RCN seems to have been affected by the site of the occlusion (10 in MCA occlusion and 2 in ICA), and the type of ischemic stroke (10 in embolic and 2 in thrombotic). The degree of leptomeningeal collateral circulation(LCC) also affected the degree of the RCN; patients with thrombotic stroke (n=5 ; 2 in good LCC and 3 in poor), a complete RCN was achieved only in patients with good LCC. The clinical outcomes of the patients with complete RCN were significantly superior to the patients with partial or no RCN. Hemorrhagic transformation was observed in 4 patients (22%), but 2 patients did not affect clinical outcome. Three patients died(17%). CONCLUSION: Considering the natural outcome and quality of life of the patients with ischemic stroke in CAT, our results suggest that superselective local infusion of UK as a treatment modality for acute major ischemic stroke is a effective method, as long as adequate clinical variables are fulfilled.
Animals ; Arteries ; Carotid Arteries* ; Cats ; Humans ; Incidence ; Prospective Studies ; Quality of Life ; Stroke* ; Urokinase-Type Plasminogen Activator*

BACKGROUND AND PURPOSE: If early middle cerebral artery signs (EMCAS) are present, prognoses are known to be poor, even if interventional therapy is performed. The aim of this study is to evaluate the clinical effect of a superselective intra-arterial urokinase infusion in cerebral infarction patients presenting EMCAS. METHODS: We conducted prospective longitudinal clinical trial and observed patients (n-22) with middle cerebral artery infarctions who manifested EMCAS in precontrast brain CT scans between January 1996 and April 1997. The patients were divided into two groups, one group (n-11) underwent superselective intra-arterial urokinase infusion; and the other (n-11) was treated with classic osmotherapy and heparinization. We evaluated the clinical outcome for each patient using the Canadian Neurological Scale (CNS) and the National Institutes of Health Stroke Scale (NIHSS) on admission (pre-treatment state) and on, the 3rd, 7th, and 30th days. RESULTS: The two patients groups had an even distribution of risk factors, EMCAS, age and the interval from the ictus to the initiation of treatment. The outcome at the 30th day after stroke therapy improved for all patients compared to their status on admission (p<0.01), and there was a significant interaction between the group and the time (p<0.01). This means that the group which underwent superselective intra-arterial urokinase infusion had better clinical outcomes. Hemorrhagic transformation occurred in 5 cases (22.7%), 2 from the superselective intra-arterial urokinase infusion group and 3 from the heparinization group. However, this did not influence the clinical outcome. CONCLUSIONS: Compared to previous reports suggesting the poor prognostic value of EMCAS, even when all patients having these signs, this study showed that the clinical outcomes in the thrombolyic therapy group were better than in the conservatively treated one. Therefore, more aggressive interventional therapies such as superselective intra-arterial urokinase infusion may be considered option.
Brain ; Cerebral Infarction ; Heparin ; Humans ; Infarction ; Infarction, Middle Cerebral Artery* ; Middle Cerebral Artery* ; National Institutes of Health (U.S.) ; Prognosis ; Prospective Studies ; Risk Factors ; Stroke ; Thrombolytic Therapy* ; Tomography, X-Ray Computed ; Urokinase-Type Plasminogen Activator

BACKGROUND AND OBJECTIVES: Mechanisms of restenosis following successful coronary angioplasty (PTCA) are knownasvascularsmoothmuscle cells(VSMCs)proliferationandmigration, elastic recoil or vascular wall remodeling. Paclitaxel whose effect on the stabilization of microtubles leads to cell death is highly lipophilic, permitting easy pass through cell membrane, and has a long-term antiproliferative effect. This study was performed to evaluate effect of paclitaxel on VSMCs proliferation and whether locally delivered paclitaxel can prevent stenosis and neointimal formation in rat carotid artery injury model. MATERIALS AND METHODS: Cultured VSMCs were exposed to sequential concentrations of paclitaxel in vitro, and proliferation inhibition was analyzed with 3H-thymidine incorporation. Paclitaxel of a suitable concentration was applied to the endothelium-denuded carotid artery of Fisher 344 inbred rats for 20 minutes. Angiogram and morphometric analysis of carotid artery was performed after 2 weeks. RESULTS: 3H-thymidine incorporation in cultured VSMCs was decreased dose-dependently from the concentration of 0.1 micromol/L (2,454+/-149cpm/ microgram protein) to 100 micromol/L (1,323+/-69cpm/ microgram protein) of paclitaxel by single and 20-minute exposure in the presence of platelet-derived growth factor (p<0.005). In the absence of platelet-derived growth factor, the decrement of 3H-thymidine incorporation was evident above the concentration of 5 micromol/L of paclitaxel. To evaluate in vivo effect, paclitaxel (0.1 or 1 micromol/L) was administered into the endothelium-denuded carotid artery by balloon injury and incubated for 20 minutes. Percent stenoses (32.2+/-9.8%) of paclitaxel-treated group was less than those (46.3+/-7.5%) of control group on histologic analysis (p<0.01). Paclitaxel-treated group also had wider lumen on carotid angiogram and less neointimal thickening than control on histologic examination (p<0.005). CONCLUSION: Proliferation of VSMCs was effectively inhibited and neointimal formation and luminal stenosis was prevented in rat carotid artery injury model by single, brief and local delivery of low-dose paclitaxel. This strategy could be applied to clinical settings for the prevention of restenosis after PTCA.
Angioplasty ; Animals ; Carotid Arteries* ; Carotid Artery Injuries ; Cell Death ; Cell Membrane ; Constriction, Pathologic ; Neointima ; Paclitaxel* ; Phenobarbital ; Platelet-Derived Growth Factor ; Rats*