Nationwide Analysis of Antimicrobial Prescription in Korean Hospitals between 2018 and 2021: The 2023 KONAS Report.

BACKGROUND: Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. MATERIALS AND METHODS: We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. RESULTS: Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/ß-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. CONCLUSION: This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

Impact of continuity of care on older adults diagnosed with mental and behavioural disorders at risk of death due to intentional self-harm: a retrospective Korean cohort study.

OBJECTIVES: The aim of this study was to evaluate the impact of continuity of care on older adults diagnosed with mental and behavioural disorders who are at risk of death due to intentional self-harm. STUDY DESIGN: This was a retrospective cohort study. METHODS: Data from the Korean National Health Insurance Service-Elderly Cohort Database (2002-2013) were used. A total of 53,980 patients who had visited the outpatient clinic three or more times within the year following the initial diagnosis of mental and behavioural disorders were included. A generalised estimating equation model was generated to examine the impact of continuity of care (CoC) on the risk of death due to intentional self-harm among older adults with mental illnesses. RESULTS: The risk of death due to intentional self-harm was significantly higher in those with poor CoC for mental and behavioural disorders than in those with good CoC. The risk ratio, adjusting for all covariates, was larger for the Usual Provider of Care index (adjusted risk ratio [aRR]: 1.63, 95% confidence interval [CI]: 1.25-2.12) than for the CoC index (aRR: 1.50, 95% CI: 1.18-1.90), indicating a stronger association with the concentration of contact with the most frequently visited provider. CONCLUSIONS: Poor CoC among Korean older adults diagnosed with mental and behavioural disorders was identified as a significant risk factor for death due to intentional self-harm. The results of this study highlight the need for interventions that can prevent suicidal behaviour in older adults, such as institutionalising the usual providers of mental health care for older adults.

New-onset dyslipidemia in adult cancer survivors from medically underserved areas: a 10-year retrospective cohort study.

BACKGROUND: Cancer survival rates are increasing; however, studies on dyslipidemia as a comorbidity of cancer are limited. For efficient management of the disease burden, this study aimed to understand new-onset dyslipidemia in medically underserved areas (MUA) among cancer survivors > 19 years. METHODS: This study used 11-year (2009-2019) data from the Korean National Health Insurance Service sample cohort. Cancer survivors for five years or more (diagnosed with ICD-10 codes 'C00-C97') > 19 years were matched for sex, age, cancer type, and survival years using a 1:1 ratio with propensity scores. New-onset dyslipidemia outpatients based on MUA were analyzed using the Cox proportional hazards model. RESULTS: Of the 5,736 cancer survivors included in the study, the number of new-onset dyslipidemia patients was 855 in MUA and 781 in non-MUA. Cancer survivors for five years or more from MUA had a 1.22-fold higher risk of onset of dyslipidemia (95% CI = 1.10-1.34) than patients from non-MUA. The prominent factors for the risk of dyslipidemia in MUA include women, age ≥ 80 years, high income, disability, complications, and fifth-year cancer survivors. CONCLUSIONS: Cancer survivors for five years or more from MUA had a higher risk of new-onset dyslipidemia than those from non-MUA. Thus, cancer survivors for five years or more living in MUA require healthcare to prevent and alleviate dyslipidemia.

Risk analysis for patients with arterial thromboembolic events after intravitreal ranibizumab or aflibercept injections.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population-based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011-2018) were obtained from Taiwan's National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11-0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41-8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35-77.2 and IS: aHR, 290.2; 95% CI, 103.1-816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections.

Association of lipid-lowering agent use and dry eye disease: A nationwide matched case-control study in Taiwan, 2002-2016.

PURPOSE: The purpose of this study is to evaluate the association between lipid-lowering agent use and the risks of diagnosed dry eye disease (DED). METHODS: This retrospective, case-control study included 780 786 patients who received lipid-lowering agents in 2002-2016, of which 17 409 were newly diagnosed with DED during a ≥2-year follow-up period. These patients were matched 1:4 with control participants for age, sex, and comorbidities. Separate odds ratios (OR) were calculated for DED and each of statin and fibrate use. RESULTS: Statin users had significantly higher odds of DED (adjusted OR = 1.12; 95% confidence interval (CI) = 1.08-1.16, p < 0.0001) than nonusers. Fibrate users did not show higher odds of DED than nonusers (adjusted OR = 1.04; 95% CI = 0.99-1.10, p = 0.125). The lipophilic statin users did not show higher odds of DED compared with the hydrophilic statin users (adjusted OR = 0.99, 95% CI = 0.93-1.06, p = 0.729). Among statin users, the odds of DED did not differ significantly between patients receiving statin therapy for >180 days vs. ≤90 days or patients receiving statin therapy for 91-180 days vs. ≤90 days (adjusted OR = 1.00, p = 0.922; adjusted OR = 0.94, p = 0.541, respectively). The odds of DED were not statistically different among patients receiving low-intensity, moderate-intensity, and high-intensity of statin therapy. CONCLUSIONS: Patients receiving statin therapy had a higher DED risk than patients not receiving statin therapy. The type of statin, the duration, and the intensity of statin use were not significantly associated with DED risks. Further studies are required to identify the relevant factors related to DED risks with statin.

Seven Years of Experiences of Preclinical Experiments of Xeno-Heart Transplantation of Pig to Non-Human Primate (Cynomolgus Monkey).

BACKGROUND: The absolute shortage of donors compared with patients requiring transplantation is currently an unsolved problem, and the only possible solution may be xenotransplantation. To establish a successful clinical trial, a preclinical study using nonhuman primates is essential. Starting in November 2011, our team initiated heterotopic abdominal heart xenotransplantation, the first in the Republic of Korea. We present here the initial 7-year results. METHODS: A total of 22 xenotransplantation procedures have been performed since 2011. Single transgenic pig (alpha-galactosidase transferase knockout [GalT KO], n = 16), double transgenic pig (GalT KO + CD46, n = 3, and GalT KO + CD39, n = 2), and triple transgenic pig (GalT KO + CD46 + CD70, n = 1) models were used. Our baseline regimen of immunosuppressants comprised CD154 ab, rituximab, anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The mean graft survival was 16 ± 16.27 days, and the mean graft survival was significantly longer in cases performed since 2014 (7.5 ± 8.03 days vs 24.67 ± 17.50; P = .01). Although the donor heart ischemic time was decreased per annum, no correlations could be found between ischemic time and survival days of the graft. Double or triple genetic manipulated hearts exhibited significantly better survival (11.63 ± 11.29 days vs 30.83 ± 20.34 days; P = .03). When the ratio of heart weight (grams) to nonhuman primate weight (kilograms) was lower, the results tended to be better (P < .05). The rate of immediate postoperative bleeding (9%, n = 2) causing death was relatively high in the earlier period, but there have been no serious surgical complications affecting graft survival since 2013. CONCLUSIONS: Investigation of effective and optimal target genes for each organ to further progression toward better results is important. In addition, the immunosuppressive regimen needs to be further studied and constantly refined.

Developing new automated alternation flicker using optic disc photography for the detection of glaucoma progression.

PurposeTo evaluate a progression-detecting algorithm for a new automated matched alternation flicker (AMAF) in glaucoma patients.MethodsOpen-angle glaucoma patients with a baseline mean deviation of visual field (VF) test>-6 dB were included in this longitudinal and retrospective study. Functional progression was detected by two VF progression criteria and structural progression by both AMAF and conventional comparison methods using optic disc and retinal nerve fiber layer (RNFL) photography. Progression-detecting performances of AMAF and the conventional method were evaluated by an agreement between functional and structural progression criteria. RNFL thickness changes measured by optical coherence tomography (OCT) were compared between progressing and stable eyes determined by each method.ResultsAmong 103 eyes, 47 (45.6%), 21 (20.4%), and 32 (31.1%) eyes were evaluated as glaucoma progression using AMAF, the conventional method, and guided progression analysis (GPA) of the VF test, respectively. The AMAF showed better agreement than the conventional method, using GPA of the VF test (κ=0.337; P<0.001 and κ=0.124; P=0.191, respectively). The rates of RNFL thickness decay using OCT were significantly different between the progressing and stable eyes when progression was determined by AMAF (-3.49±2.86 µm per year vs -1.83±3.22 µm per year; P=0.007) but not by the conventional method (-3.24±2.42 µm per year vs -2.42±3.33 µm per year; P=0.290).ConclusionsThe AMAF was better than the conventional comparison method in discriminating structural changes during glaucoma progression, and showed a moderate agreement with functional progression criteria.

Discovery of BPR1K871, a quinazoline based, multi-kinase inhibitor for the treatment of AML and solid tumors: Rational design, synthesis, in vitro and in vivo evaluation.

The design and synthesis of a quinazoline-based, multi-kinase inhibitor for the treatment of acute myeloid leukemia (AML) and other malignancies is reported. Based on the previously reported furanopyrimidine 3, quinazoline core containing lead 4 was synthesized and found to impart dual FLT3/AURKA inhibition (IC50 = 127/5 nM), as well as improved physicochemical properties. A detailed structure-activity relationship study of the lead 4 allowed FLT3 and AURKA inhibition to be finely tuned, resulting in AURKA selective (5 and 7; 100-fold selective over FLT3), FLT3 selective (13; 30-fold selective over AURKA) and dual FLT3/AURKA selective (BPR1K871; IC50 = 19/22 nM) agents. BPR1K871 showed potent anti-proliferative activities in MOLM-13 and MV4-11 AML cells (EC50 ~ 5 nM). Moreover, kinase profiling and cell-line profiling revealed BPR1K871 to be a potential multi-kinase inhibitor. Functional studies using western blot and DNA content analysis in MV4-11 and HCT-116 cell lines revealed FLT3 and AURKA/B target modulation inside the cells. In vivo efficacy in AML xenograft models (MOLM-13 and MV4-11), as well as in solid tumor models (COLO205 and Mia-PaCa2), led to the selection of BPR1K871 as a preclinical development candidate for anti-cancer therapy. Further detailed studies could help to investigate the full potential of BPR1K871 as a multi-kinase inhibitor.

Evaluation of six TPS algorithms in computing entrance and exit doses.

Entrance and exit doses are commonly measured in in vivo dosimetry for comparison with expected values, usually generated by the treatment planning system (TPS), to verify accuracy of treatment delivery. This report aims to evaluate the accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV beam. The algorithms tested were: pencil beam convolution (Eclipse PBC), analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT convolution (XiO Convolution), multigrid superposition (XiO Superposition), and Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and diode detector in water phantoms were used as a reference. Comparisons were done in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of the measured values. Exit doses computed by XiO Convolution, XiO Superposition, Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%-3%. Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume that full backscatter exists even at the exit level, leading to an overestimation of exit doses. Despite good agreements at the central axis for Eclipse AXB and Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond 11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area. The findings of this study serve as a useful baseline for the implementation of entrance and exit in vivo dosimetry in clinical departments utilizing any of these six common TPS algorithms for reference comparison.

Emergence of Enterococcus species in the infectious microorganisms cultured from patients with endophthalmitis in South Korea.

PURPOSE: To investigate the microorganisms in culture-proven endophthalmitis and their susceptibilities to antimicrobial agents commonly used in South Korea. METHODS: Medical records of consecutive patients with culture-proven endophthalmitis at eight institutions between 1 January 2004 and 31 July 31 2010 were reviewed. Four categories of endophthalmitis were studied: postoperative, posttraumatic, endogenous, and unspecified. Outcome measures were culture-proven infectious organisms, antimicrobial susceptibilities, and final visual acuity in the patients. RESULTS: A total of 93 microorganisms were identified from 103 patients during the study period. The positive culture rate was 59.2 % (103/174). The most common organisms identified were Enterococcus faecalis (in 20.8 % of patients, 20/96), Staphylococcus epidermidis (18.8 %, 18/96), other coagulase-negative staphylococci (10.4 %, 10/96), Pseudomonas aeruginosa (6.3 %, 6/96), and Klebsiella pneumoniae (6.3 %, 6/96). Two cases of Enterococcus faecium (2.1 %) were recognized. Overall, 70 of 96 (73.0 %) isolates were Gram-positive bacteria, 22 (23.0 %) were Gram-negative bacteria, and 4 (4.2 %) were fungi. The most common organisms resulting in reduced light perception were E. faecalis and K. pneumoniae. CONCLUSIONS: The emergence of E. faecalis in endophthalmitis is mainly caused by the high incidence of E. faecalis in postoperative endophthalmitis. This increase also impacts the final visual acuity of the patients.

Outcomes of alpha 1,3-GT-knockout porcine heart transplants into a preclinical nonhuman primate model.

BACKGROUND: Solid organ xenotransplantation is a potential solution to current organ shortages in allotransplantation. We performed four heart transplantations from alpha1, 3-galactosyltransferase gene-knockout (GT-KO) pigs to cynomolgus monkeys and monitored immunological parameters before and after transplantation. METHODS: After blood typing of the cynomolgus monkeys, we assessed the binding activity of immunoglobulin G (IgG) and IgM of monkey serum and serum toxicity toward porcine peripheral blood mononuclear cells (PBMCs) using flow cytometry. Immunosuppressive protocols consisted of anti-thymocyte globulin (25 mg/kg), rituximab (20 mg/kg), anti-CD154mAb (20 mg/kg), cobra venom factor (0.05 mg/kg), tacrolimus, and steroid. Cynomolgus monkeys with A or AB blood type with the lowest antibody binding and serum toxicity activity on porcine PBMCs were selected as recipients. RESULTS: Absolute numbers of CD3(+) T cells, CD20(+) B cells, and CD3(+)CD95(+) memory T cells in the peripheral blood were suppressed upto 24 days after transplantation. Interferon gamma production of T cells in response to porcine antigens were also significantly suppressed. Heart xenografts from GT-KO pigs survived for upto 24 days without pathologic evidence of rejection. CONCLUSION: We successfully performed 4 heart xenotransplantations using GT-KO pigs. We overcame hyperacute rejection by using GT-KO pigs, and all of the heart xenografts from the GT-KO pigs survived between 11 and 24 days without pathologic evidence of rejection, disseminated intravascular coagulation, or consumptive coagulopathy; however, we need to optimize protocols for immune modulation and postoperative care to attain long-term survival of solid organ xenografts.

Antibacterial activity of LCB01-0062, a novel oxazolidinone.

LCB01-0062, a novel oxazolidinone, has potent antibacterial activity against clinical isolates of Gram-positive bacteria. The in vitro activity of LCB01-0062 was compared with that of linezolid, oxacillin, erythromycin, ciprofloxacin, vancomycin and quinupristin/dalfopristin. Among the tested agents, LCB01-0062 showed the most potent antibacterial activity against meticillin-resistant Staphylococcus aureus, meticillin-resistant coagulase-negative staphylococci and vancomycin-resistant enterococci. LCB01-0062 was 4-8-fold more active than linezolid, the first oxazolidinone drug, against Gram-positive bacteria. The time-kill curves of LCB01-0062 were analysed at concentrations of 0.5×, 1×, 2×, 4× and 8× the minimum inhibitory concentration against S. aureus strains. LCB01-0062 showed bacteriostatic activity during 24 h. LCB01-0062 was also more effective than linezolid against S. aureus in a systemic mouse model of infection.

3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3).

A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells.

Discovery and evaluation of 3-phenyl-1H-5-pyrazolylamine-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3).

Preclinical investigations and early clinical trial studies suggest that FLT3 inhibitors offer a viable therapy for acute myeloid leukemia. However, early clinical data for direct FLT3 inhibitors provided only modest results because of the failure to fully inhibit FLT3. We have designed and synthesized a novel class of 3-phenyl-1H-5-pyrazolylamine-derived compounds as FLT3 inhibitors which exhibit potent FLT3 inhibition and high selectivity toward different receptor tyrosine kinases. The structure-activity relationships led to the discovery of two series of FLT3 inhibitors, and some potent compounds within these two series exhibited comparable potency to FLT3 inhibitors sorafenib (3) and ABT-869 (4) in both wt-FLT3 enzyme inhibition and FLT3-ITD inhibition on cell growth (MOLM-13 and MV4;11 cells). In particular, the selected compound 12a exhibited the ability to regress tumors in mouse xenograft models using MOLM-13 and MV4;11 cells.

A simulation study to evaluate limited sampling strategies to estimate area under the curve of drug concentration versus time following repetitive oral dosing: limited sampling model versus naive trapezoidal method.

The area under the curve (AUC) can be associated with the therapeutic or toxic effect of a drug. The limited sampling model (LSM) is an approach that is gaining popularity due to its simplicity for the estimation of AUC using 1-3 blood samples. The aim of the present simulation study was to compare the performance of LSM for various hypothetical drugs with that of the naive trapezoidal method (Trap). The 3-point (trough, peak, and downhill) sampling design following repetitive oral dosing was assumed for LSM (LSM3) and Trap (Trap3). The 2-point (trough and peak) sampling design was also assumed for LSM (LSM2) and Trap (Trap2). In addition, trough-sampling and peak-sampling designs for LSM were designated as LSM1 and LSM1', respectively. As a result, the rank order of precision of the AUC estimation designs/methods was summarized as follows: LSM3 asymptotically equal to Trap3> or =LSM2> or =Trap2 asymptotically equal to LSM1>LSM1'. The finding suggested that LSM can not always improve the estimation performance of AUC in the 3-point sampling design, and that LSM1' is insufficient to estimate the performance of AUC for the hypothetical drugs evaluated in the present study. Accordingly, LSM2 and LSM1 may be an efficient approach for estimating AUC following repetitive oral dosing. In addition, Trap3 and Trap2 may be promising alternatives, because Trap does not require a high investment to recruit a full-sampling model-development group.

Mechanisms responsible for the altered pharmacokinetics of bosentan: analysis utilizing rats with bile duct ligation-induced liver dysfunction.

The purpose of this study was to evaluate the mechanisms responsible for the pharmacokinetic variability of bosentan utilizing rats with liver dysfunction induced by 7-day bile duct ligation (BDL). Bosentan was administered intravenously at a constant infusion rate (I) of 24, 40 or 60 microg/min/kg. The blood bosentan concentration (BBC) following infusion was measured by HPLC, and apparent clearance (CL) of the drug was estimated as I/BBC. The CL values in normal rats were 30.5 and 19.3 ml/min/kg at infusion rates of 24 and 60 microg/min/kg, respectively, suggesting non-linear pharmacokinetics of bosentan. The BBC in BDL rats was much higher than that in normal rats, and the CL values in BDL rats were 3.80 and 3.08 ml/min/kg at infusion rates of 24 and 60 microg/min/kg, respectively. The CL value of bosentan at an infusion rate of 40 microg/min/kg in normal rats was decreased significantly by the coadministration of taurocholic acid or bilirubin. In addition, the hepatic mRNA expression of CYP2C6, CYP3A2, Oatp1a1, Oatp1a4 and Oatp1b2 in BDL rats decreased to 77.6%, 34.0%, 65.4%, 84.8% and 44.2% of that in normal rats, respectively. These results suggested that bile acids and/or bilirubin accumulated in BDL rat plasma inhibited the hepatic uptake of bosentan, and that the decreased bosentan clearance in BDL rats was caused at least partly by the impaired expression of hepatic drug-metabolizing enzymes and uptake transporters. Moreover, because the pharmacokinetics of bosentan was non-linear at the tested doses, the increased BBC in BDL rats might further induce the saturation of hepatic uptake and/or metabolism of bosentan.

Endovenous laser ablation of the incompetent small saphenous vein with a 980-nm diode laser: our experience with 3 years follow-up.

PURPOSE: To demonstrate the long-term treatment outcomes of endovenous laser ablation (EVA) of incompetent small saphenous veins (SSV) with a 980-nm diode laser. MATERIALS AND METHODS: Eighty-four patients (96 limbs), with varicose veins and reflux in the SSV on duplex ultrasound examination, were treated with a 980-nm diode laser under ultrasound- or fluoroscopy-guidance. Patients were evaluated at 1 week and 1, 3, 6 months, 1 year and yearly thereafter. RESULTS: In the 96 limbs, the technical success rate was 100%. The SSV remained closed in 89 of 93 limbs (96%) after 1 month, all of 82 limbs after 6 months, 77 limbs after 1 year, 71 limbs after 2 years and 55 limbs after 3 years. In four limbs where recanalisation was observed, repeat EVA was done resulting in successful obliteration of the SSV. No major complication occurred however bruising (27%), tightness or pain (13%) and paraesthesia (4.2%) were observed. CONCLUSION: Endovenous laser ablation with a 980-nm laser wavelength is an easy and safe procedure in incompetent SSVs. After successful treatment, there is a very low rate of recanalisation of the SSV, which suggests that the procedure will provide lasting results.

The effect of bupivacaine.HCl on the physical properties of neuronal membranes.

Fluorescent probe techniques were used to evaluate the effect of bupivacaine.HCl on the physical properties (transbilayer asymmetric lateral and rotational mobilities, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. An experimental procedure was used based on selective quenching of both 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer (RET) from the tryptophans of membrane proteins to Py-3-Py. Bupivacaine.HCl increased the bulk lateral and rotational mobilities, and annular lipid fluidity in SPMVs lipid bilayers, and had a greater fluidizing effect on the inner monolayer than that of the outer monolayer. The magnitude of increasing effect on annular lipid fluidity in SPMVs lipid bilayer induced by bupivacaine.HCl was significantly far greater than magnitude of increasing effect of the drug on the lateral and rotational mobilities of bulk SPMVs lipid bilayer. It also caused membrane proteins to cluster. These effects of bupivacaine.HCl on neuronal membranes may be responsible for some, though not all, of the local anesthetic actions of bupivacaine.HCl.

Malignant peripheral nerve sheath tumor of the orbit: malignant transformation from neurofibroma without neurofibromatosis.

A 52-year-old woman suffered from progressive proptosis and vision loss due to a large tumor in her right orbit. Multiple recurrences of the tumor were treated with surgical excision. The pathologic diagnosis in each recurrence was neurofibroma, and the tumor transformed to malignant peripheral nerve sheath tumor in the final pathologic diagnosis. Orbital exenteration and postoperative irradiation were applied and there has been no evidence of tumor recurrence 5 years postoperatively.