PURPOSE: To demonstrate the bystander effect in murine neuroblastoma model which transduced with HSV-TK gene in vitro and in vivo. METHODS: The LNC/TK vector was transfered in vitro into the neuro-2a cells, murine neuroblastoma cell line. Variable mixed populations of neuro-2a cells consisting of HSV-TK+ or HSV-TK- were plated into culture plates and treated with GCV for another 4 days. Surviving cells were counted and cell viability was determinated. For investigating the in vivo bystander effect, variable mixed populations of neuro-2a cells consisting of HSV-TK+ and HSV-TK- were inoculated into A/J mice. The tumor size was measured following injection of GCV for 7 days. RESULTS: The survival rate of the 100% neuro-2a/TK group was 90%, 25%, 5% and 0%, of 50% neuro-2a/TK group was 92%, 30%, 10% and 0%, and of the 10% neuro-2a/TK group was 95%, 40%, 15% and 5%. But, the survival rate of 0% neuro-2a/TK group was 120%, 150%, 180% and 220% on days 1, 2, 3, and 4 respectively. In the 100% and 50% neuro-2a/TK groups, tumor had disappeared following administration of GCV and in 10% neuro-2a/TK group, tumor size was not increased during GCV treatment. In 0% neuro-2a/TK group, tumor size increased during administration of GCV and all mice died after 6 weeks. CONCLUSIONS: We demonstrated the bystander effect in a murine neuroblastoma model which transduced with HSV-TK gene in vitro and in vivo. These results suggest that HSV-TK/GCV gene therapy may be useful for treatment of neuroblastoma.
Animals ; Bystander Effect* ; Cell Line ; Cell Survival ; Genetic Therapy* ; Mice ; Neuroblastoma* ; Survival Rate

PURPOSE: To analyze functional gains after TKA in patients with hemophilic arthropathy. MATERIALS AND METHODS: From January 1989 to December 1996, 16 total knee replacements were performed in 11 patients with hemophilia. The average age at operation was 30 years and nine months. The average follow-up period was 3.2 years (range, 1 to 7 years). There were 14 knees of hemophilia A and 2 knees of hemophilia B. Preoperatively, all patients complained of severe pain and had marked knee joint deformity of grade IV or V by Arnold and Hilgartner classification. The knee rating scale of Hospital for Special Surgery was used for clinical assessment. RESULTS: The average preoperative range of motion was 87.9 degrees (range, 25-125 degrees) and 94 degrees (range, 70-125 degrees) postoperatively. The average flexion contracture was 20.7 degrees (range, 0-40 degrees) preoperatively and 4.7 degrees (range, 0-15 degrees) postoperatively. The knee rating scale improved from 44.3 points (range, 40-76) to 88.8 points (range, 81-97). There was one case of superficial necrosis of skin. CONCLUSIONS: The range of motion was not improved significantly after total knee replacements in hemophilic patients. However, knee pain and bleeding episodes have decreased prominently.
Arthroplasty ; Arthroplasty, Replacement, Knee ; Classification ; Congenital Abnormalities ; Contracture ; Follow-Up Studies ; Hemophilia A ; Hemophilia B ; Hemorrhage ; Humans ; Knee Joint ; Knee* ; Necrosis ; Range of Motion, Articular ; Skin

BACKGROUND: The angiotensin-converting enzyme (ACE) has a major role in the degradation of bradykinin, tachykinin, substance P which are associated with bronchial hyperresponsiveness and inflammation. The other role of ACE is the genesis of angiotensin II which causes bronchial smooth muscle contraction. The deletion polymorphism of ACE gene(DDtype) may be related to the high serum level of ACE. OBJECTIVE: We studied to evaluate an association between the insertion /deletion polymorphism of the ACE gene and asthma, and its severity. Materials and methods: Sixty asthmatic patients and 44 healthy controls were enrolled. Severity of asthma was classified by the guideline of NHLBI/WHO workshop. The ACE genotypes of all the subjects were determined by polymerase chain reaction. RESULTS: The distribution of ACE genotypes were not significantly different between healthy controls and asthma group (p)0.05). In asthmatic patients, the genetic polymorphism was similar between different severity groups (p) 0.05). Conchcsion: It is suggested that I/D polymorphism of the ACE gene may not be associated with development of asthma. The severity of asthma may not be influenced by I/D polymorphism of the ACE gene.
Angiotensin II ; Asthma* ; Bradykinin ; Education ; Genotype ; Humans ; Inflammation ; Muscle, Smooth ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Substance P ; Tachykinins

OBJECTIVES: The respiratory compensation threshold(RCT) is thought to be one of parameters by some for the evaluation of physical performance despite its controversial status. The purpose of this investigation is to establish the reference values of the RCT in healthy Korean adults, and to examine the usefulness of this parameter in evaluating physical performance. METHODS: Symptom-limited maximal exercise test by Bruce protocol was carried out, and RCT and AT were determined by the aid of the computerized V-slope method, along with the VO2 max, in 441 healthy Korean adults consisting of 284 men and 157 women aged from 20`s to 60`s. In addition, correlation between RCT and AT was observed, and regression equations of the RCT were also derived. RESULTS: The RCT VO2 was tended to decrease with age in men, but not in women and the RCT VO2 of women was 26-30% less than that of men. The ratio of RCT VO2 to VO2 max (RCT VO2/VO2 max) was tended to increase with age and the RCT V was significantly correlated with AT VC4 and VO2 max in both sexes. CONCLUSION: Our study reveals that the RCT is another useful submaximal index along with the AT in evaluating physical performance. The regression equation of the RCT was RCT VO2(L/min)=1.4232-0.0102 A(age in year)+0.0204 W(weight in kg)-0.4889 S (sex, coded O for males and 1 for females).
Adult* ; Anaerobic Threshold ; Compensation and Redress* ; Exercise Test ; Female ; Humans ; Male ; Reference Values

PURPOSE: Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs. MATERIALS AND METHODS: In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations. RESULTS: We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA₂DS₂-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use. CONCLUSION: In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.
Anticoagulants ; Asian Continental Ancestry Group ; Atrial Fibrillation ; Body Weight ; Cohort Studies ; Drug and Narcotic Control ; Drug Labeling ; Female ; Hemorrhage ; Humans ; Hypertension ; Korea ; Male ; Off-Label Use ; Prescriptions ; Prospective Studies ; Risk Factors ; Rivaroxaban ; Stroke

BACKGROUND: Many genes encoding aminoglycoside modifying enzymes (AMEs) on transposon or plasmid were transferred from one strain to another strain and inserted into a staphylococcal chromosomal cassette mec (SCCmec). There are very diverse subtypes in SCCmec type to the insertion of resistant genes. Therefore, we researched the resistance rates of antibiotics and distribution of AME genes according to SCCmec type in MRSA strains. MATERIALS AND METHODS: We isolated 640 Staphylococcus aureus from non-tertiary hospitals in 2004, detected mecA, aac(6')-aph(2"), aph(3')-IIIa, and ant(4')-Ia using the multiplex PCR method, tested antibacterial susceptibility disk diffusion and minimal inhibitory concentration, and determined SCCmec type. RESULTS: Of 640 S. aureus isolates, MRSA rate was 39.7% and all MRSA isolates carried mecA gene. Among 214 MRSA selected, aminoglycoside-resistant rates were 98.1% in kanamycin and tobramycin, 68.7% in gentamicin, 30.8% in amikacin, and 2.8% in netilmicin. The detection rates for aac(6')-aph(2"), aph(3')-IIIa, and ant(4')-Ia were 77.1%, 13.1%, and 53.3%, respectively. Also, SCCmec type was 50.9% in SCCmec type II, 16.4% in type III, and 32.7% in type IV. The genes encoding AMEs were distributed aac(6')-aph(2") (49.5%) and aac(6')-aph(2")/ant(4')-Ia (36.7%) in SCCmec type II, aph(3')-IIIa/aac(6')-aph(2") (60%) and aac(6')-aph(2") (31.4%) in type III, and aac(6')-aph(2")/ant(4')-Ia (41.4%) and ant(4')-Ia (50%) in type IV. CONCLUSION: 39.7% of S. aureus isolated from non-tertiary hospitals was resistant to methicillin. More than 90% of MRSA isolates were detected aac(6')-aph(2") in SCCmec type II and III, and ant(4')-Ia in type IV. With these results, the genes encoding AMEs may be closed related to SCCmec type.
Adenosine ; Amikacin ; Amphotericin B ; Anti-Bacterial Agents ; Diffusion ; Gentamicins ; Kanamycin ; Kanamycin Kinase ; Methicillin ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Multiplex Polymerase Chain Reaction ; Netilmicin ; Plasmids ; Sprains and Strains ; Staphylococcus aureus ; Tobramycin

BACKGROUND: Many genes encoding aminoglycoside modifying enzymes (AMEs) on transposon or plasmid were transferred from one strain to another strain and inserted into a staphylococcal chromosomal cassette mec (SCCmec). There are very diverse subtypes in SCCmec type to the insertion of resistant genes. Therefore, we researched the resistance rates of antibiotics and distribution of AME genes according to SCCmec type in MRSA strains. MATERIALS AND METHODS: We isolated 640 Staphylococcus aureus from non-tertiary hospitals in 2004, detected mecA, aac(6')-aph(2"), aph(3')-IIIa, and ant(4')-Ia using the multiplex PCR method, tested antibacterial susceptibility disk diffusion and minimal inhibitory concentration, and determined SCCmec type. RESULTS: Of 640 S. aureus isolates, MRSA rate was 39.7% and all MRSA isolates carried mecA gene. Among 214 MRSA selected, aminoglycoside-resistant rates were 98.1% in kanamycin and tobramycin, 68.7% in gentamicin, 30.8% in amikacin, and 2.8% in netilmicin. The detection rates for aac(6')-aph(2"), aph(3')-IIIa, and ant(4')-Ia were 77.1%, 13.1%, and 53.3%, respectively. Also, SCCmec type was 50.9% in SCCmec type II, 16.4% in type III, and 32.7% in type IV. The genes encoding AMEs were distributed aac(6')-aph(2") (49.5%) and aac(6')-aph(2")/ant(4')-Ia (36.7%) in SCCmec type II, aph(3')-IIIa/aac(6')-aph(2") (60%) and aac(6')-aph(2") (31.4%) in type III, and aac(6')-aph(2")/ant(4')-Ia (41.4%) and ant(4')-Ia (50%) in type IV. CONCLUSION: 39.7% of S. aureus isolated from non-tertiary hospitals was resistant to methicillin. More than 90% of MRSA isolates were detected aac(6')-aph(2") in SCCmec type II and III, and ant(4')-Ia in type IV. With these results, the genes encoding AMEs may be closed related to SCCmec type.
Adenosine ; Amikacin ; Amphotericin B ; Anti-Bacterial Agents ; Diffusion ; Gentamicins ; Kanamycin ; Kanamycin Kinase ; Methicillin ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Multiplex Polymerase Chain Reaction ; Netilmicin ; Plasmids ; Sprains and Strains ; Staphylococcus aureus ; Tobramycin

Background: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.

Background: Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods: A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results: Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits.Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout.