Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Heparin, a widely used anticoagulant, is currently the anticoagulant of choice in long-term hemodialysis (HD). Heparin-induced thrombocytopenia (HIT) is one of the most serious side effects of heparin which can cause arterial or venous thromboembolism associated with substantial morbidity and mortality. We experienced two patients who had thrombocytopenia and vascular access occlusion during the induction period of HD with the use of unfractionated heparin. Thrombocytopenia was improved after discontinuation of heparin. HIT was confirmed with anti-heparin/platelet factor 4 antibody test. HD was conducted and arteriovenous fistula was created successfully after switch of heparin to argatroban (Novastan(R)) or nafamostat mesilate (Futhan(R)). Nephrologist should rule out HIT first when thrombocytopenia and thromboembolic complications occur after use of heparin, especially during the induction period of HD. For suspicious patients, immediate cessation of heparin and switch to alternative anticoagulant is very important to avoid serious complications.
Arteriovenous Fistula ; Heparin ; Humans ; Mesylates ; Mortality ; Renal Dialysis* ; Thrombocytopenia* ; Venous Thromboembolism

PURPOSE: The water exchange rate between bulk water and bound water is an important parameter in deciding the efficiency of paramagnetic contrast agents. In this study, we evaluated the water exchange rates of various Gd-chelates using oxygen-17 NMR technique. MATERIAL AND MEHTODS: The samples (Gd-DTPA, Gd-DTPA-BMA, Gd-DOTA, Gd-EOB-DTPA) were prepared by mixing 5% (17)O-enriched water (Isotech, USA). The pH of the samples was adjusted to physiological value (pH=7.0) by buffer solution. The variable temperature (17)O-NMR measurements were performed using Bruker-600 (14.1 T, 81.3 MHz) spectrometer. Bruker VT-1000 temperature control units were used to stabilize the temperature. The (17)O spin-spin relaxation times (T2) were measured using Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence with 24 echo trains. The variable temperature T2 relaxation data were then fitted into Solomon-Bloembergen equations using least square fit algorithm to estimate the water exchange times. RESULTS: From the measured (17)O-NMR relaxation rates, the determined water exchange rates at 300K are : 0.42 microsecond for Gd-DTPA, 1.99 microsecond for Gd-DTPA-BMA, 0.27 microsecond for Gd-DOTA, and 0.11 microsecond for Gd-EOB-DTPA. The Gd-DTPA-BMA showed slowest exchange whereas Gd-EOB-DTPA had fastest water exchange rate. In addition, it was found that the water exchange rates of all samples had exponential temperature dependence with different decay constant. CONCLUSION: (17)O-NMR relaxation rate measurements, when combined with variable temperature technique, provide a solid tool for studying water exchange rate, which is very important in investigating the detailed mechanism of relaxation enhancement effect of the paramagnetic contrast agents.
Contrast Media* ; Gadolinium DTPA ; Hydrogen-Ion Concentration ; Relaxation

PURPOSE: To determine the electronic spin relaxation times, T1e, of three commercially available Gd-chelated MR contrast agents, Gd-DTPA, Gd-DTPA-BMA and Gd-DOTA, using Electron Paramagnetic Resonance(EPR) technique. Material and Methods: The paramagnetic MR contrast agents, Gd-DTPA(Magnevist), Gd-DTPA-BMA(OMNISCAN) and Gd-DOTA(Dotarem), were used for this study. The EPR spectra of these contrast agents, which were prepared 2:1 methanol/water solution, were obtained at low temperatures, from-160degrees C~-20degrees C. The glassy-state EPR spectra for these contrast agents were then fitted by the simulation spectra generated with different zero-field splitting (ZFS) parameters by a computer simulation program 'GE N', which generates the EPR powder spectrum using a given ZFS in 3X3 tensor. Finally, the spin relaxation times of the contrast agents were then determined from the T2e, D, and E values of the best simulation spectra using the McLachlan's theory of average relaxation rate. Results: The electronic transverse spin relaxation times, T2e's, of Gd-DTPA, Gd-DTPA-BMA and Gd-DOTA were 0.113ns, 0.147ns and 1.81ns respectively. The g-values were 1.9737, 1.9735 and 1.9830 and the electronic spin relaxation times, T1e's, were 18.70ns, 33.40ns and 1.66micros, respectively. Conclusion: The results of these studies reconfirm that the paramagnetic MR contrast agents with larger ZFS parameters should have shorter T1e's. Among three contrast agents used for this study, Gd-DOTA chelated with cyclic ligand structure shows better electronic property then the others with linear structure. Thus, it is concluded that the exact determination of ZFS parameters is the important factor in evaluating relaxation enhancement effect of the agents and in developing new contrast agents.
Computer Simulation ; Contrast Media* ; Gadolinium DTPA ; Magnetic Resonance Imaging* ; Relaxation*

Liddle's syndrome was described in 1963 by Liddle, et al., as the disease featuring a hypertension and hypokalemia but with negligible secretion of aldosterone. This syndrome, which morphologically belongs to an abnormal intrinsic tubular disorder with normal renal function, is characterized by hypokalemia, metabolic alkalosis, and hypertension due to the abnormal increase in excretion of potassium in distal tubules or collecting duct and the increase in reabsorption of sodium in distal tubules. This syndrome, which is rare disease, is observed with the low level of plasma and urinary aldosterone and suppressed plasma renin level and is known as dominant mode of inheritance with a family background. The authors paid attention to a 79-year-old man who showed a high blood pressure of 210/130mmHg as well as musle weakness, especially lower extremities due to metabolic alkalosis featuring a hypokalemia level of 2.0mEq/L when he was admitted to our hospital, Because his serum potassium were not improved with the medication of intravenous potassium supply, and his blood pressure continued to be high without the improvement of muscle weakness, we prescribed 300mg of spironolactone for two weeks. His symptom, however, was not cured. Then, instead of spironolactone, we prescribed 150mg of triamterene and a low salt diet which finally improved his symptoms. Because there has been no reported case in the Korean medical literature, we report a case of successfully treated Liddle's syndrome due to triamterene administration.
Aged ; Aldosterone ; Alkalosis ; Blood Pressure ; Diet ; Humans ; Hypertension ; Hypokalemia ; Lower Extremity ; Muscle Weakness* ; Plasma ; Potassium ; Rare Diseases ; Renin ; Sodium ; Spironolactone ; Triamterene ; Wills

BACKGROUND: Ventrlcular tachyarrhythmias are major cause of sudden cardiac death in patients after myocardial infarction and their accurate detection seems to be important in prevention of sudden cardiac death. Clinical findings, treasmill test, holter monitoring and coronary angiography have been used to search for high risk group in sudden cardiac death. Recently electrographysiologic stimulation has been to this, but it is not practical, because of high cost and invasiveness. Signal averaged electrocardiogram(SAECG) may be helpful in prediction of high risk group in sudden cardiac death. So we try to know the values of SAECG in Korean patients without heart disease. RESULTS: 1) The mean value and standard deviation of Time domain analysis is as follows ; fQRS : 106.8+/-12.3ms, RMS : 36.2+/-21.5(micro)V, LAS : 27.2+/-8.1ms. 2) The mean value and standard deviation of Spectral turbulence analysis is a follows ; LSCR : 58.6+/-3.9, ISCM : 95.2+/-0.8, ISCSD : 71.8+/-15.7, SE : 6.9+/-1.8. CONCLUSION: There was no significant difference between male and female. Time domain analysis shows significant differences among each hour but spectral turbulence analysis did not. Spectral turbulence analysis shows high specificity.
Coronary Angiography ; Death, Sudden, Cardiac ; Electrocardiography* ; Electrocardiography, Ambulatory ; Female ; Heart Diseases* ; Heart* ; Humans ; Male ; Myocardial Infarction ; Sensitivity and Specificity ; Tachycardia

OBJECTIVES: Signal-averaged electrocardiography (SAECG) has been found to be a useful noninvasive technique for identifying patients at risk for life-threatening ventricular tachycardia. Delayed and fragmented activation of abnormal myocardial tissues causes the occurrence of high frequency low amplitude (HFLA) electocardiographic signals or late potentials. Generally, there are two methods in analyzing signal-averaged electrocardiography. Late potentials in the time domain analysis do not provide sufficient diagnostic power with regard to life-threatening Ventricular tachycardia. Buckingham et al. (1989) reported a time-domain sensitivity of 62%, a specificity of 75%. Spectral turbulence analysis (STA) of the signal-averaged ECG is the most recent frequency domain technique to improve the time domain sensitivity and specificity. So, We designed the study to compare the efficacy of Time Domain Analysis and Spectral Turbulence Analysis among five groups (Normal control, QRS widening, Postmyocardial infarction, Frequent VPC's with group beats, Nonsustained ventricular tachycardia). METHODS: 88 patients were selected from the patients who had been admitted between January 1994 and October l994, at National Medical Center. Patients were divided into five groups, which were respectively, Group A: Normal control group (n=33), Group B: QRS widening group (n=14), Group C: Postmyocardial infarction group (n=10), Group D: Frequent VPC's with group beats (n=22), Group E: Nonsustained VT group (n=9). We compared Spectral Turbulence Analysis and Time Domain Analysis of Signal-Averaged Electrocardiogram by 24 hours-Holter monitoring. RESULTS: 1) In normal control group(Group A), 9.1%(3 patients) were positive by Time Domain Analysis, but, all were negative by Spectral Turbulence Analysis. 2) In QRS widening group (Group B), 71.4%(10 patients) were positive by Time Domain Analysis, but, all were negative by Spectral Turbulence Analysis. 3) In postmyocardial infarction group (Group C), 309o were positive by Time Domain Analysis, and 10% were positive by Spectral Turbulence Analysis. 4) In frequent VPC's group (Group D), 22.7% (5 patients) were positive by Time Domain Analysis, and, 4.5%(1 patient) was positive by Spectral Tur-bulence Analysis. 5) In Nonsustained VT group (Group E), 33.3% (3 patients) were positive by Time Domain Analysis, and 11.1% (1 patient) was positive by Spectral Turbulence Analysis. CONCLUSIONS: In Time Domain Analysis, abnormal results were presented at Group R (QRS widening group) by 71.4%, which was markedly higher than other groups. But, in Spectral Turbulence Analysis, abnormal results were not presented at Group A and Group B. In Group A and Group B, Spectral Turbulence Analysis shows less false positive results than Time Domain Analysis.
Electrocardiography* ; Electrocardiography, Ambulatory* ; Humans ; Infarction ; Sensitivity and Specificity ; Tachycardia, Ventricular

OBJECTIVE: Heart rate variability(HRV) is helpful to diagnosis autonomic disturbance and sympathetic-parasympathetic imbalance in patients with myocardial infarction and diabetes mellitus. Patients with liver cirrhosis demonstrate reduced blood pressure despite increased heart rate and increased cardiac output, indicating a fall in peripheral vascular resistance. Autonomic disturbance may contribute to this phenomenon. The aim of the present study is to evaluate the degree of autonomic disturbance and the circadian rhythm of autonomic nervous system by estimating HRV with 24 hour-Holter recorder, METHODS: 24 hour-HRV with Del Mar Avionics 563 Holter recorder and cardiovascular reflex tests were carried out on 32 patients with liver cirrhosis and 20 control subjects. We evaluated the presence of autonomic disturbance, and assessed quantitatively the autonomic disturbance. RESULTS: 1) Among cardiovascular reflex tests, Valsalva test, standing test and deep breathing test were showed a significantly decreased response in liver cirrhosis compared with control groups. 2) The standard deviation of 24hours average R-R intervals were showed a significantly decrease in liver cirrhosis than control groups(P<0.0001). The HRV of low frequency(LF. P<.D.001), high frequency(HF, P<0.0001) and total power spectral density (P<0.0001) in liver cirrhosis were statistically lower than control. 3) The LF/HF ratio of patients with liver cirrhosis was showed higher than control at night CONCLUSION: Non-invasive assessment of 24 hour-HRV has a few advantages in the diagnosis and degree of autonomic disturbance, evaluation of diurnal variation of autonomic tone.
Autonomic Nervous System ; Blood Pressure ; Cardiac Output ; Circadian Rhythm ; Diabetes Mellitus ; Diagnosis ; Heart Rate* ; Heart* ; Humans ; Liver Cirrhosis* ; Liver* ; Myocardial Infarction ; Reflex ; Respiration ; Vascular Resistance

BACKGROUND: The interpretation of electrocardiographic change in treadmill exercise test is difficult when the test is performed in patients with abnormal resting electrocardiography. In patients with primary nagative T wave, normalization of primary negative T wave(pseudonormalization)is not uncommon finding during treadmill exercise test. The mechanism of pseudonormalization is uncertain and the interpretation is difficult. Thus this study was performed to evaluate the diagnostic significance of pseudonormalization during treadmill exercise test. METHODS: 200 cases who showed primary negative T wave at rest were included in this study. The results were classified as positive, borderline positive, borderline negative, negative, non-diagnostic and pseudonormalization. RESULTS: Pseudonormalization during treadmill exercise test was oberved in 78(39%) of the 200 cases who had primary negative T wave at rest. Coronary angiography and left ventriculography were performed in 13(mean age 56+/-7 year, male vs. female 1:2.25) of 78 cases who showed pseudonormalization during exercise. They had no history of acute myocardial infarction and no abnormalities such as abnormal Q wave, left ventricular hypertrophy,bundle branch block,right ventricular hypertrophy and QRS widening above 0.1ms in resting electrocardiography. There were significant stenosis in only 3 cases; 2 cases in left anterior descending coronary artery and 1 case in right coronary artery. CONCLUSION: In treadmill exercise tests, pseudonormalization appears as non-specific finding for the diagnosis of ischemic heart disease becuase it is observed in either patients with or without coronary artery stenosis.
Constriction, Pathologic ; Coronary Angiography ; Coronary Stenosis ; Coronary Vessels ; Diagnosis ; Electrocardiography ; Exercise Test* ; Female ; Humans ; Hypertrophy ; Male ; Myocardial Infarction ; Myocardial Ischemia*

The anterior cruciate ligament has been considered one of the basic stabilizers in the knee as a very complex in its function. A large number of treatment regimens and philosophies showed controversies in its treatment. And we have experienced recurrence of the instability after operation of the injured ligament. So, the authors devised a new operative technique for the loose anterior cruciate ligament, that is, distal davancement of the loose anterior cruciate ligament with a bone-block as a biomechanical fixation. We have performed 11 cases of the anterior cruciate ligament using distal advancement method. The results were as follows; 1. Eleven cases (92%) showed good results by the rating system of Cincinnati sports-medicine and Orthopaedic Center. 2. The distal advancement of the anterior cruciate ligament is technically simple and biomechanically reasonable, but further investigation is necessary to answer the question regarding the long term results.
Anterior Cruciate Ligament ; Knee ; Ligaments ; Methods ; Philosophy ; Recurrence