Drug development is a lengthy, expensive, and complex process, and clinical development is the longest and the most expensive stage of drug development. To obtain market authorization of a new drug, applicants must prove the effectiveness and the safety of a drug through clinical trials. Korea has the same requirements for new drug approval as in developed countries and bridging data are required for approval of a new drug that was developed in another country. Clinical evaluation in humans consists of 3 phases, from phase 1 to phase 3, and the failure rates remain high while the clinical trial cost increases rapidly. Not only pharmaceutical sponsors but also patients and physicians want new, innovative medicines faster, simultaneously with improved productivity of drug development. With strong competition and market forces, the pressure to accelerate drug development and to predict the efficacy and safety profile of a drug candidate at an earlier stage is increasing. To improve the productivity of new drug development, modern principles of pharmaceutical sciences, clinical pharmacology, and information technology are being researched and employed by both health authorities and sponsors. Many global pharmaceutical companies are also pursuing geographical expansion strategies to enroll subjects faster among more diverse ethnic groups. To deliver innovative medicines to patients in a faster and more cost-effective ways, close and continuous collaboration among sponsors, academia, and health authorities is essential.
Cooperative Behavior ; Developed Countries ; Drug Approval ; Efficiency ; Ethnic Groups ; Humans ; Korea ; Pharmacology, Clinical

No abstract available.

The interruption of hepatic blood flow has been adopted as a method of bleeding control in hepatectomy and liver transplantation. But this occlusion of hepatic inflow may result in significant hepatic injury by various kinds of oxygen radicals produced as a result of hepatic ischemia and following reperfusion. Arterial ketone body ratio(AKBR) is adequatc and convenient parameter by which both acute and prolonged changes of the hepatic function can be estimated. Pharmacological modulation of hepatic injury during warm ischemia and early reperfusion has shown some benefical effects. The authors conducted an experiment to evaluate the inhibitory effect of glutathione and prostaglandin E on hepatic injury due to acute hepatic ischemia and reperfusion. Thirty rabbits were divided into three groups, such as control(n=10), GSH(n=10) and PGE(n=10) groups. Acute hepatic ischemia was induced through the application of portal triad cross-clamping for 30 minutes, and thereafter hepatic reperfusion was induced with the removal of cross-clamping. A single bolus of 200 mg glutathione was injected 10 min before clamp in GSH group, and 200 ng/kg/min of PGE continuously from 10 min before clamp to 30 min after declamp in PGE group. AKBR and hepatic histological findings hefore clamp, 30 min after clamp, 5 min and 30 min after declamp, respectively were compared among 3 groups AKBR was markedly decreased during the clamping period in all groups (P<0.05). In control and PGE groups AKRR was significantly increased after reperfusion than before clamp (P<0.05), but was significantly lower than before clamp. Thirty minutes after reperfusion in GSH group AKBR returned to normal level and was significantly higher than in control group (P<0.05). On light tnicroscopic examination of liver biopsy, mild swollen hepatocytes in the centrilobular zone were seen at ischemia and reperfusion in control and GSH groups, but nearly normal hepatic architectures in PGE group. These results suggest that glutathione has some benefical effect on protection of hepatic dysfunction, and PGE1 on protection of hepatocellular injury during hepatic ischemia and reperfusion.
Alprostadil* ; Biopsy ; Constriction ; Glutathione* ; Hemorrhage ; Hepatectomy ; Hepatocytes ; Ischemia* ; Liver ; Liver Transplantation ; Prostaglandins E ; Rabbits* ; Reactive Oxygen Species ; Reperfusion Injury ; Reperfusion* ; Warm Ischemia

BACKGROUND AND OBJECTIVES: There are relatively few studies that have evaluated the optimal timing, risk of mortality, and outcome for patients with coronary artery bypass graft surgery (CABG) performed in the setting of acute myocardial infarction (AMI). MATERIALS AND METHODS: We reviewed our 18 patients who underwent CABG within 14 days after AMI, between June 1994 and June 1997. Thirteen of the patients were male and 5 were female. Their ages ranged from 41 to 77 years (mean age, 60.6+/-10.4 years), and the amount of time betweenAMIandCABGrangedfrom4hoursto14days (meantime,7.0+/-4.7days).Therewere11 anteroseptal infarctions and 7 inferior wall infarctions. Eleven patients had transmural infarctions and 7 had subendocardial infarctions. Indications of operations were postinfarction angina, cardiogenic shock and intractable ventricular arrhythmia. Six patients required preoperative intra-aortic balloon pump (IABP) support, and 3 additional patients required IABP to be separated from cardiopulmonary bypass. An average of 3.4+/-0.5 vessels per patient were bypassed. RESULTS: The early mortality rate for these 18 patients was 5.6% and late mortality rate was 5.9%, and 2-year actuarial survival rates were 89.5%. Univariate analysis of mortality showed that an ejection fraction less than 30% was associated with risk factor (p value=0.016 ). Age, sex, time to CABG, emergency operations, locations of infarctions were not significant. CONCLUSION: Although our studies have weak points in that there was only a small number of patients and the lack of long-term results, we could conclude that early myocardial revascularization is relatively safe after AMI for those individuals with an ejection fraction greater than 30%.
Arrhythmias, Cardiac ; Cardiopulmonary Bypass ; Coronary Artery Bypass ; Emergencies ; Female ; Humans ; Infarction ; Male ; Mortality ; Myocardial Infarction* ; Myocardial Revascularization ; Risk Factors ; Shock, Cardiogenic ; Survival Rate ; Transplants

A 55 year old male was admitted for dyspnea. The patient was diagnosed as acute myocardiac infarction, and coronary artery bypass grafting was performed with cardiopulmonary bypass. At postoperative day #1, Systemic Inflammatory Response Syndrome was developed with fever, leukocytosis, tachycardia, tachypnea and low systemic vascular resistance. The patient was recovered after being treated with high dose of (36 microgram/min) norepinephrine, and was discharged.
Cardiopulmonary Bypass ; Coronary Artery Bypass ; Dyspnea ; Fever ; Heart* ; Humans ; Infarction ; Leukocytosis ; Male ; Middle Aged ; Norepinephrine ; Shock* ; Systemic Inflammatory Response Syndrome* ; Tachycardia ; Tachypnea ; Thoracic Surgery* ; Vascular Resistance

A 55 year old male was admitted for dyspnea. The patient was diagnosed as acute myocardiac infarction, and coronary artery bypass grafting was performed with cardiopulmonary bypass. At postoperative day #1, Systemic Inflammatory Response Syndrome was developed with fever, leukocytosis, tachycardia, tachypnea and low systemic vascular resistance. The patient was recovered after being treated with high dose of (36 microgram/min) norepinephrine, and was discharged.
Cardiopulmonary Bypass ; Coronary Artery Bypass ; Dyspnea ; Fever ; Heart* ; Humans ; Infarction ; Leukocytosis ; Male ; Middle Aged ; Norepinephrine ; Shock* ; Systemic Inflammatory Response Syndrome* ; Tachycardia ; Tachypnea ; Thoracic Surgery* ; Vascular Resistance

BACKGROUND: Although great concerns have been raised regarding the suitability of the use of the radial artery as a bypass conduit after transradial catheterization, there has been no studies that examined this issue in Korea. The purpose of this study was to compare clinical and angiographic results of radial artery grafting between patients with and without previous transradial catheterization. MATERIAL AND METHOD: From January 2000 to February 2004, a total of 93 patients underwent coronary artery bypass grafting using the radial artery: 49 patients received preoperative transradial catheterization for coronary angiography (group I) and 44 patients did not (group II). These patients were retrospectively reviewed. RESULT: There was no significant difference in sex ratio, age, clinical diagnosis, risk factors, ejection fraction and early clinical outcomes between two groups. The graft patency rates in groups I and II were both 100% in the internal thoracic artery and in the radial artery, and 85% and 86% in the saphenous vein. respectively. The stenosis-free graft patency in groups I and II were 93% and 81% in the radial artery respectively but no statistical significance was shown. CONCLUSION: There was no significant difference in graft patency at postoperative coronary angiography between two groups. Radial artery graft after transradial catherization seems to be suitable for bypass conduit in short-term analysis.
Cardiac Catheterization ; Catheterization* ; Catheters* ; Coronary Angiography ; Coronary Artery Bypass ; Diagnosis ; Humans ; Korea ; Mammary Arteries ; Radial Artery* ; Retrospective Studies ; Risk Factors ; Saphenous Vein ; Sex Ratio ; Transplants* ; Vascular Patency

BACKGROUND: Although great concerns have been raised regarding the suitability of the use of the radial artery as a bypass conduit after transradial catheterization, there has been no studies that examined this issue in Korea. The purpose of this study was to compare clinical and angiographic results of radial artery grafting between patients with and without previous transradial catheterization. MATERIAL AND METHOD: From January 2000 to February 2004, a total of 93 patients underwent coronary artery bypass grafting using the radial artery: 49 patients received preoperative transradial catheterization for coronary angiography (group I) and 44 patients did not (group II). These patients were retrospectively reviewed. RESULT: There was no significant difference in sex ratio, age, clinical diagnosis, risk factors, ejection fraction and early clinical outcomes between two groups. The graft patency rates in groups I and II were both 100% in the internal thoracic artery and in the radial artery, and 85% and 86% in the saphenous vein. respectively. The stenosis-free graft patency in groups I and II were 93% and 81% in the radial artery respectively but no statistical significance was shown. CONCLUSION: There was no significant difference in graft patency at postoperative coronary angiography between two groups. Radial artery graft after transradial catherization seems to be suitable for bypass conduit in short-term analysis.
Cardiac Catheterization ; Catheterization* ; Catheters* ; Coronary Angiography ; Coronary Artery Bypass ; Diagnosis ; Humans ; Korea ; Mammary Arteries ; Radial Artery* ; Retrospective Studies ; Risk Factors ; Saphenous Vein ; Sex Ratio ; Transplants* ; Vascular Patency

OBJECTIVE: This multicenter, open trial with olanzapine was primarily designed to evaluate effects of olanzapine on profiles of efficacy, safety, and subjective quality of life (QoL) in hospitalized patients with schizophrenia or other psychotic disorders. Secondarily, associations of changes in QoL measures with baseline characteristics and changes in efficacy and safety measures were examined. Finally, the optimal dose of olanzapine was investigated with respect to efficacy, safety and QoL profiles. METHODS: A total of 94 inpatients at nine centers in Chungchung and Honam areas of Korea was recruited. The administered dosage of olazapine varied between 5 to 20 mg/day according to each patient's clinical status. Information on socio-demographic and clinical characteristics was collected. A variety of measures on efficacy, safety and QoL was administered at baseline (admission) and at endpoint (discharge). RESULTS: Seventy-three (78%) patients completed the study. Their mean (SD) admission period was 42 (21) days. Olanzapine was effective for reducing overall psychotic symptoms including negative and depressive symptoms. It was safe and generally well tolerated, particularly in extrapyramidal symptoms, although weight gain was substantial (2.6 kg during admission period). Furthermore, it was beneficial for improving QoL. Changes in QoL measures were independently associated with improvement of nighttime sleep. The most favorable dosages of olanzapine were 17.5 or 20 mg/day in terms of efficacy, while were 7.5 or 10 mg/day with respect to safety and QoL. CONCLUSION: Olanzapine was effective and well tolerated in the treatment of inpatients with schizophrenia and other psychotic disorders. Different optimal dosages of olanzapine might be recommended according to the target or goal of treatments.
Depression ; Humans ; Inpatients* ; Korea ; Psychotic Disorders* ; Quality of Life* ; Schizophrenia* ; Weight Gain

Retroesophageal aortic arch, in which the aortic arch crosses the midline behind the esophagus to the contralateral side, is a rare form of vascular anomaly. The complete form may cause symptoms by compressing the esophagus or the trachea and need a surgical intervention. We report a rare case of a hypoplastic left heart syndrome variant with the left retroesophageal circumflex aortic arch in which the left aortic arch, retroesophageal circumflex aorta, and the right descending aorta with the aberrant right subclavian artery encircle the esophagus completely, thus causing central bronchial compression. Bilateral pulmonary artery banding and subsequent modified Norwood procedure with extensive mobilization and creation of the neo-aorta were performed. As a result of the successful translocation of the aorta, the airway compression was relieved. The patient underwent the second-stage operation and is doing well currently.
Aorta ; Aorta, Thoracic* ; Esophagus ; Heart Defects, Congenital ; Humans ; Hypoplastic Left Heart Syndrome* ; Norwood Procedures* ; Pulmonary Artery ; Subclavian Artery ; Trachea