To evaluate the effect and mechanism of hypercholesterolemia on the sequence of changes involved in apoptosis, which counteract proliferation due to the restenosis process after vascular injury. Iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined 1, 3, 7 & 14 days after balloon injury (N = 5 to 7 animals on each occasion) using TUNEL, immunohistochemical staining of PCNA, macrophages, smooth muscle actin and p53. In media immediately after injury, apoptosis occurred comprehensively and then decreased. HC did not affect this early post-injury apoptosis but significantly (p<0.01) increased apoptosis 14 days later (D14). Immediate apoptosis in media was followed by active proliferation. HC sustained a high activity of proliferation until D14 (p<0.01). The changes of immunoreactivity caused by p53 over the same 14 day period parallels that of apoptosis. In intima, where cells were scarce initially, proliferative activity reached a peak at D7 and then decreased. HC significantly (p<0.05) enhanced proliferation at D14. In intima proliferation was accompanied by a later lower level apoptosis. HC significantly (p<0.05) enhanced this lower level stage of apoptosis at D14. These effects of HC on apoptosis and proliferation result in significantly increased areas of intima and media (p<0.01). The fundamental difference between HC & NC was the infiltration of macrophages in HC, which were colocalized with apoptosis and proliferation activities. In conclusion, balloon injury induces early massive p53-associated apoptosis followed by proliferation in media, whereas in intima, it induces active proliferation followed by a lower activity apoptosis. Hypercholesterolemia does not affect the early post-injury apoptosis but enhances proliferation and lower level apoptosis at a later stage, which in turn results in intimal and medial hyperplasia.
Actins ; Animals ; Apoptosis* ; Hypercholesterolemia* ; Hyperplasia ; Iliac Artery* ; In Situ Nick-End Labeling ; Macrophages ; Muscle, Smooth ; Proliferating Cell Nuclear Antigen ; Rabbits ; Vascular System Injuries

BACKGROUND: Alteration of thyroid hormone parameters are frequently observed in sick patients and commonly known as nonthyroidal illness syndrome(NTIS) or euthyroid sick syndrome(ESS). NTIS is seen in starvation, surgery, severe illness, and also bone marrow transplantation(BMT). The degree of reduction in thyroid hormone parameters correlated with the severity of NTIS and might predict the prognosis of underlying illness. Recently, particular attention is focused on the role of cytokines in developing the NTIS. This prospective study was designed to assess the relationship of serum thyroid hormone parameters and serum cytokine levels before and in the short-term follow-up after allogeneic BMT in order to predict patients outcome. METHODS: Included 80 patients that were mainly leukemia and severe aplastic anemia. Serum thyroid hormone parameters and serum cytokine levels were measured before and 7, 14, 21, 28 days and 3, and 6 months after BMT. RESULTS: Near-all patients experienced significant decrease of thyroid hormone levels and also significant increase of cytokine levels after BMT. After post-BMT 3 weeks, the serum cytokine levels were negatively correlated with the serum T3 and T4 levels, but not with the serum TSH levels. The patients treated with high-dose steroid or total-body irradiation tended to show lower levels of TSH and more delayed recovery compared to non-treated patients. The patients died after BMT represented generally lower levels of all thyroid hormone parameters than survival patients during entire follow-up period. CONCLUSION: Development of NTIS is associated with higher probability of fatal outcome after BMT and has prognostic relationship in this group of patients. Increased levels of cytokines, especially IL-6 and TNF-alpha, are often found in post-BMT NTIS patients and correlated with the changes in the levels of thyroid hormone parameters.
Anemia, Aplastic ; Bone Marrow Transplantation* ; Bone Marrow* ; Cytokines* ; Euthyroid Sick Syndromes ; Fatal Outcome ; Follow-Up Studies ; Humans ; Interleukin-6 ; Leukemia ; Prognosis ; Prospective Studies ; Starvation ; Thyroid Gland ; Tumor Necrosis Factor-alpha

BACKGROUND: Losartan potassium, an orally active, highly selective AT (1) angiotensin II receptor inhibitor, effectively reduces blood pressure by directly blocking receptors. The purpose of this study is to compare the antihypertensive efficacy, safety and tolerability of losartan potassium and fosinopril in patients with stage 1 to 3 hypertnesion. METHODS: In this comparative, open labelled, randomized, parallel study, the efficacy, safety and tolerability of once-daily losartan (50mg) versus once-daily fosinopril (10mg) were evaluated over twelve weeks in 96 patients with stage 1-3 hypertension. If trough sitting diastolic blood pressure was equal to or greater than 90mmHg after a 6 week treatment period, the dosage for both study drugs was doubled until the end of the study (week 12). RESULTS: After 6 weeks of treatment, mean reductions in trough sitting diastolic blood pressure were 7.4mmHg (95% confidence interval 5.0-9.9) with 50mg losartan and 6.7mmHg (95% confidence interval 4.4-9.2)with 10mg fosinopril. After 12 weeks of treatment (after dose titration), mean reductions in trough sitting diastolic blood pressure were 9.4mmHg (95% confidence interval 6.7-12.1) with losartan and 10.3mmHg (95% confidence interval 7.6-12.9) with fosinopril. At weeks 6 and 12, there were no dignificant difference in the mean reduction of through ditting diastolic blood pressure between the losartan group and the fosinopril group. Losartan and fosinopril were well tolerated without significant clinical and laboratory adverse reactions. The incidence of dry cough was lower in the losartan group than in the fosinopril group but not statistically significant. CONCLUSIONS: The antihypertensive effect of once-daily administration of losartan is similar to that of once-daily administration of fosinopril in patients with hypertension. Both losartan and fosinopril are well tolerated without significant adverse reaction.
Blood Pressure ; Cough ; Fosinopril* ; Humans ; Hypertension* ; Incidence ; Losartan* ; Receptors, Angiotensin

BACKGROUND: Carvedilol, an antihypertensive agent with beta-blocking and vasodilating pro-perties, has been demonstrated to be effective in reducing blood pressure. The purpose of this study is to compare the antihypertensive efficacy, safety and tolerability of carvedilol and atenolol in patients with stage 1 to 2 essential hypertension. METHODS: In this double-blind, double-dummy, randomized, parallel study, the efficacy, safety and tolerability of once-daily carvedilol versus once-daily atenolol were evaluated in 58 patients for 8 weeks with stage 1-2 hypertension. If mean peak sitting diastolic blood pressure was equal to or greater than 90mmHg after a 4 week treatment period, the dosage for both study drugs were doubled until the end of study. RESULTS: Data from 58 of 73 patients who completed the study were eligible for per-protocol analysis. At 4 weeks post treatment commencement, mean reductions in peak sitting diastolic blood pressure were 13.9mmHg (95% confidence interval 17.1-11.4) with 25mg carvedilol and 13.6mmHg (95% confidence interval 16.8-10.3) with 50mg atenolol. After the 8 week treatment period with dose titration, mean reductions in peak sitting diastolic blood pressure were 14.7mmHg (95% confidence interval 17.8-11.6) with 50mg carvedilol and 13.6mmHg (95% confidence interval 17.3-9.9) with 100mg atenolol. There were no statistically significant differences between the two treatments in the percentage of patients achieving a normalized blood pressure or in the degree of change in mean peak sitting diastolic blood pressure. Safety profiles were similar between treatments. One patient withdrew due to severe bradycardia development during the second week of treatment with atenolol. CONCLUSION: In patients with mild to moderate hypertension, there were no significant differences between the efficacy of carvedilol or atenolol with regard to antihypertensive effect. Both carvedilol and atenolol were well tolerated with similar safety profiles.
Atenolol* ; Blood Pressure ; Bradycardia ; Humans ; Hypertension*

Progressive muscular dystrophy (PMD) is an X-linked recessive primary muscular disease characterized by progressive muscular weakness. It causes gait disturbance and complications such as pneumonia, heart failure, and aspiration, so lead to death. Becker muscular dystrophy (BMD) is a milder type of PMD, of which incidence is 5 cases per 100,000 populations. It begins later and evolves more slowly than Duchenne muscular dystrophy (DMD). In PMD patients without heart failure symptom, there may be ECG abnormality or ventricular dilatation, impaired ventricular function which is consistent with dilated cardiomyopathy, especially in DMD. In BMD, heart failure is rare but ECG or echocardiographic abnormality is often found. With the advance of molecular genetics, mutations of the dystrophin gene is proved to be related to the pathogenesis of PMD and dilated cardiomyopathy. We confirmed the deletion of exon 43-51 in the dystrophin gene a case of BMD with asymptomatic dilated cardiomyopathy, diagnosed by echocardiography.
Cardiomyopathy, Dilated ; Dilatation ; Dystrophin* ; Echocardiography ; Electrocardiography ; Exons* ; Gait ; Heart Failure ; Humans ; Incidence ; Molecular Biology ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophies ; Muscular Dystrophy, Duchenne* ; Pneumonia ; Ventricular Function

Progressive muscular dystrophy (PMD) is an X-linked recessive primary muscular disease characterized by progressive muscular weakness. It causes gait disturbance and complications such as pneumonia, heart failure, and aspiration, so lead to death. Becker muscular dystrophy (BMD) is a milder type of PMD, of which incidence is 5 cases per 100,000 populations. It begins later and evolves more slowly than Duchenne muscular dystrophy (DMD). In PMD patients without heart failure symptom, there may be ECG abnormality or ventricular dilatation, impaired ventricular function which is consistent with dilated cardiomyopathy, especially in DMD. In BMD, heart failure is rare but ECG or echocardiographic abnormality is often found. With the advance of molecular genetics, mutations of the dystrophin gene is proved to be related to the pathogenesis of PMD and dilated cardiomyopathy. We confirmed the deletion of exon 43-51 in the dystrophin gene a case of BMD with asymptomatic dilated cardiomyopathy, diagnosed by echocardiography.
Cardiomyopathy, Dilated ; Dilatation ; Dystrophin* ; Echocardiography ; Electrocardiography ; Exons* ; Gait ; Heart Failure ; Humans ; Incidence ; Molecular Biology ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophies ; Muscular Dystrophy, Duchenne* ; Pneumonia ; Ventricular Function

OBJECTIVE AND METHODS: To evaluate the effect of hypercholesterolemia on apoptosis (APOP) & proliferation (PROL) after vascular injury, we examined iliac arteries on 1, 3, 7 & 14 days after balloon injury (N=5 at each time) in rabbits with hypercholesterolemia (HC) and normocholesterolemia (NC). RESULTS: In media im-mediately after injury, APOP occurred massively & then decreased (TUNEL index=6.3+/-1.3 at D1, 0.9+/-0.7% at D14). HC did not affect early massive APOP but significantly (p<0.01) increased APOP, 3.3+/-1.5% at D14. Massive early APOP in media was followed by active PROL (PCNA index=6.0+/-3.3 at D7, 3.9+/-2.8% at D14). HC sustained the high activity of PROL upto D14 (8.9+/-2.7% at D14) (p<0.01). In intima where cells were scanty initially, PROL activity reached peak at D7 and then decreased (6.4+/-1.8% at D7, 2.5+/-1.8% at D14). HC significantly (p<0.05) enhanced PROL at D14 (5.8+/-2.2% at D14). In intima PROL was accompanied by low-grade APOP (1.3+/-1.1% at D7, 0.3+/-0.2% at D14). HC significantly (p<0.05) enhanced this low-grade APOP at D14 (0.9+/-0.4%). These effects of HC on APOP & PROL result in a significantly increased area of intima (0.4+/-0.2 in HC, 0.2+/-0.1 in NC) & media (0.5+/-0.1 in HC, 0.4+/-0.1 in NC) (p<0.01). Fundamental difference between HC & NC was infiltration of macrophage in HC, which was colocalized with APOP & PROL activities. CONCLUSIONS: Balloon injury induces early massive APOP followed by PROL in media, whereas in intima, it induces active PROL followed by low-grade APOP. Hypercholesterolemia does not affect early massive APOP, but enhances PROL & low-grade APOP at late phase, which results in intimal & medial hyperplasia.
Apoptosis* ; Cell Proliferation* ; Hypercholesterolemia* ; Hyperplasia ; Iliac Artery* ; Macrophages ; Rabbits ; Vascular System Injuries

OBJECTIVE AND METHODS: To evaluate the effect of hypercholesterolemia on apoptosis (APOP) & proliferation (PROL) after vascular injury, we examined iliac arteries on 1, 3, 7 & 14 days after balloon injury (N=5 at each time) in rabbits with hypercholesterolemia (HC) and normocholesterolemia (NC). RESULTS: In media im-mediately after injury, APOP occurred massively & then decreased (TUNEL index=6.3+/-1.3 at D1, 0.9+/-0.7% at D14). HC did not affect early massive APOP but significantly (p<0.01) increased APOP, 3.3+/-1.5% at D14. Massive early APOP in media was followed by active PROL (PCNA index=6.0+/-3.3 at D7, 3.9+/-2.8% at D14). HC sustained the high activity of PROL upto D14 (8.9+/-2.7% at D14) (p<0.01). In intima where cells were scanty initially, PROL activity reached peak at D7 and then decreased (6.4+/-1.8% at D7, 2.5+/-1.8% at D14). HC significantly (p<0.05) enhanced PROL at D14 (5.8+/-2.2% at D14). In intima PROL was accompanied by low-grade APOP (1.3+/-1.1% at D7, 0.3+/-0.2% at D14). HC significantly (p<0.05) enhanced this low-grade APOP at D14 (0.9+/-0.4%). These effects of HC on APOP & PROL result in a significantly increased area of intima (0.4+/-0.2 in HC, 0.2+/-0.1 in NC) & media (0.5+/-0.1 in HC, 0.4+/-0.1 in NC) (p<0.01). Fundamental difference between HC & NC was infiltration of macrophage in HC, which was colocalized with APOP & PROL activities. CONCLUSIONS: Balloon injury induces early massive APOP followed by PROL in media, whereas in intima, it induces active PROL followed by low-grade APOP. Hypercholesterolemia does not affect early massive APOP, but enhances PROL & low-grade APOP at late phase, which results in intimal & medial hyperplasia.
Apoptosis* ; Cell Proliferation* ; Hypercholesterolemia* ; Hyperplasia ; Iliac Artery* ; Macrophages ; Rabbits ; Vascular System Injuries

BACKGROUND: Antibradycardia pacemaker is one of the treatment modalities for bradyarrhythmia. We present the clinical results of 440 implantations of permanent pacemaker between August 1984 and December 1997 at Department of Internal Medicine in Seoul National University Hospital. METHOD: We investigated the indication of permanent pacing, the pacing modes, the complications of permanent pacing, and the chronic pacing threshold. RESULT: The study was comprised of 440 patients (M/F : 179/261, mean age : 59+/-12 years, 58+/-14 years, respectively). Indications of the primary pacemaker implantations were sinus node dysfun-ction in 53% and atrioventricular conduction disorders in 47%. Twelve percent of total pacemaker procedures were pulse-generator replacements. Pacing modes were VVI in 59.1%, VVIR in 10.2%, DDD in 30.2%, and others in 0.5%. Complications developed in 21 cases (4.8%) during long-term follow-up. They included 8 cases of pacing failure due to increased pacing threshold, 2 cases of early power depletion, 2 cases of lead dislodgement, 6 cases of lead fracture, 3 cases of skin erosion, 3 cases of hematoma, 3 cases of infection, and 1 case of skeletal muscle stimulation. Chronic pacing thresholds at pacing width of 0.5 msec were 1.9+/-0.4 V for the epicardial ventricular leads (n=11), 1.3+/-0.5 V for the endocardial ventricular leads (n=36), and 1.1+/-0.2 V for the atrial leads (n=4) after 7 to 10 years of implantation. CONCLUSION: Sinus node dysfunction was the more common indication than atrioventricular block for the antibradycardia pacemaker implantation. Long-term follow-up of the pacemaker patients would be very useful to detect the pacing system abnormalities and to maximize the battery longevity by adjustment of pacing output according to the level of chronic pacing threshold.
Atrioventricular Block ; Bradycardia ; Dichlorodiphenyldichloroethane ; Follow-Up Studies* ; Hematoma ; Humans ; Internal Medicine ; Longevity ; Muscle, Skeletal ; Seoul ; Sick Sinus Syndrome ; Sinoatrial Node ; Skin

BACKGROUND: Antibradycardia pacemaker is one of the treatment modalities for bradyarrhythmia. We present the clinical results of 440 implantations of permanent pacemaker between August 1984 and December 1997 at Department of Internal Medicine in Seoul National University Hospital. METHOD: We investigated the indication of permanent pacing, the pacing modes, the complications of permanent pacing, and the chronic pacing threshold. RESULT: The study was comprised of 440 patients (M/F : 179/261, mean age : 59+/-12 years, 58+/-14 years, respectively). Indications of the primary pacemaker implantations were sinus node dysfun-ction in 53% and atrioventricular conduction disorders in 47%. Twelve percent of total pacemaker procedures were pulse-generator replacements. Pacing modes were VVI in 59.1%, VVIR in 10.2%, DDD in 30.2%, and others in 0.5%. Complications developed in 21 cases (4.8%) during long-term follow-up. They included 8 cases of pacing failure due to increased pacing threshold, 2 cases of early power depletion, 2 cases of lead dislodgement, 6 cases of lead fracture, 3 cases of skin erosion, 3 cases of hematoma, 3 cases of infection, and 1 case of skeletal muscle stimulation. Chronic pacing thresholds at pacing width of 0.5 msec were 1.9+/-0.4 V for the epicardial ventricular leads (n=11), 1.3+/-0.5 V for the endocardial ventricular leads (n=36), and 1.1+/-0.2 V for the atrial leads (n=4) after 7 to 10 years of implantation. CONCLUSION: Sinus node dysfunction was the more common indication than atrioventricular block for the antibradycardia pacemaker implantation. Long-term follow-up of the pacemaker patients would be very useful to detect the pacing system abnormalities and to maximize the battery longevity by adjustment of pacing output according to the level of chronic pacing threshold.
Atrioventricular Block ; Bradycardia ; Dichlorodiphenyldichloroethane ; Follow-Up Studies* ; Hematoma ; Humans ; Internal Medicine ; Longevity ; Muscle, Skeletal ; Seoul ; Sick Sinus Syndrome ; Sinoatrial Node ; Skin