Targeting Colon Cancer Cells with Fluorescent Magnetic Nanoparticles Conjugated to Anti-epidermal Growth Factor Receptor Antibodies / 대한소화기내시경학회지

BACKGROUND/AIMS: The aim of this study was to evaluate targeting the epidermal growth factor receptors (EGFRs) of colon cancer cells with fluorescent magnetic nanoparticles (FMNP) conjugated to anti-EGFR antibodies. METHODS: The expression of EGFRs was evaluated in the HT-29 colon cancer cell lines and the control H-520 lung cancer cells by performing Western blot analysis. We synthesized silica-overcoated iron oxide nanoparticles that contained rhodamine B isothiocyanate (RITC) within a silica shell of a controllable thickness. This FMNP was conjugated to anti-EGFR mouse monoclonal antibody. The cells were treated with this probe conjugate for 4 hours and then the targeting was assessed via confocal microscopy. The fluorescence properties were evaluated for their binding to the expressed EGFRs with using a FACScan flow cytometer. RESULTS: EGFR was expressed in the HT-29 cells, as assessed by Western blot analysis. Red fluorescence was only detected in the membrane regions of the HT-29 cells on the confocal microscope imaging. On the FACS analysis, there was a significant shift of fluorescence intensity for the HT-29 cells. CONCLUSIONS: Our data show the feasibility of targeting colon cancer cells with FMNP conjugated with anti-EGFR antibodies in vitro.

Prospective, Randomized, Preliminary Clinical Trial with Low-Molecular-Weight Heparin or Unfractionated Heparin as Periprocedural Anticoagulant during Elective Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: LMWH as a periprocedural anticoagulant during PCI has not yet been extensively studied. The aim of this study is to compare the clinical outcomes of enoxaparin to those of unfractionated heparin (UH) during elective PCI. SUBJECTS AND METHODS: The eligible patients were randomized 1:1 into two treatment arms, either a single IV bolus of enoxaparin (75 IU/kg) or UH (100 IU/kg). The patients who had received any anticoagulants at therapeutic doses were excluded in this study. Data on patient characteristics, angiographic complications, laboratory variables and the in-hospital and 1-month clinical outcomes were compared between the two groups. RESULTS: Of the 139 patients enrolled in this study, 68 received enoxaparin and 71 received UH. The patients' demographic and angiographic characteristics (gender, weight, creatinine and the PCI target vessel) were not different except for age between the groups. Multi-vessel angioplasty was performed in 59 (42.4%) patients. At least one stent was implanted in 130 (93.5%) patients. The sheath was removed immediately after PCI, except for one case, and then a collagen plug was applied in all the cases. There were no significant differences in angiographic complications like no reflow, thrombus at the treated lesion site, occlusion of collateral branches, distal embolism, dissection, coronary rupture or abrupt closure. Cardiac markers including CK (6 [8.8%] in the LMWH group vs 8 [11.3%] in the UH group), CK-MB (6 [8.8%] vs 8 [11.3%], respectively), and troponin-I (6 [8.8%] vs 10 [14.1%], respectively) were slightly increased after PCI compared to the last value obtained before the procedure in both groups, but the differences were not statistically significant. One patient in the enoxaparin arm and 2 patients in the UH arm developed NSTEMI during their admission. Four patients from the UH arm and 3 from the enoxaparin arm experienced hematoma at the puncture site. After discharge, no other events were reported at the 1-month follow-up. CONCLUSION: The use of enoxaparin (75 IU/kg) during elective PCI was effective and safe as using UH. Enoxaparin could be used like UH as a periprocedural anticoagulant in the elective PCI setting.

Prospective, Randomized, Preliminary Clinical Trial with Low-Molecular-Weight Heparin or Unfractionated Heparin as Periprocedural Anticoagulant during Elective Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: LMWH as a periprocedural anticoagulant during PCI has not yet been extensively studied. The aim of this study is to compare the clinical outcomes of enoxaparin to those of unfractionated heparin (UH) during elective PCI. SUBJECTS AND METHODS: The eligible patients were randomized 1:1 into two treatment arms, either a single IV bolus of enoxaparin (75 IU/kg) or UH (100 IU/kg). The patients who had received any anticoagulants at therapeutic doses were excluded in this study. Data on patient characteristics, angiographic complications, laboratory variables and the in-hospital and 1-month clinical outcomes were compared between the two groups. RESULTS: Of the 139 patients enrolled in this study, 68 received enoxaparin and 71 received UH. The patients' demographic and angiographic characteristics (gender, weight, creatinine and the PCI target vessel) were not different except for age between the groups. Multi-vessel angioplasty was performed in 59 (42.4%) patients. At least one stent was implanted in 130 (93.5%) patients. The sheath was removed immediately after PCI, except for one case, and then a collagen plug was applied in all the cases. There were no significant differences in angiographic complications like no reflow, thrombus at the treated lesion site, occlusion of collateral branches, distal embolism, dissection, coronary rupture or abrupt closure. Cardiac markers including CK (6 [8.8%] in the LMWH group vs 8 [11.3%] in the UH group), CK-MB (6 [8.8%] vs 8 [11.3%], respectively), and troponin-I (6 [8.8%] vs 10 [14.1%], respectively) were slightly increased after PCI compared to the last value obtained before the procedure in both groups, but the differences were not statistically significant. One patient in the enoxaparin arm and 2 patients in the UH arm developed NSTEMI during their admission. Four patients from the UH arm and 3 from the enoxaparin arm experienced hematoma at the puncture site. After discharge, no other events were reported at the 1-month follow-up. CONCLUSION: The use of enoxaparin (75 IU/kg) during elective PCI was effective and safe as using UH. Enoxaparin could be used like UH as a periprocedural anticoagulant in the elective PCI setting.

PPAR-gamma Agonist Attenuates Myocardial Fibrosis in a Type 2 Diabetic Rat Model

BACKGROUND AND OBJECTIVES: Receptor for advanced glycosylation end product (RAGE) plays an important role in the development of myocardial fibrosis in diabetics. Activation of peroxisome proliferator activated receptor (PPAR)-gamma agonist, rosiglitazone, reduces the RAGE expression. We investigated whether rosiglitazone could prevent left ventricle (LV) diastolic dysfunction and attenuate the myocardial fibrosis in a type 2 diabetic rat model. MATERIALS AND METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with rosiglitazone (20 mg/kg/d) for 20 weeks. At the age of 20 and 40 weeks, all rats underwent intraperitoneal glucose tolerance tests, hemodynamic studies and Doppler echocardiography. At the age of 40 weeks, the hearts were examined by performing histopathological and immunohistochemical analyses. RESULTS: At the age of 40 weeks, rosiglitazone significant improved the parameters of the LV diastolic function such as the E/A ratio (treated vs. untreated: 1.7+/-0.1 vs. 1.5+/-0.1, p<0.05), the deceleration time and the isovolumic relaxation time in the OLETF rats, and this was correlated histologically to the reduced LV collagen volume fraction in the rosiglitazonetreated OLETF rats (3.2+/-1.3% vs. 5.7+/-2.0%, respectively, p<0.001). Rosiglitazone also significantly reduced the percentage of staining of the LV CTGF (7.4+/-2.5% vs. 15.4+/-4.7%, respectively, p<0.001) and RAGE (1.1+/-0.4% vs. 2.0+/-0.8%, respectively, p<0.001), as compared with the untreated OLETF rats. CONCLUSION: These results suggest that rosiglitazone could prevent LV diastolic dysfunction and attenuate myocardial fibrosis in type 2 diabetic rats by its inhibition of the RAGE and CTGF expression. PPAR-gamma agonist may provide a potential therapeutic approach for diabetic heart disease.

Relation between Serum Carboxy-Terminal Propeptide of Type 1 Procollagen(PIP), a Marker of Myocardial Fibrosis, and Left Ventricular Diastolic Function in Patients with Early Type 2 Diabetes Mellitus

BACKGROUND AND OBJECTIVES: This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I PIP, a marker of myocardial fibrosis, was related to the change of the ventricular filling dynamics in patients with early type 2 diabetes mellitus (DM). SUBJECTS AND METHODS: Echocardiography was performed in 28 patients with type 2 DM and 32 age-matched healthy controls, ranging from 31-69 years of age, with normal left ventricular (LV) systolic function and ECG at rest. Subjects with diabetic complications, including microalbuminuria, nephropathy (Cr>1.3 mg/dL), severe obesity (BMI> or =30 kg/m2), LV hypertrophy (LV septal thickness and/or posterior wall thickness 12 mm on M-mode) and hypertension, were excluded. The serum concentrations of PIP and Transforming growth factor TGF-beta1 were measured by enzyme immunoassay methods. RESULTS: The type 2 DM group had lower mitral (Type 2 DM vs. Control: 0.88+/-0.28 vs. 1.17+/-0.34, p<0.01) and tricuspid E/A ratios (1.15+/-0.25 vs. 1.30+/-0.25, p=0.01) than the control group. The level of serum PIP was higher (p<0.05) in patients with type 2 DM than in the control group (131.1+/-45.6 vs. 109.3+/-32.5). The difference in the duration between transmitral forward (A) and pulmonary venous retrograde (Ar) waves (A-Ar) was considered an estimate of a passive diastolic function. A-Ar was inversely related with the serum PIP level in type 2 diabetes (r=-0.43, p=0.03). CONCLUSION: These results show a relationship between the LV diastolic function and the serum concentration of PIP in early type 2 DM. These findings suggest that the determination of the serum level of PIP is a useful method for the screening and early diagnosis of myocardial fibrosis associated with DM.

Bilateral Renal Artery Stenosis with Renal Insufficiency: Successful Angioplasty Using Gadopentetate Dimeglumine as a Contrast Agent / 대한신장학회잡지

With the increasing number of interventional angiographic procedures, iodinated contrast induced nephropathy has become an important cause of iatrogenic acute renal failure. Gadopentetate dimeglumine, gadolinium chelated by DTPA, are widely used in magnetic resonance imaging without adverse effect on renal function in patients with renal insufficiency. It also has sufficient radiographic density to allow visualization and has been described as an alternative contrast agent for angiography. Here we report a case of successful angioplasty using gadopentetate dimeglumine as a contrast agent in a patient with both renal artery stenosis and renal insufficiency. The patient had a history of iodinated contrast induced acute renal failure. Using this contrast agent, angioplasty was successfully performed and contrast induced acute renal failure did not occur after this procedure.

Prevalance of Helicobacter pylori infection and It's association with cardiovascular risk factors in Korean adults / 대한내과학회지

No abstract available.

Clinical Observation of Peripartum Cardiomyopathy

BACKGROUND AND OBJECTIVES: Peripartum cardiomyopathy (PPCM) is a rare form of heart failure affecting women between the last month of pregnancy and the first five months after delivery. The etiology and prognostic factors of PPCM remains poorly understood, although some risk factors have been described. SUBJECTS AND METHODS: In order to characterize the features of PPCM, clinical and echocardiographic data, obtained from 19 patients who fulfilled diagnostic criteria of PPCM, from January 1996 to march 2001, were retrospectively analyzed. We divided the sample into 2 groups, which were classified according to clinical and echocardiographic improvements. (Group I; patients who improved, Group II; patients who did not improved, or deteriorated). RESULTS: Patients with PPCM (n=19, age: 32+/-5 yrs, NYHA Class: II-IV, LVEF: 34.1+/-8.8%, follow-up period: 14.2+/-16.3 months) had a high frequencies of the following clinical factors: Anaemia (16/19, 84.2%); Pre-eclampsia (11/19, 57.9%); Multiparity (11/19, 57.9%); aged over 30 yrs old at delivery (11/19, 57.9%). During follow up, 10 patients improved to NYHA Class I, 8 patients failed to improve, or deteriorated, and 1 patient died due to ventricular fibrillation. Group II (n=9, age: 31+/-3 yrs, follow up LVEF: 38.8+/-12.9%), as compared to Group I (n=10, age: 33+/-6 yrs, follow up LVEF: 56.4+/-6.4%), had greater left ventricular end-systolic dimension (LVESD, 53.0+/-7.7 mm vs 45.9+/-4.8 mm; p<0.05). CONCLUSION: PPCM has a high rate of progression to dilated cardiomyopathy. Therefore, in pregnant women with common clinical findings of PPCM, including anemia, pre-eclampsia, multiparity and old age at delivery, the initial echocardiographic assessment for cardiac function is essential, and serial follow-up is required.

A Case of Ascending Aortic Aneurysm Associated with Congenital Bicuspid Aortic Valve

Bicuspid aortic valve is the most common form of congenital valvular disease, and its presence may predispose the patients to development of true aortic or dissecting aortic aneurysms. An intrinsic aortic weakness may underlie a bicuspid aortic valve, aortic aneurysm or aortic dissection. We experienced a case of an ascending aortic aneurysm associated with a functionally normal bicuspid aortic valve. A screening echocardiograph was performed due to atypical chest pain, which detected a large ascending aortic aneurysm and a bicuspid aortic valve. The patient underwent an operation for an ascending aortic aneurysm and, is living one year later, and is asymptomatic. To the best of our knowledge, this may be the first case of an ascending aortic aneurysm associated with a bicuspid aortic valve in Korea.

A Novel Cardiomyopathy Mimicking Acute Myocardial Infarction

We recently experienced 2 cases of a novel cardiomyopathy following various stressful conditions. Here, we report on this novel cardiomyopathy showing transient left ventricular apical wall motion abnormalities following stress. Our cases exhibited an acute onset, transient left ventricular apical wall motion abnormalities with chest symptoms, electrocardiographic changes and minimal enzyme release, which mimicked acute myocardial infarction without stenosis on the coronary angiograms. The novel cardiomyopathy developed in our patients following aggravation of a systemic disorder (acute pyelonephritis with septicemia) and noncardiac surgery (total hysterectomy). Both our cases exhibited the typical echocardiographic findings of asynergy of the apical region with hypercontraction of the basal segment of the left ventricle, and wall motion abnormalities, which improved rapidly within a few weeks.

Morphologic Differences of Vessel Wall at Sites of Focal and Diffuse Coronary Vasospasm by Intravascular Ultrasound(IVUS)

BACKGROUND AND OBJECTIVES: The coronary vasospasm has been shown to play an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general, including other forms of angina pectoris, acute myocardial infarct, and sudden death. The angiographic features of coronary vasospasm are focal and diffuse patterns in clinical setting. We attempted to clarify the differences in vessel wall morphologic appearance between the sites of focal and diffuse vasospasm by intravascular ultrasound(IVUS). MATERIAL AND METHODS: We studied 23 patients(32 segments) with variant angina in whom coronary angiograms were normal and coronary spasm was documented by intracoronary injection of acetylcholine. Coronary spasm was defined as luminal diameter reduction > or = 90% compared with baseline coronary artery diameter. Focal spasm was defined if the length of spastic narrowing was less than 10mm. By IVUS, we observed atheromatous plaques in 32 spasm segments with either focal or diffuse vasospasm. We measured maximal intimal thickness, luminal cross-sectional area(CSA), and external elastic membrane-CSA in spasm sites. RESULT: When comparing maximal intimal thickness between focal (n=15) and diffuse vasospasm segments(n=17), there was significantly greater thickness at focal spasm segments(1.21+/-0.36mm vs. 0.70+/-0.23mm, P<0.001). The maximal plaque area was similar between two groups but tended to be greater in focal spasm segments(6.03+/-2.06mm2 vs. 4.92+/-2.59mm2, P=NS). When circular shaped factor(CSF : standardized index of eccentricity) was compared, focal spasm segments were greater than diffuse spasm segments(0.89+/-0.06 vs. 0.97+/-0.02, P<0.001). At the segments of focal spasm, remodeling index was greater compared to the segments of diffuse spasm(1.02+/-0.16 vs. 0.86+/-0.13, P<0.001). CONCLUSION: Focal spasm segments were more eccentric and had greater atheromatous plaque than diffuse spasm segments. Positive remodeling pattern was observed at the segments of focal spasm and negative remodeling pattern at the segments of diffuse spasm. There were morphologic differences of vessel wall appearance between focal and diffuse spasm sites.

The Inhibition of Neointimal Hyperplasia by Combination of External Radiation and Paclitaxel in A Rat Carotid Injury Model

BACKGROUND AND OBJECTIVES: Radiation therapy is one of the promising new treatment for restenosis, which is a major problem for the long-term success after angioplasty. We compared radiation therapy only and combined therapy of paclitaxel and radiation on neointimal hyperplasia after injury of rat carotid artery to see whether we can reduce the effective dosage of radiation and thus diminish untoward consequence of radiation if paclitaxel could function as a cell-cycle selective radiosensitizer. MATERIAL AND METHODS: A standardized carotid balloon catheter arterial injury was produced in 65 rats. First group was composed of a single dose of paclitaxel 1 mg/kg body weight, 2 mg/kg or 4 mg/kg, which was administrated intraperitoneally at 2 hours after injury. Second group received external radiation at doses of 2.5 or 5 Gy at 24 hours after injury. Third group was treated with combined paclitaxel-radiation: paclitaxel was injected at 2 hours after injury and then external radiation was delivered 24 hours later. At 21 days after injury, the cross-sectional area of neointima and the ratio of intima/medial area were determined from axial sections using image analysis. RESULTS: Single dose of paclitaxel had no effect in reducing smooth muscle cell proliferation. Minimum effective single dose to inhibit neointimal hyperplasia was 5 Gy. Combined paclitaxel-radiation group except subgroup with paclitaxel 1 mg/kg and 2.5 Gy radiation showed significant reduction of neointimal area compared to group with 2.5 Gy radiation. CONCLUSION: Low-dose external radiation combined with paclitaxel can more effectively inhibit smooth muscle cell pro-liferation and neointimal hyperplasia than radiation only in the rat carotid injury model.

Clinical Experience of Cardiac Myxoma

BACKGROUND AND OBJECTIVES: Cardiac myxoma is histologically benign, but may be lethal because of their strategic position. It may mimic every cardiovascular or systemic disease, and can be missed without a high idex of suspicion. MATERIALS AND METHOD: We reviewed our clinical experience in 25 patients with cardiac myxoma between 1984 and 1999. Special attention was paid to clinical presentation, physical examination, chest X-ray, electrocardiogram, laboratory findings, echocardiographic findings, operative findings and postoperative course. RESULTS: Their age ranged from 23 to 64 (mean 48 years) and there were 6 male (24%) and 19 (76%) female patients. The myxomas were located in the left atrium in 23 (88%), in the right atrium in 2 (12%) cases. The Major presenting symptoms were intracardiac obstruction such as exertional dyspnea in 19 (76%), palpitation in 7 (28%), syncopal episodes in 3 (12%) cases while systemic embolism and constitutional symptoms accounted for 5 (20%) and 10 (40%) cases, respectively. About 70% of patients were present with abnormal, but nonspecific findings in physical examination, chest X-ray, electrocardiogram, and laboratory findings. Echocardiography is the most useful diagnostic screening tool. There was no in-hospital death after operation. But only 1 patient died 5 years after resection from severe pulmonary hypertension and right ventricular failure and 1 patient presented with recurrence at 18 months after primary resection, which was confirmed histologically into chondrosarcoma. CONCLUSION: We conclude that due to nonspecific presentation of cardiac myxoma, a high index of suspicion is needed. If considered as a possible diagnosis, it is easily recognized by echocardiography and usually curative by surgical resection.

Assessment of Autonomic Nervous System by the Analysis of Heart Rate Variability in Patients with Variant Angina

BACKGROUND AND OBJECTIVES: Autonomic nervous discharge had been implicated in the pathogenesis of coronary artery spasm although the precise mechanisms by which coronary spasm is triggered remain to be elucidated. The purpose of this study was to assess the pattern of the autonomic nervous system in patients with variant angina through the analysis of heart rate variability. MATERIALS AND METHODS: We compared the pattern of cardiac sympathetic and parasympathetic activity through the time domain and frequency domain analysis of heart rate variability with 24-hour Holter monitoring between 14 patients with variant angina and 14 healthy control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. RESULTS: 1) Among the time domain indices, the percent of successive normal NN intervals difference greater than 50 msec (pNN50) and the square root of the mean squared differences of successive NN intervals (rMSSD) in the patient group were significantly lower than those in the normal control (p <0.05, repectively). 2) In the patient group, mean R-R intervals were significantly shortened from night to early morning compared to control group (p <0.05). 3) With frequency domian analysis, low frequency (0.04 to 0.15Hz)spectrum, which is correlated with sympathetic activity, was revealed no significant difference between two groups. From night to early morning, significant increase of high frequency (0.15 to 0.4 Hz) spectrum, which is specific index for vagal activity, and significant decrease of the ratio of low to high frequency, which represents sympatho-vagal interaction, was blunted in the patient group (p <0.05). CONCLUSIONS: In variant angina, cardiac vagal influence on the heart rate was blunted and sympathetic activity was predominant at night and in the early morning.