In Mok Jung

Effect of nicotine on human umbilical vein endothelial cells (HUVECs) migration and angiogenesis

The effects of nicotine on vascular endothelial cells have not been completely elucidated. We performed this study to assess the changes in cellular behaviors of human umbilical vein endothelial cells (HUVECs) treated with nicotine. We examined changes in cell count and morphology and assayed cellular migration with Boyden chamber and microcapillary tube formation in a Matrigel matrix following treatment with various concentrations of nicotine. Compared to the control, nicotine stimulated cell proliferation, migration, and tube formation at concentrations similar to those found in smokers. Although there were no specific morphological changes in HUVECs treated with nicotine at the concentration similar to that in smokers, at high concentration (10(-4) M), morphological changes such as cytoplasmic vacuolization and irregular cell shape were observed, which were assumed to be the result of direct cytotoxicity of nicotine. In HUVECs, nicotine enhanced cellular proliferation, migration and angiogenesis in vitro, and thus caused a functional change, not a morphological change at a concentration similar to that in habitual smokers.

Combined endovenous laser treatment and ambulatory phlebectomy for the treatment of saphenous vein incompetence

Objectives The aim of this retrospective study is to assess the safety and effectiveness of endovenous laser treatment (EVLT) combined with ambulatory phlebectomy (AP) as a single procedure for treating saphenous vein incompetence. Methods The study enrolled 148 patients with saphenofemoral or saphenopopliteal junction reflux associated with saphenous vein incompetence and enlarged branch veins. Patients were treated with EVLT (135 great saphenous veins, 41 small saphenous veins) concomitantly with AP as a single procedure. All patients were followed up by clinical assessment and duplex ultrasound at one week and 12 weeks after the procedure. Results No postprocedural deep vein thrombosis and pulmonary embolism occurred. Saphenous vein recanalization rate at three months was 5.7%. Residual varicosities were found in 11.4% of the patients at three months after procedure, but only 2.3% of those required subsequent interventions. Conclusion Combined EVLT and AP could be a safe and effective treatment modality for the saphenous vein incompetence.

Restoration of Patency in Iliofemoral Deep Vein Thrombosis with Catheter-Directed Thrombolysis Does Not Always Prevent Post-Thrombotic Damage

OBJECTIVES To evaluate the long-term results of catheter-directed thrombolysis (CDT) and the feasibility of stent placement for lower extremity deep vein thrombosis (DVT). DESIGN & METHODS Retrospective study of 34 patients (10 men and 24 women, mean age 55, S.D. 13 years) with lower extremity DVT underwent CDT at Seoul National University Hospital from January 1999 to October 2003. Patient characteristics, risk factors of DVT, extent of thrombosis, and short-term and long-term results of CDT and/or stent placement were analysed. RESULTS Mean follow-up times were 47 S.D. 16 months. The primary technical success rate was 97% (complete lysis 68%, partial 29%). During the follow-up periods 11 (32%) patients showed re-thrombosis. Sixteen (47%) of 34 patients showed chronic change of vessels during the follow-up periods. By Cox Proportional Hazard analysis, extent of thrombolysis was a statistically significant factor affecting the freedom of re-thrombosis and chronic change (P=0.008 and P=0.001). Nine (44%) of 21 deployed stents were obstructed, and the overall stent patency at 3 years was 56.7%. The only factor affecting the stent patency was stent length more than 6 cm (P=0.002, HR 13, 95% CI 2.7-59). CONCLUSION Long-term results of CDT are not satisfactory because of the high recurrence rate of DVT and it cannot prevent chronic post-thrombotic damage to the affected vessels despite long-term anticoagulation therapy. Careful long-term surveillance of the venous function is highly recommended after CDT.

Recurrent focal segmental glomerulosclerosis following renal transplantation in Korean pediatric patients

Abstract: The recurrence of focal segmental glomerulosclerosis (FSGS) in transplants is a well‐known problem in pediatric renal transplantation (Tx). Recently, the race of the recipient was recognized as a major variable associated with disease recurrence. In view of this finding, we report on our single‐center experience of FSGS recurrence in Korean children, an ethnically homogeneous Far East Asian population. Clinical records and renal biopsy specimens, both native and graft, were reviewed for all pediatric renal Txs (recipient age ≤ 18 yr) performed at Seoul National University Hospital from 1984 to 1999. Twenty‐two children with primary FSGS received 22 allografts for renal replacement. The mean age of disease onset in these patients was 5.9 yr. The grafts were from 12 living‐related, six living‐unrelated, and four cadaveric donors, and all recipients were immunosuppressed with cyclosporin A (CsA)‐based regimens. Post‐transplant recurrence of FSGS was confirmed in nine patients (41%). Long‐term graft survival in recurrent and non‐recurrent groups was not significantly different. Risk factor analysis showed that patients with a disease duration shorter than 48 months (odds ratio 11.7, 95% CI 1.53–89.1) and a glomerulosclerosis percentage of < 55% by renal biopsy (odds ratio 16.0, 95% CI 1.45–176) were at greater risk of disease recurrence. These results suggest that Korean children are similar to non‐African‐American youngsters in the USA and Europe with respect to post‐transplant recurrence of FSGS. The same may be true of other Far Eastern Asian children.

Malignancy in renal transplant recipients.

With improved management of infectious and cardiovascular complications of renal transplant recipients, prolonged survival with long-term follow up duration, and increasing age of patients, cancer became an increasingly important cause of morbidity and mortality in transplant patients. Literatures indicate three to fivefold incidence of malignancy in solid organ transplant recipients compared with that of general population. Certain types of malignancy, such as skin cancer, Kaposis sarcoma, lymphoma, cervical, oral and anogenital cancer, hepatocelluar and renal cell carcinoma are particularly reported to be high in incidence. Reduction of immunosuppressive medication is the first step to be considered for the management, especially for virus-associated cancer. The inhibitor of mammalian target of rapamycin(mTORi) suppresses the growth and proliferation of tumors in various animal models, cured Kaposis sarcoma and seems to reduce the incidence of de novo malignancies of renal transplant recipients, and is therefore a valuable option for the management of cancer of these patients without increment of the risk of graft rejection.

Role of three-dimensional computed tomography venography as a powerful navigator for varicose vein surgery

PURPOSE Computed tomography venography (CTV) with three-dimensional reconstruction can provide complementary road maps for varicose vein (VV) surgery. The purpose of this study is to verify the role of CTV in the treatment of VV in terms of advantages and complications. METHODS Ninety-four consecutive patients with VV underwent conventional high ligation, stripping, and varicosectomy by a single vascular surgeon in 2007. All patients were evaluated with duplex ultrasound and CTV. Patients with renal dysfunction, allergy to radiocontrast, telangiectasia only, or treated by endovenous laser therapy (EVLT) were excluded from the study. Computed tomography (CT) examination was performed with a 16-Multidetector CT scanner (Siemens, Erlangen, Germany) and 3D images were reconstructed by personal computer-based software (Rapidia, Infinitt, Seoul, Korea). Medical records and the CT images were reviewed retrospectively. RESULTS VV surgeries were done in 127 limbs of 94 patients (both in 33, right in 29, and left in 32). There were 56 females and 38 males with the mean age of 57 years (range, 28-79 years). The CEAP classification was C(2-3) EpAsPr. Perforators larger than 1 mm near the varicose veins were detected and marked on the CT volume-rendering images. The average numbers of perforators marked by CTV were 12.07 +/- 4.27 in each limb. The perforators were evaluated by duplex for the presence of reflux (>or=0.5 sec). Mean number of perforators with reflux in each limb was 1.41 +/- 1.67, which were ligated during the surgery. Incidental detections of other disease were done in six patients, including uterine myomas, an ovarian cyst, a gallstone, a scrotoal varicocele, and a pes anserine bursitis. Operation was performed with the CTV images on screen. CTV was helpful in designing the operation in most patients. Three-D CTV images of saphenopopliteal junction especially provided thorough understanding of the complex variable anatomy of the lesion. There were no CT-related complications, such as renal dysfunction or allergic reaction. CONCLUSIONS CT venography can provide excellent road map for VV surgery without significant complications. It cannot replace duplex ultrasound, but can provide powerful 3D images for designing operation as well as education and research.

Epstein-Barr virus, beta-catenin, and E-cadherin in gastric carcinomas

Activated beta-catenin is suggested to inhibit NF-kappaB activation, and we previously demonstrated that NF-kappaB nuclear positivity was more frequent in Epstein-Barr virus (EBV)-infected gastric carcinomas. It is controversial that beta-catenin and E-cadherin are prognostic markers in gastric carcinomas. To define a relationship between beta-catenin and EBV, and the prognostic value of beta-catenin and E-cadherin, we analyzed in situ hybridization for EBV-encoded small RNAs, beta-catenin, and E-cadherin immunohistochemistry, and clinicophatological features in 111 gastric carcinomas. EBV infection was detected in seven carcinomas (6.3%); none of seven showed beta-catenin nuclear accumulation, and five out of seven revealed beta-catenin membranous loss or cytoplamic expression. Eighty cases (72.1%) showed beta-catenin alteration; i.e., loss of membrane staining in 65 (58.6%), cytoplasmic expression in 35 (31.5%), and nuclear accumulation in 15 (13.5%). E-cadherin alteration was observed in 34 cases (30.6%) and correlated with beta-catenin alteration. On multivariate analysis, the combined immunoexpression group of beta-catenin nuclear accumulation/ E-cadherin alteration and the advanced TNM cancer stage group showed poor patients survival (p<0.05). In conclusion, beta-catenin activation through nuclear accumulation hardly occurred in EBV-infected gastric carcinomas. The combined immunoexpression pattern of beta-catenin and E-cadherin can be used as a prognostic marker in gastric carcinomas.

Consensus for the Treatment of Varicose Vein with Radiofrequency Ablation

The objective of this paper is to introduce the schematic protocol of radiofrequency (RF) ablation for the treatment of varicose veins. Indication: anatomic or pathophysiologic indication includes venous diameter within 2–20 mm, reflux time ≥0.5 seconds and distance from the skin ≥5 mm or subfascial location. Access: it is recommended to access at or above the knee joint for great saphenous vein and above the mid-calf for small saphenous vein. Catheter placement: the catheter tip should be placed 2.0 cm inferior to the saphenofemoral or saphenopopliteal junction. Endovenous heat-induced thrombosis ≥class III should be treated with low-molecular weight heparin. Tumescent solution: the composition of solution can be variable (e.g., 2% lidocaine 20 mL+500 mL normal saline+bicarbonate 2.5 mL with/without epinephrine). Infiltration can be done from each direction. Ablation: two cycles’ ablation for the first proximal segment of saphenous vein and the segment with the incompetent perforators is recommended. The other segments should be ablated one time. During RF energy delivery, it is recommended to apply external compression. Concomitant procedure: It is recommended to do simultaneously ambulatory phlebectomy. For sclerotherapy, it is recommended to defer at least 2 weeks. Post-procedural management: post-procedural ambulation is encouraged to reduce the thrombotic complications. Compression stocking should be applied for at least 7 days. Minor daily activity is not limited, but strenuous activities should be avoided for 2 weeks. It is suggested to take showers after 24 hours and tub baths, swimming, or soaking in water after 2 weeks.

Expression of cell cycle regulators during smooth muscle cell proliferation after balloon catheter injury of rat artery.

Intimal hyperplasia is defined as the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) with deposition of extracellular matrix. However, the cell cycle regulatory mechanisms of injury-induced VSMC proliferation are largely unknown. To examine the expression kinetics of cell cycle regulatory factors which is known to be worked positively or negatively, we used rat balloon injury model. Marked induction of proliferating cell nuclear antigen (PCNA), G1/S cyclin-dependent kinase (cdk2), and its regulatory subunit (cyclin E) occurred between 1 and 3 days after balloon arterial injury, and this was sustained for up to 7 days and then declined. However, the induction of the negative regulators, p21 and p27, occurred between 3 and 5 days of injury, peaked after 7 and 14 days and was then sustained. VSMC proliferation after balloon catheter injury of the rat iliac artery is associated with coordinated expression of positive (cdk2, cyclin E and PCNA) and negative (p21, p27) regulators. Cell cycle regulators such as cdk2, cyclin E, p21, p27 may be suitable targets for the control of intimal hyperplasia.

Modification of a Rodent Hindlimb Model of Secondary Lymphedema: Surgical Radicality versus Radiotherapeutic Ablation

Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of superficial and deep lymphatic vessels, surgery alone was not enough to sustain increased hindlimb volume. Radiotherapy was necessary to prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The applicability of this model for studies of therapeutic lymphangiogenesis was subsequently tested by injecting muscle-derived stem cells previously cocultured with the supernatant of human lymphatic endothelial cells in vitro. There was a tendency for increased lymphatic flow which significantly increased lymphatic vessel formation after cell injection, but attenuation of hindlimb volume was not observed. These results suggest that further refinement of the rodent hindlimb model is needed by titration of adequate radiation dosage, while stem cell lymphangiogenesis seems to be a promising approach.