Yang Jin Park

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.

Evaluation of the efficacy of the forearm basilic vein transposition arteriovenous fistula

PURPOSEnSince the publication of Dialysis Outcomes Quality Initiative (DOQI) guidelines, the use of native veins for the construction of arteriovenous fistulas (AVF) for hemodialysis has been highly recommended rather than prosthetic arteriovenous grafts (AVG). Upper arm basilic vein transposition (BVT) has been accepted widely, with superior patency compared with AVG, but only a few studies have reported outcomes of forearm BVT (FBVT). This study evaluated the efficacy of FBVT compared with direct AVF (DAVF) and AVG in a tertiary referral center.nnnMETHODSnFrom January 2005 to December 2007, 461 patients underwent AV access for hemodialysis in Seoul National University Hospital. We retrospectively reviewed the medical records and dialysis sheets and evaluated the current AVF function in the outpatient clinic or by telephone interviews. Patients were grouped by the operation type: DAVF, FBVT, and AVG. The outcomes compared were primary, assisted-primary and secondary patency rates, maturation failure, and complications.nnnRESULTnThe mean age was 59 years (range, 14-92 years), and 280 patients (60.7%) were male. By operation type, the 461 accesses were 389 DAVF (84.4%), 34 FBVT (7.4%), and 38 AVG (8.2%). Mean follow-up duration was 21 months (range, 1-51 months). The primary patency rates for DAVF, FBVT, and AVG were 67.6%, 41.5%, 35% at 12 months and 53.9%, 30.2%, 10.3% at 24 months, respectively. The secondary patency rates were 89.2%, 79.1%, 78.3% at 12 months and 83.8%, 74.4%, 64.9% at 24 months, respectively. Maturation failure occurred in five DAVF patients and in one FBVT patient. The infection rate was 0.3% in DAVF and 12.5% in AVG, but no infection occurred in patients with FBVT. Multivariate analysis revealed that age and history of previous access were associated with lower primary patency.nnnCONCLUSIONnForearm BVT showed an acceptable, high 2-year patency rate and fewer thromboses and infectious complications than AVG. Forearm BVT could be considered before forming an upper arm AVF or forearm AVG, if the basilic vein is available.

Moderate-to-severe early-onset hyperuricaemia: a prognostic marker of long-term kidney transplant outcome

BACKGROUNDnHyperuricaemia commonly occurs in renal transplant recipients (RTRs), but the effects of post-transplant hyperuricaemia on kidney transplant outcome have not been clearly established. This work was designed to explore the impact of hyperuricaemia on renal transplant outcome.nnnMETHODSnThe authors examined this issue by analysing the clinical outcome of 281 RTRs. Hyperuricaemia (defined as UA > 7.0 mg/dl in men and >6.0 mg/dl in women for at least two consecutive tests, n = 121) was classified as early onset (within 1 year of transplant, n = 90) or late onset (n = 31). Graft function was estimated using the MDRD Study Equation 7 (eGFR(MDRD)).nnnRESULTSnAs late-onset hyperuricaemia was found to be induced by a progressive decline in the graft function (P < 0.01), data from early-onset hyperuricaemic recipients were used. Early-onset moderate-to-severe hyperuricaemia (defined as UA >or= 8.0 mg/dl) was found to be a significant risk factor for chronic allograft nephropathy (P = 0.035) and a poorer graft survival (P = 0.026) by multivariate analysis, whereas mild hyperuricaemia was not. The impact of moderate-to-severe hyperuricaemia on renal transplant survival was dependent on the duration of exposure. Likewise, the detrimental effect of early-onset hyperuricaemia on the graft function was dependent on UA levels and exposure time. After control of the baseline graft function by analysis of only recipients with a good graft function at 1 year post-transplantation (eGFR(MDRD) > 60 ml/min), moderate-to-severe early-onset hyperuricaemia was also found to be a marker of long-term graft dysfunction and failure.nnnCONCLUSIONnModerate-to-severe early-onset hyperuri- caemia may be a prognostic marker of the long-term graft outcome in RTRs, which needs further investigation.

Sequential evolution of IL-17 responses in the early period of allograft rejection.

In addition to CD4+CD25+Foxp3+ regulatory T (Treg) cells which protect against autoimmune tissue injury, IL-17-producing CD4+ T (Th17) cells have been recently described and shown to play a crucial role in autoimmune injury. It appears that there is a reciprocal developmental pathway between Th17 and Treg cells. Although IL-17 is known to be associated with allograft rejection, the cellular source of IL-17 and the nature of Th17 in the context of allograft rejection remain unknown. In the current study, the dynamics of Treg and IL-17-producing cells after syngeneic and allogeneic transplantation were examined using a wild-type murine cardiac transplantation model. Ly6G+ cells were found to produce IL-17 during the early postoperative period and CD8+ as well as CD4+ T cells were also found to produce IL-17 during alloimmune response. Graft-infiltrating Ly6G+, CD4+, and even CD8+ cells were found to express IL-17 highly compared to those in spleen. Although the frequencies of Th17 and Treg were found to gradually increase in both syngeneic and allogeneic recipients, Th17/Treg ratios were significantly higher in recipients with allograft rejection than in syngeneic recipients. In conclusion, IL-17 is produced by neutrophils during the early postoperative period and subsequently by Th17 and CD8+ T cells during allograft rejection. Th17/Treg imbalance is associated with the development of allograft rejection. This study would provide basic information on Th17 biology for future investigation in the field of transplantation.

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

OBJECTIVESnTo evaluate the long-term results of catheter-directed thrombolysis (CDT) and the feasibility of stent placement for lower extremity deep vein thrombosis (DVT).nnnDESIGN & METHODSnRetrospective 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.nnnRESULTSnMean 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).nnnCONCLUSIONnLong-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.

Trends in Deceased Organ Donation and Utilization in Korea: 2000-2009

Continuous efforts have been made by the organ donation and transplantation community in Korea to increase organ donation by the deceased. The authors detailed trends of organ donation and utilization over the past 10 yr using data provided by the KONOS. The yearly number of deceased donors has grown gradually since 2003. The number and percentage of old donors (≥50 yr) and donors dying from intracranial hemorrhage has increased continuously. Therefore, the percentage of standard criteria donors (SCD) has been declining significantly, from 94% in 2000 to 79.2% in 2009. The number of organs transplanted per donor (OTPD) has also declined slightly since 2007, from 3.28 in 2007 to 2.95 in 2009. This decline may be attributable to increases in the number and percentage of extended criteria donors (ECD) and donors after cardiac death (DCD), since the OTPD was 2.25 for DCD, 2.5 for ECD, and 3.09 for SCD in 2009. In summary, the makeup of donors has changed significantly. There is an urgent need for establishment of an institutional framework including an independent organ procurement organization and for improvement for the National Transplant Act to increase deceased donor pool and to optimize management of ECD and DCD.

Changes of Clinicopathologic Characteristics and Survival Outcomes of Anaplastic and Poorly Differentiated Thyroid Carcinoma.

BACKGROUNDnThis study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC).nnnMETHODSnA retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci.nnnRESULTSnThe five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; pu2009<u20090.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; pu2009<u20090 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, pu2009=u20090.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (pu2009=u20090.013).nnnCONCLUSIONSnThe choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer.

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

PURPOSEnComputed 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.nnnMETHODSnNinety-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.nnnRESULTSnVV 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.nnnCONCLUSIONSnCT 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.

An abdominal aortic aneurysm in an 8-month-old girl with tuberous sclerosis.

The association between an abdominal aortic aneurysm (AAA) and tuberous sclerosis (TS) is rare. An 8-month-old girl presented with a seizure, and the clinical evaluation revealed TS. An abdominal evaluation showed a 3-cm infrarenal AAA. A normal diameter of infrarenal aorta for an 8-month-old girl is about 6mm. The patient underwent an open repair with a polytetrafluoroethylene (PTFE) prosthesis. The pathology showed a loss of elastin fibres in the media of the aorta. The graft was patent on computed tomography (CT) angiography, performed 4 months after the operation. However, the patient died of complications related to seizures 5 years after the surgery. The graft remained patent until the time of death.

Genetic predisposition of donors affects the allograft outcome in kidney transplantation; polymorphisms of stromal-derived factor-1 and CXC receptor 4.

Genetic interaction between donor and recipient may dictate the impending responses after transplantation. In this study, we evaluated the role of the genetic predispositions of stromal-derived factor-1 (SDF1) [rs1801157 (G>A)] and CXC receptor 4 (CXCR4) [rs2228014 (C>T)] on renal allograft outcomes. A total of 335 pairs of recipients and donors were enrolled. Biopsy-proven acute rejection (BPAR) and long-term graft survival were traced. Despite similar allele frequencies between donors and recipients, minor allele of SDF1 rs1801157 (GA+AA) from donor, not from recipients, has a protective effect on the development of BPAR compared to wild type donor (GG) (Pu200a=u200a0.005). Adjustment for multiple covariates did not affect this result (odds ratio 0.39, 95% C.I 0.20–0.76, Pu200a=u200a0.006). CXCR4 rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. SDF1 was differentially expressed in renal tubular epithelium with acute rejection according to genetic variations of donor rs1801157 showing higher expressions in the grafts from GG donors. Contrary to the development of BPAR, the presence of minor allele rs1801157 A, especially homozygocity, predisposed poor graft survival (Pu200a=u200a0.001). This association was significant after adjusting for several risk factors (hazard ratio 3.01; 95% C.Iu200a=u200a1.19–7.60; Pu200a=u200a0.020). The allelic variation of recipients, however, was not associated with graft loss. A donor-derived genetic polymorphism of SDF1 has influenced the graft outcome. Thus, the genetic predisposition of donor should be carefully considered in transplantation.