Malignancy after Kidney Transplantation / 대한이식학회지

Purpose: Development of malignancy is one of the key issues in the renal transplant recipients after long term follow up. Methods: We reviewed our renal transplant registry for the incidence of de novo malignancy after renal transplantation. Results: Among the 1006 renal transplant recipients from July 1969 until January 2006, 47 cases of de novo malignancy developed in 43 patients: stomach cancer (7 cases), Kaposi's sarcoma (6), post-transplantation lymphoproliferative disorder (PTLD, 7), primary liver cancer (4), thyroid cancer (3), skin cancer (4), colon cancer (3),), renal cell carcinoma (2), bladder cancer (2), anal cancer (2), sarcoma (3) and one malignancy case from conjunctiva, pancreas, uterine cervix, and tongue, respectively. Mean age at the time of diagnosis of cancer was 45.8+/-12.0 years (mean+/-standard deviation). The cancer diagnosis was made at 97.1+/-73.6 months after the renal transplantation. We have high prevalence of cancers with suspected viral etiology - i.e., Kaposi's sarcoma, PTLD, primary liver cancer and uterine cervix cancer. Conclusion: Careful surveillance of malignancy in renal allograft recipients is highly recommended.

A comparison of the effect of Anastrozole and Clomiphene citrate in anovulatory patients / 대한산부인과학회지

OBJECTIVE: To compare the clinical effectiveness of Anastrozole in ovulation induction with that of clomiphene citrate. METHODS: Sixty anovulatory women were randomly divided into 4 groups (1 mg, 2 mg and 4 mg of Anastrozole groups and Clomiphene citrate group). The ovulation induction was tried with 3 dosages of Anastrozole or 100 mg of Clomiphene citrate for 5 days. The serum level of estradiol, testosterone, FSH and LH were serially monitored (on 3rd, 5th and 8th days of treatment). Serum estradiol level at the time of hCG injection was also measured. Ovulation rate, number of dominant follicles, endometrial thickness, and pregnancy rate were measured and compared across the study groups. RESULTS: There was no statistically significant difference in estradiol, testosterone, or LH level between women treated with Anastrozole and Clomiphene citrate. In patients treated with 4 mg of Anastrozole, serum FSH level was higher than that of the women treated with Clomiphene citrate (P<0.05). Endometrial thickness was greater in patients treated with Anastrozole than women treated with Clomiphene citrate (P<0.05). Number of dominant follicles in patients treated with Clomiphene (1.56) was slightly greater than in women treated with Anastrozole (1.0-1.1), but there was no statistically significant difference. CONCLUSION: Anastrozole had similar clinical effectiveness in ovulation induction when compared to Clomiphene citrate. At 1 mg or 2 mg of Anastrozole, ovulatory rate remained below the effectiveness of Clomiphene citrate, therefore considering the expensive cost of Anastrozole, it should not be considered as first-line medication for ovulation induction but reserved for those who have certain conditions such as thin endometrium and polycystic ovarian syndrome.

Changes in the Total Antioxidant Ability and Antioxidant Vitamin Levels in the Maternal Venous Plasma of Preeclampsia / 대한산부인과학회지

OBJECTIVE: This study was aimed to compare lipid peroxide level, total peroxyl radical-trapping antioxidative parameter (TRAP) value, and antioxidant vitamin level in the maternal venous plasma between normal pregnancy and preeclampsia. METHODS: Samples of venous plasma were obtained from 38 normal and 24 preeclamptic women. Lipid peroxides levels were measured by thiobarbituric acid reaction. The TRAP values were measured by Wayner's method, although some reaction conditions were modified. Ascorbic acid, retinol, alpah-tocopherol, and gamma-tocopherol were measured by high performance liquid chromatography. RESULTS: There was no significant correlation between the lipid peroxides level in the maternal venous plasma and gestational age in normal pregnancy (n=38, r=0.04, p=NS). The lipid peroxide level in the maternal venous plasma of preeclampsia (n=24) was significantly higher than that of gestational age-matched normal pregnancy (n=26), (4.39 +/- 0.38 vs. 3.23 +/- 0.15 nmol/mg protein, p<0.01). There was no significant correlation between the TRAP value in the maternal venous plasma and gestational age in normal pregnancy (n=38, r=0.02, p=NS). The TRAP value in the maternal venous plasma of preeclampsia (n=24) was significantly lower than that of gestational age-matched normal pregnancy (n=26), (0.33 +/- 0.02 vs. 0.38 +/- 0.02 mM, p<0.05). Ascorbic acid level in the maternal venous plasma of preeclampsia was significantly lower than that of normal pregnancy (377.8 +/- 23.6 vs. 552.2 +/- 52.1 nmol/mL, p<0.05). However, there was no significant difference in maternal venous plasma retinol, alpah-tocopherol, and gamma-tocopherol levels between normal pregnancy and preeclampsia. CONCLUSION: The above results suggest that the imbalance of increased lipid peroxidation and decreased antioxidant activity were in the maternal blood of preeclampsia, and an antioxidant vitamin, ascorbic acid, may be decreased result from counteracting free radical-mediated cell disturbance.

Two Cases of Pure Red Cell Aplasia Due to Anti-erythropoietin Antibodies / 대한신장학회잡지

We reported upon two Korean patients who developed pure red cell aplasia (PRCA) due to anti- erythropoietin (EPO) antibodies. The first patient became refractory to EPO treatment after a good response for an initial 26 months. Anti-EPO antibodies were detected by ELISA and by radioimmunoprecipitation, and these were found to inhibit the formation of erythroid colonies by in-vitro bioassay. In the second patient, the anemia became aggravated, and wheals appeared at the EPO injection site 3 months after the initiation of subcutaneous EPO treatment. Anti-EPO antibodies were detected by ELISA, and he showed partial response to the second course of corticosteroid treatment. Our cases showed that PRCA due to anti-EPO antibodies becomes an important issue in Asian as well as Caucasians.

Down-regulation of MHC class I Expression in Porcine Aortic Endothelial Cells by Introduction of hCMV US Genes / 대한이식학회지

PURPOSE: Direct recognition of porcine MHC proteins by human T cells is an impediment to successful xenotransplantation. Therefore, reducing human T cell response initiated by the interaction between TCR/CD8 cell and MHC class I on pig endothelial cell may be beneficial in successful pig- to-human xenotransplantation. METHODS: We examined MHC expression on porcine endothelial cell line, MYP30 cells in the absence or presence of IFN-g by FACS analysis. We introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce MHC class I expression on the cell surface after infection, into MYP30 cells in order to test the feasibility of modifying these cells to reduced MHC class I antigens by the introduction of hCMV US genes such as US2, 3, 6 or 11. RESULTS: MHC class I expressions in MYP30 cells were dramatically induced by IFN-gamma treatment. FACS analysis showed that cells transfected with the hCMV US2, 3, 6 or 11 genes exhibited 30~40% of MHC class I expression compared with mock-transfected cells. We next established stable cell lines expressing US6 gene, which had been found to exert best down-regulation effect on MHC class I expression. Stable cell line expressing US6 gene products exhibited more than 10% reduced expression level of the MHC class I compared with transiently transfected cells. CONCLUSION: Although the further analysis of the cytotoxicities of T and NK cells on the hCMV US gene transfected cells are needed to clarify the feasibility of their application, these results suggest that virus stealth technology can be exploited for xenotransplantation.

Single Center Study about Post-transplant Anemia (PTA) in Korean Renal Transplant Recipients: Prevalence and Risk factors for PTA / 대한이식학회지

PURPOSE: Post-transplant anemia (PTA) is one of the most important risk factors for cardiovascular disease, which is the most common cause of mortality in renal transplant recipients. We retrospectively evaluated the prevalence and risk factors of PTA in patients who underwent kidney transplantation in Seoul National University Hospital. METHOD: We reviewed medical records of 223 patients who received renal transplants in Seoul National University Hospital from 1997 to 2003. We analyzed data to evaluate the prevalence of PTA and to define the risk factors for the development of PTA. RESULTS: The mean follow-up period was 33.5+/-21.9 months. Male-to-female ratio was 1.7 : 1 and mean age was 38.4+/-11.9. The mean hemoglobin (Hb) at the time of transplantation was 9.7+/-1.7g/dL. At the time of transplantation 213 patients (96.4%) had anemia. PTA was frequent in early phase, but in many cases it resolved spontaneously. The prevalence of PTA reached a plateau in 1 year without further decrement (around 30%). The correlation between low Hb and low glomerular filtration rate (GFR) became stronger in the late posttransplant period. Recipients' age (50) and female sex were significantly associated with PTA in the early and late post- transplant period (P<0.05). CONCLUSION: About 30% or more patients had persistent anemia after 1 year of kidney transplantation. Persistent PTA requires thorough evaluation and management, especially in patients with risk factors for PTA.

MHC Antigen Expressions in Human Embryonic Neural Stem Cells and Adult Breast Epithelial Stem Cells / 대한이식학회지

PURPOSE: Due to their unique capacity to self-renew and for multiple differentiation, stem cells are considered potent candidates for cell replacement therapy in many devastating diseases. However, studies on immune rejection, which is a major problem facing successful stem cell therapy, are rare. Thus, we examined MHC expression of human stem cells and effects of IFN-gamma on the MHC class I expression of the cells in order to determine whether human stem cells might be rejected after transplantation. METHODS: The MHC antigen expressions of human embryonic neural stem cell line (HB1.F3) and human breast epithelial stem cell line (M13SV1) were examined by RT-PCR and FACS. The effects of varying concentrations of IFN-gamma and of varying incubation times with IFN-gamma on the expression of MHC class I antigens in these stem cell lines were also examined by FACS. RESULTS: The results show low expression levels of MHC class I antigens on surfaces of these cells. A dramatic induction of MHC class I expression was observed when the cells were treated with IFN-gamma. Maximal induction of MHC class I antigen expression in HB1.F3 and M13SV1 cells was observed at above the concentrations of 20 ng/mL and 5 ng/mL of IFN-gamma 48 h after treatment, respectively. Elevated MHC class I levels in HB1.F3 and M13SV1 cells were sustained for 48 h and 72 h after withdrawing IFN-gamma, respectively. CONCLUSION: These results suggest that human stem cells express high levels of MHC class I antigens, and thus may be rejected on transplantation unless they are modified. Therefore, in addition to studies on stem cell differentiation, studies on overcoming the immunological barriers to stem cell transplantation are prerequisite for successful clinical application of stem cell therapy.

Down-regulation of MHC Expression in Human Stem Cells by Introduction of hCMV US Genes / 대한이식학회지

PURPOSE: Stem cells are considered promising candidates for cell replacement therapy in many devastating diseases. However, it is assumed that stem cells may be rejected on transplantation. Therefore, we introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce MHC class I expression on the cell surface after infection, into two known stem cell lines in order to test the feasibility of modifying these cells to reduced MHC class I antigens by the introduction of hCMV US genes. METHODS: The MHC class I expressions of mock-transfected or hCMV US gene-transfected human embryonic neural stem cell line (HB1.F3) and human breast epithelial stem cell line (M13SV1) were examined by FACS. RESULTS: MHC class I expressions in HB1.F3 and M13SV1 cells were dramatically induced by IFN-gamma treatment. In FACS analysis, cells transfected with the hCMV US2, 3, 6 or 11 genes exhibited a dramatic reduction (40~60%) of MHC class I expression compared with mock-transfected cells. CONCLUSION: Our results suggest that human stem cells express high levels of MHC class I antigens, and thus may be rejected on transplantation unless they are odified. In addition introduction of hCMV US genes can be exploited for stemcell transplantation.

Late Postpartum Eclampsia: A Case Report / 대한주산의학회잡지

Although the technique of antenatal care is developed, the incidence of late postpartum eclampsia has been increased and its prevention is difficult. In addition, the diagnosis is more difficult if the patient did not show any symptoms of preeclampsia before delivery. We described one case of late postpartum eclampsia that occurred on 7th day after preterm delivery and has not been diagnosed before delivery including a review of this literature.

The Expression Patterns of CD44 and CD45RB on Peripheral Blood T Lymphocytes in the Rejection of Allogeneic Skin Transplantation in Mice / 대한이식학회지

PURPOSE: Until now, the rejection was diagnosed through a biopsy, but this method of diagnosis reflected the advanced tissue damage of the transplanted organ and contained the innate problem of being invasive. Activation of T lymphocytes, which occurs before the overt tissue damage has a pivotal role in rejection. In relation, our research attempted to evaluate the viability of analyzing the surface antigens of the peripheral blood activated T lymphocytes in mice after skin transplantation as a noninvasive and early diagnostic tool for diagnosis of rejection. METHODS: After the mouse's skin was transplanted, the expression patterns of activated T lymphocyte markers, CD44 and CD45RB were analyzed along with T lymphocyte markers, CD3, CD4, and CD8 using flow cytometry. The skins from the tails of allogeneic Balb/c (H2(d)) mice and syngeneic C57BL/6J mice were transplanted to C57BL/6J (H2(b)) mice as test and control groups, respectively. Peripheral blood, which was sampled from the tail every other day from day 3 to day 15 was stained with anti-CD44 (or CD45RB), anti-CD4 (or CD8) and anti-CD3 monoclonal antibodies simultaneously, and analyzed by 3-color FACS. Repeated ANOVA test and Mann-Whitey test were used to analyze the differences between the expression patterns of peripheral blood T lymphocyte surface antigen in the control and test groups (SPSS 8.0). RESULTS: Rejection occurred only in the test group from day 8 to day 13 (median: day 10). Although the proportions of CD3(+)lymphocytes (CD3(+)%), CD4(+)lymphocytes (CD4(+) %), and CD8 lymphocytes (CD8(+)%) showed no difference between the control and test groups, the total number of peripheral blood lymphocytes and the number of CD3(+)lymphocytes (CD3(+)) and CD8(+)lymphocytes (CD8(+)) decreased more sharply in the control group after day 7. The proportion and the number of CD44 CD3(+)lymphocytes, CD44 CD4(+)lymphocytes, and CD44(+) CD4(+) CD3(+)lymphocytes began to increase after day 7, to peak on day 11, and then to decrease, showing a significant difference from those of the control group. The proportion and number of CD44(+) CD3(+)lymphocytes, in particular, showed the most significant difference among these significant markers. The proportion and number of CD44(+) CD8(+) lymphocytes and CD44(+) CD8(+) CD3(+)lymphocytes showed similar trends to those of CD44(+) CD3(+) or CD44(+) CD4(+), but the differences between the subset proportions in control and test groups were statistically insignificant. No significant difference was observed in any subsets of the CD45RB antigen. CONCLUSION: CD44(+)CD3(+) lymphocytes representing activated T lymphocytes increased significantly compared to the control group during the rejection period of skin transplantation. The analysis of the expression patterns of surface antigen CD44 on peripheral blood T lymphocytes using flow cytometry is sensitive, safe, easily repeatable, and controllable, and, therefore, can be considered a promising tool for the diagnosis of rejection. However, the clear change in CD44 occurred between day 9 and day 13, when rejection was observed grossly. Therefore, it is regarded more useful as a screening test or follow-up indicator rather than as an early diagnostic tool.

Eczema Herpeticum in Darier's Disease

Eczema herpeticum is a herpes simplex virus infection with disseminated skin involvement superimposed on a pre-existing dermatosis. Dariers disease has been reported to be among the dermatoses susceptible to the sudden onset of a widespread vesicular eruption accompanied by high fever known as Kaposis varicelliform eruption. We report a case of eczema herpeticum in a 46-year-old woman associated with Dariers disease.

Clinical Characteristics of Hypernatremia / 대한신장학회잡지

Hypematremia is a rare but important medical condition and is associated with mortality rate of 40 to 70%. However, little has been known about its prognostic factors or treatment guidlines. To evaluate the prognostic factors and the outcome following treatment, we reviewed 22 available medical records among twenty five hypernatremic patients (0.2%) in 12841 admissions at medical ward from January to December 1995. We defined hypernatremia as serum sodium concentration more than or equal to 150 mEq/L. Of these patients, two had hypematrernia at admission and the remaining patients became hypernatremic during admission. Mean peak serum sodium concentration was 158 (150-178) mEq/L and mean total body water deficit was 11.4 (6.7-21.3)%. Factors correlated with the development of hypernatremia were diverse and multiple, and the most frequent factor was diminished access to water. Mortality rate was 59%, but mortality was not correlated with age, correction rate of hyper-natremia, primary route of fluid loss, and the severity of hypernatremia or total body water deficit. Mortality rate was higher in patients whose serum sodium concentrations were below 130 mEq/L at admission (P<0.05). In our study, development of hypernatremia from initial hyponatremic state was significantly associated with poor outcome, and age, rapidity of correction, route of fluid loss, and the severity of hypernatremia or total body water deficit were not.

Histological Changes of the Skin of a Guinea Pig after Irradiation with the Erbium YAG Laser / 대한피부과학회지

BACKGROUND: Laser resurfacing has beneficial effects in the treatment of several skin problems such as acne and chicken pox scars. Recently pulsed erbium YAG laser has been used for skin resurfacing, but not enough is known about the scientific basis of such treatment. OBJECTIVE: The purpose of the study was to assess the macroscopic and microscopie changes after irradiation with the pulsed Er-YAG laser. METHODS: We did two tests on guinea pig skin, First, the laser was used to irradiate the skin of a guinea pig with the intensity of 500 mJ, 5 watt until pinpoint bleeding began. Skin biopsies were performed immediately, one, two and four weeks after the irradiation. Second, the laser was used to irradiate the skin of a guinea pig with the intensity of 300mJ(3watt), 500mJ(5watt), 700mJ(7watt) until pinpoint bleeding began, Skin biopsies were examined immediately, one, two and four weeks after the irradiation. RESULTS: 1. Histological changes to the dermis over time after laser irradiation with 500 mJ, 5 watt are as follows: After one week, complete reepithelization and proliferation of the blood vessels within the dermis occured. A reaction of th dermis which consisted of newly formed collagen and was distinguisbed from the lower dermis was also examined. The reaction was rnost active after two weeks and lasted up to four weeks. 2. Histological changes to the dermis over time after laser irradiations with different intensities of 300 mJ(3watt), 500 mJ(5watt), and 700 mJ(7watt) are as follows : In all the cases of laser irradiation with different intensities, edema, neovascularization and fine collagen fiber in the upper dermis were observed. At higher intensities, the dermal reactions were stronger and were sustained for a longer time. CONCLUSION: Pulsed erbium YAG laser had effects on the epidermis and dermis. Therefore, pulsed erbium YAG laser can be used for skin resurfacing effectively and safely.