Clinical efficacy of serum human epididymis protein 4 as a diagnostic biomarker of ovarian cancer: A pilot study

OBJECTIVE: To compare accuracy of serum human epididymis protein 4 (HE4) levels with cancer antigen 125 (CA-125) levels as biomarkers for ovarian cancer. METHODS: The study population included 94 Korean women, including 32 patients with a diagnosis of ovarian cancer and 62 patients with a diagnosis of benign ovarian tumor. All diagnoses were confirmed by histopathological analysis. Serum HE4 levels were assessed using an HE4 enzyme immunoassay, which were performed according to the manufacturer's instructions. Serum CA-125 levels were determined using a Modular analytics E170 module. RESULTS: The median serum CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than those with other benign tumors (CA-125, 394.1 U/mL vs. 22.7 U/mL; HE4, 56.7 pM vs. 18.5 pM; P < 0.05 in both). An additional comparison revealed that the patients with endometriosis had greater median serum CA-125 levels than those with other benign ovarian tumors (32.0 U/mL vs. 17.9 U/mL, P = 0.03). Conversely, the median serum HE4 levels were similar among the two benign ovarian tumor groups, with no statistically significant difference observed (19.0 pM vs. 18.2 pM, P = 0.49). The receiver operating characteristics curve analysis for the benign ovarian tumor and ovarian cancer patients showed that HE4 showed a greater area under the curve with borderline significance when compared with CA-125 in both groups (0.93 vs. 0.85). CONCLUSION: Serum HE4 levels may not only allow for the detection of ovarian cancer, but also allow for better differentiation of cases of ovarian cancer versus other benign ovarian tumors compared with serum CA-125.

Plasma levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in women with cervical neoplasia / 부인종양

OBJECTIVE: The goal of this study was to investigate the relationship between plasma levels of insulin-like growth factors-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) and the risk for cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: Plasma levels of IGF-1 and IGFBP-3 of 44 cervical cancer patients, 82 CIN patients and 40 neoplasm-free patients were investigated. Then the associations of the plasma levels of IGF-1 and IGFBP-3 with cervical neoplasm or its clinicopathologic parameters were analyzed. RESULTS: The mean IGF-1 concentrations were significantly different among the control, CIN, and cervical cancer groups; the levels were higher in the CIN group compared to the controls. According to the quartile category, the plasma IGF-1 level was significantly higher (p=0.0015) in the CIN group than in the controls. The IGFBP-3 level showed no association between the controls and CIN groups (p=0.842). Although the mean IGF-1/IGFBP-3 molar ratio had borderline significance (p=0.08) among the study population, the quartile comparison showed a significantly higher IGF-1/IGFBP-3 molar ratio in the CIN group compared to the control group (p=0.041). CONCLUSION: Plasma levels of IGF-1 and the IGF-1/IGFBP-3 molar ratio might be useful for the development early detection of cervical lesions and used as an adjuvant diagnostic tool for cervical neoplasia after more larger scale research.

Effect of Dexamethasone on the Production of Nitric Oxide in Trabecular Meshwork Cells

PURPOSE: To investigate the effects of dexamethasone (DEX) on the production of nitric oxide (NO) and its enzymatic synthetic pathway in cultured human trabecular meshwork (HTM) cells. METHODS: Primarily cultured HTM cells were exposed to 0, 10, 100, 1000 nM of DEX for 3 days. In addition, 100 micrometer sepiapterin, 100 micrometer ascorbic acid, and 10 micrometer methotrexate were co-exposed to DEX. The cellular survival and nitrite production rates were assessed by MTT assay and Griess assay, respectively. RESULTS: DEX did not significantly affect the survival of cultured HTM cells. DEX decreased the NO production in a dose-dependent manner. With co-exposure of DEX, ascorbic acid nullified the DEX-induced decrease of NO production. Sepiapterin and methotrexate did not affect DEX-induced decrease of NO production. CONCLUSIONS: DEX decreased NO production in HTM cells and the de novo pathway of tetrahydrobiopterin may be involved. This decrease may raise intraocular pressure by decreasing trabecular outflow.

Effect of Dexamethasone on the Production of Nitric Oxide in Trabecular Meshwork Cells

PURPOSE: To investigate the effects of dexamethasone (DEX) on the production of nitric oxide (NO) and its enzymatic synthetic pathway in cultured human trabecular meshwork (HTM) cells. METHODS: Primarily cultured HTM cells were exposed to 0, 10, 100, 1000 nM of DEX for 3 days. In addition, 100 micrometer sepiapterin, 100 micrometer ascorbic acid, and 10 micrometer methotrexate were co-exposed to DEX. The cellular survival and nitrite production rates were assessed by MTT assay and Griess assay, respectively. RESULTS: DEX did not significantly affect the survival of cultured HTM cells. DEX decreased the NO production in a dose-dependent manner. With co-exposure of DEX, ascorbic acid nullified the DEX-induced decrease of NO production. Sepiapterin and methotrexate did not affect DEX-induced decrease of NO production. CONCLUSIONS: DEX decreased NO production in HTM cells and the de novo pathway of tetrahydrobiopterin may be involved. This decrease may raise intraocular pressure by decreasing trabecular outflow.

Current management of borderline ovarian tumor / 대한산부인과학회지

The mainstream in management of borderline ovarian tumor has been thorough surgical staging and close observation. Recent trends prefer conservative management especially for the young, reproductive aged women due to the good prognosis profile and wide use of laparoscopy, although the safety for oncologic outcome of conservative treatment has not been fully established. The present article updates published literatures respecting management of borderline ovarian tumor. A proper staging procedure is necessary for all the patients to estimate the risk of recurrence. Fertility-sparing surgery is a tolerable option in young patients with stage I disease. Patients with advanced-stage disease or who are finished childbearing are treated with radical surgery. The roles of adjuvant chemotherapy or laparoscopic staging are not definite up to now.

A Case of Pseudo-Duane's Retraction Syndrome With Old Medial Orbital Wall Fracture

We report a case of pseudo-Duane's retraction syndrome with entrapment of the medial rectus muscle in an old medial orbital wall fracture presenting identical clinical symptoms as Duane's retraction syndrome. A 15-year-old boy presented with persistent limited right eye movement since a young age. Examination showed marked limited abduction, mildly limited adduction, and globe retraction accompanied by narrowing of the palpebral fissure during attempted adduction in the right eye. He showed a right esotropia of 16 prism diopters and his head turned slightly to the right. A slight enophthalmos was noted in his right eye. A computed tomography scan demonstrated entrapment of the medial rectus muscle and surrounding tissues in an old medial orbital wall fracture. A forced duction test revealed a marked restriction of abduction in the right eye. A 5 mm recession of the right medial rectus muscle was performed. Postoperatively, the patient's head turn and esotropia in the primary position were successfully corrected, but there was still some limitations to his ocular movement. The importance of several tests such as the forced duction test and an imaging study should be emphasized in making a diagnosis for limitation of eye movement.

Vascular endothelial cell growth factor (VEGF) polymorphisms and haplotypes in Korean women with advanced endometriosis / 대한산부인과학회지

OBJECTIVE: Endometriosis is the presence of normal endometrial mucosa (glands and stroma) abnormally implanted on the outside of uterus. The pathophysiology of endometriosis is not clear yet, but Sampson's theory of the transplantation of endometrial tissue onto the pelvic peritoneum via retrograde menstruation is most widely accepted. Vascular endothelial cell growth factor (VEGF) is involved in the pathophysiology of endometriosis via its angiogenetic property. This study was designed to investigate whether single nucleotide polymorphism and its haplotype and diplotype of VEGF genes are associated with the risk of advanced endometriosis or not. METHODS: This study investigated 260 patients of endometriosis; they underwent operation, and were diagnosed with endometriosis stage III, IV histopathologically. And control group of 199 women underwent surgery with benign ovarian cyst. The single nucleotide polymorphisms of VEGF gene were -2578C>A, 405G>C, 936C>T. They were analyzed by polymerase chain reaction and restriction fragment length polymorphism, and haplotype and diplotype analysis were done. RESULTS: The result of this study showed no association among -2578C/A, 405G>C, 936C>T single nucleotide polymorphisms and severe endometriosis. Haplotype and diplotype of -2578C>A, 405G>C, 936C>T in the VEGF gene were shown to have no association with endometriosis. We found no association between VEGF genetic polymorphism and risk of endometriosis. And haplotype and diplotype analysis also revealed no statistically significant value between VEGF polymorphism and endometriosis. CONCLUSIONS: So, the results of this study suggest polymorphism of VEGF gene may not be associated with risk of endometriosis in Korean women.

Two cases of paratubal cysts manifesting as huge pelvic masses in young women / 대한산부인과학회지

Paratubal cysts come from paraovarium of the broad ligament between the fallopian tube and ovary. Overall, these cysts constitute 10% of all adnexal masses and are commonly incidental findings upon surgical exploration for other reasons. They more commonly occur in women between 30 and 40 years of age. We report two cases of rapidly growing, huge paratubal cysts in young women, which are presented with brief review of literature.

Effect of Nitric Oxide on the Migration and Fibroblast-mediated Contraction of Collagen Gels

PURPOSE: To investigate the role of nitric oxide (NO) on the migration of cultured human Tenon's capsule fibroblasts (HTCF) and contraction of collagen gel. METHODS: After artificial wounding, the primarily cultured HTCF were exposed to an NO donor such as sodium nitroprusside (SNP), S-Nitroso-N-acetylpenicillamine (SNAP), or dexamethasone at various concentrations. The cellular migration was measured up to five days. After embedding the cells in the collagen gels, the amount of contraction by the gels was also measured. Cellular survival and NO production were measured with MTT assay and Griess assay, respectively. RESULTS: Cellular survival was decreased by both NO donors but not by dexamethasone. SNP inhibited migration of HTCF in a dose-dependent manner and enhanced contraction of collagen gels. However, SNAP had no effect on the cellular migration or gel contraction. Dexamethasone inhibited cellular migration but did not affect the contraction of collagen gels. CONCLUSIONS: Among the NO donors, only SNP inhibited migration of HTCF and enhanced contraction of collagen gels in vitro. Thus, the effects between the two NO donors on fibroblast induced wound healing differ.

Tenascin-X and leukemia inhibitory factor receptor are down-regulated in leiomyoma compared with normal myometrium / 부인종양

OBJECTIVE: Uterine leiomyomas are the most common tumor of the uterus. But the molecular causes of uterine leiomyoma remain unclear. We conducted the current investigation in order to elucidate the molecular mechanisms in the development of uterine leiomyoma. METHODS: We employed a new and accurate reverse transcription-polymerase chain reaction (RT-PCR) method that involved annealing control primers (ACPs) to identify the genes that are differently expressed in uterine leiomyoma. RESULTS: Using 120 ACPs, we identified and sequenced 14 differently expressed genes (DEGs) in uterine leiomyoma compared with normal myometrium. Basic Local Alignment Search Tool (BLAST) searches were performed to examine the known functions of these genes associated with uterine leiomyoma. We confirmed differently expressed patterns in more cases using the RT-PCR method. We also detected two novel genes, Tenascin-X and Leukemia Inhibitory Factor Receptor (LIFR), which had not yet been reported to have any functions associated with uterine leiomyoma. RT-PCR confirmation shows that both of these two genes are down-regulated in uterine leiomyoma. CONCLUSION: Our results suggest that Tenascin-X and LIFR may play a role in the development of uterine leiomyoma. Although further studies are required to establish the precise mechanisms with which these genes are involved in the genesis of uterine leiomyoma, the present research is significant in that it is the first study which detects down-regulated novel genes in uterine leiomyoma using the ACP system.

Tailored selective termination in second trimester in twin pregnancy / 대한산부인과학회지

OBJECTIVE: Recently, selective termination is employed in multifetal pregnancies, in the presence of an abnormal fetus, or in the complication of twin pregnancies. The purpose of this study is to evaluate effectiveness, safety of the tailored selective termination in multifetal pregnancies. METHODS: This study was retrospective and involved six cases. Indication of termination were 3 cases of structural anomalies (anencephaly, encephalocele, body stalk anomaly), 1 case of chromosomal anomaly (21 trisomy) and 2 cases of monochorionic twin complications (acardiac twin, twin to twin transfusion syndrome). RESULTS: We used KCL injection in 4 cases, they were all confirmed dichorionic twin, and in 2 cases of monochorionic twin, we used alcohol ablation of intra-abdominal umbilical artery in 1 case, and radiofrequency ablation of the cord in 1 case. CONCLUSION: All procedures were successful, and all normal infants were delivered in 3rd trimester. Tailored selective termination in 2nd trimester is effective and safe in abnormal multifetal pregnancies.

Tissue viability of human placental explants in normoxic and hypoxic culture / 대한산부인과학회지

OBJECTIVE: In vitro study systems for research of placental hypoxia are needed, among which human placental villous explant culture technique under experimentally variable condition is commonly used. So we performed this study to assess the viability of placental villous explant in normoxic and hypoxic culture that can provide validity for that system. METHOD: Placental villous explant tissues obtained from 9 cases of normal term pregnancies were incubated in normoxic (20% O2) and hypoxic (2~5% O2) condition for 72 hours. The viability of tissue was evaluated morphologically by microscopic examination and biochemically by LDH assay at variable time interval (0, 6, 12, 24, 48, 72 hours). The apoptosis of the tissue was assessed by TUNEL assay. RESULT: By light microscope, all of H&E stained placental explant tissue sections in normoxic and hypoxic culture showed intact villous integrities without definitive syncytial sloughing and fibrinoid necrosis as time elapsed. Tissue viability of LDH assay during 6, 24, 48, 72 hours of placental villous explants showed over all 52.3~67.6% and didn't show statistically significant difference between normoxic and hypoxic culture. Tissue viability in both groups maintained 61.2~67.6% for the first 24 hours and eventually decreased with time. TUNEL assay showed over all negative findings in normoxic and hypoxic culture at different time periods. CONCLUSION: In vitro human placental explant culture system can be a useful and feasible technique for research of placental hypoxia which is related to development of obstetrical complications such as preeclampsia, intrauterine fetal growth restriction and preterm labor and so on. But our in vitro placental explant system needs some modification in culture condition and technique for maximizing viability of the tissue.

Efficacy of erythropoietin in renal function of pre-dialysis patients with chronic renal failure / 대한내과학회지

BACKGROUND: Anemia is one of the most important risk factors for cardiovascular morbidity and mortality in patients with chronic renal failure. The most effective treatment modality for anemia is erythropoietin injection. Besides erythropoietic effect, erythropoietin has multiple beneficial effects such as anti-oxidant, anti-hypoxic, anti-apoptotic and vasculogenetic effects, and prevents tubular lesions and interstitial fibrosis. Despite lots of advantages of erythropoietin therapy, the number of patients treated with this agent is modest, particularly during the pre-dialysis chronic renal failure. We conducted a clinical trial to evaluate the effects of erythropoietin on renal function in the anemic pre-dialysis patients with chronic renal failure. METHODS: Data of 23 pre-dialysis patients with chronic renal failure were analyzed retrospectively 6 months prior, and prospectively 6 months after the initiation of erythropoietin therapy. Erythropoietin was admitted at a dose of 3000 IU weekly with supplementary iron. RESULTS: The average hematocrit and hemoglobin rose from 22.1+/-2.5%, 7.4+/-0.8 g/dL to 28.4+/-4.2%, 9.6+/-1.5 g/dL, respectively. When linear regression analysis was applied to pre- and post-erythropoietin glomerular filtration rate and 1/Cr, mean rate of decline of glomerular filtration rate were significantly delayed (p=0.039) but that of 1/Cr had a tendency to be delayed but was not statistically meaningful (p=0.099). CONCLUSIONS: Treatment of the anemia with low dose erythropoietin in pre-dialysis patients with chronic renal failure is relatively safe and may slow the rate of renal function deterioration.

Clinical significance of atypical glandular cells on Pap smear / 부인종양

OBJECTIVE: We determine the rate of an atypical glandular cells (AGC) on cervical cytology and the incidence of clinical significant lesion on subsequent follow up biopsies. In this study, we attempted to assess the clinical significance of a cytologic diagnosis of atypical glandular cells (AGC). METHODS: A total of 60,174 Pap smears were obtained between January 1st 2000 and December 31th 2005 at Ewha Womans University Mokdong Hospital. Among these smears, 26 patients had a diagnosis of AGC. Follow up was available for 23 patients (88.5%) and these patients had histologic follow up including cervical biopsy, endocervical curettage (ECC), and/or endometrial biopsy (EMB). RESULTS: Among 23 patients with AGC, eight (34.8%) were found to have a clinically significant malignant lesions on subsequent histologic follow up, including 2 endometrial adenocarcinoma cases, 1 cervical adenosquamous cell carcinoma case, 1 endocervical adenocarcinoma case, 2 vault adenocarcinoma cases, 1 MMMT case and 1 squamous cell carcinoma case. We found the differences in incidence of malignant lesions between premenopausal (23.5%) and postmenopausal (66.8%) patients with marginal significance (p=0.057). CONCLUSION: The incidence of AGC in Pap smear was 0.04%. The patients with AGC had a substantial risk of having a significant number of squamous or glandular, premalignant or malignant lesions. This study strongly suggests the need for the close follow up of patients with a diagnosis of AGC, especially in postmenopausal women.

Estimation of Body Height in Korean Elderly

BACKGROUND: Height is essential variable for assessing nutritional status, estimating glomerular filtration rate, and drug dosage besides in epidemiologic study. In old age, spinal deformity and thinning of the intervertebral discs may produce a spurious decrease in height. In the nonambulants, standard methods of height measurement may be impractical. The present study has been designed to predict the height using regression analysis by long bone measurement. METHODS: One hundred twelve persons in one elderly welfare facility were studied. Standing height was measured. Total arm length, upper arm length, forearm length, tibial length in erect and supine position were measured. A nomogram has been prepared from these data to predict height. RESULTS: Multiple regression analysis was used to measure relationship between measured height, age, sex, and each of the measured parameters. Among the parameters in the erect position, height was best predicted by erect tibial length(ETL)(p<0.01). Among the parameters in the supine position, height was best predicted by supine total arm length(STAL)(p<0.05). Estimation of height was calculated by linear regression analysis. Estimation of height(cm)=93.036+2.383 x ETL(cm)-0.233 x age-5.747 x sex(R2=.815). Estimation of height(cm)=87.985 + 1.775 x STAL(cm)-0.151 age-6.787 x sex(R2=.803). CONCLUSION: In the present study it has been shown that erect tibial length and supine total arm length may be a good predictor of total height. The nomogram may provide the prediction of height in the nonambulant elderly.

The clinical impact of the referral pattern to nephrologist in patients with chronic renal failure / 대한내과학회지

BACKGROUND: It has been speculated that many factors including age, hemoglobin serum albumin level and socioeconomic factors are closely related with the mortality and morbidity of patients with end-stage renal disease (ESRD). Optimal management of the patients with pre-dialysis chronic kidney disease has been thought to be very important for the prognosis of end-stage renal disease patients on dialysis. METHODS: In order to evaluate the clinical impact of referral pattern of chronic renal failure patients to nephrologist, 217 patients (male 129, female 88) who initiated hemodialysis from Jan. 1998 to Jul. 2002 in Chungnam National University Hospital were included in this retrospective analysis. Patients were defined as early referral (n=129) when hemodialysis was initiated at least 90 days after the first visit to nephrologist and as late referral (n=88) when hemodialysis was performed within 90 days after the first visit to nephrologist. RESULTS: Male gender and medical aid coverage were significantly more prevalent in late referral than early referral group (p<0.05, p<0.05, respectively). Late referral group had more combined medical problems than those of early referral group (p<0.05). Serum albumin level of early referral group was significantly higher than that of late referral group at the initiation of hemodialysis (p<0.001). At the initiation of hemodialysis, temporary central catheter for the blood access was needed in 85.2 % of late referral group. However, only 41.6% of early referral group needed such temporary catheter (p<0.001). One year after initiation of hemodialysis treatment, early referral group showed significantly lower mortality rate than that of late referral group (p<0.001). CONCLUSION: The early referral of chronic renal failure patients to nephrologist has beneficial effects including higher one-year survival after beginning of hemodialysis.