ABSTRACT
Glucuronidation by the uridine diphosphateglucuronosyltransferase 1A enzymes (UGT1As) is a major pathway for elimination of particular drugs and endogenous substances, such as bilirubin. We examined the relation of eight single nucleotide polymorphisms (SNPs) and haplotypes of the UGT1A gene with their clinical factors. For association analysis, we genotyped the variants by direct sequencing analysis and polymerase chain reaction (PCR) in 218 healthy Koreans. The frequency of UGT1A1 polymorphisms, -3279T>G, -3156G>A, -53 (TA)(6>7), 211G>A, and 686C>A, was 0.26, 0.12, 0.08, 0.15, and 0.01, respectively. The frequency of -118 (T)9>10 of UGT1A9 was 0.62, which was significantly higher than that in Caucasians (0.39). Neither the -2152C>T nor the -275T>A polymorphism was observed in Koreans or other Asians in comparison with Caucasians. The -3156G>A and -53 (TA)6>7 polymorphisms of UGT1A were significantly associated with platelet count and total bilirubin level (p=0.01, p=0.01, respectively). Additionally, total bilirubin level was positively correlated with occurrence of the UGT1A9-118 (T)(9>10) rare variant. Common haplotypes encompassing six UGT1A polymorphisms were significantly associated with total bilirubin level (p=0.01). Taken together, we suggest that determination of the UGT1A1 and UGT1A9 genotypes is clinically useful for predicting the efficacy and serious toxicities of particular drugs requiring glucuronidation.
Subject(s)
Humans , Asian People , Bilirubin , Genotype , Haplotypes , Platelet Count , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Single Nucleotide , UridineABSTRACT
OBJECTIVE: The involvement of IGF system in hyperandrogenism and abnormal follicular development is controversial. This study is to assess whether IGF system contribute to it in the women with polycystic ovary(PCO). METHODS: Baseline serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone (T), androstenedione (ADD), prolactin, thyroid stimulating hormone (TSH), free insulin-like growth factor(IGF)-I, free IGF-II, insulin-like growth factor binding protein(IGFBP)-1, and IGFBP-3 were measured in twelve healthy regularly cycling volunteers and forty-two women with PCO then, the changes of baseline serum levels were evaluated after laparoscopic ovarian electrocauterization in nine PCO patients. In addition, the expression pattern of IGF-I and IGF-II was examined in the ovary of control and PCO group. RESULTS: Baseline levels of LH, ADD, free IGF-II, and IGFBP-3 were significantly higher in PCO group. However, there were no significant differences in the levels of free IGF-I and IGFBP-1, although free IGF-I showed decreasing tendency in PCO group. And there was a significant positive correlation between the LH and free IGF-II level in the PCO(P=0.011, r2=0.3899), but not in the control. After ovarian electrocauterization, LH, T, and ADD levels decreased, and free IGF-I and IGFBP-3 level increased. While free IGF-II and IGFBP-1 level showed no significant changes. In the ovary, expression of both IGFs showed similar pattern in normal and PCO ovaries. CONCLUSIONS: The elevated IGFBP-3 level may alter the bioavailability of IGF(s) in the PCO. The change in IGF-I level and resumption of ovulation after electrocauterization, suggest a possible role of IGF system in the impairment of follicular development in the PCO.
Subject(s)
Female , Humans , Androstenedione , Biological Availability , Carrier Proteins , Estradiol , Follicle Stimulating Hormone , Hyperandrogenism , Insulin-Like Growth Factor Binding Protein 1 , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor I , Insulin-Like Growth Factor II , Luteinizing Hormone , Ovary , Ovulation , Prolactin , Somatomedins , Testosterone , Thyrotropin , VolunteersABSTRACT
OBJECTIVES: To study the distributions of pH and gas values in umbilical arterial(UA) blood of normal newborns following uncomplicated pregnancies and vaginal births. Methods: In 457 consecutive normal term infants who were born between March 1995 and June 1998, we examined the UA pH and blood gas values obtained immediately following delivery. Maternal inclusion criteria were defined as an uncomplicated singleton pregnancy and a normal full term spontaneous vaginal delivery. And also neonatal inclusion criteria were defined as a normal intrauterine growth appropriate for gestational age without any malformations and Apgar score of 7 or more at both one and five minutes after birth. Umbilical artery blood samples were collected at each birth and were evaluated for pH, carbon dioxide pressure (PaCO2), oxygen pressure (PaO2) and actual bicarbonate. RESULTS: Histogram of UA pH value resemble normal distribution curve. The lowest UA pH was 7.04 and the 10th percentile value was 7.23. The median UA pH was 7.31 and 5% was below 7.20. The lowest UA PaO2 was 4.6mmHg and the 10th percentile value was 11.5mmHg. The highest UA PaCO2 was 67.2mmHg and the 90th percentile value was 56.5mmHg. The lowest bicarbonate value was 13.2mmol/L and the 10th percentile value was 18.4mmol/L. CONCLUSION: The distributions of the UA pH and gas values of the collective of normal newborns were illustrated. None of the UA pH was below 7.0.
Subject(s)
Humans , Infant , Infant, Newborn , Pregnancy , Apgar Score , Blood Gas Analysis , Carbon Dioxide , Gestational Age , Hydrogen-Ion Concentration , Oxygen , Parturition , Umbilical ArteriesABSTRACT
OBJECTIVE: The ovarian cycle is characterized by repeating patterns of cellular proliferation and differentiation that accompany follicular development and the formation and regression of the corpus luteum (CL). That angiogenesis may play an important role in this process. Angiogenesis is supposed to be regulated by vascular endothelial growth factor (VEGF). The goal of the present investigation, therefore, was to determine whether the expression of VEGF was changed in the normally cycling human ovary. We also investigated VEGF expression in the regressed CL (ie, nonfunctiong CL) of normal term pregnancy to define the association with steroidogenic activity. To our knowledge there is no report available on VEGF expression in the CL of term pregnancy. METHODS: We assessed VEGF expression in ovaries obtained from, 26-42 yr of age, and from patients undergoing hysterectomy and salpingo-oophorectomy for nonendocrinological or nonovarian disorders. Tissue samples from premenopausal women included specimens from follicular (n=4) and luteal (n 4) phases. In addition, we studied ovarian specimens from pregnant women (n=3). Immunohistochemical analysis for VEGF was performed using a rabbit polyclonal antibody directed against human VEGF. RESULTS: These data demonstrate a development-related VEGF expression in the follicle and indirectly show that VEGF expression may be up to the existence of LH-receptor. And also, VEGF was overexpressed in the regressed CL of pregnant women compared with the functioning CL of nonpregnant cycles CONCLUSION: This study suggests that the intensity of VEGF expression is not correlated with steroidogenic activity, although both of them are stimulated by LH.
Subject(s)
Female , Humans , Pregnancy , Cell Proliferation , Corpus Luteum , Hysterectomy , Menstrual Cycle , Ovarian Follicle , Ovary , Pregnant Women , Vascular Endothelial Growth Factor AABSTRACT
To evaluate the clinical efficacy of emergency cervical cerclage in the treatment of advanced cervical incompetence, a prospective clinical trial was performed in 18 patients with advanced cervical incompetence at 20 to 25 weeks gestation. Modified McDonalds operation with or without transabdominal amniocentesis was used for cervical cerclage. Pregnancy was prolonged for a sufficient time to deliver viable fetuses in 56.3% of patients. The median procedure-to-delivery interval was 8.6 (range 0.1 to 20.5) weeks for the entire group, and 13.9 (range 6.5 to 20.5) weeks for 9 patients who achieved live birth. The median gestational age at delivery was 38.6 (range 28.3 to 41.0) weeks for the live infants. The median birthweight of the live infants was 3062 g (range 1050 to 3620 g). The lack of significant matemal morbidity combined with the results for the fetus-infant supports further efforts in this area.
Subject(s)
Humans , Infant , Pregnancy , Amniocentesis , Cerclage, Cervical , Emergencies , Fetus , Gestational Age , Live Birth , Prospective StudiesABSTRACT
Normal and abnormal follicular growth and steroidogenesis depend on gonadotropins as well as intraovarian peptides, which may mediate or potentiate gonadotropin action. Inhibin also affect follicular development and steroidogenesis and may play a role in dominant follicle selection and follicular atresia. Therefore, we studied the differences of serum inhibin, gonadotropin and androgen levels in the women with only the ultrasound findings and no disorder, and polycystic ovary (PCO) with ovulatory disturbance. We prospectively analysed forty-three women with PCO. The diagnosis of PCO was based on typical appearance of the ovaries on TVS. Twelve women with regular menstrual cycle and normal ovarian morphology were selected as control. Basal levels of inhibin, luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), testosterone(T), androstenedione(ADD), dehydroepiandrosterone-sulfate(DS), prolactin and TSH in serum were determined. There were significant differences in basal LH levels and LH/FSH ratio between the control and the women with PCO. The basal levels of inhibin and E2 in the oligo-amenorrheic PCO (N=34) were significantly higher than those in the control. There was higher negative correlation between the inhibin and T levels in the oligo-amenorrheic PCO, but, not in the regular cycling PCO. Also, there was higher positive correlation between the LH and T levels in the oligo-amenorrheic PCO, but not in the regular cycling PCO. These data presume that the initial event of PCO is elevated pituitary LH secretion. Elevated levels of LH may down-regulate LH receptors on granulosa cells and also cause hypertrophy of the thecal layer. High level of androgen secreted by the hypertrophied thermal layer may stimulate inhibin secretion from granulosa cells and can be converted to estrogen by extraovarian tissues and could serve to augment pituitary sensitivity to GnRH with a resultant secretion of more LH follicular development and dominant follicle selection resulted in ovulatory disturbance.
Subject(s)
Female , Humans , Diagnosis , Estrogens , Follicular Atresia , Gonadotropin-Releasing Hormone , Gonadotropins , Granulosa Cells , Hypertrophy , Inhibins , Lutein , Menstrual Cycle , Ovary , Peptides , Prolactin , Prospective Studies , Receptors, LH , UltrasonographyABSTRACT
The association of major fetal malformations with amniotic bands has been known for many years. However, we are apt to ignore the possibility of amniotic band syndrome. In this case, fetal anencephaly was diagnosed at 17 weeks, menstrual age on the basis of sonographic findings. Following pregnancy termination, examination of the abortus rev- ealed the cerebral remnant which is similar to that found in dysraphic anencephaly, but collateral evidence of amniotic band was found. Therefore, when confronted with severe cranial or cerebral malformation amniotic band syndrome should be in the differential dia- gnosis.
Subject(s)
Infant, Newborn , Pregnancy , Amniotic Band Syndrome , Anencephaly , Skin , UltrasonographyABSTRACT
Thiamine deficiency is known to lead to certain neurological sequelae including Wernicke-Korsakoff syndrome. Signs attributable to this condition include ataxia, ophthalmoplegia, nystagmus, and mental confusion. The prompt use of thiamine prevents progression of the disease and reverses those lesions that have not yet progressed to the point of fixed structual change. We have experienced a case of Wernicke-Korsakoff syndrome associated with hyperemesis gravidarum, which seemed to be developed by prolonged thiamine-free dextrose therapy, we emphasise the need for thiamine supplementation in hyperemesis gravidarum patient.
Subject(s)
Female , Humans , Pregnancy , Ataxia , Glucose , Hyperemesis Gravidarum , Korsakoff Syndrome , Ophthalmoplegia , Thiamine , Thiamine DeficiencyABSTRACT
Recent evidence suggests that a high level of serum LH during follicular recruitment and development is associated with poor reproductive outcome. Consequently, exogenous LH administration for controlled ovarian hyperstimulation(COH) in in vitro fertilization and embryo transfer(IVF-ET) may be harmful to folliculogenesis. The purpose of this clinical study was to evaluate and compare the efficacy of human menopausal gonadotropin(hMG) and human follicle-stimulating hormone(hFSH) for COH with long protocol of gonadotropin-releasing hormone(GnRH) agonist in IVF-ET program. Randomized clinical trial was performed in 125 patiens undergoing IVF-ET at Seoul National University Hospital from May to Septebmer, 1995. The inclusion criteria of patients included age < 40 years and normal semen analysis, and the study population was also classified into two groups by the etiology of infertility : Group T - 95 patients with only tubal factor and Group O - 30 patients with endometriosis or anovulatory factor. There were no statistically significant differences in dosage(29.0+/-7.9 vs 26.0+/-6.8 ampoules) and duration(12.3+/-1.3 vs 12.2+/-1.5 days) of gonadotropin administration, serum E2 level on hCG day(1,943+/-1,255 vs 1,580+/-1,067 pg/mL), cancellation rate(7.5% vs 6.7%), number of oocytes retrieved(9.9+/-6.0 vs 11.3+/-6.0), fertilization rate(68.4% vs 64.5%), number of embryos transferred(4.7+/-2.0 vs 4.7+/-2.0), and preganancy rate per cycle(26.3% vs 24.4%) and per ET(28.4% vs 26.2%) between hMG(N=80) and hFSH(N=45) Groups. In Group T, no significant differnces in results of IVF-ET were also detected between hMG (N=61) and hFSH(N=34) Groups. In Group O, serum E2 level on hCG day was significantly higher in hMG Group (N=19) compared with hFSH Group(N=11), but other results of IVF-ET were similar in both Groups. As this study could not demonstrate any significant differences in results of IVF-ET between hMG and hFSH when used for COH in IVF-ET program, it could be concluded that hFSH is at least as efficacious as hMG for COH.
Subject(s)
Female , Humans , Embryo Transfer , Embryonic Structures , Endometriosis , Fertilization , Fertilization in Vitro , Follicle Stimulating Hormone , Follicle Stimulating Hormone, Human , Gonadotropins , Infertility , Oocytes , Semen Analysis , SeoulABSTRACT
Women with Polycystic ovaries(PCO) are often overweight and obesity has been regarded as a possible basis for the development of PCO. This study was designed to evaluate the differences of the basic hormonal concentrations and sonographic features in obese and non-obese patients with PCO. We prospectively analysed eighty-six patiens with PCO on transvaginal sonography and twelve control women with regular menstrual cycle and ovarian morphology from Feb. 1994 to May 1996. Eighty-six women with PCO, of whom sixty-seven women were non -obese with body mass index(BMI) of 25(=group 2). Sonographic morphology of ovary was evaluated in PCO. Basal concent- rations of LH, FSH, estrone, estradiol, testosterone(T), prolactin, TSH and sex hormone- binding globulin(SHBG) in serum were measured. Although sonographic morphology of ovary was not significantly different between group 1 and group 2, number of small follicles was tend to increase in group 2. The LH/ FSH ratio was significantly higher in group 1 compared to group 2, but SHBG was higher in group 2. Conclusively, in obese women, obesity causes an increase in free androgen through the decrease in SHBG, which might cause a disturbance in gonadotropin secretion leading to the typical changes of polycystic ovary. In non-obese women, relative increase of LH/FSH ratio stimulates excessive production of androgen.
Subject(s)
Female , Humans , Body Mass Index , Estradiol , Estrone , Gonadotropins , Menstrual Cycle , Obesity , Ovary , Overweight , Prolactin , Prospective Studies , UltrasonographyABSTRACT
Pregnancy maintenance is dependent on the presence of a functional corpusluteum (CL) for a few weeks after implantation. However, the factors responsible for the rescue of the CL during earlypregnancy have not been fully clarified. This study was designed to evaluate whether the change in size of the CL ofearly pregnancy, serum concentration of progesterone, 17alpha-hydroxyprogesterone,or beta-hCG correlated with the gestational age or were predictive of pregnancyoutcome. We retrospectively analysed thirty-six women between 4~9 weeks' gestation. All women underwent transvaginal ultrasound measurement of the CL size andgestational sac(or crown-rump length). Blood was drawn from each patient on the day of the ultrasound examinationto measure hormone concentration. Fifteen women experienced vaginal bleeding and abdominal pain.Among them, four women were aborted. There was no significant positive correlation between CL size and serumprogesterone, 17alpha-hydroxyprogesterone or beta-hCG both in normal and abnormal pregnancy. A positive correlation was observed between the gestational age and progesterone orbeta-hCG in normal pregnancy, but not in abnormal pregnancy(threatened or spontanousabortion). In conclusion, close correlation between the gestational age and serum concentrationof progesterone or beta-hCG may reflect the normal function of CL. Therefore, abnormal response of CL or abnormal production of beta-hCG cause a disturbancein progesterone secretion leading to the abnormal pregnancy.
Subject(s)
Female , Humans , Pregnancy , Corpus Luteum , Gestational Age , Pregnancy Maintenance , Progesterone , Retrospective Studies , Ultrasonography , Uterine HemorrhageABSTRACT
Pregnancy maintenance is dependent on the presence of a functional corpusluteum (CL) for a few weeks after implantation. However, the factors responsible for the rescue of the CL during earlypregnancy have not been fully clarified. This study was designed to evaluate whether the change in size of the CL ofearly pregnancy, serum concentration of progesterone, 17alpha-hydroxyprogesterone,or beta-hCG correlated with the gestational age or were predictive of pregnancyoutcome. We retrospectively analysed thirty-six women between 4~9 weeks' gestation. All women underwent transvaginal ultrasound measurement of the CL size andgestational sac(or crown-rump length). Blood was drawn from each patient on the day of the ultrasound examinationto measure hormone concentration. Fifteen women experienced vaginal bleeding and abdominal pain.Among them, four women were aborted. There was no significant positive correlation between CL size and serumprogesterone, 17alpha-hydroxyprogesterone or beta-hCG both in normal and abnormal pregnancy. A positive correlation was observed between the gestational age and progesterone orbeta-hCG in normal pregnancy, but not in abnormal pregnancy(threatened or spontanousabortion). In conclusion, close correlation between the gestational age and serum concentrationof progesterone or beta-hCG may reflect the normal function of CL. Therefore, abnormal response of CL or abnormal production of beta-hCG cause a disturbancein progesterone secretion leading to the abnormal pregnancy.
Subject(s)
Female , Humans , Pregnancy , Corpus Luteum , Gestational Age , Pregnancy Maintenance , Progesterone , Retrospective Studies , Ultrasonography , Uterine HemorrhageABSTRACT
Doppler sonography has been introduced to evaluate uterine and ovarian diseases. It has been reported to be used to distinguish benign from malignant adnexal masses. The purpose of this study was to assess the blood flow characteristics of adnexal masses and to determine the optimal cut-off points for the Doppler indices obtained, resistance index and pulsatility index, to best differentiate benign from malignant lesions. We performed pulsed Doppler ultrasound in seventy-eight adnexal masses between February 1989 and June 1994. The pulsatility and resistance index were calculated from the waveforms generated from blood flow within the ovary. There were 51 benign and 27 malignant histologically proved ovarian lesions. All women have been operated on. The results were as follows ; Benign tumors and cysts had a significantly higher pulsatility index(mean, 1.23+/-0.74; range, 4.46-3.36) and resistance index(mean, 0.64+/-0.19; range 0.34-1.43) than did malignant tumors(pulsatility index : mean, 0.87+/-0.49; range, 0.31-2.27; resistance index : mean, 0.50+/-17; range, 0.23-0.8). However, some overlap in individual values for benign and malignant lesions was found. In conclusion, our data suggest that high pulsatility and resistance indices may indicate benign adnexal masses ; however, considerable overlap in pulsatility and resistance indices between benign and malignant lesions were noted, and further work will be needed before the validity of these factors is proved.
Subject(s)
Female , Humans , Ovarian Diseases , Ovary , UltrasonographyABSTRACT
The recent introduction of chemotherapy in the treatment of gynecological malignancies has gained wide acceptance along with prstoperative and prostperative adjuvant therapy and with preradiation and concurrent chemoradiation therapy. But, the side effects of chemotherapy including bleeding and infection due to, bone marrow suppression have reaulted in delayed treatment and a reduction in the chemotherspeutic agent used. Recent efforts overcome this bone marrow suppression have led to development of the various human colony-stimulating factor indluding recombinant granulocyte colony-stimulating factor. The author investigated the clinical benefita and toxicity of G-CSF used during chemotherapy of various gynecological malignancies at the Departent of Obstetrics & Gynecology at Hanyang University between August, 1991 and July, 1992. The results were as follows ; 1. An increase in the number of neutrophils following a single injection of G-CSF was noted in 19 out of 21 cases(600~1,000/mm3 before injection, 4,500~12,000/mm3 after injection). The remaining 2 cases showed an increase after 3~5 continuous injections. 2. To assess the increase in neutrophils according to the dosage of G-CSF given, 100 and 300microgram/m* of G-CSF were injected in each trial of chemotherapy in a single case of ovarian cancer. The results were a 1.5 time increase when injected when injected with 300microgram/m*. 3. After injecting into a patient with recurrent endometrial cancer who was managed with 15gm of ifosfamide, 50gm of cis-platinum, 50gm of adriamycin and 3gm of mesna following surgery, no evidence of neutropenia could be found after 4days of prophylactic G-CSF injections. 4. Patients with cervix cancer with metastasis to the lung were first treated with GM-CSF in one trial and G-CSF in the nest. Patients treated with Gm-CSF for a period of 7 days showed leukocytosis(3,600/mm3) but the number was reduced to 1,400/mm3 after 7 days. On the other hand, patients treated with G-CSF showed an increase of 5,700/mm3 within one day and this figure did not decrease until 20 days later. 5. The toxic effects of G-CSF included on case of severe back pain was easily managed by administration acetaminophen. Others were headache, chills, general weakness and redness of the oral mucosa and injection area. Most of these symptoms disappeared within 2 days. The G-CSF is effective in neutropenia during chemotherapy thereby decreasing the incidence of treatment delay or dose reduction. It also increases the amount of chemotherapeutic agent administered and its toxicity is more tolerable making a rigid systemic chemotherapeutic regime possible.