OBJECTIVE: To investigate the role of ERK and PPAR gamma on the TGF-beta1 induced human endometrial stromal cell decidualization in vitro. METHOD: Endometrial stromal cells are cultured under the following condition: DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4). TGF-beta1 (5 ng/ml), Rosiglitazone (50 nM), and PD98059 (20 microgram) were added according to experimental purposes. Trypan-Blue and hematocytometer were utilized to count cell number. Enzyme-linked immunosorbent assay (ELISA) and western blotting were utilized to detect proteins. RESULT: TGF-beta1 inhibited proliferation of cultured human endometrial stromal cells and induced expression of PGE2 and prolactin. This effect was mediated by Smad and ERK activation. Administration of rosiglitazone, PPAR gamma agonist, prevented TGF-beta1 effect on cell proliferation. Furthermore, Rosiglitazone inhibited TGF-beta1 induced activation of ERK, consequently reduced PGE2 and prolactin production. CONCLUSION: TGF-beta1 induced decidualization of endometrial stromal cell through Smad and ERK phosphorylation. PPAR gamma acts as a negative regulator of human endometrial cell decidualization in vitro.
Blotting, Western ; Cell Count ; Cell Proliferation ; Dinoprostone ; Enzyme-Linked Immunosorbent Assay ; Humans* ; Peroxisome Proliferator-Activated Receptors* ; Phosphorylation ; PPAR gamma ; Prolactin ; Stromal Cells* ; Transforming Growth Factor beta1*

BACKGROUND: LB03002[somatropin(rDNA origin) for injectable suspension] is a sustained release formulation of human growth hormone to be administered by once-a-week subcutaneous injections. Less frequent administration could provide a considerable improvement on compliance and convenience. OBJECTIVE: To determine the efficacy and safety of a LB03002 administered in children with GHD once weekly for 6 months. DESIGN: Open-label, active-controlled, randomised, parallel group, phase II study. PATIENTS: A total of forty-two naive or previously treated, pre-pubertal children with GHD, confirmed by two different GH provocation tests, were randomised and received either LB03002(0.3 or 0.5 mg/kg/week) or Eutropin(TM)(daily rhGH, 0.3 mg/ kg/week divided 6 times a week) for 6 months. RESULTS: The pre-treatment(HV0) and 6-month annualised height velocity(HV6) are shown(mean+/-SD) in the table below: ----------------------------------------------------------------------- LB03002 LB03002 EutropinTM 0.3 mg/kg/week 0.5 mg/kg/week 0.3 mg/kg/week ----------------------------------------------------------------------- N 10 13 13 HV0 3.1+/-1.0 3.9+/-1.5 3.0+/-1.1 HV6 9.3+/-2.3 10.2+/-2.3 11.1+/-2.5 ----------------------------------------------------------------------- Mean IGF-I and IGFBP-3 levels were significantly elevated from baseline values in all the study groups. LB03002 at all dose groups was safe and well tolerated. No clinically relevant adverse events or abnormal laboratory parameters were observed and there were no remarkable differences between groups or changes over time within groups regarding parameters for glucose and lipid metabolism including fasting glucose and haemoglobin A1c. Injection site reactions were mostly mild to occasionally moderate and resolved within 2 to 3 days post-dose without intervention. CONCLUSIONS: Treatment with LB03002 by weekly administration of the doses tested in the study resulted in comparable safety and efficacy to daily rhGH in pre-pubertal children with GHD.
Child* ; Compliance ; Fasting ; Glucose ; Growth Hormone* ; Human Growth Hormone* ; Humans* ; Injections, Subcutaneous ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Lipid Metabolism

PURPOSE: Neutropenia is common in patients receiving myelotoxic chemotherapy. The aim of this study is to compare the efficacy, safety and adverse events between prophylactically administered Leukokine and Grasin. METHODS: An open-label, randomized, phase III study was designed to compare the effects of a subcutaneous injection of Leukokine (CJ Corp.) 100mug/m2 with Grasin (Jeil Pharm. Inc.) in patients receiving induction chemotherapy for acute leukemia. All patients received one dose of G-CSF every day during the study period. Total period of G-CSF injection was not over 14 days. The administration of G-CSF began on day 14 after beginning of chemotherapy under CCG strategy. In other chemotherapies, the injection of G-CSF started on day 1 from end of chemotherapy. Injection of G-CSF stopped after absolute neutrophil count recovery was achieved. RESULTS: The median numbers of times of administration were 9.6 (2~14) /cycle for Leukokine and 8.8 (2~14) /cycle for Grasin. The time to needed for neutrophil recovery more than 1, 000/mm3 was 6.6 4.9 day and 4.7 4.8 day of the Leukokine and Grasin, respectively (P=0.14). The mean duration of neutropenia less than 500/mm3 was 7.6 5.6 days for Leukokine and 6.1 6.0 days for Grasin (P=0.28). The results for the two groups were also not significantly different in adverse events, physical examination and laboratory findings. CONCLUSION: Leukokine was safe and well tolerated in these patients population. Injection of Leukokine provided neutrophil recovery with safety and efficacy similar to that provided by Grasin.
Drug Therapy ; Granulocyte Colony-Stimulating Factor ; Humans ; Induction Chemotherapy* ; Injections, Subcutaneous ; Leukemia* ; Neutropenia ; Neutrophils ; Physical Examination

PURPOSE: The purpose of this study was to measure the strains of normal and lax anterior cruciate ligament (ACL) under serial loading using specially designed ACL strain analyzer (ASA) during arthroscopic examination. MATERIALS AND METHODS: The study is based on sixty-eight patients. Before the arthroscopic examination, all cases were divided into three groups according to their laxity based on Lachman test, KT2000 arthrometer, and magnetic resonance imaging. During arthroscopic examination, the ASA was connected with ACL using anteromedial portal with the knee flexed in 90. Under serial loading to ACL, the strains were illustrated and calculated. RESULTS: A statistically significant differences had been shown in strains between normal and lax ACL. Using ANOVA test, the ASA results according to preoperatively divided groups showed no significant differences between all groups and each loads. CONCLUSION: We had designed newly diagnostic method for estimate of ACL laxity, and measured the strains of lax ACL compared with normal ACL. This diagnostic method will be helpful to establish treatment plan for injuried ACL during arthroscopic examination.
Anterior Cruciate Ligament* ; Humans ; Knee ; Magnetic Resonance Imaging

OBJECTIVES: In order to investigate the maturational process of intracellular signal transduction system in rat brain, we studied the induction of the immediate early genes(IEGs)c-fos, junB, and TIS1 in each developmental stage after kainic acid(KA)induced seizure in young rat hippocampus and then compared these with the results after electroconvulsive shock(ECS) And to elucidate the induction mechanism of c-fos via mitogen-activated protein kinase(MAPK)by KA in each developmental stage, we investigated the phosphorylation of p42, p44 MAPK and Elk-1 after KA treatment in young rat hippocampus. METHODS: We examined the induction patterns of IEGs by northern blot analysis, and the phosphorylation of p42, p44 MAPK and Elk-1 by immunoblotting in rat hippocampus at post-natal day 7, 14, and 21(P7, P14 & P21) respectively after intraperitoneal injection of KA. RESULTS: Unlike ECS, KA did not induce c-fos, junB, and TIS1 in P7 hippocampus. But these genes were apparently induced at P14 and to an adult level at P21. These three IEGs showed similar temporal patterns of induction in each developmental stage. Although the basal level of phosphorylated 42p, 44p MAPK was considerable in P7 rat hippocampus, the increase of phosphorylation after KA treatment was observed at P14 . While the phosphorylation of Elk-1 was detected with high basal level in P7 rat, the amount of phosphorylated Elk-1 was not changed after KA treatment. CONCLUSION: Our results suggest that the differences in IEGs induction patterns between KA and ECS may be due to the differences in the activated signal transduction pathways. And our results also implicate that the signal transduction system involved in MAPK phosphorylation after KA treatment mature with aging and c-fos induction via MAPK activation may be regulated through some pathways other than Elk-1 in rat hippocampus.
Adult ; Aging ; Animals ; Blotting, Northern ; Brain ; Genes, Immediate-Early* ; Hippocampus* ; Humans ; Immunoblotting ; Injections, Intraperitoneal ; Kainic Acid* ; Mitogen-Activated Protein Kinase 3* ; Phosphorylation* ; Rats* ; Seizures ; Signal Transduction

PURPOSE: Thyroid disease is the most common endocrine disease in childhood. Thyroid hormone has critical effects on growth and development, especially in childhood. We survey the prevalence, sex and age distribution, symptoms and thyroid function states of thyroid diseases in childhood. METHODS: Three hundred ninety one children who were diagnosed as having thyroid disease at department of pediatrics, St. Mary's hospital from Jan. 1987 to Dec. 1998 enrolled in this study. RESULTS: 1) The ratio between male and female patients was 1: 5.3. Age distribution was puberty, school age and infancy in their order of frequency. 2) The results of thyroid function tests showed normal function in 210 cases (53.7%), increased function in 95 cases(24.3%), and decreased function in 86 cases (22%). 3) Simple goiter, Graves disease, and chronic lymphocytic thyroiditis were the most common diseases in euthyroid, hyperthyroid, and acquired hypothyroid state, respectively. 4) The most common sign and symptom was goiter in euthyroid(100%), hyperthyroid(98.8%) and acquired hypothyroid state(96.2%). Forty of 68 cases(58.8%) with congenital hypothyroidism were detected by neonatal screening. CONCLUSION: Simple goiter, chronic lymphocytic thyroiditis and Graves disease were common acquired thyroid diseases in childhood, and goiter is the most common clinical manifestation in acquired thyroid disease. Recently, increasing number of congenital hypothyroidism was detected by neonatal screening test.
Adolescent ; Age Distribution ; Child ; Congenital Hypothyroidism ; Endocrine System Diseases ; Female ; Goiter ; Graves Disease ; Growth and Development ; Hashimoto Disease ; Humans ; Infant, Newborn ; Male ; Neonatal Screening ; Pediatrics ; Prevalence ; Puberty ; Thyroid Diseases* ; Thyroid Function Tests ; Thyroid Gland*

BACKGROUND: Many studies indicated that the predictive accuracy of propofol TCI may be compromised by premedication with benzodiazepine which has been shown to reduce markedly the induction dose. This study was designed to examine the influence of midazolam premedication on certain parameters of treatment using the propofol TCI. METHODS: One hundred and sixty ASA I or II patients undergoing elective surgery were randomly allocated to two groups according to premedication: Group 1, glycopyrrolate 0.2 mg; Group 2, glycopyrrolate 0.2 mg and midazolam 0.07 mg/kg IM 1hr before induction. Each group divided to four subgroups (n=20 for each subgroup) according to expected target propofol concentration (4~7 microgram/ml for group 1 and 3~6 microgram/ml for group 2). Anesthesia induction within 3 min was considered as successful. Induction dose and time, success rate of induction, calculated concentration when successful induction, context sensitive decrement time when awakening concentration was 1.2 microgram/ml and side effects were checked. RESULTS: Successful induction rate was higher in group 2 (53.3% vs 77.8% at target concentration of 5 microgram/ml, P<0.05). Mean target concentration of propofol were lower in group 2 (5.18 vs 3.87 microgram/ml, P<0.05). Induction time and dose were decreased 48.4% and 36.8% at target concentration of 4 g/ml, respectively in group 2 (P<0.05). Vital signs, average pain score and incidence of pain showed no differences between groups, but incidence of apnea was significantly increased in group 2 (P<0.05). CONCLUSION: Group 2 showed better quality of propofol induction using a TCI in terms of induction time, induction dose and lower selected target without significant vital sign changes, but showed increased incidence of apnea compared with group 1.
Anesthesia ; Apnea ; Benzodiazepines ; Glycopyrrolate ; Humans ; Incidence ; Midazolam* ; Premedication* ; Propofol* ; Vital Signs

Epinephrine ; Pulmonary Edema

PURPOSE: We planned to evaluate the toxicity and efficacy of DA-3030 to determine the recommended dose for phase III clinical trial based on the biologically active doses from phase I/II clinical trial. MATERIALS AND METHODS: Open non-randomized phase I/II study was carried out in 64 cancer patients with chemotheray-induced myelosuppression. After 1 cycle of control period (chemotherapy without DA-3030), DA-3030 was started 24 hours after the second cycle of chemotherapy to 4 groups of patients with the doses of 50 microgram/m2/day (step I), 100 microgram/m2/day (step II), 150 microgram/m2/day (step III), 200microgram/m2/day (step IV) by once-a-day subcutaneous administration for 10 days. RESULTS: Of the 64 enrolled patients, 46 patients were evaluable. Tmax reached after 2 hours of injection in step I and 4 hours in step II-IV. Terminal half life was 1.8 hours in step I and 3.2 hours in step II, 3.3 hours in step III, 3.0 hours in step IV. Area under the curve (AUC) and AUMC increased dose dependently from step I through step IV. Total clearance rate decreased in a dose dependent manner but the volume of distribution showed no differences between the steps.The mean nadir count of total WBC and neutrophil increased in all 4 steps of DA-3030 administration. Also the duration of leukopenia, equal to or less than 2,000/uL or neutropenia and the recovery time of WBC or neutrophil from nadir decreased with DA-3030 administration in all 4 steps. But no differece of DA-3030 effect was found among 4 steps. When we compared the clinical efficacy of DA-3030 with total WBC and neutrophil criteria, it was 58.3% and 58.3% in step I, 90.0% and 80.0% in step II, 91.7% and 91.7% in step III, 75.0% and 70.0% in step IV. Although the duration of antibiotics administration showed no difference between control and DA-3030 administration period in step I, it decreased with DA-3030 administration in step II-IV. Infection was found only in step I. Life-threatening side effect was not found in all steps. Only mild myalgia was found without any dose relationship. CONCLUSION: When we considered the efficacy, toxicity and pharmacokinetic parameters, we suggest that 100microgram/m2 is an appropriate dosage for the phase III clinical trial.
Anti-Bacterial Agents ; Drug Therapy* ; Half-Life ; Humans ; Leukopenia ; Myalgia ; Neutropenia* ; Neutrophils

Central retinal artery occlusion occurs rarely as a complication of spine surgery under general anesthesia in prone position, but is quite tragic. The suggested causes are hypotension during anesthesia and increased external ocular pressure by headrest, sand bag or others. We experienced a case of left central retinal artery occlusion following cervical spine surgery under general anesthesia using a horseshoe headrest. The patient was 53 years old male whose medical history was non remarkable except dislocation of cervical spine. He was positioned prone after induction. The vital signs were stable during opreration. At the recovery room, he presented left visual field disturbance and investigations revealed that left central retinal artery occlusion occured. This case demonstrates that proper positioning of the head on an adequate head rest and contineous cautious inspection during surgical procedure are important to prevent retinal damage.
Anesthesia ; Anesthesia, General* ; Dislocations ; Head ; Humans ; Hypotension ; Male ; Middle Aged ; Prone Position* ; Recovery Room ; Retinal Artery Occlusion* ; Retinal Artery* ; Retinaldehyde ; Silicon Dioxide ; Spine* ; Visual Fields ; Vital Signs