OBJECTIVE: Antidepressants are known to positively influence several factors in patients with depressive disorders, resulting in increased neurogenesis and subsequent relief of depressive disorders. To study the effects of venlafaxine during neural differentiation at the cellular level, we looked at its effect on protein expression and regulation mechanisms during neural differentiation. METHODS: After exposing NCCIT cell-derived EBs to venlafaxine during differentiation (1 day and 7 days), changes in protein expression were analyzed by 2-DE and MALDI-TOF MS analysis. Gene levels of proteins regulated by venlafaxine were analyzed by real-time RT-PCR. RESULTS: Treatment with venlafaxine decreased expression of prolyl 4-hydroxylase (P4HB), ubiquitin-conjugating enzyme E2K (HIP2) and plastin 3 (T-plastin), and up-regulated expression of growth factor beta-3 (TGF-beta3), dihydropyrimidinase-like 3 (DPYSL3), and pyruvate kinase (PKM) after differentiation for 1 and 7 days. In cells exposed to venlafaxine, the mRNA expression patterns of HIP2 and PKM, which function as negative and positive regulators of differentiation and neuronal survival, respectively, were consistent with the observed changes in protein expression. CONCLUSION: Our findings may contribute to improve understanding of molecular mechanism of venlafaxine.
Antidepressive Agents ; Depression ; Depressive Disorder ; Humans ; Neurogenesis ; Neurons ; Prolyl Hydroxylases ; Proteomics ; Pyruvate Kinase ; RNA, Messenger ; Venlafaxine Hydrochloride

BACKGROUND: Cefcapene pivoxil hydrochloride (CFPN-PI) is an oral ester cephalosporin antibiotic with a broad spectrum. In this study, we investigated the pharmacokinetics (PK) and tolerability of CFPN-PI following single oral administration in healthy Korean subjects. METHODS: An open label, dose escalation, parallel group study was conducted in 18 healthy male volunteers. A single dose of CFPN-PI was administered to 6 subjects in each treatment group of 100, 150 and 200 mg. Serial blood and urine samples were collected up to 12 h and 24 h after dosing, respectively. Plasma and urine concentrations of cefcapene were measured by HPLC-UV. PK parameters were estimated using non-compartmental analysis. For the safety evaluation, adverse event monitoring, clinical laboratory tests and physical examination were performed throughout the study. RESULTS: Median values of time to peak plasma concentration were observed around 1.5 to 2.0 h. Maximum plasma concentrations (Cmax) were 1.04 +/- 0.22, 1.24 +/- 0.46 and 1.56 +/- 0.43 mg/L (mean +/- SD), and area under the plasma concentration time curve (AUCinf) were 2.94 +/- 0.46, 3.97 +/- 1.28 and 4.70 +/- 1.19 h*mg/L in 100, 150 and 200 mg dose groups, respectively. The differences of dose normalized Cmax and AUCinf among three groups were not statistically significant. The fractions of drug excreted in urine unchanged were 31.5 % - 42.9 %. There were no serious adverse events or clinically significant abnormalities related to CFPN-PI. CONCLUSION: CFPN-PI was well tolerated with single oral administration and showed a linear PK property within 100 - 200 mg in healthy Korean male subjects.
Administration, Oral* ; Humans ; Male ; Pharmacokinetics ; Physical Examination ; Plasma

BACKGROUND: Exaggerated blood pressure (BP) response to exercise can be an independent risk factor for cardiovascular mortality and morbidity. The purpose of this study was to define the factor that effect on early systolic BP response to exercise. METHODS: We examined echocardiographic data, BP, heart rate from graded exercise test and brachial ankle pulse wave velocity (PWV) of 205 patients (137 men and 68 women; mean age 58 +/- 11 years; range, 19 to 83 years). Graded exercise test was conducted in BRUCE protocol. We define delta systolic blood pressure (SBP) as systolic BRUCE stage "n" BP minus baseline BP. RESULTS: Resting BP (127 +/- 16 mm Hg) was elevated to 171 +/- 26 mm Hg after peak graded exercise test. Resting heart rate (80 +/- 15 bpm) was increased to 146 +/- 27 bpm after peak graded exercise test. Stepwise regression test between baseline SBP, delta SBP, maximal SBP and left atrial volume index (LAVI) was done. Supine SBP, delta SBP, maximal SBP was not associated with LAVI (p > 0.5). But increased LAVI was significantly associated with delta SBP1 in woman (R2 = 0.192, p = 0.002). PWV was significantly associated with base line (R2 = 0.311, p < 0.01) and maximal SBP (R2 = 0.051, p < 0.01). However, PWV was not associated with delta SBP. CONCLUSIONS: LAVI and PWV were not associated with early SBP response to exercise. But in women, elevation of early SBP during exercise is associated with LAVI.
Blood Pressure* ; Exercise Test* ; Female ; Heart Rate* ; Heart ; Humans ; Male ; Pulse Wave Analysis* ; Risk Factors

BACKGROUND: Eplerenone is a selective mineralocorticoid receptor antagonist which effectively blocks mineralocorticoid receptors in various tissues throughout the body. The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients post acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The aim of this study was to evaluate pharmacokinetic characteristics and tolerability after multiple oral administration of eplerenone 100 mg for 7 days in healthy Korean volunteers. METHODS: A double-blind, randomized, placebo-controlled, parallel study was conducted in 22 healthy Korean subjects. Healthy males and females between age of 20 and 55 years were enrolled. Each subject received 100 mg eplerenone (N=16) or placebo (N=6) for 7 days. Blood samples for pharmacokinetic parameter determination on day 7 were collected pre-dose and up to 36 hours after last drug administration. Adverse events were reported throughout the treatment period. RESULTS: The steady-state concentration of eplerenone reached after multiple administration of eplerenone 100 mg for 7 days. The mean eplerenone Cmax of 1620.1 ng/mL was obtained at 1.0 hour (range 0.5 to 2 hours). The mean AUC0-24h,ss at day 7 was 8763.6 ng/mL*h. The mean oral clearance and mean terminal half-life of eplerenone were 13.0 L/h and 3.4 hours. There were some drug-related mild adverse events after eplerenone administration, but all adverse events recovered without any treatment. CONCLUSION: In this study, the pharmacokinetic parameters after multiple oral doses of eplerenone 100 mg for 7 days were evaluated and eplerenone at these doses were well tolerated in healthy Korean subjects.
Administration, Oral ; Female ; Half-Life ; Heart Failure ; Humans ; Male ; Myocardial Infarction ; Receptors, Mineralocorticoid ; Spironolactone ; Ventricular Dysfunction, Left

PURPOSE: Insular carcinoma is a rare subtype of thyroid cancer which was first described by Carcangiu in 1984. Its aggressiveness is intermediate between well differentiated and anaplastic thyroid carcinoma. But its origin, clinical features and prognosis are not yet clearly understood. We wanted to evaluate the clinical features, histologic characteristics and prognosis of insular thyroid carcinoma. METHODS: We studied 4 cases of insular thyroid carcinoma treated in Samsung Medical Center from March 1996 to April 1998. Age, sex, clinical features, treatment, pathology and follow up findings were reviewed, retrospectively. RESULTS: All patients were female and the mean age was 44 years. Three of all patients complained of anterior neck mass and one patient complained of low back pain and paresthesia of the right thigh. Two patients had metastatic bone lesions at the time of diagnosis. Preoperative fine needle aspiration cytology diagnosed follicular neoplasm in 2 cases and papillary carcinoma in 1. We performed total or completion total thyroidectomy and radioactive iodine therapy in 3 cases and radioactive iodine therapy alone in one. Extrathyroidal invasion, vascular invasion and multicentricity were noted in two cases. All four patients showed recurrence or distant metastasis in follow up over a period of 10 to 31 months and 2 of them died of distant metastasis during this follow up period. CONCLUSION: Insular carcinoma is a special type of thyroid carcinoma with aggressive clinical course. Recurrence and extrathyroidal involvements are common and the prognosis is poorer than other well differentiated thyroid carcinomas.
Biopsy, Fine-Needle ; Carcinoma, Papillary ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Iodine ; Low Back Pain ; Neck ; Neoplasm Metastasis ; Paresthesia ; Pathology ; Prognosis ; Recurrence ; Retrospective Studies ; Thigh ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

PURPOSE: Insular carcinoma is a rare subtype of thyroid cancer which was first described by Carcangiu in 1984. Its aggressiveness is intermediate between well differentiated and anaplastic thyroid carcinoma. But its origin, clinical features and prognosis are not yet clearly understood. We wanted to evaluate the clinical features, histologic characteristics and prognosis of insular thyroid carcinoma. METHODS: We studied 4 cases of insular thyroid carcinoma treated in Samsung Medical Center from March 1996 to April 1998. Age, sex, clinical features, treatment, pathology and follow up findings were reviewed, retrospectively. RESULTS: All patients were female and the mean age was 44 years. Three of all patients complained of anterior neck mass and one patient complained of low back pain and paresthesia of the right thigh. Two patients had metastatic bone lesions at the time of diagnosis. Preoperative fine needle aspiration cytology diagnosed follicular neoplasm in 2 cases and papillary carcinoma in 1. We performed total or completion total thyroidectomy and radioactive iodine therapy in 3 cases and radioactive iodine therapy alone in one. Extrathyroidal invasion, vascular invasion and multicentricity were noted in two cases. All four patients showed recurrence or distant metastasis in follow up over a period of 10 to 31 months and 2 of them died of distant metastasis during this follow up period. CONCLUSION: Insular carcinoma is a special type of thyroid carcinoma with aggressive clinical course. Recurrence and extrathyroidal involvements are common and the prognosis is poorer than other well differentiated thyroid carcinomas.
Biopsy, Fine-Needle ; Carcinoma, Papillary ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Iodine ; Low Back Pain ; Neck ; Neoplasm Metastasis ; Paresthesia ; Pathology ; Prognosis ; Recurrence ; Retrospective Studies ; Thigh ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

BACKGROUND: A fibroadenoma is a common benign breast tumor with little potential for malignancy. There are, however, increasing numbers of reports that it is associated with a certain increase in breast cancer. METHODS: We reviewed the medical records of 4 patient's who were diagnosed as intraductal carcinoma within a fibroadenoma. RESULTS: The patient's age were relatively young (32, 36, 52, and 36 years), and the tumor presented as a lump of recent onset in 3 patients and as an abnormal mammography in one patient. None of the patients could be diagnosed as having malignancy by using mammography, ultrasonography, or cytologic examination. However, a radiologic study showed microcalcifications in the masses in two patients, and cytological examination demonstrated atypical cells in three patients. Breast-conservation surgery was performed in two patients; a wide excision was used in one and a localization & excision in the other. Pathologic features were ductal carcinomas in situ within fibroadenomas in all. Estrogen and progesteron receptors were all positive. CONCLUSION: Possibility of malignancy should be excluded in patients with a fibroadenoma, especially when microcalcifications are observed within the mass or atypical cells are suspected based on cytologic examination. Fine needle aspiration cytology, ultrasonography and even excisional biopsy should be performed to evaluate the possibility of malignancy in these patients.
Biopsy ; Biopsy, Fine-Needle ; Breast Neoplasms ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Estrogens ; Fibroadenoma* ; Humans ; Mammography ; Medical Records ; Ultrasonography

PURPOSE: Insular carcinoma is a rare subtype of thyroid cancer which is first described by Carcangiu in 1984. It is intermediate in aggressiveness between well differentiated and anaplastic thyroid carcinoma. But its origin, clinical features and prognosis are not yet clearly understood. We wanted to evaluate the clinical features, histologic characteristics and the prognosis of the insular thyroid carcinoma. MATERIALS AND METHODS: We studied 4 cases of insular thyroid carcinoma treated in Samsung Medical Center from March 1996 to April 1998. Age, sex, clinical features, treatment, pathology and follow up findings were reviewed, retrospectively. RESULTS: All patients were female and mean age was 44 years. Three of four patients complained anterior neck mass and one patient complained low back pain and paresthesia of right thigh. Two patients had metastatic bone lesions at the time of diagnosis. Preoperative fine needle aspiration cytology could diagnose follicular neoplasm in 2 cases and papillary carcinoma in 1. We performed total or completion thyroidectomy and radioactive iodine therapy in 3 cases and radioactive iodine therapy alone in one. Extra- thyroidal invasion, vascular invasion and multicentricity was noted in two cases. All four patients showed recurrence or distant metastasis in follow up period of 10~31 months and 2 of them died of distant metastasis. CONCLUSION: Insular carcinoma is a special type of thyroid carcinoma with aggressive clinical course. Recurrence and extrathyroidal involvements are common and the prognosis is poorer than other well differentiated thyroid carcinoma.
Biopsy, Fine-Needle ; Carcinoma, Papillary ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Iodine ; Low Back Pain ; Neck ; Neoplasm Metastasis ; Paresthesia ; Pathology ; Prognosis ; Recurrence ; Retrospective Studies ; Thigh ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

PURPOSE: Solid and papillary neoplasms and nonfunctioning islet cell tumors are both rare pancreatic tumors, and their clinical and pathological features are similar which makes it hard to differentiate between them. Because both tumors have different prognoses, it is important to have precise diagnosis. The etiology of solid and papillary neoplasm is not precisely known. The role of sexual hormone has been debated as this tumor occurs mostly in women. METHODS: We retrospectively reviewed the medical records of 13 patients with solid and papillary neoplasm and 11 patients with nonfunctioning islet cell tumors who had been treated by surgical resection between October 1994 and May 1999 at Samsung Medical Center. Immunohistochemical stainings were performed for neuron-specific enolase (NSE), chromogranin, somatostatin, alpha 1-antitrypsin, estrogen (ER), and progesterone (PR) receptors. RESULTS: The average ages of the patients with solid and papillary neoplasms and nonfunctioning islet cell tumors were 39.5 and 47.8 respectively. The male to female ratio was 2 to 11 and 6 to 5, respectively and solid and papillary neoplasms were more common in women. CT showed a cystic mass in 76.9% (10/13) of the solid and papillary neoplasm patients and 20% (2/10) of nonfunctioning islet cell tumor patients. Lymphadenopathy was noted in 0% (0/13) of the solid and papillary neoplasm cases and in 50% (5/10) of the nonfunctioning islet cell tumor cases, and calcifications were present in 46.2% (6/13) and 0% (0/10) of those cases, respectively. The solid and papillary neoplasms were located most commonly inthe tail of the pancreas (7 cases), and nonfunctioning islet cell tumors were located most commonly in the head of the pancreas (5 cases). No malignancies were detected in the solid and papillary neoplasms. Seven cases of the nonfunctioning islet cell tumors (63.6%) were malignant. Both solid and papillary neoplasms and nonfunctioning islet cell tumors stained positive for NSE and alpha 1-antitrypsin in all cases and they were chromogranin positive in 25% (3/12) and 100% (10/10) and somatostatin positive in 25% (3/12) and 60% (6/10) of the cases, respectively. A solid and papillary neoplasm stained positive for ER in 1 case and for PR in 5 cases. However, only 1 case of a nonfunctioning islet cell tumor stained positive for PR. CONCLUSION: A nonfunctioning islet cell tumor is more malignant tumor than a solid and papillary neoplasm, and age, presence of cysts, lymphadenopathy, calcification, and chromogranin staining can all be used for differential diagnoses of these tumors. Both the solid and papillary neoplasms and the nonfunctioning tumors are thought to originate from a stem cell capable of differentiating into endocrine cells. The sexual hormone seems to have a role in the development of solid and papillary neoplasms.
Adenoma, Islet Cell* ; alpha 1-Antitrypsin ; Diagnosis* ; Diagnosis, Differential ; Endocrine Cells ; Estrogens ; Female ; Head ; Humans ; Islets of Langerhans* ; Lymphatic Diseases ; Male ; Medical Records ; Pancreas ; Pancreatic Neoplasms ; Phosphopyruvate Hydratase ; Progesterone ; Prognosis ; Retrospective Studies ; Somatostatin ; Stem Cells

PURPOSE: Fine needle aspiration cytology (FNA) and frozen section (FS) have been extremely valuable tools in the evaluation of thyroid nodules. However, in follicular carcinomas, it is often difficult to distinguish between a benign and a malignant lesion. The aims of this study were to evaluate the characteristic clinicopathologic findings and sensitivities of FNA and FS examination in the diagnosis of follicular carcinomas and to delineate the influence of preoperative and intraoperative clinicopathologic findings and the prognostic factors on the extent of surgery. METHODS: The cases of 33 patients who had undergone thyroid surgery and who had been histologically diagnosed as having follicular thyroid carcinomas were reviewed for age, sex, laboratory findings, FNA findings, frozen-section results, extent of surgery, completion thyroidectomy, and coexistent pathology. RESULTS: There were 28 women and 10 men (2.3:1 ratio) whose ages ranged from 14 to 75 years with a mean of 40.8 years. The mean follow-up was 27.2 months. The most prominent sign was an asymptomatic palpable anterior neck mass, which was present in 29 (87.8%) cases. Fine needle aspiration cytology was performed in 31 patients, revealing a follicular neoplasm in 16 patients (sensitivity=51.6%), an adenomatous goiter in 6 (19.4%), a papillary carcinoma in 5 (16.1%), and an anaplastic carcinoma in 1 (3.2%); the specimens were inadequate in 3 patients (9.7%). Among the 32 patients having an intraoperative frozen sections, only 7 patients (sensitivity=21.2%) were correctly diagnosed as having cancer. The diagnoses were deferred (reported as a follicular neoplasm) in 21 patients (65.6%) and were changed from benign at frozen section to malignant on final diagnosis in 4 patients (12.6%). Among the 21 patients diagnosed as having a follicular neoplasm on frozen section, 10 patients (47.6%) were treated with a subtotal thyroidectomy, 6 patients (28.6%) with a total thyroidectomy taking into consideration the gross findings at operation and prognostic factors such as AGES and AMES to reduce the incidence of a completion thyroidectomy.Only 5 patients (23.8%) underwent a lobectomy followed by a reoperation (a completion thyroidectomy). CONCLUSION: Fine needle aspiration cytology and frozen section results are not good indicators in making the decision regarding the extent of the thyroidectomy. A definitive decision to avoid a completion thyroidectomy should be made during the initial operation based on gross findings, frozen-section results, and prognostic factor such as age, tumor grade, tumor size, and the presence of extracapsular spread or distant metastasis.
Adenocarcinoma, Follicular ; Biopsy, Fine-Needle* ; Carcinoma ; Carcinoma, Papillary ; Diagnosis ; Female ; Follow-Up Studies ; Frozen Sections* ; Goiter ; Humans ; Incidence ; Male ; Neck ; Neoplasm Metastasis ; Pathology ; Reoperation ; Thyroid Gland ; Thyroid Nodule ; Thyroidectomy