Phytochemical Constituents from the Rhizomes of Osmunda japonica Thunb and Their Anti-oxidant Activity

Eleven compounds (1–11) were isolated from the rhizomes of Osmunda japonica, and their structures were elucidated based on 1H, 13C-NMR and LC-IT-TOF MS data. Of these compounds, all compounds (1 – 11) have been previously reported, although five (6 – 9, 11) have not previously been isolated from this plant. The antioxidant activities of isolated compounds (1 – 11) were measured by DPPH and ABTS assays, and compound 10 showed the high antioxidant activity.

Beneficial Effect of Lespedeza cuneata (G. Don) Water Extract on Streptozotocin-induced Type 1 Diabetes and Cytokine-induced Beta-cell Damage

The aim of this study was to evaluate the anti-diabetic effects of the water extract of Lespedeza cuneata (LCW) using rat insulinoma (RIN) m5F cells and streptozotocin (STZ)-induced diabetic rats. The effect of LCW on the protection of pancreatic beta cells was assessed using MTT assay, and nitric oxide production was assessed using Griess reagent. STZ-induced diabetic rats were treated with 100 and 400 mg/kg body weight of LCW for 5 weeks. In results, LCW significantly protected cytokine-induced toxicity and NO production, and increased insulin secretion in RINm5F cells. LCW significantly decreased serum blood glucose, thiobarbituric acid reactive substances (TBARS), blood urea nitrogen (BUN) and advanced glycation end products (AGEs) levels, and renal fibronectin expression in STZ-induced diabetic rats. Also, LCW effectively improved BW loss in STZ-induced diabetic rats. Thus, our results suggest that LCW has a beneficial effect on cytokine-induced pancreatic beta cell damage and biomarkers of diabetic complication in hyperglycemic rats.

Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro / 한국실험동물학회지

Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.

Cardioprotective Effect of Fimasartan, a New Angiotensin Receptor Blocker, in a Porcine Model of Acute Myocardial Infarction

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Time-Dependent Effects of Prognostic Factors in Advanced Gastric Cancer Patients

PURPOSE: This study aimed to identify time-dependent prognostic factors and demonstrate the time-dependent effects of important prognostic factors in patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: We retrospectively evaluated 3,653 patients with AGC who underwent curative standard gastrectomy between 1991 and 2005 at the Korea Cancer Center Hospital. Multivariate survival analysis with Cox proportional hazards regression was used in the analysis. A non-proportionality test based on the Schoenfeld residuals (also known as partial residuals) was performed, and scaled Schoenfeld residuals were plotted over time for each covariate. RESULTS: The multivariate analysis revealed that sex, depth of invasion, metastatic lymph node (LN) ratio, tumor size, and chemotherapy were time-dependent covariates violating the proportional hazards assumption. The prognostic effects (i.e., log of hazard ratio [LHR]) of the time-dependent covariates changed over time during follow-up, and the effects generally diminished with low slope (e.g., depth of invasion and tumor size), with gentle slope (e.g., metastatic LN ratio), or with steep slope (e.g., chemotherapy). Meanwhile, the LHR functions of some covariates (e.g., sex) crossed the zero reference line from positive (i.e., bad prognosis) to negative (i.e., good prognosis). CONCLUSIONS: The time-dependent effects of the prognostic factors of AGC are clearly demonstrated in this study. We can suggest that time-dependent effects are not an uncommon phenomenon among prognostic factors of AGC.

A Case of Bilateral Peripheral Tapia's Syndrome Subsequent to Coronary Artery Bypass Graft / 대한이비인후과학회지

The Tapia's syndrome means symptom complex that result from unilateral vago-hypoglossal nerve paralysis. This syndrome is rare disease entity, bilateral attack is extremely rare. Only three cases have been reported in English literature. A-66-year-old man received the coronary artery bypass graft in our hospital. After the operation, he complained of severe dyspnea, voice change and drooling. The laryngoscopic findings showed the bilateral vocal cord palsy. He could not move the tongue toward any directions. We diagnosed as bilateral Tapia's syndrome. Usually, unilateral Tapia's syndrome is related to the complications of anesthesia and position of the patient's head during surgery. Otherwise, our case may be associated with the complications of operation and anesthesia. The patient's recovered three months later, but the right vocal cord palsy is persistent. We report the very unique disease entity with literature review.

Clinical Aspects of Peritonitis in Peritoneal Dialysis Patient: A Single Center Experience

OBJECTIVE: Peritonitis is one of major complication of peritoneal dialysis. It is the most important reason for removal of peritoneal catheter, death, or converting to hemodialysis. There is a debate that peritonitis decreases residual renal function. Thus, the authors carried out a study to grasp the prognosis of peritonitis which affects residual renal function (RRF) and assessed the risk factors of its clinical course. METHODS: Among 245 patients who had been on peritoneal dialysis in Soonchunhyang University Bucheon Hospital from April 2001 to March 2012, the author selected 91 patients who had kept on peritoneal dialysis for more than 3 months and experienced more than one episode of peritonitis. The medical records and laboratory findings were reviewed. RESULTS: During the average period of 36.3+/-22.8 months of peritoneal dialysis, total of 182 episodes of peritonitis developed in 91 study subjects. Among them, the 15 cases (8.2%) did not improve despite of intraperitoneal antibiotics and peritoneal catheter was subsequently removed. Eight patients were dead because of peritonitis related complications. The lactic dehydrogenase (LDH) level of peritoneal fluid at the third day of treatment had a significant correlation with peritonitis treatment failure (odds ratio [OR], 1.079; P=0.009) and death (OR, 1.071; P=0.049), respectively. The RRF after peritonitis became significantly low (P=0.011) compared to before peritonitis. But the slopes of declining rate of RRF were not different between before and after peritonitis (P=0.932). CONCLUSION: The LDH level of peritoneal fluid at the third day of treatment was correlated with treatment failure or death. The declining rate of RRF was not affected after peritonitis.

Predictive Factors for Delayed Virologic Response of Adefovir Add-on Therapy in Lamivudine-resistant Chronic Hepatitis B

OBJECTIVE: Lamivudine (LAM) is the first nucleoside analog approved for chronic hepatitis B (CHB) patients, but acquired mutation of the reverse transcriptase of the virus during long-term therapy is limiting its use. Adeforvir dipivoxil (ADV) add-on therapy with ongoing LAM use has been a standard therapy for LAM resistance. The aim of this study was to explore the predictive factors associated with delayed virologic response at 12 months in patients who could not achieved initial virologic response (IVR) of add-on therapy. METHODS: One hundred and ninety three LAM-resistant CHB patients who had been on ADV add-on therapy with LAM and were not achieved IVR at 6 months were enrolled. They were classified into delayed viral response (DVR) group and non-DVR group, according to delayed viral response (VR) at 12 months of add-on therapy. Clinical factors predicting delayed VR at 12 months of add-on therapy were evaluated. RESULTS: DVR rate was 20.7% (n=40) at 12 months after the add-on treatment. Female (adjusted odds ratio, 3.463; P=0.002), lower hepatitis B virus (HBV) DNA at baseline ( or =7.0 log copies/mL; adjusted odds ratio, 0.369; P=0.012), and negative HBeAg at baseline (adjusted odds ratio, 0.332; P=0.034) were significant independent factors predicting DVR after 12 months of treatment. CONCLUSION: In LAM-resistant CHB patients with ADV add-on therapy, although there was no IVR after 6 months treatment, we could consider maintenance of treatment if patient is female, lower HBV DNA state, or HBeAg negative state at the time of starting add-on therapy.

The Clinical Significance of Simplified Scoring Criteria as a Diagnostic Tool for Overlap Syndrome in Korea / 대한내과학회지

BACKGROUND/AIMS: The diagnosis of primary billiary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome remains challenging. In 2008, a simplified scoring system was proposed by the International Autoimmune Hepatitis Group, which aimed for wider applicability in routine clinical practice. We evaluated the performance of the new simplified AIH scoring criteria as a diagnostic tool for overlap syndrome. METHODS: We retrospectively reviewed the clinical histories, chemistry, autoimmune studies, and liver biopsy results of 25 patients diagnosed with PBC who visited Soonchunhyang University Hospital, Bucheon and Seoul, between November 2004 and December 2009. Parameters relevant to the revised and simplified scoring criteria were recorded, and outcomes were compared between those with and without features of overlap syndrome. RESULTS: Of 25 patients with a definite diagnosis of PBC, five (20%) were diagnosed with overlap syndrome using the revised criteria, and 18 patients (72%) were diagnosed with the simplified criteria. Those patients diagnosed according to the simplified scoring criteria revealed an increased frequency of anti-nuclear antibody (p = 0.030) and serum IgG levels (p = 0.092). Additionally, advanced fibrosis was significantly more frequent in patients with overlap syndrome (p = 0.017). CONCLUSIONS: The simplified scoring criteria seemed to be useful as a diagnostic tool to recognize overlap syndrome in Korea. However, a relatively small number of patients were included in our study, so further clinical trials based on larger populations should be performed.

A Rapid Improvement of Heart Failure after Treatment of Hyperthyroidism

BACKGROUND: Heart failure is a rare condition of thyrotoxicosis. We report a case of thyrotoxicosis-inducing heart failure. CASE REPORT: A 29-year old female had been suffered from thyrotoxicosis for 3 years without proper medication. She complained progressive dyspnea and palpitation with atrial fibrillation with rapid ventricular response. Marked cardiomegaly, and severe right ventricular dysfunction with biatrial enlargements were found on Two-dimensional (2D) echocardiography. We treated her with medications for heart failure and thyrotoxicosis, and the patient's symptoms and objective cardiac functions are improved after two weeks. CONCLUSION: Severe heart failure caused by thyrotoxicosis could be reversible with proper management. Patients who have thyrotoxicosis should be assessed closely, and suitable treatment can markedly improve the patient's prognosis.

Two Cases of Ascending Aortic Intramural Hematoma Combined with Cardiac Tamponade Treated with Different Strategies

Aortic intramural hematoma (IMH) is classically defined as a variation of aortic dissection where blood collects within the aortic media without the presence of an intimal flap. Ascending IMH is known to have worse clinical outcomes than IMH of the descending aorta or aortic arch. Therefore, some patients with higher risk of disease progression require surgical corrections. However, the indications and the benefits of surgical management of ascending IMH, compared with medical treatment only, have not yet been established. We present two cases of IMH in the ascending aorta that presented with cardiac tamponade; patients were treated differently according to risk factors.

Different Prognostic Significance of Bcl-2 Based on Cancer Molecular Subtype / 한국유방암학회지

PURPOSE: B-cell lymphoma (bcl)-2 is an anti-apoptotic gene, and it is a poor prognostic factor in various malignant tumors. However, the prognostic significance of bcl-2 expression in breast cancer remains controversial. We investigated the prognostic significance of bcl-2 according to cancer molecular subtype. METHODS: We analyzed 411 patients with primary invasive breast cancer who underwent surgery at our institution between 1999 and 2001. The subtypes were classified as luminal (estrogen receptor [ER]+ and/or progesterone receptor [PR]+, irrespective of human epidermal factor receptor 2 [HER2]), triple-negative (ER-, PR-, and HER2-), or HER2 (ER- ,PR-, and HER2+). RESULTS: A total of 236 (57.4%) cases were positive for bcl-2, and bcl-2 expression was significantly associated with earlier stage, lower grade, expression of hormone receptor positivity, and HER2 negativity. No difference in disease-free survival (DFS) was observed based on bcl-2 expression. However, the prognostic significance of bcl-2 varied with subtype; bcl-2 was not a prognosticator in patients with the luminal and HER2 subtypes. However, patients with bcl-2(+) tumors of the triple-negative subtype showed significantly worse DFS than those with bcl-2(-) tumors (p=0.048). In a multivariate analysis, bcl-2 expression remained a significant predictor of recurrence in patients with the triple-negative subtype (hazard ratio, 3.26; 95% confidence interval, 1.40-7.59; p=0.006). CONCLUSION: The prognostic significance of bcl-2 varied with molecular subtype; bcl-2 expression was a poor prognosticator in patients with the triple-negative subtype, but not in those with the luminal and HER2 subtypes.

The Phase 4 Randomized, Public, Parallel, Comparative, Clinical Trial to Compare Efficacy and Safety of S-(-)-Amlodipine Nicotinate with Ramipril in Hypertensive Patients

BACKGROUND: The aim of this study was to compare the antihypertensive effect of S-(-)-amlodipine nicotinate with ramipril in patients with essential hypertension. METHODS: Total 138 patients (54.5 +/- 10.5 years, 69 males) were enrolled in this study between 2008 and 2010. Amlodipine 2.5 mg or ramipril 2.5 mg was treated once in a day for 8 weeks. Epidemiologic analysis was performed in intend-to-treat (ITT) group. Efficacy analysis was performed in the differences of diastolic blood pressure in study groups. Abnormal reactions were divided with severities and drug-relationship. RESULTS: The change of diastolic blood pressures were more prominent with -12.7 +/- 7.02 mm Hg in amlodipine group, and -9.6 +/- 7.38 mm Hg in ramipril group (p = 0.023). The change of systolic blood pressures was higher in amlodipine group with -18.1 +/- 7.91 mm Hg, and -14.3 +/- 11.96 mm Hg in ramipril group (p = 0.047). Blood pressure normalization rates were 81.3% (48 of 59 patients) in amlodipine group, and 61.4% (35 of 57 patients) in ramipril group (p = 0.017). Abnormal reaction occurred in 5.8% (4 of 68 patients) of amlodipine group and 14.2% (10 of 70 patients) of ramipril group (p = 0.102). The most frequent abnormal reaction was respiratory symptom. CONCLUSIONS: S-Amlodipine-Nicotinate was more effective than ramipril in hypertensive patients without significant abnormal reaction.

Changes in Pain, Mood and Posttrauma Risk Level of Patients with Acute Hand Microsurgery / 재활간호학회지

PURPOSE: The purposes of this study were to explore changes in pain, mood and the level of posttrauma risk for 2 weeks after acute hand microsurgery and determine predictors of pain 2-week after microsurgery. METHOD: Using a sample of 84 patients with hand microsurgery, pain, mood, and posttrauma risk were measured by the Brief Pain Inventory-Korea, the modified Profile of mood states, and the Posttrauma risk checklist at 1-day, 1-week and 2-week post-microsurgery. Repeated measures ANOVA and Multiple regression analysis were conducted to evaluate changes in pain, mood, and posttrauma risk over time after the surgery and determine predictors of pain 2-week after the surgery. RESULTS: Pain significantly decreased (F=63.22, p<.001), mood significantly improved (F=41.04, p<.001) 2 weeks after microsurgery and interestingly, posttrauma risk significantly decreased from baseline to 1-week microsurgery but increased at 2-week after microsurgery (F=24.66, p<.001). Approximately 57% of the variance of pain 2-week post-microsurgery was explained by pain at 1-week post-microsurgery, mood and the numbers of injured fingers. CONCLUSION: The findings suggest the pain control for 1week after acute surgery being critical and posttrauma rehabilitation of injured finger being necessary. Developing nursing interventions is urgently needed to help individuals with impending hand microsurgery.

The Relationship among Pain, Body Image and Satisfaction in Hand-injured Workers / 산업간호학회지

PURPOSE: The purpose of this study was to explore relationship among pain, body image and satisfaction in hand-injured workers. METHODS: Using a sample of 96 out-patient workers with hand injuries, pain, body image and satisfaction were measured by VAS and Modified Jung Keum-hee's Tennesee Self Concept Scale. Repeated measured ANOVA and a Bonferroni correction for multiple statistical testing during post hoc analyses were conducted to evaluate relationship among pain, body image and satisfaction in hand-injured workers. RESULT: Functional satisfaction(r=.46, p<.001) and appearance satisfaction(r=.55, p<.001) significantly increased by treatment satisfaction. Functional satisfaction(r=.35, p= .001) and appearance satisfaction(r=.31, p= .002) increased by body image. But treatment satisfaction(r=-.20, p=.049), functional satisfaction (r=-.34, p=.001) and appearance satisfaction (r=-.39, p<.001) significantly decreased by pain. CONCLUSION: Poor pain management was related to bad body image and treatment satisfaction. Therefore, interventions targeting at pain management are needed for hand-injured workers.

Clinical pattern changes in elderly patients who underwent percutaneous coronary intervention in the last ten years / 대한내과학회지

BACKGROUND/AIMS: The objective of this study was to observe changes in the clinical patterns of Korean patients over 65 years of age who received percutaneous coronary intervention (PCI) in the past 10 years. METHODS: In total, 3,209 patients over 65 years of age [male:female; 1,950 (71.4+/-5.21 years):1,259 (72.5+/-5.47 years)] who underwent PCI between June 1999 and June 2009 were divided into four groups according to time period. Clinical characteristics, gender differences, coronary angiographic findings, and major adverse cardiac events (MACE) during a 1-year follow-up period were compared among the four groups. RESULTS: The gender ratio was male-dominant and no significant change was observed over the observed time period [male (60.8):female (39.2%)], but the age increased [1999-2001:2002-2004:2005-2007:2008-2009=71.2+/-5.11:71.4+/-5.26:71.9+/-5.25: 72.6+/-5.57 years; p=0.001]. The prevalence of hypertension increased over time (p=0.028), but smoking decreased (p=0.002). Hypertension was the major risk factor for males, whereas obesity was the major risk factor for female patients. MACE-free 1-year survival increased over the observed period (p=0.014). Males had higher survival rates than females (p=0.007). MACE developed in 105 (3.27%) patients during the 1-year follow-up period and predictive factors for the development of MACE were being female (p=0.001), old age (p=0.008), hypertension (p=0.049), diabetes mellitus (p=0.004), smoking (p=0.009), and low Thrombolysis In Myocardial Infarction (TIMI) flow (p=0.048) by a multivariate analysis. CONCLUSIONS: The age of elderly patients undergoing PCI and the prevalence of hypertension increased, whereas smoking decreased over the last 10 years. Predictive factors for patients developing MACE during the one-year follow-up were associated with female gender, hypertension, diabetes mellitus, smoking, old age, and low TIMI flow.

Lyn Expression in Osteoblastic Osteosarcoma Tissues and Its Correlation with Clinicopathologic Factors

BACKGROUND: The Src family kinases (SFKs) are involved in multiple aspects of tumorigenesis, such as, proliferation, migration, and angiogenesis, and are involved in the generation and progression of many types of tumors. Furthermore, dasatinib, a general SFKs inhibitor was recently approved for use in chronic myeloid leukemia. This study was performed to evaluate the expression of Lyn, a member of the SFKs, in osteosarcoma tissues. METHODS: One hundred and sixteen patients with osteoblastic osteosarcoma were selected for Lyn expression analysis. The correlation between Lyn expression in tumor sections and patients' clinicopathologic characteristics and the prognostic significance of Lyn expression were evaluated. RESULTS: Lyn was found to be expressed in 52 of the 116 patients (44.8%), and Lyn positive tumor was found to be significantly associated with a lytic tumor pattern on plain radiographs (p = 0.04). Furthermore, those positive for Lyn showed longer metastasis free survival (5-year metastasis free survival, 65.2% for Lyn positive and 46.8% for Lyn negative; p = 0.06), though this was only marginally significant. CONCLUSIONS: Lyn was found to be overexpressed in osteosarcoma tissues, and this overexpression was found to be correlated with osteolysis.

A Comparison of Outcomes for the Patients with Pathologically Node-negative Breast Cancer and Who Were Treated Either with Sentinel Lymph Node Biopsy Only or with Conventional Axillary Lymph Node Dissection / 한국유방암학회지

PURPOSE: False negative results obtained with the use of a sentinel lymph node biopsy (SLNB) can result in down staging of tumors, whereas the use of a more elaborated pathological examination of sentinel lymph nodes might lead to upstaging of tumors. The purpose of this study was to compare results after performing only an SLNB as compared with performing conventional axillary lymph node dissection (ALND) without an SLNB in pathologically node negative (pN0) breast cancer patients. METHODS: From April 2004 to June 2007, SLNBs were performed for patients with primary breast cancer who had no clinical evidence of a lymph node metastasis. A total of 272 patients were treated with only an SLNB. During the same period, 278 patients were confirmed as pN0 after conventional ALND without an SLNB. A prospectively collected database and medical records of these patients were reviewed. RESULTS: For patients that had undergone only an SLNB, there was no local or regional recurrence. A distant metastasis developed in four patients (1.5%). In patients that had undergone ALND without an SLNB, a recurrence was found in 13 patients (4.7%). Patients that had undergone only an SLNB showed significantly better disease-free survival as compared to patients that had undergone ALND without an SLNB (p=0.032). CONCLUSION: pN0 patients treated with only an SLNB showed a significantly better outcome as compared to patients treated with conventional ALND without an SLNB. These results suggest that performing an SLNB might result in the upstaging of a subset of patients who would have been understaged by the use of conventional ALND.

Suspicious stress induced cardiomyopathy following hemorrhoidectomy under spinal anesthesia: A case report / 대한마취과학회지

A 48-year-old healthy woman was admitted in our hospital for elective hemorrhoidectomy. She developed sudden headache and chest pain, and showed sinus bradycardia, arrhythmia and hypotension forty minutes after spinal anesthesia with 0.5% hyperbaric bupivacaine. An EKG showed ST depression and an transthoracic echocardiogram performed in PACU demonstrated mild LV dysfunction with hypokinesia of LV inferolateral wall. An coronary angiography on postoperative day 1 revealed normal coronary vessel and akinesia of LV inferior wall. Levels of CK-MB and Troponin I were mildly elevated. With medical therapy, the patient's symptoms improved and recovered without any complication.

Serum methotrexate level is inversely related to the outcome of osteosarcoma patients / 소아과

PURPOSE: To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). METHODS: To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). RESULTS: Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean+/-SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14+/-12.83 micrometer, 9.29+/-3.89 micrometer, 1.73+/-1.37 micrometer, and 0.58+/-0.44 micrometer, respectively. The peak MTX serum level was 1292.14+/-12.83 micrometer. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level (3.4 micrometer) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than 1,400 micrometer (P=0.002) and mean 24-h MTX level of less than 3.4 micrometer (P=0.011). CONCLUSION: The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.