Disthabanchong S.,Mahidol University |
Disthabanchong S.,Ramathibodi Hospital |
Treeruttanawanich A.,Mahidol University
American Journal of Nephrology | Year: 2010
Background/Aims: Metabolic acidosis (MA) in chronic kidney disease (CKD) associates with protein energy malnutrition, osteoporosis, abnormal endocrine function and increased mortality. Oral sodium bicarbonate has been shown to improve nutritional status and preserve renal function in CKD. Depressed thyroid function has been described in CKD and was believed to be related to MA. This is a prospective randomized study that examined the effect of oral sodium bicarbonate on thyroid function in predialysis CKD with MA. Methods: Predialysis CKD patients with serum total CO2 ≤22 mM were randomized into two groups. The treatment group received increasing dose of oral sodium bicarbonate until serum total CO2 was ≥24 mM. Control patients were kept on the same medications. Thyroid function tests were measured at baseline and again after 8-12 weeks. Results: All patients had a glomerular filtration rate <35 ml/min/1.73 m2. Serum total CO2 increased significantly in the treatment group and was unchanged in the control group. At baseline, over half of the patients had T3 below the lower limit of normal. At study completion, free T3 declined further in the control group, whereas free T3, total T3, free T4 and TSH rose significantly in the treatment group. Percentage changes of total CO2 from baseline were strongly associated with the changes of T3 parameters. Glomerular filtration rate was maintained in the treatment group but declined significantly in the control group. Conclusion: Oral sodium bicarbonate, through correction of MA, improved thyroid function in predialysis CKD. Copyright © 2010 S. Karger AG, Basel.
Chailurkit L.-O.,Ramathibodi Hospital |
Kruavit A.,Box Hill Hospital |
Rajatanavin R.,Ramathibodi Hospital
Nutrition | Year: 2011
Objective: The prevalence of hypovitaminosis D varies in different countries. Therefore, the current study was designed to assess vitamin D status and bone health in elderly women in Thailand, which is situated near the equator. Methods: This cross-sectional study was performed in 446 healthy women aged 60-97 y. Results: Serum 25-hydroxyvitamin D (25(OH)D) was 67.6 ± 15.7 (mean ± SD) nmol/L. Daily calcium intake was 309.5 ± 147.2 mg/d. Serum 25(OH)D levels tended to decline with bone mineral density (BMD) status. Based on functional health-based reference values, plasma-intact parathyroid hormone began to rise below serum 25(OH)D level 70 nmol/L and increase significantly when serum 25(OH)D was ≤60 nmol/L. Thirty-two percent of elderly women had 25(OH)D insufficiency (≤60nmol/L). There was no trend toward a decrease in the concentration of serum 25(OH)D with age (r = -0.078, P = 0.10) and no significant inverse relationship with plasma intact parathyroid hormone values (r = -0.079, P = 0.097). However, a positive relationship was observed between serum 25(OH)D level and femoral neck BMD (r = 0.156, P = 0.001) but not lumbar spine L2-L4 BMD (r = 0.093, P = 0.050). In addition, BMD at the femoral neck but not lumbar spine of the vitamin D insufficiency group was significantly lower than that of the vitamin D sufficiency group. Conclusion: The optimum level of serum 25(OH) value in Thai elderly women should be higher than 70 nmol/L. Vitamin D insufficiency is observed in one-third of elderly women in Bangkok. © 2011 Elsevier Inc.
Keeratijarut A.,Ramathibodi Hospital
The Southeast Asian journal of tropical medicine and public health | Year: 2013
Human pythiosis is a life-threatening infectious disease caused by the oomycete Pythium insidiosum. Diagnosis of pythiosis relies on culture identification, serodiagnosis, and molecular-based assay. Preparation of a serodiagnostic test requires culture filtrate antigen (CFA) extracted from the live pathogen. A 74-kDa immunoreactive protein of P. insidiosum, is encoded by the exo-1,3-beta-glucanase gene (PinsEXO1). PinsEXO1 protein is recognized by sera from pythiosis patients but not by sera from uninfected patients; therefore, this protein could be used to detect anti-P. insidiosum antibodies. In this study we aimed to: identify, synthesize, and evaluate an antigenic determinant (epitope) of PinsEXO1 to be used to serodiagnose pythiosis based on peptide ELISA, and to compare the diagnostic performance of that test with the current CFA-based ELISA. Two antigenic determinants of PinsEXO1 (Peptide-A and -B) were predicted using the PREDITOP program. The sera from 34 pythiosis patients and 92 control subjects were evaluated. Peptide-A, Peptide-B, and CFA-based ELISAs all had a specificity of 100%. Peptide-B ELISA had a sensitivity of 91% and an accuracy of 98% and both Peptide-A and CFA-based ELISAs had a sensitivity of 100% and an accuracy of 100%. Peptide-A is a more efficient epitope than Peptide-B, and can be used as an alternative antigen to develop a serodiagnostic assay for pythiosis.
Pongcharoen P.,Mahidol University |
Jinawath A.,Ramathibodi Hospital |
Tohtong R.,Mahidol University
Clinical and Experimental Metastasis | Year: 2011
We studied the expression pattern and the role of CD44 in regulating the malignant behavior of two cholangiocarcinoma (CCA) cell lines which expressed different levels of CD44 using the siRNA technique. KKU-100, the high CD44 expresser, exhibited a high degree of in vitro invasiveness, migration and adhesion to Matrigel compared to HuCCA-1. Silencing of CD44 by siRNA did not have a significant effect on cell proliferation. However, in vitro invasiveness, directional migration (chemotaxis) and adhesion to Matrigel were markedly reduced in both cell lines, although chemokinesis and MMP secretion were variable, demonstrating the distinct functional role and requirement for CD44 in different cellular activities and in different cell types. In addition, immunohistochemical analysis suggested that CD44 may be involved in the differentiation process or tumor progression, depending on the macroscopic type of CCA. Taken together, our data indicate that CD44 is an important requirement for the invasive phenotype of CCA cells, although the role that CD44 plays may vary depending on the CCA type and the cellular activity in which it is engaged. © 2011 Springer Science+Business Media B.V.
Nimitphong H.,Ramathibodi Hospital |
Nimitphong H.,Boston University |
Holick M.F.,Boston University |
Fried S.K.,Boston University |
Lee M.-J.,Boston University
PLoS ONE | Year: 2012
1,25(OH)2D3 inhibits adipogenesis in mouse 3T3-L1 adipocytes, but little is known about its effects or local metabolism in human adipose tissue. We showed that vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1), the enzyme that activates 25(OH)D3 to 1,25(OH)2D3, were expressed in human adipose tissues, primary preadipocytes and newly-differentiated adipocytes. Preadipocytes and newly-differentiated adipocytes were responsive to 1,25(OH)2D3, as indicated by a markedly increased expression of CYP24A1, a primary VDR target. 1,25(OH)2D3 enhanced adipogenesis as determined by increased expression of adipogenic markers and triglyceride accumulation (50% to 150%). The magnitude of the effect was greater in the absence of thiazolidinediones. 1,25(OH)2D3 was equally effective when added after the removal of differentiation cocktail on day 3, but it had no effect when added only during the induction period (day 0-3), suggesting that 1,25(OH)2D3 promoted maturation. 25(OH)D3 also stimulated CYP24A1 expression and adipogenesis, most likely through its conversion to 1,25(OH)2D3. Consistent with this possibility, incubation of preadipocytes with 25(OH)D3 led to 1,25(OH)2D3 accumulation in the media. 1,25(OH)2D3 also enhanced adipogenesis in primary mouse preadipocytes. We conclude that vitamin D status may regulate human adipose tissue growth and remodeling. © 2012 Nimitphong et al.
Butthep P.,Ramathibodi Hospital |
Chunhakan S.,Ramathibodi Hospital |
Yoksan S.,Ramathibodi Hospital |
Tangnararatchakit K.,Ramathibodi Hospital |
Chuansumrit A.,Ramathibodi Hospital
Pediatric Infectious Disease Journal | Year: 2012
BACKGROUND: The leakage of plasma during febrile episodes in dengue-infected patients is a severe condition leading to dengue shock syndrome. Alteration of cytokines/chemokines is suspected to be a major cause of endothelial cell damage in these patients. The study was designed to demonstrate the alteration of cytokines and chemokines in dengue-infected patients during febrile episodes. METHODS: The blood samples from 164 patients with dengue fever, dengue hemorrhagic fever and other febrile illnesses were collected daily from the day of hospitalization until discharge and also in the convalescent stage. The levels of cytokines/chemokines were determined using a sandwich chemiluminescent immunoassay, and the hematological parameters were examined by the ADVIA hematological analyzer. RESULTS: Two patterns of cytokines/chemokines alteration were detected at different time points during the febrile episode. The increased factors included interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, interferon-γ and monocyte chemoattractant protein-1 whereas IL-1β, IL-2, vascular endothelial growth factor and epidermal growth factor were decreased. Several cytokines were correlated with disease severity especially in dengue hemorrhagic fever/dengue shock syndrome patients. CONCLUSIONS: The alteration in the cytokine/chemokine kinetics during a febrile episode can be used as a predictor for severe dengue infection. The increased and decreased levels at different time points can indicate the disease progression related to vascular leakage in dengue hemorrhagic fever/dengue shock syndrome patients. © 2012 by Lippincott Williams & Wilkins.
Anothaisintawee T.,Ramathibodi Hospital |
Teerawattananon Y.,Ministry of Public Health |
Wiratkapun C.,Mahidol University |
Kasamesup V.,Mahidol University |
Thakkinstian A.,Mahidol University
Breast Cancer Research and Treatment | Year: 2012
The number of risk prediction models has been increasingly developed, for estimating about breast cancer in individual women. However, those model performances are questionable. We therefore have conducted a study with the aim to systematically review previous risk prediction models. The results from this review help to identify the most reliable model and indicate the strengths and weaknesses of each model for guiding future model development. We searched MEDLINE (PubMed) from 1949 and EMBASE (Ovid) from 1974 until October 2010. Observational studies which constructed models using regression methods were selected. Information about model development and performance were extracted. Twenty-five out of 453 studies were eligible. Of these, 18 developed prediction models and 7 validated existing prediction models. Up to 13 variables were included in the models and sample sizes for each study ranged from 550 to 2,404,636. Internal validation was performed in four models, while five models had external validation. Gail and Rosner and Colditz models were the significant models which were subsequently modified by other scholars. Calibration performance of most models was fair to good (expected/observe ratio: 0.87-1.12), but discriminatory accuracy was poor to fair both in internal validation (concordance statistics: 0.53-0.66) and in external validation (concordance statistics: 0.56-0.63). Most models yielded relatively poor discrimination in both internal and external validation. This poor discriminatory accuracy of existing models might be because of a lack of knowledge about risk factors, heterogeneous subtypes of breast cancer, and different distributions of risk factors across populations. In addition the concordance statistic itself is insensitive to measure the improvement of discrimination. Therefore, the new method such as net reclassification index should be considered to evaluate the improvement of the performance of a new develop model. © 2011 Springer Science+Business Media, LLC.
Reungwetwattana T.,Ramathibodi Hospital |
Reungwetwattana T.,Roswell Park Cancer Institute |
Dy G.,Roswell Park Cancer Institute
Journal of Carcinogenesis | Year: 2013
The iterative discovery in various malignancies during the past decades that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by "druggable" protein kinases has led to a revolutionary change in drug development. In non-small cell lung cancer (NSCLC), the ErbB family of receptors (e.g., EGFR [epidermal growth factor receptor], HER2 [human epidermal growth factor receptor 2]), RAS (rat sarcoma gene), BRAF (v-raf murine sarcoma viral oncogene homolog B1), MAPK (mitogen-activated protein kinase) c-MET (c-mesenchymal-epithelial transition), FGFR (fibroblast growth factor receptor), DDR2 (discoidin domain receptor 2), PIK3CA (phosphatidylinositol-4,5-bisphosphate3-kinase, catalytic subunit alpha)), PTEN (phosphatase and tensin homolog), AKT (protein kinase B), ALK (anaplastic lym phoma kinase), RET (rearranged during transfection), ROS1 (reactive oxygen species 1) and EPH (erythropoietin-producing hepatoma) are key targets of various agents currently in clinical development. These oncogenic targets exert their selective growth advantage through various intercommunicating pathways, such as through RAS/RAF/MEK, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin and SRC-signal transduction and transcription signaling. The recent clinical studies, EGFR tyrosine kinase inhibitors and crizotinib were considered as strongly effective targeted therapies in metastatic NSCLC. Currently, five molecular targeted agents were approved for treatment of advanced NSCLC: Gefitinib, erlotinib and afatinib for positive EGFR mutation, crizotinib for positive echinoderm microtubule-associated protein-like 4 (EML4)-ALK translocation and bevacizumab. Moreover, oncogenic mutant proteins are subject to regulation by protein trafficking pathways, specifically through the heat shock protein 90 system. Drug combinations affecting various nodes in these signaling and intracellular processes are predicted and demonstrated to be synergistic and advantageous in overcoming treatment resistance compared with monotherapy approaches. Understanding the role of the tumor microenvironment in the development and maintenance of the malignant phenotype provided additional therapeutic approaches as well. More recently, improved knowledge on tumor immunology has set the stage for promising immunotherapies in NSCLC. This review will focus on the rationale for the development of targeted therapies in NSCLC and the various strategies employed in preventing or overcoming the inevitable occurrence of treatment resistance.
Kiertiburanakul S.,Ramathibodi Hospital
Journal of the Medical Association of Thailand | Year: 2010
Tuberculosis (TB) remains an important problem in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). Concomitant administration therapy of both TB and HIV is fraught with difficulties. Despite the fact that the use of highly active antiretroviral therapy (HAART) led to significant improve quality of life and decrease morbidity including mortality-associated to HIV/AIDS, adverse drug effects lead to interruptions in both HIV and TB therapy. In addition, an important problem when HAART is initiated in patients with TB is the possibility of developing immune reconstitution inflammatory syndrome (IRIS). A six-month regimen consisting of isoniazid, rifampicin, pyrazinamide, and ethambutal for two months followed by isoniazid and rifampicin for four months is a standard regimen for the treatment of known or presumed drug-susceptible TB disease. The following strategy may minimize the risk of IRIS. Patients with CD4 cell counts < 100 cells/mm3, efavirenz-based HAART regimen is recommended and should be initiated as soon as the patients can tolerate TB treatment. Patients with CD4 cell counts 100-350 cells/mm3, HAART should be started at two months after TB treatment initiation. HAART should be deferred with closed follow-up of CD4 cell counts if patients have CD4 cell counts > 350 cells/mm3.
Wattanakrai P.,Ramathibodi Hospital |
Mornchan R.,Ramathibodi Hospital |
Eimpunth S.,Ramathibodi Hospital
Dermatologic Surgery | Year: 2010
Background Pigment lasers have been used in melasma with unsatisfactory results. Objective To determine the effectiveness and safety of 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd:YAG) laser treatment of melasma in Asians. Materials and Methods Split-face randomized study comparing combination QS-Nd:YAG laser and 2% hydroquinone with topical treatment in dermal or mixed-type melasma. Twenty-two patients were treated with 1,064-nm QS-Nd:YAG laser, 6-mm spot size, 3.0- to 3.8-J/cm2 fluence for five sessions at 1-week intervals. Pigmentation was objectively recorded using a colorimeter (lightness index score), and subjective assessments were evaluated using the modified Melasma Area and Severity Index (mMASI) score. Results After five laser treatments, statistically significant improvement of melasma from baseline was observed in colorimeter (p<.001) and mMASI score (p<.001) on the laser side. The laser side achieved an average 92.5% improvement in relative lightness index and 75.9% improvement in mMASI, compared with 19.7% and 24%, respectively, on the control side (p<.001). Mottled hypopigmentation developed in three patients. During follow-up, four of 22 patients developed rebound hyperpigmentation, and all patients had recurrence of melasma. Conclusion QS-Nd:YAG laser treatment for melasma in Asians produced only temporary improvement and had side effects. Common complications were hypopigmentation, melasma recurrence, and rebound hyperpigmentation. The authors have indicated no significant interest with commercial supporters. © 2010 by the American Society for Dermatologic Surgery, Inc.