Siriraj Hospital

Bangkok, Thailand

Siriraj Hospital

Bangkok, Thailand
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Avirutnan P.,University of Washington | Avirutnan P.,Siriraj Hospital | Hauhart R.E.,University of Washington | Somnuke P.,University of Washington | And 4 more authors.
Journal of Immunology | Year: 2011

The complement system plays a pivotal protective role in the innate immune response to many pathogens including flaviviruses. Flavivirus nonstructural protein 1 (NS1) is a secreted nonstructural glycoprotein that accumulates in plasma to high levels and is displayed on the surface of infected cells but absent from viral particles. Previous work has defined an immune evasion role of flavivirus NS1 in limiting complement activation by forming a complex with C1s and C4 to promote cleavage of C4 to C4b. In this study, we demonstrate a second mechanism, also involving C4 and its active fragment C4b, by which NS1 antagonizes complement activation. Dengue,West Nile, or yellow fever virus NS1 directly associated with C4b binding protein (C4BP), a complement regulatory plasma protein that attenuates the classical and lectin pathways. Soluble NS1 recruited C4BP to inactivate C4b in solution and on the plasma membrane. Mapping studies revealed that the interaction sites of NS1 on C4BP partially overlap with the C4b binding sites. Together, these studies further define the immune evasion potential of NS1 in reducing the functional capacity of C4 in complement activation and control of flavivirus infection. Copyright © 2011 by The American Association of Immunologists, Inc.


Davies A.,University of Southampton | Merli F.,Hematology Unit | Mihaljevic B.,University of Belgrade | Siritanaratkul N.,Siriraj Hospital | And 7 more authors.
The Lancet Oncology | Year: 2014

Background: Intravenous rituximab is a mainstay of treatment for follicular lymphoma. A subcutaneous formulation that achieves equivalent rituximab serum concentrations might improve convenience and save health-care resources without sacrificing clinical activity. We aimed to assess pharmacokinetic non-inferiority of 3 week cycles of fixed-dose subcutaneous rituximab versus standard intravenous rituximab. Methods: In our two-stage, randomised, open-label, phase 3 trial, we enrolled patients with previously untreated grade 1-3a, CD20-positive follicular lymphoma at 67 centres in 23 countries. In stage 1, we randomly allocated patients 1:1 with the Pocock and Simon algorithm to intravenous rituximab (375 mg/m2) or fixed-dose subcutaneous rituximab (1400 mg), stratified by induction chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, prednisone or cyclophosphamide, vincristine, prednisone), Follicular Lymphoma International Prognostic Index score, and region. After randomisation, patients received one induction dose of intravenous rituximab in cycle 1 and then allocated treatment for cycles 2-8. Patients with a complete or partial response following induction therapy continued intravenous or subcutaneous rituximab as maintenance every 8 weeks. The primary endpoint was the ratio of observed rituximab serum trough concentrations (Ctrough) between groups at cycle 7 (before cycle 8 dosing) of induction treatment in a per-protocol population. Patients were analysed as treated for safety endpoints. Stage 2 follow-up is ongoing and is fully accrued. This study is registered with ClinicalTrials.gov, number NCT01200758. Findings: Between Feb 4, 2010, and Oct 21, 2011, we enrolled 127 patients. Pharmacokinetic data were available for 48 (75%) of 64 patients randomly allocated intravenous rituximab and 54 (86%) of 63 patients randomly allocated subcutaneous rituximab. Geometric mean Ctrough was 83·13 μg/mL in the intravenous group and 134·58 μg/mL in the subcutaneous group (ratio 1·62, 90% CI 1·36-1·94), showing non-inferiority of subcutaneous rituximab. 57 (88%) of 65 patients in the intravenous rituximab safety population had adverse events (30 [46%] grade ≥3), as did 57 (92%) of 62 patients in the subcutaneous rituximab safety population (29 [47%] grade ≥3). The most common grade 3 or worse adverse event in both groups was neutropenia (14 [22%] patients in the intravenous group and 16 [26%] patients in the subcutaneous group). Adverse events related to administration were mostly grade 1-2 and occurred in 21 (32%) patients in the intravenous group and 31 (50%) patients in the subcutaneous group. Interpretation: Stage 1 data show that the pharmacokinetic profile of subcutaneous rituximab was non-inferior to intravenous rituximab and was not associated with new safety concerns. Stage 2 will provide data for efficacy and safety of the subcutaneous administration. Funding: F Hoffmann-La Roche. © 2014 Elsevier Ltd.


Werarak P.,Siriraj Hospital
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012

Nosocomial pneumonia (NP) is an important cause of morbidity and mortality in hospitalized patients. Acinetobacter baumannii is one of the common causative pathogens in NP. The prevalence of multi-drug resistance in A. baumannii has been increasing. The information on clinical features and clinical courses of A. baumannii NP in Thai patients are limited. To determine the clinical features, risk factors and clinical courses of A. baumannii NP in Thai patients hospitalized in tertiary care hospitals in Thailand. This was a prospective, hospital-based, active surveillance study on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in adults hospitalized in 12 tertiary care hospitals in Thailand between 2008 and 2009. There were 651 NP patients. A. baumannii was the most common cause of NP in 198 patients (30.4%). Most of NP patients were males with median age of 71 years. About 80% had late onset NP with the median duration of 10 days after admission in both A. baumannii and non-A. baumannii NP. Most of NP occurred in patients hospitalized in general medical wards. Most of the features of NP in A. baumannii NP and non-A. baumannii NP were not significantly different. The initial antibiotics prescribed were concordant in about 50% of the patients in both groups. Colistin was usually prescribed to the patients who received antibiotic modifications. The initial clinical responses in A. baumannii NP were less favorable than those in non-A. baumannii NP. The mortality rate in A. baumannii NP seemed to be more than that in non-A. baumannii NP. There was a trend of more persistence of pathogen in A. baumannii NP. Most isolates of A. baumannii were resistant to antibiotics including carbapenems. The patients with extensive drug resistant A. baumannii NP had less favorable responses than NP due to other bacteria, including non-extensive drug resistant A. baumannii. VAP, NP developed in medical ICU and NP with bilateral lung involvements on chest X-ray were associated with A. baumannii as the isolated pathogen. A. baumannii is the most common causative pathogen for NP in tertiary care hospitals in Thailand and most of A. baumannii isolates were resistant to many antibiotics including carbapenems. The hospitalized patient in tertiary care hospitals with VAP, or NP that was developed in medical ICU, or NP with bilateral lung involvements on chest x-ray was likely to be due to A. baumannii. Many NP patients received inappropriate initial antibiotic regimens leading to a high mortality.


Srimuninnimit V.,Siriraj Hospital
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012

The aim of the present prospective study was to evaluate the correlation between the change of serum c-reactive protein (CRP) levels and response to chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer. Patients with locally advanced or metastatic non-small cell lung cancer who received the first line chemotherapy were measured serum CRP levels prior to treatment. Chemotherapy regimen was given to patients according to physicians and radiologic imaging was evaluated after two or three cycles of treatment. Serum CRP levels were measured first time at pre-treatment and second time in patients who had pre-treatment serum CRP levels greater than normal range (3 mg/l) at the time of response assessment or clinical progression. The primary endpoint was the correlation between change of serum CRP levels and radiologic response. The secondary endpoint was the prevalence of elevated CRP levels in advanced NSCLC patients and correlation between initial CRP levels and progression free survival (PFS). Fifty four patients were enrolled. Prevalence of elevated CRP levels in advanced NSCLC was 76%. Thirty patients had serial serum CRP measured. There was correlation between change in serum CRP levels and response to treatment (r = 0.43, p = 0.018, spearman rank). There was significant correlation between response to treatment and decrease in CRP levels greater than 50% (p = 0.009, Fisher's exact test). In contrast there was no correlation between progression and increase in CRP levels (p = 0.640, Fisher's exact test). All patients with serial CRP levels decreased to normal range (< 3 mg/ l) had response to chemotherapy. High pre-treatment CRP levels (> 100 mg/l) correlated with poor PFS. Median PFS for patients with pre-treatment CRP levels of 3-30 mg/l, 30-100 mg/l and >100 mg/l was 23.0 weeks, 13.0 weeks and 6.3 weeks, respectively. Patients with serial CRP levels less than 3 mg/l had greater PFS than patients with serial CRP levels higher than 3 mg/l (p = 0.026, log rank test). The present study suggested that high levels of pre-treatment serum CRP and persistent CRP in serum was a poor prognostic factor. The decrease in CRP levels greater than 50% was a simple method to predict the response to treatment in patients with locally advanced or metastatic non-small lung cancer.


Surachatkumtonekul T.,Siriraj Hospital
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012

To evaluate the causes and the treatment outcomes of third, fourth and sixth cranial nerve palsy Medical records of 157 cases with extra-ocular muscle palsy from third, fourth or sixth cranial nerve palsy between January 1995 and December 2009 were reviewed. Demographic data, age, causes of extra-ocular muscle palsy and treatment outcomes were record and analyzed. The patients who were followed-up less than 6 months, myasthenia gravis and extra-ocular muscles fibrosis were excluded from the present study. One hundred and fifty-seven cases from 600 cases were included in the present study. The most common cranial nerve palsy was the sixth cranial nerve with 63 cases (40.1%). Of 157 cases, the causes were trauma 41 cases (26.1%), microvascular occlusion cause 34 cases (21.7%) and congenital cause 21 cases (13.4%). Cranial nerve palsy patients from microvascular occlusion cause spontaneously improved 25 of 34 cases (73.50%) in 6 months. All patients (21 cases)from congenital cranial nerve palsy had extra-ocular muscle surgery and 17 patients (80.9%) were successful. Sixth cranial nerve palsy was the most common cranial nerve palsy. Most patients with cranial nerve palsy from vascular cause spontaneously improved in 6 months. Congenital cranial nerve palsy patients need extra-ocular muscle surgery and most cases were successful


Chierakul N.,Siriraj Hospital
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012

To determine the optimum number of sputum specimens for smear and culture in the diagnosis of pulmonary tuberculosis. A retrospective study was conducted in culture-positive pulmonary tuberculosis patients at Siriraj Hospital during April 2009 to October 2010. Number of sputum specimens and microbiological results were retrieved from the microbiologic laboratory. Positive yield and incremental yield of each sputum specimen were calculated. There were 401 patients during the study period, 153 (38.2%) had positive smear for acid-fast bacilli. Overall diagnostic yields of solid culture media and liquid culture media, were 72.1% and 95.3% respectively. Incremental of overall diagnostic yield from 1 to 2 and 2 to 3 sputum specimens were 8% and 6% respectively. In place where a routinely combined smear and culture for every sputum sample submitted to the microbiologic laboratory, two specimens are sufficient for the diagnosis in nearly all pulmonary tuberculosis patients.


Eamsobhana P.,Siriraj Hospital
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012

The purpose of the present study is to evaluate the clinical and radiographic outcomes after open reduction and Z-lengthening technique with annular ligament reconstruction for the treatment of a chronic Monteggia fracture-dislocation. The authors postoperatively investigated the clinical and radiographic outcomes for ten children with a chronic Monteggia fracture. The present study group included seven boys and three girls mean age of nine years and one month at the time of open reduction. Each patient had been treated with open reduction of the radial head combined with ulna osteotomy and elongation, bending with z-plasty technique and annular ligament reconstruction. Clinical and radiographic outcomes were reviewed over a mean duration of follow-up of thirty-eight months. The postoperative Mayo Elbow Performance Index (MEPI) at the time of follow-up ranged from 95 to 100 and no poor results. The radial head remained in a completely reduced position in ten patients. In three patients, osteoarthritic changes were observed at the radiohumeral joint. Radiographically, there were seven good, three fair and no poor results. A fair radiographic result was obtained in the patients who had undergone open reduction more than three years after the injury and two patients was operation at the age of eleven and thirteen years old. Good clinical and radiographic outcomes can be expected if open reduction for the treatment of a chronic Monteggia fracture is performed when the patient is less than twelve years of age or within three years after the injury. Open reduction and Z-lengthening technique with annular ligament reconstruction for the treatment of a chronic Monteggia fracture-dislocation is safe with good clinical and radiologic outcomes without the need for bone graft. No nonunion is report in our series.


Eamsobhana P.,Siriraj Hospital
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012

To study the results of treatment of tibial hemimelia with limb salvage procedure in term of patient satisfaction, clinical results and complications. From 1993 to 2007 the authors treated six cases of tibial hemimelia with limb salvage procedures. Three legs of type Ia and four legs of type IV tibial hemimelia classified by Jones classification. The age at the operation ranged from 2 to 11 years. For type Ia cases, the Brown procedure,foot centralization and ilizarov lengthening of the fibula were used to correct limb length discrepancy. For type IV the foot centralization, soft tissue release and ilizarov lengthening were used to correct limb length discrepancy. The follow-up range from 4 to 10 years. In two patients with type Ia, one patient could bear weight without gait aids, the other walked with orthosis and axillary crutch because this patient had bilateral Ia type and knee instability with progressive flexion contracture due to weakness of the quadriceps muscle. All patients with type IV can walk independently without gait aids. Three patients were performed limb lengthening. One case was fibular lengthening following Brown procedure in Ia type. Two cases were tibial lengthening in type IV The mean lengthening was 5.1 cm. Mean lengthening index was 2.4. Satisfactory functional and cosmetic results were achieved in all patients with partial deficiency, whereas in patients with completely deficiency of the limbs, none of the 3 knees treated by fibular transfer achieved a satisfactory functional result because of insufficient quadriceps strength, progressive knee flexion contracture and persistent ligamentous instability. Nevertheless, in these 3 legs, all patients were ultimately able to withstand weight bearing. Patients and families were satisfied even though patients must have multiple surgery to correct deformities of the foot and the knee joint, as well as leg-length discrepancy and also a prolong treatment time. Limb salvage procedure in tibial hemimelia is appropriate in Thai culture because patients can weight with bare feet in the house and have sensation in the feet.


Eamsobhana P.,Siriraj Hospital
Journal of the Medical Association of Thailand = Chotmaihet thangphaet | Year: 2012

The purpose of the present study was to describe the clinical and radiographic results obtained with the combined osteotomy in patients with severe Legg-Calve-Perthes disease. During 2000 to 2010 patients with Legg-Calve-Perthes disease who intervened with combined osteotomy at Siriraj Hospital were evaluated. Clinical evaluation was categorized by Ratliff classification and radiographic evaluation was performed by Moss index, Lloyd Roberts classification and Stulberg classification. Twenty patients intervened with combined osteotomy. There were nineteen males and one female with a mean age of 7.7 years. The average follow-up was 49 months. Nine had a Catterall III and eleven had a Catterall IV. According to Herring classification, fourteen patients were Herring B and six were Herring C. In accordance with the Ratliff classification, the postoperative clinical results: fifteen good, three fair and two poor. According to Mose scale, eight patients had good results, nine had fair results and three had poor results. According to the Lloyd-Roberts classification eight patients had good results, nine had fair results and three had poor results. Based on the Stulberg classification, there were ten patients in class II, nine in class III and one in class V. The surgical treatment for severe Perthes disease with the best expected outcome is still a challenge. According to the results reported here, the combined osteotomy is safe and effective procedure for patients with severe Perthes disease in whom the femoral head cannot be contained by conventional forms of treatment.


Eamsobhana P.,Siriraj Hospital | Kaewpornsawan K.,Siriraj Hospital
International Orthopaedics | Year: 2013

Purpose: The purpose of this study was to report double dome osteotomy used to correct paediatric cubitus varus and to avoid lateral prominence after correction. Methods: Eighteen children with cubitus varus underwent double dome osteotomy. Preoperative templating created from radiographs was used to determine the bone cuts. Double dome osteotomy created a proximal and distal cut, then varus deformity and sagittal alignment were corrected. The osteotomies were fixed with K-wires and immobilised in a long-arm cast. Radiographics and clinical histories were evaluated. Ulno-humeral angle pre and postoperative, range of motion and lateral prominent index were evaluated. Results: The osteotomy was performed in 18 patients, with an average age of 7.5 years. All patients ended up with flexion of 130 or greater with full and symmetrical pronation and supination. The average ulno-humeral angle difference compared to the uninjured side was 3.27. The mean of the lateral prominent index was -0.91. The mean follow up was 50.3 months (30-115 months). All of the patients had excellent clinical and radiographic alignment. No revisions were made in this series. One transient radial nerve palsy and one superficial infection occurred. Conclusion: This series demonstrates that double dome osteotomy can provide reliable correction of varus deformity and prevent lateral prominence with a minimal complication rate. © 2013 Springer-Verlag Berlin Heidelberg.

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