Biomedical subjects

Apichai Khongphatthanayothin

Publications and source records attributed to Apichai Khongphatthanayothin.

13 recordsLinked to original sources

PubMed2026

Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at the SCN5A locus in Brugada syndrome.

Brugada syndrome (BrS) is an inherited cardiac condition characterized by a hallmark ECG pattern and an increased risk of sudden cardiac death. Central to the aetiology of BrS, the SCN5A region harbours both common non-coding risk variants and rare coding variants that are causative in approximately 20% of patients. However, rare non-coding genetic variation in this region remains largely unexplored. Here, we used whole-genome sequencing (WGS) of 752 European-ancestry BrS cases and 1,827 ancestry-matched controls to identify BrS-associated rare non-coding genetic variation at the SCN5A locus. Sliding-window and cis-regulatory element (CRE)-based rare-variant aggregate testing implicated three conserved CREs, including a dense aggregation of case singleton variants within a 178 bp enhancer in intron 17 of SCN5A which replicated in an independent BrS cohort. Prioritised BrS-associated rare and low-frequency non-coding variants within these elements were predicted to alter cardiac transcription factor motifs, and altered CRE activity in hiPSC-CM luciferase assays or were associated with BrS-relevant ECG endophenotypes in the UK Biobank. Single-variant analysis across the region identified a Bonferroni-significant five-fold case-enriched low-frequency variant within a known CRE in intron 1 of SCN5A, which replicated, was associated with slower cardiac conduction in the UK Biobank and accounted for part of the BrS GWAS signal at this locus. Structural variant analyses identified a 10.5 kb deletion upstream of SCN5A in a BrS case that encompassed a cardiac CRE and reduced sodium current density in a hiPSC-CM model, as well as a 6 kb BrS-enriched retrotransposon insertion in SCN5A that appeared to underlie part of the GWAS signal in this region. Together, these findings implicate rare and low-frequency non-coding variation at the SCN5A locus in BrS susceptibility and demonstrate the value of targeted WGS analysis of key disease loci.

Journal Article↗

PubMed2006

Increased levels of serum hyaluronan in patients with dengue infection.

OBJECTIVE: Serum hyaluronan (HA) is ubiquitously distributed in connective tissues. Circulating HA is degraded by hepatic sinusoidal endothelial cell. The aim of the present study was to evaluate serum HA levels and to determine their importance in dengue fever (DF)/dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) patients. METHODS: Serum HA levels were measured by an ELISA-based method in 16 patients with DF, 14 patients with DHF and 10 patients with DSS. The HA levels were compared with those in 48 acute hepatitis A patients; 8 healthy blood donors serve as controls. RESULTS: In acute phase, mean serum HA levels significantly increased in patients with DSS (7316.3+/-10,359.0 ng/ml) in comparison to patients with hepatitis A (93.8+/-50.4 ng/ml; P<0.0001), and healthy controls (48.3+/-16.3 ng/ml; P<0.0001). Serum levels of HA in patients with DSS rapidly decreased during the convalescent phase, but were still significantly higher than those in healthy controls (915.2+/-1294.8, and 48.3+/-16.3 ng/ml; P<0.0005). CONCLUSIONS: The increased HA in dengue patients could be attributed to sinusoidal endothelial damage rendering the endothelium incapable of HA clearance. The elevation of HA production may involve the pathogenesis of dengue infection. Further studies are needed to determine whether the increase in the HA production or decrease in its clearance is responsible for the elevated serum HA.

Adolescent↗

PubMed2006

Serum levels of sICAM-1 and sE-selectin in patients with dengue virus infection.

The purpose of this study was to measure the serum level of sICAM-1 and sE-selectin as markers for endothelial damage in patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Twenty-nine patients with serologically-proven dengue virus infection (age 10.6 +/- 2.4 years, 55% male, DF = 13 and DHF = 16) were enrolled. Serum samples were collected from 25 healthy children (age 10.6 +/- 2.3 years, 40% male) as the control group. A follow-up was done at a mean interval of 15.9 +/- 1.6 days. The level of sICAM-1 at the toxic stage was significantly elevated compared to its level at the follow-up (494.1 +/- 107.4 versus 358.2 +/- 67.6 ng/ml, P = 0.001), but no difference was found between patients with DF and patients with DHF (444.1 +/- 158.0 versus 465.1 +/- 154.6 ng/ml, P = 0.74). The sICAM-1 level at the follow-up was similar to that of the control group (396.9 +/- 113.0 ng/ml, P = 0.56). The level of sE-selectin at the toxic stage was not different from its level at the follow-up (75.9 +/- 33.0 versus 75.5 +/- 31.7 ng/ml, P = 0.96), and no difference was found between the DF group and the DHF group (64.1 +/- 25.7 versus 78.8 +/- 39.9 ng/ml, P = 0.30). These levels were not elevated compared to the sE-selectin level that was determined in 8 patients in the control group (94.7 +/- 20.5 ng/ml, P = 0.12). In conclusion, there is evidence of endothelial activation by an increased sICAM-1 level in patients with dengue virus infection. However, the degree of endothelial activation alone may be similar for patients with DF and patients with DHF, and this fact by itself cannot explain the difference between the two clinical syndromes of dengue virus infection. The sE-selectin level was not elevated for patients included in this study.

Child↗

PubMed2006

Clinical course and outcome of children with single ventricle physiology at King Chulalongkorn Memorial Hospital.

BACKGROUND: Children with single ventricle physiology comprise 10% of all children with congenital heart disease (CHD) and one-third of children with cyanotic CHD seen at King Chulalongkorn Memorial Hospital. The prognosis of these children is generally thought to be poor but no study of the outcome has previously been done in this hospital and in Thailand. OBJECTIVES: To study the clinical course and outcome of children with single ventricle physiology at King Chulalongkorn Memorial Hospital during the current era. MATERIAL AND METHOD: One hundred and seventeen patients with single ventricle physiology were initially seen at this hospital during the year 1999-2001. Retrospective chart reviews were carried out in 90 children with available medical records. The status of the patients was determined in 2003 at clinic visits, by phone calls and mail. RESULTS: The main diagnoses were tricuspid atresia (TA, n = 10), pulmonary atresia with intact ventricular septum (PA/IVS, n = 16), single ventricle associated with cardiac malposition or heterotaxy syndrome (malposition, n = 35), hypoplastic left heart syndrome (HLHS, n = 11) and other complex single ventricle (others, n = 18). Most children did not have other major anomalies. Survival of patients with TA and PA/IVS was approximately 92 and 87% at 1 and 4 years, respectively. For patients in the other three groups, 1 and 4 year survival was 69 and 42%, respectively. Patients with HLHS had the worse survival, partly because of decisions not to pursue further treatments by the parents. Among HLHS patients who underwent Norwood procedure, the 1 and 4 year survival were 83% and 42%, respectively. Approximately 40 and 90% of all patients underwent heart surgery at 1 and 4 years follow-up, respectively. CONCLUSION: Despite limited resource, the short-term outcome of Thai children with single morphologic left ventricle (TA and PA/IVS) is reasonably good. Timely evaluation and treatment of these children toward Fontan procedure should be ensured. After proper discussion with the parents, palliative care is still acceptable for patients with single morphologic right ventricle or other complex single ventricle due to poor survival in the current era. As access to health care improves, re-evaluation of these outcomes is necessary to find the best strategy for the management of these patients.

Child↗

PubMed2005

Hepatosplanchnic circulatory dysfunction in acute hepatic infection: the case of dengue hemorrhagic fever.

The mechanism of shock in patients with dengue hemorrhagic fever (DHF) has not yet been fully understood. In this study, we investigated the possibility of splanchnic venous pooling as a contributor for circulatory dysfunction in these patients. Ultrasonographic studies of portal vein and inferior vena cava were done in 45 patients with serologically or PCR-confirmed diagnosis of dengue virus infection. The size of portal vein and inferior vena cava, mean blood flow velocity in the right portal vein, and modified portal vein congestion index were compared between patients with dengue fever (DF, n = 20), DHF without shock (n = 14), and dengue shock syndrome (DSS, n = 11) during the toxic stage, convalescent stage, and at follow-up. The portal vein was significantly more dilated in patients with shock (DSS) than DHF without shock and than DF during the toxic and convalescent stages (P < 0.05), but not at follow-up. The change in the size of inferior vena cava followed the opposite trend (not statistically significant). Portal vein blood flow velocity was lower and congestion index was higher in shock cases (DSS) than DHF without shock and than DF at toxic and convalescent stages (P < 0.01). The differences disappeared at follow-up. Hepatosplanchnic venous pooling and/or dysfunction occur and correlate with the severity of circulatory derangement and shock in patients with DHF. The cause(s) and significance of hepatosplanchnic circulatory dysfunction in DHF and possibly other viral hepatic diseases deserve further study.

Adolescent↗

PubMed2005

Infective endocarditis in pediatric patients: an eighteen-year experience from King Chulalongkorn Memorial Hospital.

OBJECTIVES: To review the clinical features and outcome of the pediatric patients diagnosed with infective endocarditis (IE) at King Chulalongkorn Memorial Hospital over an 18-year period. MATERIAL AND METHOD: From January 1987 to December 2004, 57 pediatric patients; 28 females and 29 males, age ranged from 2 months to 15 years, mean of 8.64 +/- 3.82 years, classified as "definite" IE according to the Duke criteria were reviewed. RESULTS: Of the 57 patients, 42 patients (74%) had underlying congenital heart diseases, 7 patients (12%) had underlying rheumatic heart disease, 8 patients (14%) had previously normal heart. Nine patients had history of previously palliative or corrective surgery. Blood cultures were positive in 26 patients (46%). Streptococci and staphylococci were the most commonly isolated organisms. Two-dimensional echocardiography demonstrated vegetations in 56 patients (98%). The location of the vegetations was in the right heart in 30 patients (54%) and in the left heart in 26 patients (46%). Complications occurred in 28 patients (49%). Common complications included congestive heart failure, cerebral emboli, septic shock, and mycotic aneurysm. The overall mortality was 11% (6 patients). By statistical analysis, vegetations in the left heart had a higher incidence of complication than that in the right heart. The vegetation size of > or =10 mm had a significant higher incidence of embolic events. CONCLUSION: The clinical features and outcomes of the present study have a similar pattern as the earlier studies. The rates of complications and mortality are still high.

Adolescent↗

PubMed2005

Pediatric heart surgery waiting time in Thailand and its effect on mortality: A cooperative study from Chulalongkorn, Children and Chiang Mai University hospitals.

BACKGROUND: Thai children who need cardiac surgery are often put on a waiting list. The waiting time and mortality during waiting have not been previously systematically studied. MATERIAL AND METHOD: A cooperative study was conducted at King Chulalongkorn Memorial hospital (Chula), Children hospital (CH), and Chiang Mai University hospital (CMU). The status of children who were referred for cardiac surgery at these hospitals in the year 1999-2000 (Chula and CMU) and the year 2000 (CH) were analyzed by Kaplan-Meier survival curve. The patients who lost to follow up and could not be contacted were censored at the time of last clinic visit. Log-Rank test was used to compare the survival curve and waiting time between three hospitals. RESULTS: The averaged annual referrals for cardiac surgery at the three hospitals were 846 cases (205 for Chula, 462 for CH and 179 for CMU). Mean age was 4.3 +/- 4.2 years and 51% were male. Follow up data were complete in 96.3%. Surgical procedures were correction of simple shunt lesions (ASD, VSD, AV canal) in 33.9%, close heart surgery (PDA ligation, coarctation repair, BT shunt) in 29.9%, total repair TOF in 19.6%, complex surgery in neonate and infants (arterial switch, TAPVR repair, Norwood procedure, truncus and interrupted aortic arch repair) in 4.2% and others in 12.3%. Median waiting time was 195 days and was significantly different between the three hospitals (p < 0.01). Mortality while waiting were approximately 5% at 2 years at Chula and CH, which was significantly higher than CMU (0%, p = 0.02). Further analysis revealed difference in age (lower Chula than CH than CMU) and types of surgery (more complex at Chula and CH) which may be the causes for difference in the mortality observed. CONCLUSION: Waiting time for cardiac surgery for children in Thailand is long and should be viewed as a problem in public health policy. Optimal waiting time at each hospital may not have to be the same, depending on the type and severity of the disease seen at each particular center Attempt should be made to solve this problem at the national level.

Cardiac Surgical Procedures↗

PubMed2003

Hemodynamic profiles of patients with dengue hemorrhagic fever during toxic stage: an echocardiographic study.

OBJECTIVE: To study left ventricular performance and hemodynamic abnormalities during different stages of dengue hemorrhagic fever (DHF). DESIGN AND SETTING: Observational study in a tertiary medical school hospital. PATIENTS: Twenty-four patients with serologically confirmed diagnosis of dengue virus infection and DHF according to the WHO criteria. METHODS: Echocardiography was performed during toxic, convalescent stages and at least 2 weeks after discharge (recovery). Left ventricular ejection fraction, rate-corrected velocity of circumferential fiber shortening adjusted for end-systolic meridional wall stress (VCFC/ESS) Z score, end-diastolic volume Z score, cardiac index, heart rate, mean arterial pressure, and total systemic vascular resistance (SVR) were compared between different stages of DHF. RESULTS: Ejection fraction and VCFC/ESS were significantly lower during the toxic stage than after recovery. End-diastolic volume was low during toxic stage and returned to normal during convalescence and recovery. Cardiac index was low during the toxic stage due to decreased preload (low end-diastolic volume) and depressed left ventricular ejection fraction. Cardiac index remained subnormal during convalescence due to sinus bradycardia. Wide variation in heart rate during toxic stage resulted in a small, nonsignificant increase compared to recovery. With treatment, heightened SVR resulted in relatively normal mean arterial pressure throughout the course of the illness. CONCLUSIONS: The mechanism of decreased cardiac output during toxic stage of DHF is complex. Decreased preload is accompanied by decreased left ventricular performance, and possibly a subnormal heart rate response in some patients.

Analysis of Variance↗

PubMed2003

Roxithromycin induced torsade de pointes in a patient with complex congenital heart disease and complete atrioventricular block.

We reported a 6-year-old girl who developed torsade de pointes (TdP) after taking roxithromycin. The patient had congenital complete heart block and complex cyanotic heart disease. Before taking roxithromycin, her corrected QT interval (QTc) was 0.39 second with a ventricular rate of 55-60 beats/min. Repetitive bursts of TdP with prolonged QT interval (QTc = 0.55 s) developed after taking roxithromycin. After stopping the medication, her QT interval normalized (QTc = 0.38 s). This case demonstrated the potential of roxithromycin in causing TdP especially in a patient with other risk factors for prolong QT interval and TdP.

Anti-Bacterial Agents↗

PubMed2003

Single midline approach for permanent pacemaker implantation in children.

Permanent pacemaker implantation was carried out in 12 children with a mean age of 1.4 years (range, 2 days to 4 years) and a mean weight of 8.6 kg (range, 2.4-13.6 kg), using a single midline approach for placement of both the epicardial lead and the pacemaker generator (intermuscular abdominal implantation). Platinized porous-tipped steroid-eluting epicardial leads were used in all patients. The pacemakers worked well, and there was no early postoperative complication. This technique was found to be rapid, simple, and safe in children, especially neonates and infants.

Cardiac Pacing, Artificial↗

PubMed2003

A cost-benefit analysis of intravenous immunoglobulin treatment in children with Kawasaki disease.

To determine the long-term cost-benefit of intravenous immunoglobulin (IVIG) treatment in Children with Kawasaki Disease (KD), a model was made to compare the total cost for management of these children with and without the use of IVIG. Long-term (10-21 years) follow-up of 594 KD patients treated in the pre-IVIG era reported by Kato, et al. was used to calculate cost using previous cost studies from Chulalongkorn Hospital. Reduction of CAA from 25 per cent to 4 per cent with IVIG treatment was assumed based on previous published data. Total cost was slightly lower for the non-IVIG treatment group compared to the IVIG treatment group (33,451,129 baht vs 35,001,195 baht) for the duration of follow-up in Kato's model. Cost per effectiveness analysis showed more effectiveness in the IVIG treatment group (359,576 baht vs 383,614 baht). Net cost analysis similarly demonstrated lower costs in the IVIG treatment group (25,365,215 baht vs 33,451,129 baht). Incremental cost-effectiveness analysis demonstrated supplementary costs of 13,663 baht for one case in the reduction of coronary involvement and 387,517 baht for one life saved in the IVIG-treated group. Estimation of total costs for follow-up and treatment for healthy life (until 60 years old) was more expensive in the non-IVIG treatment than the IVIG treated group (75,482,803 baht vs 29,883,833 baht). The authors conclude that treatment of all KD cases in Thailand with IVIG is likely to result in lower cost and better outcome when compared to no treatment with the IVIG policy.

Adolescent↗

PubMed2003

Prevalence of idiopathic long QT syndrome in congenital sensori-neural hearing loss students of Songkhla School for the Deaf.

OBJECTIVES: To survey the prevalence of the long QT syndrome (LQTS), especially Jervell-Lange-Nielsen syndrome (JLNS), in Thai children (The first such study). BACKGROUND: LQTS is a rare inherited disease with a prevalence of 0.21 per cent in children with congenital deafness from other reports. These patients carry a high risk of recurrent syncope and fatal ventricular arrhythmia. STUDY DESIGN: Cross-sectional survey from January 2000 to August 2000. METHOD: A total of 276 children with congenital sensori-neural hearing loss were included. A questionnaire was employed and all children were examined by a pediatric cardiologist to rule out organic heart disease. EKGs were obtained and QTc intervals were blindly measured using standard methods in L2, V5 or any other leads with the longest QTc interval by three pediatric cardiologists. If QTc interval is prolonged, additional EKG (up to 3) were done to confirm the finding. Schwartz criteria was used to identify index cases with LQTS after repeated EKGs, and exercise stress tests. Also, echocardiography were done in patients suspected of having LQTS. RESULTS: A total of 14 children needed a third EKG and more work ups due to persistent long QTc interval after 2 consecutive EKG studies with QTc intervals ranged from 456 msec to 466 msec, and Schwartz score from 1.5 to 2.5. There were 6 twins and no triplets in the study. Finally, two subjects (not twins or siblings) had persistent prolonged QTc intervals after 3 EKG studies. After the exercise stress test, both still had a prolonged QTc interval, not corrected to the normal QTc interval even at the exercise peak. There was no cardiac abnormality either structurally or functionally from the 2D echocardiogram and Doppler color flow study. CONCLUSION: The possible prevalence of JLNS was 0.7 per cent (2/276). Both children were in the low-risk group for having LQTS.

Adolescent↗

PubMed2002

Resident recruitment: what are good predictors for performance during pediatric residency training?

The authors evaluated the value of the Cumulative Grade Point Average (GPAX), letters of recommendation and personal interview in predicting performance of first year residents at the Department of Pediatrics, Faculty of Medicine, Chulalongkorn University. The pre-residency data of 25 first year pediatric residents were compared to the results of the Pediatric In-training Examination (PIE) and clinical evaluation by faculty during the first 7 months of training. The Clinical Performance Rating Score (CPRS) developed by the Royal College of Pediatricians of Thailand was used for clinical performance evaluation. GPAX correlated strongly with PIE score (r = 0.69, p < 0.001) while letters or recommendation and interview score were not predictive. For the majority of residents who graduated from Chulalongkorn University, including the undergraduate program into the regression model improved this association (r = 0.90, p < 0.001). Interview score correlated moderately (r = 0.49, p = 0.02) with clinical performance measured by CPRS which entailed the evaluator to assess a resident in 6 specific areas. GPAX and letters of recommendation showed a trend toward positive correlation with clinical performance, but these associations were weak (r = 0.32-0.39). Further analysis of letters of recommendation found a significant difference between the score given by evaluators in community hospital settings compared to the score given by medical school faculty or evaluators in large regional or provincial hospitals. The authors conclude that the cognitive function of pediatric resident candidates can be assessed reliably by GPAX. Research on how to adjust for the variability of GPAX given by an individual undergraduate program will improve the residency selection process. A structured interview may correlate better with global clinical performance than GPAX or letters of recommendation but all methods are at best moderately predictive of clinical performance. Improvement can be made by continuous evaluation and adjustment of the selection process.

Adult↗