Increased alanine aminotransferase level and future risk of type 2 diabetes and impaired fasting glucose among the employees in a university hospital in Thailand.

AIM: The purpose of this study was to determine the association between baseline alanine aminotransferase (ALT) levels, and future risk of impaired fasting glucose and type 2 diabetes among the employees of a university hospital in Bangkok, Thailand. METHODS: Totally, 2370 and 1619 workers without diabetes and impaired fasting glucose (IFG) at baseline, respectively, who were 35 years or older were followed during 2001-2005. Diagnosis of IFG and type 2 diabetes was based on the fasting plasma glucose levels of 100-125 and greater or equal to 126 mg/dl, respectively. RESULTS: Higher baseline ALT levels were associated with future diabetes risk in an obvious dose-response manner (the OR [95% CI] for the groups with baseline ALT of 17-22, 23-38, and greater than 38 mg/dl comparing to the group with baseline ALT of 1-16 mg/dl were 4.75 [1.25-18.10], 6.14 [1.54-24.45], and 7.19 [1.32-39.16], respectively). Magnitude of association were even higher among those with existing IFG at baseline. The association patterns were consistent for both genders. Concerning the IFG risk, while those who developed IFG had significantly higher baseline ALT levels than those who remained normal at the end of follow-up period, further analyses did not show that baseline ALT was significantly associated with future IFG risk. CONCLUSION: Present study provided supporting evidence from a cohort of Asian subjects about the ALT and future type 2 diabetes risk.

The correlation between markers of oxidative stress and risk factors of coronary artery disease in Thai patients.

An imbalance between oxidative damage and antioxidative protection in association with the pathophysiology of atherosclerosis has been suggested. The aim of our study was to investigate the relationship between plasma lipids, the antioxidant system and oxidative damage in Thai patients with stable coronary artery disease (CAD). Sixty-one patients (40 males, 21 females), who were angiographically defined as having CAD and were clinically stable, participated in this study. Thirty-two healthy subjects (20 males, 12 females) served as normal controls. The investigation included the measurements of plasma lipid profiles and plasma total antioxidative status (TAS) such as plasma vitamin E erythrocyte glutathione (GSH) and glutathione peroxidase (GPx), as well as malondialdehyde (MDA) and total plasma total protein thiols (P-SH). In patients with CAD, erythrocyte GSH and GPx were significantly lower than those found in controls. However plasma TAS and vitamin E were not significantly different between groups. Patients with CAD also had higher MDA and lower P-SH levels than the controls, which represents the oxidative damage products of lipid and proteins. Multiple regression analysis revealed negative correlations between GSH and cholesterol, GSH and low density lipoprotein (LDL), vitamin E and MDA, as well as P-SH and MDA. This study demonstrated the status of oxidative stress in patients with stable CAD. Since oxidative stress is the imbalance between the total oxidants and antioxidants in the body, any single oxidant/antioxidant parameter may not reflect the overall oxidative stress system. Thus, in patients with CAD, diets with various types of antioxidants may be more beneficial in increasing antioxidant activity than any particular antioxidant supplementation.

New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives.

AIMS: Sudden unexplained death syndrome occurs in previously healthy South-east Asian young adults without any structural cause of death. The common electrocardiographic (ECG) change in sudden unexplained death syndrome survivors is right bundle branch block and ST elevations in leads V(1) to V(3), which are similar to the ECG pattern in the Brugada syndrome (Brugada sign). It is difficult to diagnose the Brugada sign with the 12-lead ECG in sudden unexplained death syndrome survivors and their family members because the ECG could be transiently normalized. We proposed using the higher intercostal space V(1) to V(3) lead ECG, together with procainamide to detect the Brugada sign. METHODS AND RESULTS: Among 20 ventricular fibrillation cardiac arrest patients, 13 sudden unexplained death syndrome survivors and their relatives (n=88) were studied using the single standard 12-lead ECG and the new six higher intercostal space V(1) to V(3) lead ECG (-V(1) to -V(3) and -2V(1) to -2V(3)). Ten sudden unexplained death syndrome survivors and relatives (n=48) who had a normalized ECG were also infused with procainamide (10 mg x kg(-1)i.v.) to unmask the Brugada sign and both ECG methods were recorded. Forty healthy individuals and 13 spouses served as the control group. Prior to the procainamide infusion, the Brugada sign could be detected in nine sudden unexplained death syndrome survivors (69.2%) and three (3.4%) relatives with the standard ECG and in 12 (92.3%) and nine (10.2%) with the new six-lead ECG. After the procainamide infusion, the Brugada sign could be demonstrated in seven sudden unexplained death syndrome survivors (70%) and seven (14.6%) relatives with the standard ECG and in nine (90%) (P=0.26) and 23 (47.9%) (P=0.0004) with the new six-lead ECG, respectively. All the controls were negative for the Brugada sign. CONCLUSIONS: Our data suggest that the new higher intercostal space lead ECG, with or without the procainamide test is helpful in detecting the Brugada sign in sudden unexplained death syndrome survivors and their relatives.

Pattern of inheritance in three sudden unexplained death syndrome ("Lai-tai") families.

Sudden Unexplained Death Syndrome (SUDS) (or Lai-tai) is sudden death in previously healthy young adults without any structural cause of death from autopsy findings. Our previous data showed that familial SUDS is not X-linked recessive. The objective of this study was to determine the pattern of inheritance in familial SUDS using the ECG markers of Brugada syndrome (RBBB and ST-segment elevation in V1 to V3), SUDS and presumptive SUDS as phenotypes. We employed the standard 12-lead ECG and higher intercostal space (ICS) V1 to V3 (-V1 to -V3 and -2V1 to -2V3) leads ECG in SUDS relatives after procainamide and drew the pedigree. We studied 62 relatives of 9 SUDS victims who died in Singapore and selected 3 families (n = 34) for the procainamide test and ECG. The mean age was 36.4 +/- 23.6 years (4-78 years). Three SUDS families showed the same pattern of inheritance of autosomal dominant.

Potassium status of Northeast Thai constructors in three different geographic locations.

Sudden and unexpected death of young adults during sleep is a phenomenon among Southeast Asians and particularly young Northeast (NE) Thailand constructors in Singapore. Survivor of sudden unexplained death syndrome (SUDS) without structural heart disease with idopathic ventricular fibrillation (VF) has been documented. Low plasma potassium (K) and depletion of K can occur simply through a reduction of K intake and are associated with increased risk of VF. The K-status of the populations was evaluated in the NE (Group 1, n=30), Bangkok (Group 2, n=48) and Singapore (Group 3, n=46). Groups 2 and 3 were further subdivided into Group 2A (worked in Bangkok < or = 1 year, n=8), Group 2B (worked in Bangkok > 1 year, n=40), Group 3A (consumed self-prepared or ready-to-buy meals, n=25) and Group 3B (regularly consumed foods provided free-of-charge by construction companies, n=21). Thirty-four male healthy university personnels from the NE and Bangkok served as the control--Group 4. Two 24-h urine samples and a fasting blood sample were collected from each subject. Dietary-K from food was determined by duplicated meal analysis. All these samples were then analyzed for their K-content. Group 3A had the lowest K-status: their K-intake, serum-K, and urinary-K level were 29 +/- 5.8 mmol/day (% low K-intake=100), 3.43 +/- 0.34 mmol/L (% hypokalemia=48) and 19.23 +/- 8.2 mmol/day (% hypokaliuria=87.5), respectively. Among the construction workers, average K-intake, serum-K and urinary-K levels were 45.5 +/- 6.1 mmol/day (% low K-intake = 37.5), 3.93 +/- 0.2 mmol/L (% hypokalemia = 2.5) and 39.6 +/- 9.2 mmol/day (% hypokaliuria = 12.5), respectively. The values of Group 2B were similar to Group 4. In addition, when the data from all of the groups were compared, there was a positive correlation between dietary-K (intake) and urinary-K (excretion) (r=0.881, p<0.001). In conclusion, NE Thailand constructors from various locations exhibited low K status with low dietary-K, high incidence of hypokalemia, and low urinary-K. From the present study, this low K status may be an important trigger factor for VF in construction workers and associated with increase risk of SUDS.

STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target.

BACKGROUND: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. OBJECTIVE: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. METHODS: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115-180 mg/dL and triglyceride levels of < or = 400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of < or = 100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of < or = 115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. RESULTS: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels < or = 100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level < or = 115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001). Simvastatin was well tolerated across the dose range. Overall, 40 patients (30.1%) had > or = 1 clinical adverse experience. Only 14 (10.5%) had adverse experiences that were possibly, probably, or definitely related to study drug; none of these experiences were considered serious. The most common adverse experiences (> or = 3% incidence) were abdominal pain (6%); chest pain (5%); dizziness (4%); and asthenia/fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection (3% each). No new or unexpected adverse experiences were seen at the higher doses. CONCLUSIONS: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of < or = 100 mg/dL.

Right ventricular electrocardiographic leads for detection of Brugada syndrome in sudden unexplained death syndrome survivors and their relatives.

BACKGROUND: Sudden unexplained death syndrome (SUDS) is a sudden death syndrome in previously healthy Southeast Asian young adults without any structural causes of death. Many SUDS survivors show electrocardiographic (ECG) evidence of RSR' and ST elevation in leads V1 to V3, which is similar to the ECG pattern in Brugada syndrome. However, in many cases transient normalization of the ECG does not make diagnosis with standard 12-lead ECG possible. HYPOTHESIS: To overcome this problem, we utilized the new right ventricular ECG leads to detect the Brugada syndrome in SUDS survivors. METHODS: The subject was a Thai male patient who presented with a SUDS-like syncopal attack. He had cardiac arrest due to idiopathic ventricular fibrillation. RESULTS: Post-resuscitation standard 12-lead ECG showed no diagnostic features of Brugada syndrome. However, ECG patterns of RSR' and ST elevations typical for Brugada syndrome could be detected at the higher intercostal space leads V1 to V3. We observed similar findings in 2 of the other 10 SUDS survivors and 4 of 23 healthy family members. CONCLUSIONS: Our data suggest that these new right ventricular leads ECG may be helpful in detecting Brugada syndrome in SUDS survivors and their relatives.

Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24.

BACKGROUND: Dilated cardiomyopathy (DCM) and sensorineural hearing loss (SNHL) are prevalent disorders that occur alone or as components of complex multisystem syndromes. Multiple genetic loci have been identified that, when mutated, cause DCM or SNHL. However, the isolated coinheritance of these phenotypes has not been previously recognized. METHODS AND RESULTS: Clinical evaluations of 2 kindreds demonstrated autosomal-dominant transmission and age-related penetrance of both SNHL and DCM in the absence of other disorders. Moderate-to-severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade. DNA samples from the larger kindred (29 individuals) were used to perform a genome-wide linkage study. Polymorphic loci on chromosome 6q23 to 24 were coinherited with the disease (maximum logarithm of odds score, 4.88 at locus D6S2411). The disease locus must lie within a 2.8 cM interval between loci D6S975 and D6S292, a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy. The epicardin gene, which encodes a transcription factor expressed in the myocardium and cochlea, was assessed as a candidate gene by nucleotide sequence analysis; no mutations were identified. CONCLUSIONS: A syndrome of juvenile-onset SNHL and adult-onset DCM is caused by a mutation at 6q23 to 24 (locus designated CMD1J). Recognition of this cardioauditory disorder allows for the identification of young adults at risk for serious heart disease, thereby enabling early intervention. Definition of the molecular cause of this syndrome may provide new information about important cell physiology common to both the ear and heart.

Efficacy of rapid infusion of streptokinase in patients with acute myocardial infarction.

The early use of thrombolytic agents is now the most important treatment in acute myocardial infarction (AMI). The earlier reperfusion should result in a higher survival rate. To determine whether the faster infusion of streptokinase (SK) will produce earlier reperfusion, 40 patients were enrolled to the trial. Half of them received 1.5 mu. of SK in one hour while the others received 1.5 mu. in half an hour. The rapid infusion group tended to have earlier reperfusion but there was no statistically significant difference in the reperfusion time. Hypotension was observed in both groups but more in the conventional group and responded to intravenous fluid replacement. Bleeding complication was low in both groups. Four patients died, one from re-occlusion and developed severe bradycardia, the remainder had cardiogenic shock which did not respond to treatment. It can be concluded that SK infusion in half an hour is safe but the beneficial effect remains to be seen in a large scale study.

Safety and acceptable initial outcomes of reused balloon catheters for percutaneous transluminal coronary angioplasty.

OBJECTIVES: This study was conducted to compare the safety and initial outcomes applying reused balloon (RB) catheters with those of attained new balloon (NB) catheters when performing percutaneous transluminal coronary angioplasty. BACKGROUND: Recently, PTCA procedures have been used increasingly for the treatment of patients with coronary heart disease. In the era of national economic constraint, reused balloon catheters will reduce the cost of expensive, imported coronary angioplasty devices. Hence, data concerning the safety and success rate of RB catheters compared with NB catheters are urgently required. METHODS: Prospective comparative study between reused and new balloon catheters for coronary angioplasty. Data forms were completed after each procedure and before the patient was discharged after an 18-month period. RESULTS: From July 1996 to December 1997, 221 cases (121-RB, 100-NB) were enrolled. Mean age, ejection fraction, diseased vessel and lesion characteristics were similar in both groups. The number of lesions was much higher performed in the RB than in the NB group (1.7 +/- 0.9 vs 1.4 +/- 0.8, p = 0.02). The RB group had more cases of acute myocardial infarction than the NB group (7.4% vs 1%, p = 0.003), however, the angiographic and case success rate were the same (99.5% vs 97.9% and 98.3% vs 97% respectively). Major adverse cardiac events in RB amounted to 1.7 per cent and for NB to 1.0 per cent (p = ns). The total amount of balloons used in RB was much higher than in the NB group (1.5 +/- 0.6 vs 1.1 +/- 0.3, p = <0.0001). There were neither infection nor positive blood cultures in either group. CONCLUSIONS: Reused balloon catheters can be safely used for percutaneous transluminal coronary angioplasty with a high success rate. The total cost of angioplasty can be reduced without a decline in efficacy.

Hereditary postlingual sensorineural hearing loss mapping to chromosome Xq21.

BACKGROUND: Mutations on the X-chromosome clinically manifesting different phenotypes of hearing loss have been mapped to the long arm at different loci, DFN1-DFN3. Another defect in a family with sex-linked, postlingual, progressive sensorineural hearing loss was mapped to Xq. METHODS: Clinically, the family was evaluated by physical and audiometric examination of 17 members including computerized tomographic (CT) evaluation of the proband. Molecular evaluation consisted of polymerase chain reaction amplification of patient genomic DNA and resolution 32P-labeled fragments by polyacrylamide gels. Inheritance of DNA alleles and deafness were analyzed using the MLINK computer program. RESULTS: Five affected males demonstrated symmetrical sensorineural hearing loss as significant as 100 decibels (dB). Two carrier females had a milder loss with frequency findings of 10 dB to 60 dB. Computerized tomography (CT) evaluation of the temporal bones of the proband was normal. The odds were 200:1 that the responsible gene was linked to locus DXS986 (maximum lod score = 2.3 at 0 = 0). Analysis of recombination events defined by family members demonstrates that the responsible gene lies in a 21 cM (30 MB) interval, between loci DXS12175 and 1106. The disease locus in this family does not appear to map to DFN1 or DFN3. CONCLUSION: The family described here, with affected males who have progressive, postlingual sensorineural hearing loss and mildly affected females maps most compatibly to the DFN2 locus. Analysis of hereditary deafness in this family refines the DFN2 locus to a 9.2 Mb region in chromosome X band q21 between DXS990 and DXS106.

Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy.

BACKGROUND: Mutations in the gene for cardiac myosin-binding protein C account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy. The spectrum of disease-causing mutations and the associated clinical features of these gene defects are unknown. METHODS: DNA sequences encoding cardiac myosin-binding protein C were determined in unrelated patients with familial hypertrophic cardiomyopathy. Mutations were found in 16 probands, who had 574 family members at risk of inheriting these defects. The genotypes of these family members were determined, and the clinical status of 212 family members with mutations in the gene for cardiac myosin-binding protein C was assessed. RESULTS: Twelve novel mutations were identified in probands from 16 families. Four were missense mutations; eight defects (insertions, deletions, and splice mutations) were predicted to truncate cardiac myosin-binding protein C. The clinical expression of either missense or truncation mutations was similar to that observed for other genetic causes of hypertrophic cardiomyopathy, but the age at onset of the disease differed markedly. Only 58 percent of adults under the age of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68 of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete through the age of 60 years. Survival was generally better than that observed among patients with hypertrophic cardiomyopathy caused by other mutations in the genes for sarcomere proteins. Most deaths due to cardiac causes in these families occurred suddenly. CONCLUSIONS: The clinical expression of mutations in the gene for cardiac myosin-binding protein C is often delayed until middle age or old age. Delayed expression of cardiac hypertrophy and a favorable clinical course may hinder recognition of the heritable nature of mutations in the cardiac myosin-binding protein C gene. Clinical screening in adult life may be warranted for members of families characterized by hypertrophic cardiomyopathy.

The Bjornstad syndrome (sensorineural hearing loss and pili torti) disease gene maps to chromosome 2q34-36.

We report that the Bjornstad syndrome gene maps to chromosome 2q34-36. The clinical association of sensorineural hearing loss with pili torti (broken, twisted hairs) was described >30 years ago by Bjornstad; subsequently, several small families have been studied. We evaluated a large kindred with Bjornstad syndrome in which eight members inherited pili torti and prelingual sensorineural hearing loss as autosomal recessive traits. A genomewide search using polymorphic loci demonstrated linkage between the disease gene segregating in this kindred and D2S434 (maximum two-point LOD score = 4.98 at theta = 0). Haplotype analysis of recombination events located the disease gene in a 3-cM region between loci D2S1371 and D2S163. We speculate that intermediate filament and intermediate filament-associated proteins are good candidate genes for causing Bjornstad syndrome.