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C-K Wong

Publications and source records attributed to C-K Wong.

14 recordsLinked to original sources
PubMed2006

Genome-wide scan identifies a susceptibility locus for familial primary cutaneous amyloidosis on chromosome 5p13.1-q11.2.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder in South America and Southeast Asia. Most cases of PCA are sporadic but familial aggregation has been reported from South America and Taiwan. The different susceptibility among ethnic groups suggests that genetic factors may play an important role in its pathogenesis. OBJECTIVES: We aimed to perform a genome-wide scan by linkage analysis across 15 families with familial primary cutaneous amyloidosis (FPCA) to map the disease gene(s) for FPCA. PATIENTS AND METHODS: A total of 15 FPCA families including 50 individuals affected with PCA were recruited. Throughout the 22 autosomes, 369 polymorphic microsatellite markers were used initially. Regions showing a LOD score > 1 identified in the initial scan were further analysed with additional markers. Two-point and multipoint linkage analysis were performed by using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. RESULTS: A maximum two-point LOD score of 4.76 for the marker D5S1490 (theta = 0.10, alpha = 0.60) and a multipoint LOD score of 4.50 between D5S822 and D5S623 (alpha = 0.60) were obtained under the assumption of heterogeneity. A peak NPL score of 5.23 (P value = 0.000007) was found from D5S1490 to D5S2076. Further analysis focusing on two major families identifies a common haplotype shared by all affected individuals between D5S1490 and D5S623. To our knowledge, this is the first report of genome-wide analysis of a large number of FPCA pedigrees. CONCLUSIONS: Our study provides evidence for significant linkage to chromosome 5p13.1-q11.2 in a subset of FPCA families.

Adolescent↗
PubMed2005

Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23.

BACKGROUND: There is a high incidence of primary cutaneous amyloidosis (PCA) in South America, South-east Asia and Taiwan. To date, the aetiology of PCA remains unknown, but it is believed to be multifactorial. Although most cases are sporadic, some patients have a family history. Familial aggregation and different susceptibility to PCA among ethnic groups suggest that genetic factors may play an important role in its pathogenesis. However, no genetic loci for familial PCA (FPCA) have been identified so far. OBJECTIVES: In order to identify the susceptibility gene of FPCA, we took a candidate gene approach and performed linkage analysis on chromosome 1q21.3-24.2, including the 1q23.2 region where the gene encoding serum amyloid P component (APCS) is located. PATIENTS AND METHODS: Nine FPCA families including 29 individuals affected with PCA were recruited for this linkage study. Initially, 11 highly polymorphic microsatellite markers spanning the region from 1q21.3 to 1q24.2 were genotyped and revealed a suggestive linkage region. This region was further fine-mapped with seven additional markers. We also re-sequenced the 2.5-kb genomic region of the APCS gene in 29 affected and 42 control individuals. Two-point and multipoint linkage analyses were performed using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. RESULTS: Both two-point and multipoint linkage analysis for all 11 markers generated negative or small positive total lod scores for all nine families. However, when we considered only three families, a maximum two-point total lod score of 2.09 was obtained for the marker D1S2844 at theta = 0.01. A plateau of multipoint total lod score between D1S2768 and D1S2878 with a maximum of 2.48 at the marker D1S2844 was observed. A maximum NPL score of 3.11 (P = 0.008) was also obtained for the marker D1S2878. However, re-sequencing of the APCS gene identified no functional mutation. CONCLUSIONS: Both parametric and nonparametric linkage evidence suggested that a possible susceptibility locus for a subset of FPCA might exist on chromosome 1q23. This is the first report demonstrating suggestive evidence of linkage of FPCA to a locus in this candidate region. No functional sequence variations of the APCS gene were found to be associated with this disease among the study families. Our data imply the existence of at least one additional locus responsible for FPCA in these families, confirming genetic heterogeneity of this skin disorder.

Adolescent↗
PubMed2005

Implications of the new definition of myocardial infarction.

The new definition of acute myocardial infarction is based primarily on raised troponin levels because of the sensitivity and specificity of these markers and their correlation with the pathophysiology of acute coronary syndromes with plaque fissuring or rupture and embolisation of platelets causing myocyte necrosis. Raised troponin levels are associated with increased risks of death and recurrent myocardial infarction. Greater treatment benefit with low molecular weight heparin, IIb/IIIa antagonists and revascularisation is seen when troponin levels are raised. There are many implications for patients and society of the new definition including changes in insurability and ability to continue certain occupations. Many more patients, who would previously been diagnosed as having unstable angina, will now be diagnosed as having had an acute myocardial infarction. In addition case fatality rates will fall and comparison with previous epidemiological studies using the old definition will be problematic. However, the new definition may result in greater use of evidence based therapies with improved patient outcomes and decreased community death rates.

Angioplasty, Balloon, Coronary↗
PubMed2004

Lack of association between baseline plasma homocysteine concentrations and restenosis rates after a first elective percutaneous coronary intervention without stenting.

OBJECTIVE: To evaluate the association between baseline homocysteine concentrations and restenosis rates in patients electively undergoing their first percutaneous coronary intervention (PCI) without stenting. DESIGN: Prospective, single centre, observational study. SETTING AND PATIENTS: Patients electively undergoing their first PCI without stenting at a tertiary referral centre between 1990 and 1998. METHODS: Blood samples were collected from all patients at baseline and assayed to determine the patients' homocysteine concentrations. Patients whose PCI was successful underwent repeat angiography at a median of 6.4 (interquartile range 6-6.8) months. Their baseline and follow up angiograms were compared by quantitative coronary angiography to assess the incidence of restenosis. For the analysis, the patients were divided into two groups based on whether their baseline homocysteine concentrations were above or below the median value. These two groups were compared to determine whether there was any association between their baseline homocysteine concentrations and the incidence of restenosis at six months. RESULTS: 134 patients had a successful first PCI without stenting (involving 200 lesions). At six month angiography, restenosis was observed in 33 patients (49.3%) with baseline homocysteine concentrations above the median value and in 31 patients (46.3%) with concentrations below the median value (p = 0.74). There was no difference in the percentage of lesions developing restenosis (38 (39.6%) v 40 (38.5%), respectively, p = 0.87) or late lumen loss (0.40 mm v 0.31 mm, respectively, p = 0.24). On multivariable analysis, there was no association between homocysteine concentrations and late lumen loss (r = -0.11, p = 0.11) or the percentage diameter stenosis at follow up (r = -0.07, p = 0.32). CONCLUSION: Baseline homocysteine concentrations were not associated with six month restenosis rates in patients electively undergoing their first PCI without stenting.

Angioplasty, Balloon, Coronary↗
PubMed2004

Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus.

Twelve systemic lupus erythematosus (SLE) patients with mild to moderate disease activity (SLEDAI of > or = 6 and on prednisolone < 0.5 mg/kg/day) were included in a prospective, randomized, double-blind, placebo-controlled pilot study for 24 weeks. Six were randomized to receive oral leflunomide and six received placebo. Primary outcome of this study included the mean change of SLEDAI at 24 weeks. Secondary outcomes included the changes in proteinuria, complement levels, anti ds-DNA binding, and prednisolone dosage. The mean age of the 12 patients was 41+/-9 years, and the mean disease duration was 8.5+/-5.8 years. All were female except one patient. The disease activity of both groups of patients decreased significantly after six months of treatment (14.7+/-6.0 to 3.7+/-2.3 in leflunomide group, P = 0.028, and 9.7+/-3.4 to 5.2+/-4.1 in placebo group, P = 0.027). Reduction in the SLEDAI from baseline to 24 weeks was significantly greater in the leflunomide group than the placebo group (11.0+/-6.1 in the leflunomide group and 4.5+/-2.4 in the placebo group respectively, P = 0.026). Minor adverse events included transient elevation in ALT, hypertension and transient leucopenia. In summary, leflunomide was more effective than placebo in treating SLE patients with mild to moderate disease activity and was safe and well-tolerated.

Adult↗
PubMed2003

Associations between ST depression, four year mortality, and in-hospital revascularisation in unselected patients with non-ST elevation acute coronary syndromes.

OBJECTIVE: To determine the associations between changes on the presenting ECG, in-hospital revascularisation, and four year mortality in patients with non-ST elevation acute coronary syndromes. DESIGN: Prospective evaluation of all consecutive patients admitted in 1993 to the Green Lane Hospital coronary care unit, Auckland, New Zealand. Late follow up was undertaken at a median of 52 months. The ECGs were analysed after the hospital admission. SETTING: Tertiary referral centre with direct local coronary care unit admissions. INTERVENTIONS: Patients underwent physician recommended in-hospital revascularisation or initial conservative management. RESULTS: The four year survival was 88% in the 115 patients who underwent revascularisation (65 (19%) percutaneous and 53 (16%) surgical revascularisation), compared with 75% in 316 patients managed conservatively (p = 0.024). Four year survival for patients undergoing revascularisation versus initial conservative management with respect to ECG groups was: no ECG changes (n = 101), 97% v 92% (p = 0.35); T wave inversion or 0.5 mm ST depression (n = 108), 89% v 78% (p = 0.18); ST depression > or = 1 mm (n = 122), 80% v 58% (p = 0.014); chi2 = 29, p < 0.001 for the linear trend across the groups. On multivariate analysis, independent predictors of four year mortality were: age (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.08; p = 0.0046); ECG group (OR 1.88, 95% CI 1.21 to 2.95; p = 0.043); radiological pulmonary oedema (OR 2.81, 95% CI 1.18 to 7.05; p = 0.025); and revascularisation (OR 0.43, 95% CI 0.20 to 0.90; p = 0.023). CONCLUSIONS: Among unselected patients with non-ST elevation acute coronary syndromes, in-hospital revascularisation is associated with decreased mortality at up to four years after admission. This association appears greater in patients with ST depression of > or = 1 mm on the presenting ECG.

Analysis of Variance↗
PubMed2002

Usefulness of the presenting electrocardiogram in predicting myocardial salvage with thrombolytic therapy in patients with a first acute myocardial infarction.

AIMS: Patients with Q waves and T-wave inversion are generally at a later stage of the infarction process than patients without these changes. Our aim was to investigate whether a single assessment of electrocardiographic parameters at presentation would predict the proportion of myocardium salvageable by thrombolytic therapy. METHODS AND RESULTS: Electrocardiographic algorithms to calculate the potential and final infarct size have been developed and allow the proportion of myocardium salvageable with therapy to be calculated. This was measured in 146 patients with acute myocardial infarction who had angiography at a median of 91 min after streptokinase. The relationship between myocardial salvage and the electrocardiographic parameters at presentation (Q waves, T-wave inversion, quantitative ST segment changes, and the initial QRS score), was examined together with the 90-min angiographic parameters (TIMI flow grade and collateral grade), clinical parameters (haemodynamics and age), and time to therapy. Parameters that correlated with myocardial salvage included the initial QRS score (r=-0.56, P<0.0001), Q wave grade (r=-0.36, P<0.0001), number of leads with ST depression (r=0.28, P<0.001), maximum ST depression (r=0.27, P<0.01), T-inversion grade (r=-0.26, P<0.01), and TIMI flow grade at 90 min (r=0.21, P<0.02). The time from symptom onset to thrombolytic therapy did not correlate with salvage (r=-0.09). On multivariate analysis, only the initial QRS score and T-inversion grade on the initial electrocardiogram were independent predictors of salvage (multivariate r using both variables combined=0.57, P<0.001). CONCLUSIONS: The QRS score and T-wave inversion grade on the presenting electrocardiogram provide important information in predicting myocardial salvage. These parameters may help triage patients to appropriate therapies.

Angiography↗
PubMed2002

Slowed ST segment recovery despite early infarct artery patency in patients with Q waves at presentation with a first acute myocardial infarction. Implications of initial Q waves on myocyte reperfusion.

BACKGROUND: The presence of Q waves at presentation with a first acute myocardial infarction reflects a more advanced stage of the infarction process. When infarct-related artery patency (Thrombolysis in Myocardial Infarction 2 or 3 flow) is restored, resolution of ST segment elevation indicating successful myocyte reperfusion may differ according to how far the infarction process has progressed. METHODS AND RESULTS: In 144 patients with a first acute myocardial infarction treated with streptokinase in the first Hirulog Early Reperfusion Occlusion trial, information was obtained from continuous ST segment monitoring, the presenting electrocardiogram and early angiography performed at a median time of 99 min after the commencement of streptokinase (interquartile range 89-108 min). We determined how many patients had 50% ST recovery within 120 min and in how many cases it was sustained over 4h. In the 109 patients with patent infarct-related arteries, 50% ST recovery occurred in 95% of patients without vs 80% of those with initial Q waves (P=0.03), and sustained ST recovery occurred in 67% of patients without vs 47% of those with initial Q waves (P=0.03). On multivariate analysis including the time from symptom onset to streptokinase therapy, the presence of Q waves at presentation was the only predictor of failure to achieve 50% ST recovery (odds ratio 5.08, 95% confidence interval 1.29-20.01, P=0.02). TIMI 2 flow, as opposed to TIMI 3 flow, was the only predictor of failure to achieve stable ST recovery (odds ratio 2.63, 95% confidence interval 1.15-5.88,P =0.02). CONCLUSION: The presence of initial Q waves predicts slower and less complete ST recovery, reflecting reduced myocyte reperfusion, even in those with early infarct artery patency. These patients may be targeted for new therapeutic strategies to improve microvascular reperfusion.

Acute Disease↗
PubMed2002

Management and outcome of patients with atrial fibrillation during acute myocardial infarction: the GUSTO-III experience. Global use of strategies to open occluded coronary arteries.

OBJECTIVE: To investigate the use of antiarrhythmic agents and electrical cardioversion in the management of patients with atrial fibrillation complicating acute myocardial infarction, and their relation to 30 day and one year mortality. DESIGN: Prospective study of 1138 patients with atrial fibrillation from the GUSTO-III trial. INTERVENTIONS: Of the 1138 study patients, 317 (28%) received antiarrhythmic treatment, including class I antiarrhythmic agents (12%), sotalol (5%), and amiodarone (15%); electrical cardioversion was attempted in 116 (10%). RESULTS: Sinus rhythm was restored in 72% of patients receiving class I antiarrhythmic agents, 67% of those receiving sotalol, 79% of those receiving amiodarone, and 64% of those having electrical cardioversion. After adjusting for baseline characteristics and complications occurring before the onset of atrial fibrillation, there was no difference among the treatment groups in the incidence of sinus rhythm at the time of discharge or before deterioration to hospital death. However, the use of class I antiarrhythmic drugs or sotalol was associated with a lower unadjusted 30 day and one year mortality. After adjustment for baseline factors and pre-atrial fibrillation complications, the odds ratios for 30 day and one year mortality were 0.42 (95% confidence interval (CI) 0.19 to 0.89) and 0.58 (95% CI 0.33 to 1.04) with class I agents, and 0.31 (95% CI 0.07 to 1.32) and 0.31 (95% CI 0.09 to 1.02) with sotalol. In contrast, there was no association between the use of amiodarone or electrical cardioversion and 30 day or one year mortality. CONCLUSIONS: There was a strong trend towards lower mortality associated with the use of class I antiarrhythmic agents or sotalol in managing patients with atrial fibrillation after acute myocardial infarction. Randomised trials are indicated.

Aged↗