Stereochemistry and biological activities of constituents from Cynanchum taiwanianum.

The stereochemistry of new acetophenones, cynandione B-D (2-4), isolated from Cynanchum taiwanianum, elucidated by computer modelling calculation and NOESY spectrum. It establishes the absolute configurations of cynandiones B-D (2-4) as 7R; 7"S, 7S; 7"S and 7R; 7"R, respectively. Cynandione B (2) strongly inhibited the release of beta-glucuronidase and lysozyme in formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated rat neutrophils in a concentration-dependent manner with IC50 values of 1.5 +/- 0.2 and 1.6 +/- 0.2 microM, respectively. 2,5-Dihydroxyacetophenone (6) strongly inhibited the aggregation of washed rabbit platelets induced by arachidonic acid in a concentration-dependent manner with an IC50 value of about 4.8 microM. In human citrated platelet-rich plasma, 2,5-dihydroxyacetophenone (6) inhibited the secondary phase, but not the primary phase, of aggregation induced by adrenaline and ADP. These results suggest that the antiplatelet effect of 2,5-dihydroxyacetophenone (6) is due to inhibition of the formation of thromboxane A2.

The Gln-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan.

Paraoxonase (PON1) is a high density lipoprotein-associated enzyme capable of hydrolyzing lipid peroxides, and thus, might protect lipoproteins from oxidation. A common polymorphism due to an amino acid substitution (Gln-Arg) at codon 191 is considered to be a major determinant of variation in serum PON1 activity. Recent studies have suggested that the PON1-191 polymorphism is an independent risk factor for coronary atherosclerosis in patients with or without diabetes mellitus. The association of PON1-191 polymorphism genotypes and coronary artery disease (CAD) among Chinese subjects in Taiwan was examined. The genotype of 218 angiographically documented CAD patients and the same number of age- and sex-matched control subjects was determined. Genotypes AA, AB and BB were present in 25 (11%), 102 (47%) and 91 (42%) of control subjects, respectively, and in 30 (14%), 96 (44%) and 92 (42%) of CAD patients, respectively (chi2 = 0.57, P = 0.75 between groups). The frequency of the A allele was 0.36 for the control group and 0.35 for CAD patients (P = 0.94). No significant differences in the PON1-191 genotype frequencies could be found between groups when multivariate logistic regression analysis was performed, or different subgroups of age, sex or risk factors were analyzed. Among control subjects, there was also no significant difference between genotypes of the PON1-191 polymorphism and various clinical and lipid variables. In conclusion, our data suggest that there is no association between the Gln-Arg 191 polymorphism of the human PON1 gene and CAD among Chinese subjects in Taiwan.

Usefulness of pulmonary venous flow pattern and maximal mosaic jet area detected by transesophageal echocardiography in assessing the severity of mitral regurgitation.

Pulmonary venous flow pattern detected by transesophageal echocardiography (TEE) has been reported to be a good marker of mitral regurgitation (MR) severity. In 89 patients with MR detected by TEE, both pulmonary venous flow pattern and maximal mosaic jet area were recorded for evaluating the severity of MR. Cardiac catheterization was performed in all patients for grading the severity of MR. Systolic reversed flow in pulmonary veins was a good marker for angiographic grade 3 or 4 MR with a sensitivity of 97% (33 of 34) and specificity of 95% (52 of 55). Maximal mosaic jet area had a good correlation with the grading of MR (r = 0.79). When a maximal mosaic jet area of > 6 cm2 was used to detect grade 3 or 4 MR, the sensitivity and specificity were lower than those of the systolic reversed flow (sensitivity 82 vs 97%, p = 0.073; specificity 80 vs 95%, p = 0.013). The accuracy of systolic reversed flow was not influenced by the cardiac rhythm or jet eccentricity. However, the sensitivity of maximal mosaic jet area was lower in patients with an eccentric jet than in patients with a central jet (67 vs 95%, p = 0.046). In conclusion, systolic reversed flow in pulmonary veins detected by TEE is better than the maximal mosaic jet area in detecting grade 3 or 4 MR, especially in patients with eccentric jet.

Reappraisal by transesophageal echocardiography of the significance of left atrial thrombi in the prediction of systemic arterial embolization in rheumatic mitral valve disease.

Systemic arterial embolization imparts a significant risk of serious complications throughout the lives of patients with rheumatic heart disease. Left atrial (LA) thrombi have been thought to be the major source of emboli. A transesophageal echocardiography (TEE) study of 260 consecutive patients with rheumatic mitral valve disease was performed during a period of 24 months, with particular reference to understanding the association between LA thrombi and embolic complications. Of these patients, 155 had predominant mitral stenosis, 24 had significant mitral regurgitation, and the remaining 81 with xenograft mitral valve replacement developed valvular dysfunction (25 resulted in predominant mitral stenosis and 56 in significant mitral regurgitation). LA thrombi were detected in 38 patients (group A) and absent in 222 (group B). Group A patients had a higher frequency of recent (less than or equal to 1 week before TEE study) and remote (greater than 1 week before) embolization than did group B patients (recent: 26.3 vs 5.4% [p less than 0.001]; remote: 18.4 vs 5.0% [p less than 0.01]). The frequency of atrial fibrillation was also greater in group A patients (100 vs 74.3%; p less than 0.001). The exclusion of patients with significant mitral regurgitation and sinus rhythm had no effect on the association between LA thrombi and evidence of previous embolization. It is concluded that TEE is a convenient diagnostic modality that can be used to identify a subset of patients with rheumatic mitral valve disease at high risk for systemic embolization. Consequently, preventive anticoagulation for possible embolic complications should be more vigorously adhered to in patients with rheumatic mitral valve disease and LA thrombi.

On-line multiplane transesophageal echocardiography for balloon mitral commissurotomy.

This study describes in detail the technique and results of on-line multiplane transesophageal echocardiographic guidance of balloon mitral commissurotomy in 150 consecutive patients with symptomatic mitral stenosis. The mitral valve area improved significantly and there were no in-hospital deaths, strokes, or emergency valve operations.

Idiopathic hypertrophic cardiomyopathy in identical twins. Morphological heterogeneity of the left ventricle.

We report a pair of identical twins with HC with varying extent of left ventricular hypertrophy and some degree of left ventricular outflow tract obstruction. The diagnosis of identical twins was based on the same sex, blood typings, HLA typings and hybridization patterns to four hypervariable DNA probes. Identical twins are derived from a single zygote and are genetically homogeneous human beings. The present report suggests that heterogeneity in the morphologic expression of HC may not be solely attributed to genetic factors. Environmental factors also may play an important role.

Left atrial spontaneous echo contrast in patients with rheumatic mitral valve disease in sinus rhythm. Implication of an altered left atrial appendage function in its formation.

Thirty-nine patients who had rheumatic mitral valve disease in sinus rhythm were studied to compare echocardiographic and hemodynamic characteristics between those with and without left atrial (LA) spontaneous echo contrast. Patients were divided into two groups according to the presence (group 1, n = 17) or absence (group 2, n = 22) of the echo contrast. Transthoracic echocardiography and transesophageal echocardiography were performed in all patients within 1 week of cardiac catheterization study. Group 1 patients (5 men and 12 women; mean age, 47.7 +/- 13.1 years) showed smaller mitral valve area, greater transmitral valve pressure gradient, and absence of moderate to severe mitral regurgitation compared with group 2 patients (7 men and 15 women; mean age, 47.8 +/- 14.3 years). There was no significant difference in LA dimension, left ventricular end-systolic and end-diastolic dimensions, or in left ventricular ejection fraction between the two groups of patients. Left atrial appendage function was studied with Doppler in 26 patients. Patients (n = 10) with LA spontaneous echo contrast had significantly lower LA appendage ejection fraction (20.34 +/- 10.76% vs 34.16 +/- 13.13%; p < 0.05) and lower LA appendage peak emptying velocity (0.17 +/- 0.09 m/s vs 0.27 +/- 0.12 m/s; p < 0.05) than those (n = 16) without echo contrast. It is concluded that obstruction to mitral flow and altered LA appendage contractile function, not the LA size, are likely to be more important factors for the development of LA and LA appendage spontaneous echo contrast in patients with rheumatic mitral valve disease (predominant mitral stenosis) who are in sinus rhythm. These findings further substantiate that blood stasis in the LA cavity and the LA appendage is the mechanism fundamental to the formation of such spontaneous echo contrast.

Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. A case-control study.

OBJECTIVE: To determine the current status of hyperhomocysteinemia, which is a known risk for venous thrombosis (DVT), in Taiwan. SUBJECTS: 101 unselected patients with a minimum of one episode of deep leg DVT, either initial inpatients or current compliant outpatients in a teaching hospital. METHODS: Various thrombophilic risks, gene polymorphism and clinical predisposition were evaluated. RESULTS AND CONCLUSIONS: Patients presented higher fast total plasma homocysteine (hcy) levels than age- and sex-matched controls did (14.1 vs. 9.94 microM). Based on the 95th percentile of control values, hyperhomocysteinemia had a four- to nine-fold risk for DVT, irrespective of clinical predisposition, as well as other thrombophilic risks surveyed. Polymorphism of a metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), was not associated with DVT, although homozygous thermolabile mutation tended to have higher plasma hcy levels. Factor V Leiden was absent in analysis of 80 patients. In complete evaluation (hcy, antithrombin (AT), protein S (PS), protein C (PC), lupus anticoagulant (LA), anticardiolipin antibody) of a subset of 83 patients hyperhomocysteinemia was the most prevalent risk (33.7%), with PC or PS deficiencies following (22.9%). Thus, hyperhomocysteinemia is a prominent risk for DVT in Taiwan.

Catheterization-documented coronary artery disease in young Chinese adults.

We conducted a retrospective study among 31 young (age<40 years) Chinese patients with catheterization-documented coronary artery disease. Male gender and smoking were the most important risk factors. Most of them had a single or two-vessel coronary artery disease. Standard treatment strategies could be applied. The prognosis appeared to be excellent.

Clinical implications of left atrial appendage function: its influence on thrombus formation.

This study evaluated the relation between left atrial appendage (LAA) function and LAA spontaneous echo contrast (SEC) or thrombus formation. Seventy-five patients (45 men and 30 women, aged 14-79 years) referred for transesophageal echocardiography (TEE) were examined for LAA area (maximal and minimal), LAA ejection fraction ([LAA maximal area--LAA minimal area]/LAA maximal area), LAA peak emptying velocity, and these patients were classified into three groups by different LAA blood flow patterns: Group 1--25 patients with well-defined biphasic configuration of LAA flow; Group 2--28 patients with multiphasic configuration of LAA flow; Group 3--22 patients with very low LAA blood flow and, sometimes, barely detected Doppler signal. All the 25 patients in Group 1 had a sinus rhythm during TEE study, while the other 50 patients in Groups 2 and 3 were in atrial fibrillation. The patients in Group 3 had the lowest LAA ejection fraction and the lowest peak emptying velocity of these three groups. LAA SEC was present in five of 28 patients in Group 2 and 14 of 22 patients in Group 3, but in none of 25 patients in Group 1 (P < 0.001). LAA thrombus was present in one of 25 patients in Group 1, two of 28 patients in Group 2, and seven of 22 patients in Group 3 (P < 0.05). In conclusion, this study found that patients with poor LAA function, which was represented by lower LAA ejection fraction and lower peak emptying velocity, had higher incidence of LAA SEC or thrombus formation.

Gender differences in baseline variables, therapies and outcomes in Chinese patients with acute myocardial infarction.

We prospectively studied the gender differences of baseline variables, therapies, and outcomes among a cohort of 369 Chinese patients with acute myocardial infarction from 1990 to 1995. There were 277 male and 92 female patients. The male gender had a younger mean (+/-SD) age (61.5+/-10.7 vs. 67.1+/-11.7 years, P<0.0001). Hypercholesterolemia (201.2+/-44.2 vs. 187.5+/-43.7 mg/dl, P=0.0111) and obesity (25.0 vs. 15.9%, P=0.0494) were more prominent in the female. Smoking was more prevalent in the male (78.3 vs. 18.5%, P<0.0001). The male group also had more frequent use of thrombolytic agents (19.1 vs. 9.8%, P=0.0377), beta-blockers (61.7 vs. 47.8%, P=0.0191) and heparin (25.3 vs. 12.0%, P=0.0075); but less use of angiotensin-converting enzyme inhibitors (6.9 vs. 15.2%, P=0.0149). The condition on admission was worse in the female group (Killip classification (1.5+/-0.9 vs. 1.9+/-1.0, P=0.0022), myocardial failure (8.7 vs. 2.9%, P=0.0178) and cardiomegaly (65.2 vs. 53.1%, P=0.0419). During a follow-up duration of 26.4+/-24.1 and 22.9+/-23.9 months respectively, the mortality rate was lower in the male (19.5 vs. 30.4%, P=0.0288). However after adjustment for the effect of age, the differences in Killip classification, myocardial failure, cardiomegaly and mortality became insignificant.

Genetic heterogeneity for familial hypertrophic cardiomyopathy in Chinese: analysis of six Chinese kindreds.

OBJECTIVE: Familial hypertrophic cardiomyopathy (FHCM) is a primary myocardial disease characterized by unexplained ventricular hypertrophy. The application of the techniques of reverse genetics has identified at least five chromosomal loci as the major causes for FHCM in diverse ethnic populations, suggesting substantial genetic heterogeneity for FHCM. Recently, the defective gene loci of two Chinese families with FHCM have been mapped to chromosome 11 and 14q1, respectively. For further understanding of the molecular basis of FHCM in Chinese, we analyzed the linkage between four other Chinese kindreds and DNA markers from chromosome 14q1. METHODS: Six unrelated Chinese families with FHCM, including two previously reported, were studied. Totally 90 family members were included for analysis. DNA from 80 individuals was extracted and polymerase chain reactions were performed using the primers designed according to the sequences derived from the alpha and beta myosin heavy chain gene. Totally four polymorphisms were studied, including three polymorphic microsatellite sequences and one single strand conformation polymorphism. Genetic linkage analysis were performed using the Linkage program. RESULTS: In the six studied families, 39 of the 90 family members were found to be affected diagnosed either by echocardiography or by clinical evaluation. The pattern of inheritance in all six studied families was most consistent with an autosomal dominant trait with a high degree of penetrance. Genetic linkage analysis using polymorphisms on the alpha and beta MHC genes showed a combined maximal lod score of 6.2 for trinucleotide repeat polymorphism AMHC-I 15 at theta = 0.00 for three studied families without recombination. Exclusion of linkage to the chromosome 14q1 location was noted in two of three other families with the maximal lod score of -2 or less. CONCLUSIONS: These results provide further evidence that FHCM in Chinese is genetically heterogeneous. Chromosome 14q1 locus, probably the beta myosin heavy chain gene, is important as the molecular basis for FHCM in Chinese.

Swyer-James syndrome associated with Noonan syndrome: report of a case.

A 28-year-old man with Noonan syndrome associated with unilateral hyperlucent lung is reported. He had the typical craniofacial appearance and short stature of Noonan syndrome; he had mild mental retardation, atrophic testis, mild funnel chest and kyphosis. cardiovascular abnormalities included asymmetric hypertrophic cardiomyopathy and a significantly different caliber of the left and right pulmonary arteries. The unilateral hyperlucent lung was shown to result from acquired nondestructive emphysema caused by nonvalvular obstruction of the bronchi (Swyer-James syndrome or Macleod's syndrome). To the authors' knowledge, this is the first reported case of Noonan syndrome associated with Swyer-James syndrome.

Metastasis of hepatocellular carcinoma to the heart: unusual patterns in three cases with antemortem diagnosis.

Unusual patterns of cardiac metastasis were noted in three cases of hepatocellular carcinoma (HCC): one patient was noted to have a large right ventricular (RV) tumor mass with intracavitary growth and myocardial invasion; the second had massive pulmonary and left atrial (LA) metastasis; and the third patient had a right atrial tumor mass with concomitant RV and LA involvement. Tumor implantation to the RV without right atrial involvement and extensive myocardial invasion is unusual in HCC. The LA involvement is probably related to tumor growth from the pulmonary veins following massive metastasis to the lung, direct invasion of the atrial septum or tumor implantation via a subclinical right-to-left shunt through the patent foramen ovale. To the best of our knowledge, such unusual intracavitary metastases in HCC have not been reported previously. Cardiac metastasis, without local gross recurrence, may be one of the presentations after lobectomy in patients with HCC.

Lack of association between the Glu298Asp variant of the endothelial nitric oxide synthase gene and the risk of coronary artery disease among Taiwanese.

BACKGROUND AND PURPOSE: Endothelial nitric oxide synthase (eNOS) plays a key role in atherosclerosis, because its product, nitric oxide, possesses antiatherogenic properties. Recent reports of molecular genetic analysis have suggested that genetic polymorphisms of the eNOS gene may be associated with coronary artery disease (CAD) or myocardial infarction (MI). However, some studies have reported discrepant results. The aims of this study were to assess whether any association exists between the Glu298Asp variant of the eNOS gene and the risk of CAD and/or MI among Taiwanese. METHODS: The subjects included 218 CAD patients and the same number of age- and sex-matched control subjects from Taiwan. Subjects' DNA was extracted from their blood and genotypes were determined by polymerase chain reaction and restriction mapping using the restriction enzyme MboI. The alleleic and genotypic frequencies were analyzed. RESULTS: The frequencies of the eNOS genotypes were similar for CAD patients (GG:GT:TT = 81.7%:17.4%:0.9%) and controls (81.2%:17.4%:1.4%; p = 0.904). No evidence of difference was found in the frequency of the T allele between CAD patients (9.6%) and controls (10.1%; p = 0.822), or between MI patients (7.5%) and controls (p = 0.322). Subjects with the GT or TT genotype did not demonstrate an increased risk of CAD compared with those with a GG genotype (p = 0.89; OR = 0.98; 95% confidence interval, CI, 0.76-1.27) in multivariate logistic regression, or when different subgroups of age, sex, or risk factors were analyzed. CONCLUSIONS: In the present case-control study, we found no evidence of an association between the Glu298Asp variant of the eNOS gene and CAD/MI among Taiwanese.

Inheritance of hypertrophic cardiomyopathy in Chinese--M-mode and two-dimensional echocardiographic analysis of 28 families.

To determine the mode of inheritance and degree of penetrance of hypertrophic cardiomyopathy (HC) in Chinese, 132 family members of 28 probands with HC were assessed by M-mode and two-dimensional echocardiography. Of these 132, 103 cases were first-degree relatives of the probands. Twenty-seven (20.4%) family members, including 19 cases of first-degree relatives of the probands, had HC. Familial occurrence of HC was noted in 13 (46.4%) families. In 10 families, the affected relatives were identified in successive generations, and the mode of inheritance was most consistent with an autosomal dominant trait. The frequency with which HC was identified in relatives increased significantly with the number of subjects studied and a positive family history of sudden death. Subgroup analysis, using multivariate logistic regression analysis, revealed that increasing age was independently associated with a higher frequency of definite cases in first-degree relatives of the probands. In contrast, by multivariate analysis, there were no significant differences between frequency of definite cases in female and male relatives or in different familial relationships (parent, sibling, offspring) to the probands.

Obstructive hypertrophic cardiomyopathy in Taiwanese adults.

The purpose of this study was to analyze the clinical profiles, echocardiographic findings, and mortality among adult Taiwanese patients with obstructive hypertrophic cardiomyopathy (HCM) at Chang Gung Memorial Hospital, a university-affiliated tertiary referral center in suburban Taipei. We reviewed the medical records of all adult (> 15 years of age) patients referred to our laboratory for echocardiographic examinations of cardiac diseases from May 1990 through December 1996. The diagnosis of obstructive HCM required an outflow gradient of above 10 mm Hg and the presence of asymmetric septal hypertrophy of the left ventricle. Follow-up information on was obtained from hospital records, questionnaires, interviews, or the National Death Certificate Registry. Of the 6.798 adults who underwent echocardiographic examinations during the study period 122 (1.79%) had obstructive HCM. The mean +/- standard deviation age of the patients was 62.2 +/- 12.6 years, and females predominated (n = 76, 62.3%). During the mean follow-up period of 3.2 years, the annual all-cause mortality rate was 4.7%. Most deaths were due to concurrent medical conditions. The annual cardiac mortality rate was 0.99%. Logistic regression analysis identified medication with calcium channel blockers as the only negative predictor (relative risk = 0.26, 95% confidence interval = 0.07-0.96) of all-cause mortality, and left atrial size as the only positive predictor (relative risk = 1.18, 95% confidence interval = 1.02-1.37) of cardiac mortality. Cox regression analysis confirmed the former association, but not the latter. Thus, in our institution, obstructive HCM had a low prevalence among adult patients referred for echocardiographic examination. These patients were elderly and often had other associated medical conditions. The high all-cause mortality rate was largely due to non-cardiac causes. These findings suggest that obstructive HCM tends to have a benign clinical course. Large atrial size could be an independent predictor of cardiac mortality, but this possibility requires further confirmation.

Linkage and mutation analysis in two Taiwanese families with long QT syndrome.

Long QT syndrome (LQT) is a cardiovascular disorder causing syncope and sudden death from arrhythmias. Mutations in KCNQ1, KCNH2, KCNE1, KCNE2, and SCN5A genes encoding cardiac potassium and sodium ion channels cause LQT. Two Taiwanese LQT families were screened for mutations in these ion channel genes. In family H87, the diagnosis was made in the 25-year-old female proband and six family members based on recurrent syncope and/or a prolonged QT interval. Genotyping revealed a novel nonsense mutation, R744X (C to T transition in codon 744), in the KCNH2 potassium channel gene, resulting in truncation of the putative cyclic nucleotide-binding domain and C-terminal region of the HERG K(+)-channel in all affected family members. The mutation was confirmed by DdeI endonuclease digestion of the DNA from each family member. The 26-year-old female proband in family L89 developed repeated syncope with QTc of 0.61 seconds. After linkage and mutation analysis, the syndrome in this family was associated with a novel KCNQ1 missense mutation, T309I, causing the substitution of a threonine residue at position 309, in the pore region of the KvLQT1 K(+)-channel, with an isoleucine. By Tsp45I restriction analysis, the mutation was noted in the proband and the proband's asymptomatic brother, but was not detected in 100 unrelated normal individuals. Identification of a mutation has clinical implications for presymptomatic diagnosis and therapy.

Unusual electrocardiographic manifestations in acute isolated right ventricular infarction.

Electrocardiographic (ECG) manifestation of ST-segment elevation in the precordial leads during acute myocardial infarction is usually due to anterior myocardial infarction secondary to occlusion of the left coronary artery. Herein, we reported a rare case of isolated right ventricular infarction (RVI) in which the ECG mimicked that of acute anterior left ventricular infarction (LVI). A 64-year-old man had acute isolated RVI documented by positive cardiac enzymes and echocardiographic and angiographic findings. He developed hypotension. His ECG showed ST-segment elevation in the precordial leads V1 to V3 simulating that of acute anterior wall infarction. Coronary angiogram revealed total occlusion of the proximal right coronary artery with well-established collaterals from the left coronary artery to the posterior descending artery. This case report reminds us that the presence of diffuse ST-segment elevation in the precordial leads could be due to acute isolated RVI rather than acute anterior LVI. The differentiation of these two entities is important, as their therapies are quite different.

Fracture of a perfusion balloon catheter during coronary angioplasty.

In a 74-year-old patient with increasing angina, an attempt was made to dilate an ostial stenosis in the first diagonal artery. The initial attempt with a long balloon catheter was unsuccessful. Because of chest pain associated with hypotension during balloon inflations, a second attempt with a perfusion balloon catheter resulted in fracture of this catheter's tip (14 mm long) in the artery. Bypass graft surgery was performed and the retained fragment was easily removed by arteriotomy. The patient made an uneventful recovery.