Platelet-activating factor-acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction.

BACKGROUND: Oxidation of low density lipoproteins is an initial step of atherogenesis that generates pro-inflammatory phospholipids, including platelet-activating factor (PAF). PAF is degraded by PAF-acetylhydrolase (PAF-AH), which has been postulated to be a risk factor for myocardial infarction (MI). The role of PAF-AH for the onset of premature MI is unclear. METHODS: Polymorphisms located in putatively functional regions were investigated in a cohort of patients having premature MI onset prior to 46 years of age (n = 200) and a sex-age-matched control group (n = 200). The activity of PAF-AH and coronary angiograms were evaluated for the severity of coronary atherosclerosis. RESULTS: The V allele of A379V (exon 11) polymorphism on PAF-AH gene was more frequent in patients with premature MI (P = 0.001). This V allele polymorphism was also associated with a lower activity of plasma PAF-AH and a more complex coronary atherosclerosis (p Trends <0.05). Multiple logistic regression analysis showed that this polymorphism was an independent risk factor (Odds Ratio [OR] 1.66, 95% CI 1.14.1 to 5.80, P = 0.008) as well as smoking (OR 3.72, 95% CI 1.77 to 9.28, P = 0.001), diabetes mellitus (OR 2.25, 95% CI 1.40 to 5.32, P = 0.007) and hypertension (OR 1.88, 95% CI 1.25 to 5.36, P = 0.003) for the onset of premature MI. CONCLUSION: We conclude that a functional and significant association between the A379V polymorphism on exon 11 of PAF-AH gene and premature MI exists in this Taiwanese population. This polymorphism is significantly associated with the PAF-AH activity and the severity of coronary atherosclerosis.

Stromelysin-1 promoter 5A/6A polymorphism is an independent genetic prognostic risk factor and interacts with smoking cessation after index premature myocardial infarction.

OBJECTIVE: To evaluate the prognostic roles of multiple polymorphisms and smoking cessation for premature myocardial infarction (MI). METHODS: We studied 170 patients with MI onset before the age of 45 years (range 27-45 years, 84% men) and analyzed the traditional risk factors and several candidate genes' associations with their subsequent coronary events. RESULTS: Follow-up data were available for a total of 162 individuals (95.3%) with the other 38 individuals (4.7%) being lost-to-follow-up premature MI patients. During a mean period of 4.43 years' follow-up, diabetes mellitus (DM), hypertension, hypercholesterolemia and Killip's status > or =II were more frequent among patients with subsequent cardiac events (all P-values <0.05). The frequency of 5A allele of stromelysin-1 gene was significantly higher among event group (P = 0.01). Smoking cessation after MI, use of beta-blocker or angiotensin-converting enzyme inhibitor (ACEI) could improve outcome (all P-values <0.05). After multivariate analysis, we found that DM was an independent risk factor for survival [Hazard ratio (HR) 2.45, P = 0.01]. Successful smoking cessation and therapy with ACEI could have a protective effect (HR 0.33 and 0.09, P = 0.01 and <0.01, respectively). The stromelysin-1 5A gene polymorphism was also an independent survival predictor (HR 2.51, P = 0.03). In addition, smoking cessation could significantly modify the risk, especially among patients with 5A allele polymorphism (HR 6.75 vs. 1.50). CONCLUSION: We thus conclude that the stromelysin-1 gene polymorphism alone or in combination with smoking cessation can influence the prognosis after index premature MI.

Identification of ligand effector binding sites in transmembrane regions of the human G protein-coupled C3a receptor.

The human C3a anaphylatoxin receptor (C3aR) is a G protein-coupled receptor (GPCR) composed of seven transmembrane alpha-helices connected by hydrophilic loops. Previous studies of chimeric C3aR/C5aR and loop deletions in C3aR demonstrated that the large extracellular loop2 plays an important role in noneffector ligand binding; however, the effector binding site for C3a has not been identified. In this study, selected charged residues in the transmembrane regions of C3aR were replaced by Ala using site-directed mutagenesis, and mutant receptors were stably expressed in the RBL-2H3 cell line. Ligand binding studies demonstrated that R161A (helix IV), R340A (helix V), and D417A (helix VII) showed no binding activity, although full expression of these receptors was established by flow cytometric analysis. C3a induced very weak intracellular calcium flux in cells expressing these three mutant receptors. H81A (helix II) and K96A (helix III) showed decreased ligand binding activity. The calcium flux induced by C3a in H81A and K96A cells was also consistently reduced. These findings suggest that the charged transmembrane residues Arg161, Arg340, and Asp417 in C3aR are essential for ligand effector binding and/or signal coupling, and that residues His81 and Lys96 may contribute less directly to the overall free energy of ligand binding. These transmembrane residues in C3aR identify specific molecular contacts for ligand interactions that account for C3a-induced receptor activation.

Cloning, nucleotide sequence and characterization of a full-length cDNA encoding the myosin heavy chain from adult chicken pectoralis major muscle.

Four cDNA clones, encoding the chicken adult sarcomeric MyHC, have been isolated from a pectoralis major muscle cDNA library using gene-specific DNA probes. These clones were sequenced and then subcloned into a full-length, 6-kb, chicken adult sarcomeric MyHC cDNA. The entire cDNA consists of 5873 nucleotides with 19 bp 5'-untranslated region and 34 bp 3'-untranslated region. The complete cDNA encodes a 1939-aa polypeptide whose molecular weight is 223 kDa. The calculated isoelectric point of this protein is approximately 5.7. Analysis of the deduced amino acid sequence and comparison with a previously published amino-acid sequence of the same MyHC isoform reveals that six amino acid residues are different. Hydrophilicity analysis of this adult MyHC amino-acid sequence shows a similar pattern as the embryonic MyHC. A recombinant baculovirus, carrying this full-length adult MyHC cDNA, has also been generated and expressed in the Sf9 insect cell line. A approximately 220-kDa recombinant MyHC was synthesized and reacted specifically with chicken adult MyHC monoclonal antibodies.

Role of BMK1 in regulation of growth factor-induced cellular responses.

Big mitogen-activated protein kinase (MAPK) 1 (BMK1), also known as ERK5, is a recently identified member of the mammalian MAPK family. Cellular stimulation of BMK1 is induced in response to growth factors, oxidative stress, and hyperosmolar conditions. Specific members of the myocyte enhancer factor 2 family of transcription factors that regulate growth factor-induced early gene expression have been identified as direct downstream targets of BMK1 activity. Recent studies have shown that growth factors of the epidermal growth factor family mediate the sequential activation of a kinase cascade consisting of MAPK kinase kinase 3, MAPK kinase 5, and BMK1. Most importantly, the activation of this signal transduction pathway has been shown to be required for growth factor-mediated cell proliferation and cell-cycle progression. Collectively, these studies establish BMK1 as an important regulator of growth factor-induced cellular responses.

Correlation of homocytsteine levels with the extent of coronary atherosclerosis in patients with low cardiovascular risk profiles.

Elevation of homocysteine is now known as an independent risk factor for vascular diseases. However, influences of homocysteine to the extent of coronary atherosclerosis in patients with different coronary risk profiles have not been studied. In this study, we used angiographic "diffuse score" and "clinical vessel score" to evaluate the extent of coronary atherosclerosis, and examined the correlation between levels of serum total homocysteine and angiographic scores among patients with high- and low-risk profiles. Seventy consecutive patients (58 men and 12 women, mean age 50 years) undergoing selective coronary angiography for the first time were recruited for this study. Patients were divided into high-risk (risk factor > or =3, n = 35) and low-risk (risk factor <3, n = 35) groups. Linear regression analysis revealed that levels of serum homocysteine were only significantly correlated with diffuse (r = 0.217, p = 0.007) and clinical vessel (r = 0.078, p = 0.037) scores in low-risk patients. These correlations could not be observed in diffuse (r = 0.070, p = 0.319) and clinical vessel (r = -0.001, p = 0.970) scores in the high-risk group. In conclusion, levels of homocysteine correlated with the extent of coronary atherosclerosis only among patients with low cardiovascular risk profiles.

G-33A mutation in the promoter region of thrombomodulin gene and its association with coronary artery disease and plasma soluble thrombomodulin levels.

Thrombomodulin is an endothelial glycoprotein that decreases thrombin activity and activates protein C. A recent study has shown that G-33A promoter mutation of the thrombomodulin gene occurs particularly in Asians. In this study, we analyzed the distribution of G-33A mutation in the promoter region of the thrombomodulin gene in the Chinese population and determined whether the mutation might be a risk for coronary artery disease (CAD). In addition, the influence of this mutation on plasma soluble thrombomodulin levels in patients with CAD was also examined. We studied 320 consecutive patients (mean age 63 years; 73% men) with CAD and 200 age- and sex-matched control subjects. Screening for thrombomodulin G-33A promoter mutation was conducted using polymerase chain reaction, single-strand conformation polymorphism, and direct deoxyribonucleic acid sequencing. The frequency of the G-33A mutation (GA+AA genotypes) was significantly higher in the CAD group (23.8% vs 15.5%, odds ratio [OR] 1.70, p = 0.031). Multiple logistic regression analysis showed that the mutation was an independent risk factor (OR 1.81, p = 0.016) for CAD, as was hypertension (OR 1.44, p = 0.040), diabetes mellitus (OR 2.50, p <0.001), and smoking (OR 2.15, p <0.001). In CAD patients with GG genotype, the soluble thrombomodulin level increased with the extent of CAD (36 +/- 15 vs 47 +/- 18 vs 55 +/- 36 ng/ml in 1-, 2-, or 3-vessel CAD, p <0.001). However, in CAD patients with G-33A mutation, there was no difference between the levels of soluble thrombomodulin (39 +/- 17 vs 37 +/- 15 vs 42 +/- 18 ng/ml, p = NS) in 1-, 2-, or 3-vessel CAD. Our observations suggest that there is a significant association of the G-33A mutation in thrombomodulin gene with CAD, and this mutation may influence the soluble thrombomodulin levels in patients with CAD.

Association of follow-up change of left atrial appendage blood flow velocity with spontaneous echo contrast in nonrheumatic atrial fibrillation.

STUDY OBJECTIVES: To evaluate the time-related change of left atrial (LA) appendage flow velocity in chronic atrial fibrillation (AF) by follow-up transesophageal echocardiography (TEE) and to investigate its association with the occurrence of LA spontaneous echo contrast. DESIGN: Prospective follow-up study. SETTING: University-based, tertiary referral medical center. PATIENTS: Forty-seven patients with chronic nonrheumatic AF. INTERVENTIONS: All studied patients underwent both a baseline and follow-up TEE during a mean period of 13 +/- 7 months. MEASUREMENTS AND RESULTS: Baseline TEE revealed that LA spontaneous echo contrast was present in 28 patients (group 1) and was absent in 19 patients (group 2). The LA appendage flow velocity profiles at baseline were significantly lower in group 1 than in group 2; on follow-up, the appendage flow velocities decreased significantly in group 2, but were not significantly changed in group 1. Follow-up TEE revealed that spontaneous echo contrast was persistent in all group 1 patients. In group 2, LA spontaneous echo contrast was newly observed in 9 patients (group 2A) but was persistently absent in 10 patients (group 2B). In group 2A, all of the LA appendage flow velocity profiles decreased significantly at the follow-up study. In group 2B, however, only LA appendage inflow velocity integral showed significant decrease on follow-up; there were no significant changes in LA appendage outflow velocity indexes and peak inflow velocity. CONCLUSIONS: LA appendage flow velocity may decrease with time in some patients with AF, and this change is associated with a new occurrence of LA spontaneous echo contrast. For patients without LA spontaneous echo contrast, serial follow-up of the LA appendage flow velocity profiles may be useful for predicting future development of spontaneous echo contrast. Once LA spontaneous echo contrast occurs in AF patients, it tends to persist with time and the LA appendage is usually under a persistently low flow state.

Effect of atrial fibrillation on pulmonary venous flow patterns assessed by Doppler transesophageal echocardiography.

STUDY OBJECTIVES: To investigate the effect of atrial fibrillation (AF) on pulmonary venous flow (PVF) patterns in a cohort with nonrheumatic AF. DESIGN AND SETTINGS: A prospective and controlled study undertaken at a tertiary referral medical center. PATIENTS AND MEASUREMENTS: The echocardiographic parameters of left superior PVF as assessed by Doppler transesophageal echocardiography in 40 patients with chronic AF (group 1) were compared to those of 33 volunteers with sinus rhythm (group 2) and well-matched baseline characteristics. RESULTS: : All group 1 patients presented with single systolic forward flow (SFF) patterns. In contrast, single and double SFF patterns were found equally in group 2. With regard to reverse flow (RF), most group 1 patients (33 of 40) had an early systolic RF and none had atrial RF; however, most group 2 subjects (29 of 33) had an atrial RF. Some of the group 1 patients (17%) had a late systolic RF in the absence of significant mitral regurgitation. In group 1, the SFF appeared later and disappeared earlier than in group 2. The mean systolic peak velocity and time-velocity integral (TVI) of the SFF were significantly lower in group 1 compared to group 2. The diastolic peak velocity and TVI were not significantly different between groups. CONCLUSIONS: : Our data indicate that AF independently and significantly affects the PVF and leads to characteristic flow patterns different from sinus rhythm. The presence of AF reduces SFF in addition to the absence of atrial RF. These changes in the flow patterns should be taken into account while interpreting the implications of PVF in the presence of AF.

Value of 18F-fluoro-2-deoxyglucose positron emission tomography in the evaluation of recurrent colorectal cancer.

To evaluate the clinical value of positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (FDG) in recurrent colorectal cancer, the records of 33 patients who underwent 34 FDG-PET scans were reviewed and compared with computed tomography (CT) and carcinoembryonic antigen (CEA). The final diagnosis was based on operative, histopathological findings or clinical follow-up > 1 year. FDG-PET detected all 15 patients with recurrent diseases (9 local recurrences, 4 lymphatic metastases, 2 hepatic metastases and 8 pulmonary metastases) and 1 primary lung cancer. However, there were 3 false positive cases. The overall sensitivity and specificity of FDG-PET were 100% and 83%, respectively. The sensitivity and specificity of CEA were 33% and 86%, respectively, for detecting recurrent colorectal cancer. Abdominal CT had a sensitivity and specificity of 78% and 61% for detecting local recurrence and detected one lymphatic and one hepatic metastasis. In conclusion, the FDG-PET was more accurate than CT and CEA for the detection of recurrent colorectal cancer. In addition, it accurately detected distant metastases or occult secondary malignancy and may affect clinical management.

Decreased left atrial appendage function is an important predictor of elevated left ventricular filling pressure in patients with congestive heart failure.

OBJECTIVE: The aim of this study was to investigate whether left atrial (LA) appendage function, as indicated by LA appendage blood flow velocities and its ejection fraction, could identify elevated left ventricular filling pressure in patients with chronic congestive heart failure. METHODS: Using transesophageal echocardiography, adequate pulsed Doppler LA appendage active emptying and filling velocities could be recorded in 25 consecutive patients (16 men and 9 women, aged 57+/-10 years) with chronic congestive heart failure (symptom duration > or =1 year). LA appendage ejection fraction calculated as (LA appendage maximal area)-(LA appendage minimal area)/(LA appendage maximal area) x 100 was also determined in these patients. Left ventricular end-diastolic pressure was recorded during cardiac catheterization performed within 24 h of echocardiographic study. RESULTS: Left ventricular end-diastolic pressure was 2 to 47 mm Hg. There were close negative correlations of LA appendage emptying velocity (r=-0.508; P<0.01), filling velocity (r=-0.429; P<0.05) and LA appendage ejection fraction (r=-0.523; P<0.005) with left ventricular end-diastolic pressure. LA appendage active emptying velocity <30 cm/s predicted left ventricular end-diastolic pressure >25 mm Hg with a sensitivity of 72.7%, a specificity of 92.9% and a positive and negative predictive value of 88.9 and 81.3%. CONCLUSIONS: The findings suggest that measurement of LA appendage blood flow velocities and contractile function by transesophageal echocardiography can be used to predict elevated left ventricular filling pressure in patients with congestive heart failure.

Sick sinus syndrome in a patient with single coronary artery anomaly.

Single coronary artery anomaly is very rare. The reported manifestations include angina pectoris and congestive heart failure. Here we describe a case of single coronary artery anomaly presenting as sick sinus syndrome, which has no literature precedence. A 47-year-old woman had complained of intermittent dizziness for years. A Holter electrocardiogram showed sinus bradycardia and junctional or ventricular rhythm with a maximal ventricular pause of up to 3.2 seconds. Electrophysiologic study revealed prolonged corrected sinus nodal recovery time. Coronary angiography showed that the left anterior descending artery had a long course with a side branch originating from the proximal part and coursing anteriorly to the territory of the proximal portion of the right coronary artery. The sinus node is usually supplied by the sinoatrial branch via the right coronary artery. Aortography showed that the right coronary artery ostium was absent. A permanent pacemaker was implanted and the patient was discharged in good condition. The present case suggests that coronary artery anomaly may lead to compromised blood supply to the sinus node, and hence sick sinus syndrome.

Prognostic determinants of infective endocarditis in the 1990s.

The clinical profiles of infective endocarditis (IE) might have changed in recent years, owing to the advent of transesophageal echocardiography, the introduction of new diagnostic criteria, and the increased frequency of intravenous drug abuse. In this retrospective study, we sought to identify factors affecting the in-hospital outcome of IE patients in a single tertiary referral center in the 1990s (1990-1997). Eighty-eight episodes of IE in 80 consecutive patients admitted from January 1990 through June 1997 were evaluated. Clinical variables that were significantly associated with in-hospital mortality in univariate analyses were entered into a multiple logistic regression model. A total of 22 patients (25%) died. Fatal episodes were significantly more likely than non-fatal episodes to involve older patients (> or = 50 years), use of coumadin, short interval between symptom onset and hospitalization (< 15 days), noncardiac shock, and complications of the heart, central nervous system, and kidneys. White blood cell counts and C-reactive protein concentrations were also significantly higher in fatal than in non-fatal episodes of IE. Multivariate analysis showed that in-hospital mortality was associated with noncardiac shock, neurological complications, cardiac complications, and older age (> or = 50 years). Compared with previous reports, our findings suggest that the clinical profiles of IE have undergone some changes in the 1990s. The most important prognostic predictors of in-hospital mortality in patients with IE were noncardiac shock and neurologic complications.

Successful delayed thrombolytic therapy in a patient with massive pulmonary embolism.

Pulmonary embolism can be a catastrophic event leading to early death or serious hemodynamic instability. Thrombolytic therapy, in addition to heparin therapy, may improve the clinical condition and reduce the chance of recurrent pulmonary embolism in some cases. However, the acceptable "time window" for thrombolytic therapy is not well documented, though it has been used successfully as late as 14 days after pulmonary embolism. Successful delayed thrombolytic therapy beyond this "time window" in patients with massive pulmonary embolism has not been reported. We report a case of massive pulmonary embolism in which thrombolytic therapy was delayed more than 1 month after symptom onset. A 56-year-old woman was taken to National Cheng Kung University Hospital because of an episode of recurrent syncope, followed by progressive shortness of breath of 1 month's duration. Hypoxemia and hemodynamic instability were noted on admission. Echocardiography and a lung perfusion scan provided strong evidence of pulmonary embolism. Subsequent pulmonary angiography confirmed the diagnosis of multiple pulmonary emboli. The patient received a standard dose of intravenous tissue plasminogen activator 7 days after admission because of persistent symptoms and hypoxemia. Her clinical condition dramatically improved after treatment. Follow-up imaging studies showed resolution of the emboli. She was discharged in good condition. This case suggests that delayed thrombolytic therapy in patients with massive pulmonary embolism can still be beneficial in selected cases, even if given more than 2 weeks after symptom onset.

Amebic liver abscess complicated with cardiac tamponade and mediastinal abscess.

Amebic pericarditis is an extremely rare complication of liver abscess and an uncommon etiology of sterile pericardial effusion with cardiac tamponade. The association of mediastinal abscess in this clinical setting has not been reported in the literature. Herein, we describe a case of amebic liver abscess complicated with mediastinal abscess and amebic pericarditis with cardiac tamponade. A 44-year-old man was admitted to our hospital because of shortness of breath for the previous 2 days. Cardiac tamponade was diagnosed and emergency pericardiectomy was performed. Chocolate-like pus was found in the pericardial sac and mediastinal space during surgery. Abdominal computed tomography revealed an ill-defined hypodense lesion over the left lobe of the liver, suggesting a liver abscess. Amebic liver abscess and pericarditis were diagnosed on the basis of a high serum titer of amebic antibodies on hemagglutination test. The patient was treated with metronidazole for 2 weeks and discharged in good condition. This case should alert clinicians to the possibility of amebic pericarditis in patients with cardiac tamponade associated with chocolate-like sterile pus in the pericardium and mediastinum. To establish the diagnosis of amebic pericarditis, one should investigate the presence of a liver abscess, a high serum titer of amebic hemagglutination antibodies, and the presence of Entamoeba histolytica trophozoites in the pericardium or pericardial aspirate.

Ga-67 scan to detect intra-abdominal infection in patients after colorectal surgery.

PURPOSE: Intra-abdominal infection is still an important issue in colorectal surgery. The Ga-67 scan is relatively inexpensive, but the delay in diagnosis and the intense physiologic bowel activity are considerable drawbacks to its use in abdominal investigations. In this study, the authors performed 24-hour Ga-67 scans and read the images with the surgeon to detect abdominal infection in patients who underwent colorectal surgery. METHODS: Sixty-one patients who underwent colorectal surgery were enrolled in this study. Ga-67 scintigraphy was performed 24 hours, and later as needed, after the injection of 111 MBq (3 mCi) Ga-67 citrate. All scans were interpreted together by a nuclear medicine specialist and the surgeon. The intensity of Ga-67 uptake was recorded as grade 0: no uptake; grade 1: less than liver uptake; grade 2: equal to liver uptake; or grade 3: greater than liver uptake. When the intensity of Ga-67 uptake was equal to or greater than grade 2, the pattern of Ga-67 uptake was classified as changing or unchanging. A positive Ga-67 scan was defined as having an intensity of grade 2 or 3 with an unchanging pattern. RESULTS: Nineteen abdominal infections were diagnosed, all by Ga-67 scans, for a diagnostic sensitivity rate of 100%. Of the 42 patients with no intra-abdominal infection, only 2 had positive Ga-67 scans. This resulted in a specificity rate of 95.2%. The overall accuracy of the Ga-67 scan in the detection of intra-abdominal infection after colorectal surgery was 96.7%. CONCLUSIONS: The Ga-67 scan is useful for detecting intra-abdominal infection after colorectal surgery. Reading the images with the surgeon and using a lateral view can decrease the false-positive rate. A negative Ga-67 scan can rule out intra-abdominal infection, whereas a positive Ga-67 scan indicates the need for further patient evaluation after colorectal surgery.

Abdominal abscesses in patients having surgery: an application of Ga-67 scintigraphic and computed tomographic scanning.

PURPOSE: Early detection of occult abscesses is important in patients with persistent fever after colorectal surgery. In this study, the authors evaluated the relative merits of computed tomographic (CT) and Ga-67 scans in the detection of intra-abdominal abscesses in patients who had just undergone colorectal surgery. MATERIALS AND METHODS: Thirty-four patients who underwent colorectal surgery were enrolled in the study. Ga-67 and CT scans were obtained in all patients. Ga-67 scintigraphy was performed 24 hours, and later as needed, after the injection of 111 MBq (3 mCi) Ga-67 citrate. RESULTS: Intra-abdominal abscesses were diagnosed in 16 of the 34 (47%) patients who had colorectal surgery. For CT scans, the overall accuracy, sensitivity, and specificity rates were 97.1%, 93.7%, and 100%, respectively. For the Ga-67 scans, the diagnostic accuracy, sensitivity, and specificity rates were 91.2%, 100%, and 95.2%, respectively. In addition, the whole-body Ga-67 scans successfully detected two cases of extra-abdominal infection, one case of pneumonia, and one case of cellulitis. CONCLUSIONS: Computed tomographic and Ga-67 scans offer complementary information and play an important role in the investigation of sources of infection in patients after colorectal surgery.

Real time optical edge enhancement using a Hughes liquid crystal light valve.

A new real time edge enhancement effect using a Hughes CdS liquid crystal light valve and ts use in optical correlation are reported.