[Can urine albumin/creatinine ratio replace 24 hours urinary albumin?]

Objective: To analyze the correlation between urinary albumin/creatinine ratio (ACR) and 24-hour urinary microalbumin (UMA) and evaluate the predictive value of ARC for early diabetic nephropathy. Methods: A total of 368 patients with type 2 diabetes mellitus were retrospectively collected. Early diabetic nephropathy was defined as 24h UMA 30~<300 mg/24h. The correlation between ACR and 24hUMA, and the area under the receiver operating characteristic (ROC) curve of ACR in diagnosis of early diabetic nephropathy were calculated. Gender, age, course of disease, fasting venous blood glucose, glycosylated hemoglobin, blood pressure, triglyceride and total cholesterol were used as adjusting variables to establish univariate and multivariate logistic models of ACR for early diabetic nephropathy, respectively. A regression model was used to evaluate the diagnostic value of ACR for early diabetic nephropathy. Results: The correlation between ACR and 24h UMA was 0.658. The area under ROC curve of ACR for early diabetic nephropathy was 0.907 before and 0.933 after adjustments of gender, age, course of disease, fasting venous blood glucose, glycosylated hemoglobin, blood pressure, triglyceride and total cholesterol, respectively. The OR value of ACR of diabetic nephropathy was 2.016 before and 2.762 after same adjustments. The calibration of Hosmer-Lemeshow chi-square test evaluation model was 19.362 before (P=0.13) and 14.928 after adjustments (P=0.061). Conclusion: ACR is a better predictor for early diabetic nephropathy although its value is influenced by gender, age, course of disease, blood sugar, lipid, and blood pressure.

ViQuaS: an improved reconstruction pipeline for viral quasispecies spectra generated by next-generation sequencing.

MOTIVATION: The combined effect of a high replication rate and the low fidelity of the viral polymerase in most RNA viruses and some DNA viruses results in the formation of a viral quasispecies. Uncovering information about quasispecies populations significantly benefits the study of disease progression, antiviral drug design, vaccine design and viral pathogenesis. We present a new analysis pipeline called ViQuaS for viral quasispecies spectrum reconstruction using short next-generation sequencing reads. ViQuaS is based on a novel reference-assisted de novo assembly algorithm for constructing local haplotypes. A significantly extended version of an existing global strain reconstruction algorithm is also used. RESULTS: Benchmarking results showed that ViQuaS outperformed three other previously published methods named ShoRAH, QuRe and PredictHaplo, with improvements of at least 3.1-53.9% in recall, 0-12.1% in precision and 0-38.2% in F-score in terms of strain sequence assembly and improvements of at least 0.006-0.143 in KL-divergence and 0.001-0.035 in root mean-squared error in terms of strain frequency estimation, over the next-best algorithm under various simulation settings. We also applied ViQuaS on a real read set derived from an in vitro human immunodeficiency virus (HIV)-1 population, two independent datasets of foot-and-mouth-disease virus derived from the same biological sample and a real HIV-1 dataset and demonstrated better results than other methods available.

[Effects of ammonium pyrrolidine dithiocarbamate (PDTC) on osteopontin expression and autophagy in tubular cells in streptozotocin-induced diabetic nephropathy rat].

Objective: To investigate the effects of ammonium pyrrolidine dithiocarbamate (PDTC) on tubulointerstitial inflammatory molecules and autophagy in diabetic nephropathy (DN) rats. Methods: Twenty-four male Sprague-Dawley rats were assigned to DN group (n=6) and DN+ PDTC group (n=6, PDTC, ip, 100 mg·kg-1·d-1), all received streptozotocin (STZ) 60 mg/kg intraperitoneally, and the other 12 rats were randomly divided into control group (n=6) and PDTC group (n=6). At the end of 12 weeks, after serum creatine (Scr) and 24-hour urinary protein were determined, rats were sacrificed to determined the renal pathological damages and the changes of nuclear factor (NF)-κB p65, p62, osteopontin (OPN), microtubule associated protein 1 light chain 3 (LC3)-Ⅱ/LC3-Ⅰ, nuclear p-NF-κB p65 by immunohistological stainning and Western blot, and ultrastructural changes of autophagic process was observed by electron microscopy (EM). Results: Scr was similar among the four groups (P>0.05). The levels of urinary protein in DN group and DN + PDTC group were significantly higher than the other two groups (all P<0.01), but the level of urinary protein in DN + PDTC group was lower than that of DN group (P<0.05). DN + PDTC group had less tubulointerstitial damage compared with DN group (P<0.05). Among the four groups, expressions of p62, p65, OPN of tubulointerstitial area in DN group were significantly higher than that of the other groups (all P<0.05), and Western blot showed that DN+ PDTC group had less expressions of NF-κB p65, nuclear p-p65, OPN and more expresssion of LC3-Ⅱ/LC3-Ⅰ compared with DN group (all P<0.05), which were consistent with the decreased autophagic vacuoles and increased mitochondria dysfunction revealed by EM. Correlation analysis showed that renal LC3-Ⅱ/LC3-Ⅰ was negatively correlated the expressions of nuclear p-p65 and OPN (r=-0.45, P=0.02; r=-0.50, P=0.01), and p62 was positively correlated the expressions of nuclear p-p65 and OPN (r=0.33, P=0.01; r=0.41, P=0.01). Conclusion: Tubular NF-κB activation is closely related to autophagy dysfunction in DN rats, and PDTC may enhance autophagy activity in tubule cells by blocking NF-κB activity.

Accurate reconstruction of viral quasispecies spectra through improved estimation of strain richness.

BACKGROUND: Estimating the number of different species (richness) in a mixed microbial population has been a main focus in metagenomic research. Existing methods of species richness estimation ride on the assumption that the reads in each assembled contig correspond to only one of the microbial genomes in the population. This assumption and the underlying probabilistic formulations of existing methods are not useful for quasispecies populations where the strains are highly genetically related. RESULTS: On benchmark data sets, our estimation method provided accurate richness estimates (< 0.2 median estimation error) and improved the precision of ViQuaS by 2%-13% and F-score by 1%-9% without compromising the recall rates. We also demonstrate that our estimation method can be used to improve the precision and F-score of ShoRAH by 0%-7% and 0%-5% respectively. CONCLUSIONS: The proposed probabilistic estimation method can be used to estimate the richness of viral populations with a quasispecies behavior and to improve the accuracy of the quasispecies spectra reconstructed by the existing methods ViQuaS and ShoRAH in the presence of a moderate level of technical sequencing errors. AVAILABILITY: http://sourceforge.net/projects/viquas/.

Impact of GATA4 variants on stable warfarin doses in patients with prosthetic heart valves.

Interindividual variability in stable warfarin doses is largely attributed to VKORC1 and CYP2C9 variants. On the basis of a recent finding of the role of GATA4 in control of CYP2C9 expression, we tested a possible effect of GATA4 genotypes on variability in warfarin response using 201 Korean patients with prosthetic cardiac valves. Two single-nucleotide polymorphisms (SNPs), rs2645400 (G>T) and rs4841588 (G>T), were significantly associated with stable warfarin doses in patients carrying CYP2C9 wild-type homozygotes; homozygote carriers of these two SNPs required higher doses than those with other genotypes (5.94±1.73 versus 5.34±1.88 mg, P=0.026; 5.94±1.66 versus 5.37±1.92, P=0.036, respectively). Multivariate analysis showed that two GATA4 combinations, rs867858 (G>T)/rs10090884 (A>C) and rs2645400 (G>T)/rs4841588 (G>T), increased contribution to the overall warfarin dose variability from 36.4 to 40.9%. This study revealed that GATA4 can be predictive of stable warfarin dose and extended warfarin pharmacogenetics further to the regulation of CYP2C9 expression.

MYH9 gene polymorphisms may be associated with cerebrovascular blood flow in patients with type 2 diabetes.

Genetic factors play an important role in type 2 diabetes (T2D) complications. Alteration of cerebrovascular blood flow (CBF) is a direct result of cerebrovascular diseases. However, few studies have reported the role of genetics on CBF in patients with T2D. We investigated whether single-nucleotide polymorphisms (SNPs) in metabolic disease genes are associated with CBF in patients with T2D. CBF velocities of CBF were measured in 337 Han Chinese patients with T2D using transcranial Doppler sonography, with 54 cerebrovascular blood flow parameters documented. Fifty-two SNPs from 31 metabolic disease candidate genes were genotyped in patients. Quantitative allelic association and haplotype analyses were performed for candidate gene SNPs and CBF phenotypes. Spearman correlation was used to determine the relationship between CBF parameters and basic clinical characteristics, particularly, body mass index, lipids, fibrinogen, and GHbA1c. MYH9 gene SNPs (rs875726 and rs735853) may be associated with the peak velocity of the right-middle cerebral artery. SNPs rs875726, rs2009930, and rs375246 of the MYH9 gene may be associated with the mean velocity of the right-anterior and posterior cerebral artery. The haplotype G-C-A (rs2239782-rs3752462- rs2269532) of MYH9 may be associated with CBF. MYH9 gene polymorphisms may be associated with multiple CBF phenotypes in Chinese patients with T2D. However, whether MYH9 is a candidate gene for cerebrovascular diseases in Chinese patients with T2D remains unknown.

Quantitative candidate gene association studies of metabolic traits in Han Chinese type 2 diabetes patients.

Recent genome-wide association studies have identified many loci associated with type 2 diabetes mellitus (T2DM), hyperuricemia, and obesity in various ethnic populations. However, quantitative traits have been less well investigated in Han Chinese T2DM populations. We investigated the association between candidate gene single nucleotide polymorphisms (SNPs) and metabolic syndrome-related quantitative traits in Han Chinese T2DM subjects. Unrelated Han Chinese T2DM patients (1975) were recruited. Eighty-six SNPs were genotyped and tested for association with quantitative traits including lipid profiles, blood pressure, body mass index (BMI), serum uric acid (SUA), glycated hemoglobin (HbA1c), plasma glucose [fasting plasma glucose (FPG)], plasma glucose 120 min post-OGTT (P2PG; OGTT = oral glucose tolerance test), and insulin resistance-related traits. We found that CAMTA1, ABI2, VHL, KAT2B, PKHD1, ESR1, TOX, SLC30A8, SFI1, and MYH9 polymorphisms were associated with HbA1c, FPG, and/or P2PG; GCK, HHEX, TCF7L2, KCNQ1, and TBX5 polymorphisms were associated with insulin resistance-related traits; ABCG2, SLC2A9, and PKHD1 polymorphisms were associated with SUA; CAMTA1, VHL, KAT2B, PON1, NUB1, SLITRK5, SMAD3, FTO, FANCA, and PCSK2 polymorphisms were associated with blood lipid traits; CAMTA1, SPAG16, TOX, KCNQ1, ACACB, and MYH9 polymorphisms were associated with blood pressure; and UBE2E3, SPAG16, SLC2A9, CDKAL1, CDKN2A/B, TCF7L2, SMAD3, and PNPLA3 polymorphisms were associated with BMI (all P values <0.05). Some of the candidate genes were associated with metabolic and anthropometric traits in T2DM in Han Chinese. Although none of these associations reached genome-wide significance (P < 5 x 10(-8)), genes and loci identified in this study are worthy of further replication and investigation.

Association of gene polymorphisms with the risk of warfarin bleeding complications at therapeutic INR in patients with mechanical cardiac valves.

WHAT IS KNOWN AND OBJECTIVE: Pharmacogenetic studies of the genetic regulation of warfarin dose requirement have been reported, but few have been on the bleeding complications at therapeutic international normalized ratio (INR). This study aimed to evaluate the effect of gene polymorphisms of CYP2C9, VKORC1, thrombomodulin (THBD) and C-reactive protein (CRP) on the risk of bleeding complications of warfarin at therapeutic INR in Korean patients with mechanical cardiac valves. METHODS: A retrospective warfarin pharmacogenetic association study was performed. One hundred and forty-two patients with mechanical cardiac valves who were on warfarin anticoagulation therapy and maintained INR levels of 2·0-3·0 for 3 consecutive time intervals were followed up. CYP2C9 rs1057910, VKORC1 rs9934438, CRP rs1205, THBD rs1042580 and THBD rs3176123 were genotyped. The association between genotypes and warfarin bleeding complications was evaluated using logistic regression analysis, adjusted for demographic and clinical factors. RESULTS AND DISCUSSION: Of 142 eligible patients, 21 patients (14·8%) had bleeding complications at therapeutic INR. Patients with the G allele in THBD rs1042580 (AG or GG) had a lower risk of bleeding than patients with the AA genotype (adjusted OR: 0·210, 95% CI: 0·050-0·875, P = 0·032). The THBD rs3176123 polymorphism did not show any association with bleeding. For CRP rs1205, patients with the A allele (GA or AA genotype) had a higher risk of bleeding than patients with the GG genotype (adjusted OR: 5·575, 95% CI: 1·409-22·058, P = 0·014). Variant VKORC1 and CYP2C9 genotypes did not confer a significant increase in the risk for bleeding complications. WHAT IS NEW AND CONCLUSIONS: As expected, no association could be found between bleeding complications and two dose-related genes (CYP2C9*3 and VKORC1 rs9934438). In contrast, our results suggest that two genetic markers (THBD rs1042580 and CRP rs1205) could be predictors of bleeding complications of warfarin at normal INR. Given the retrospective study design and the relatively small sample size, our hypothesis requires further independent validation using more robust prospective designs. However, additional retrospective studies similar to ours but in populations with different genetic backgrounds should also be useful.

Long-term clinical outcomes and risk factors for the occurrence of post-operative complications after cardiovascular surgery in patients with Behçet's disease.

OBJECTIVES: Cardiovascular surgery in patients with Behçet's disease (BD) frequently leads to postoperative complications such as anastomotic leakage, occlusion or pseudoaneurysm. We evaluated the clinical outcomes and related risk factors of postoperative complications in BD patients undergoing cardiovascular surgeries, as well as the long-term efficiency of postoperative immunosuppressive treatment. METHODS: Forty-one patients with BD who had undergone cardiovascular surgery between 1990 and 2009 were studied. We evaluated the patients' clinical data, postoperative complications, and survival rate. Risk factors related to the occurrence of postoperative complications were identified by univariate analysis using the Kaplan-Meier method with the log-rank test and multivariate analysis using the Cox proportional hazards regression model. RESULTS: Fifty-nine operations were performed in 41 patients. During the mean follow-up period of 65.3±48.1 months, complications such as paravalvular leakage, dehiscence, fistula, graft occlusion, or pseudoaneurysm occurred in 29 operations (49.2%). The cumulative occurrence rate of postoperative complication was 10.2% at three months, 32.8% at 12 months, and 43.8% at 24 months. Upon univariate analysis, young age, high Creactive protein levels, lack of postoperative immunosuppression, and short disease duration were identified as significant factors responsible for the occurrence of postoperative complications. In multivariate analysis, postoperative immunosuppression was found to independently lower the risk of complications. The 5-year survival rate was significantly higher in patients with postoperative immunosup immunosuppression than in those without (84.5% vs. 45.0%, p=0.011). CONCLUSIONS: The present study suggests that postoperative immunosuppressive therapy after cardiovascular surgeries in BD patients is important for reducing the development of serious postoperative complications.

Fast splice site detection using information content and feature reduction.

BACKGROUND: Accurate identification of splice sites in DNA sequences plays a key role in the prediction of gene structure in eukaryotes. Already many computational methods have been proposed for the detection of splice sites and some of them showed high prediction accuracy. However, most of these methods are limited in terms of their long computation time when applied to whole genome sequence data. RESULTS: In this paper we propose a hybrid algorithm which combines several effective and informative input features with the state of the art support vector machine (SVM). To obtain the input features we employ information content method based on Shannon's information theory, Shapiro's score scheme, and Markovian probabilities. We also use a feature elimination scheme to reduce the less informative features from the input data. CONCLUSION: In this study we propose a new feature based splice site detection method that shows improved acceptor and donor splice site detection in DNA sequences when the performance is compared with various state of the art and well known methods.

Splice site identification using probabilistic parameters and SVM classification.

BACKGROUND: Recent advances and automation in DNA sequencing technology has created a vast amount of DNA sequence data. This increasing growth of sequence data demands better and efficient analysis methods. Identifying genes in this newly accumulated data is an important issue in bioinformatics, and it requires the prediction of the complete gene structure. Accurate identification of splice sites in DNA sequences plays one of the central roles of gene structural prediction in eukaryotes. Effective detection of splice sites requires the knowledge of characteristics, dependencies, and relationship of nucleotides in the splice site surrounding region. A higher-order Markov model is generally regarded as a useful technique for modeling higher-order dependencies. However, their implementation requires estimating a large number of parameters, which is computationally expensive. RESULTS: The proposed method for splice site detection consists of two stages: a first order Markov model (MM1) is used in the first stage and a support vector machine (SVM) with polynomial kernel is used in the second stage. The MM1 serves as a pre-processing step for the SVM and takes DNA sequences as its input. It models the compositional features and dependencies of nucleotides in terms of probabilistic parameters around splice site regions. The probabilistic parameters are then fed into the SVM, which combines them nonlinearly to predict splice sites. When the proposed MM1-SVM model is compared with other existing standard splice site detection methods, it shows a superior performance in all the cases. CONCLUSION: We proposed an effective pre-processing scheme for the SVM and applied it for the identification of splice sites. This is a simple yet effective splice site detection method, which shows a better classification accuracy and computational speed than some other more complex methods.

Synthesis and characterization of a new fluorescent phospholipid.

A novel fluorescent phospholipid, whose structure was tentatively assigned as 1-(2'-thio-1'-hydroxyethyl)-2-(ethylphosphatidyl)isoindole), was synthesized by reacting O-phthalaldehyde and beta-mercaptoethanol with phosphatidylethanolamine. The fluorescent lipid product was purified by silicic acid chromatography. The purity was demonstrated by thin-layer chromatography. This fluorescent phospholipid could not form stable lipid vesicles. However, a mixture of phosphatidylcholine and this fluorescent phospholipid did form stable vesicles after sonication, as demonstrated by Sepharose 4B column chromatography and electron microscopy. The absorption and fluorescence properties of this lipid, both as aqueous micelles or incorporated into vesicles, have been determined. The potential usage of this new fluorescent phospholipid in membrane studies is discussed.

Circadian rhythm and effect of posture on plasma aldosterone concentration in primary aldosteronism.

The effect of circadian rhythm and alterations in posture on plasma aldosterone concentration was studied in 13 patients with primary aldosteronism (six adenoma, five idiopathic hyperplasia, two carcinoma) to define the regulatory mechanism in each of these pathologic subtypes. Blood samples for aldosterone, cortisol, renin, and potassium concentrations were obtained every 4 h during prolonged recumbency (32 h) and upright posture (16 h). During recumbency, aldosterone and cortisol followed a normal circadian pattern in patients with adenoma and hyperplasia, with peak values at 0400-0800 h and the nadir at 1600-2400 h. Normalized aldosterone and cortisol values correlated significantly in both groups (adenoma r=+0.66, P less than 0.001; hyperplasia r=+0.42, P less than 0.01). With upright posture, aldosterone levels declined parallel to the normal circadian fall in cortisol in patients with adenoma (r=+0.68, P less than 0.001); whereas aldosterone levels increased in patients with hyperplasia parallel to small increments in renin (r=+0.65, P less than 0.001) and potassium (r=+0.64, P less than 0.001). During the administration of dexamethasone, aldosterone no longer correlated with cortisol in patients with adenoma but continued to correlate with renin during upright studies in patients with hyperplasia (r=+0.77, P less than 0.01). Aldosterone circadian rhythm was abnormal in patients with carcinoma and no effect of posture was noted. Unilateral adrenalectomy restored the normal postural relationship in four patients with adenoma. These studies suggest that aldosterone secretion is under continuous ACTH control regardless of posture in patients with adenoma, whereas persistent adrenal responsiveness to small increments in renin and/or potassium mediate the postural increase in plasma aldosterone in patients with hyperplasia. True adrenal autonomy occurs only in patients with adrenal carcinoma and when ACTH is suppressed in those with adenoma.

The constant plasma 18-hydroxycorticosterone to aldosterone ratio: an expression of the efficacy of corticosterone methyloxidase type II activity in disorders with variable aldosterone production.

Aldosterone and 18-hydroxycorticosterone (18-OHB) are produced by the adrenocortical zona glomerulosa. Under normal conditions, plasma 18-OHB levels parallel and are influenced by the same trophic factors that regulate aldosterone production. To evaluate corticosterone-methyl-oxidase II activity, the final step of aldosterone biosynthesis, in conditions associated with chronic derangements of the pituitary-adrenal and/or renal-adrenal axis, we measured the plasma 18-OHB to aldosterone ratio, cortisol, PRA or plasma renin concentration, and potassium (K) in 104 such patients and 15 normal subjects. The 18-OHB to aldosterone ratios in the pituitary-adrenal group were not significantly different from normal regardless of elevated or reduced ACTH and/or cortisol levels [patients with Cushing's syndrome, 3.55 +/- 0.68 (+/-SE); ACTH deficiency, 2.03 +/- 0.34; 21-hydroxylase deficiency, 3.09 +/- 0.23; normal subjects, 2.50 +/- 0.15]. The renal-adrenal group also had normal ratios regardless of plasma renin concentration and K levels [patients with aldosterone-producing adenomas, 2.85 +/- 0.15; idiopathic hyperaldosteronism, 2.14 +/- 0.19; salt-losing nephropathy, 3.06 +/- 0.54; Bartter's syndrome, 2.89 +/- 0.20; isolated (hyporeninemic) hypoaldosteronism, 3.20 +/- 0.39]. Only in patients with 17 alpha-hydroxylase deficiency (230.1 +/- 118.6) was the ratio abnormally high. Chronic perturbations of aldosterone production by ACTH, the renin-angiotensin system, and/or K did not alter this last step of aldosterone biosynthesis (corticosterone-methyloxidase II), as defined by their plasma concentrations. Any influence of these trophic factors must be proximal to the site of 18-OHB production.

Echocardiographic and morphologic characteristics of left atrial myxoma and their relation to systemic embolism.

We examined the relation between the echocardiographic morphology of cardiac myxoma and systemic embolism in 25 patients. Two distinct types of myxoma could be identified by echocardiography: round type characterized by solid and round shape with nonmobile surface (n = 13, 52%), and polypoid type characterized by soft and irregular shape with mobile surface (n = 12, 48%); multiple regression analysis revealed the polypoid type of tumor was the only independent predictor of systemic embolism (p = 0.0029).

The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure.

On the basis of the known electrophysiologic mechanisms of atrial fibrillation, multiple surgical procedures were designed and tested in dogs to determine the feasibility of developing a surgical cure for human atrial fibrillation. These experimental studies culminated in a surgical approach that effectively creates an electrical maze in the atrium. The atrial incisions prevent atrial reentry and allow sinus impulses to activate the entire atrial myocardium, thereby preserving atrial transport function postoperatively. Since September 1987, this surgical procedure has been applied in seven patients, five with paroxysmal atrial fibrillation of 2 to 9 years' duration and two with chronic atrial fibrillation of 3 and 10 years' duration. All seven patients have been cured of atrial fibrillation and none is receiving any postoperative antiarrhythmic medications.

Intracardiac tuberculoma.

We examined a case of endocardial tuberculoma at the proximal superior vena cava and the right atrium in a 17-year-old male patient. He had frequent palpitations and general weakness for about 7 months and was referred for evaluation of incessant atrial tachyarrhythmia. Results of echocardiography and magnetic resonance imaging showed an intracardiac mass, which was excised using cardiopulmonary bypass. Histology of the mass was consistent with the diagnosis of tuberculoma. The patient's postoperative course was uneventful and he was discharged with antituberculous medication. Five months after the operation, the patient was well without tachycardia, and follow-up echocardiography showed complete disappearance of the mass.

Computerized activation sequence mapping of the human atrial septum.

To delineate the propagation of electrical activation in the atrial septum, atrial epicardial and atrial septal maps were recorded intraoperatively using a 156-channel computerized mapping system in 12 patients during sinus rhythm (n = 10), supraventricular tachycardia associated with septal pathways in Wolff-Parkinson-White syndrome (n = 3), atrioventricular (AV) node reentrant tachycardia (n = 4), and atrial flutter (n = 5). The epicardial and septal data were recorded simultaneously from 156 atrial electrodes, digitized, analyzed, and displayed as isochronous maps on a two-dimensional diagram of the atria. During sinus rhythm, the activation wave fronts propagated most rapidly along the large muscle bundles of the atrial septum. During supraventricular tachycardia associated with Wolff-Parkinson-White syndrome, the earliest site of retrograde atrial activation usually corresponded to the position of atrial insertion of the septal pathways. However, the earliest site of activation during orthodromic supraventricular tachycardia was different from that during ventricular pacing in 1 patient with a posterior septal accessory pathway localized by the epicardial mapping study. The data document the rationale for dividing the ventricular end of the accessory pathways (ie, the endocardial technique) rather than the atrial end (ie, the epicardial technique) in patients with Wolff-Parkinson-White syndrome. During AV node reentrant tachycardia, atrial activation data suggested that atrial tissue lying outside the confines of the anatomical AV node is a necessary link in this common arrhythmia. Thus, these atrial septal maps explain why surgical dissection, or properly positioned small cryolesions placed in the region of the AV node, can ablate AV node reentrant tachycardia without altering normal AV node function. The maps recorded during atrial flutter suggest the importance of the atrial septum as one limb of a macroreentrant circuit responsible for the arrhythmia, and imply that atrial flutter is amenable to control by surgical techniques. These studies demonstrate the details of normal atrial septal activation, the importance of the atrial septum in a variety of different atrial arrhythmias, and the basis of and potential for surgical ablation of the most common types of supraventricular arrhythmias.

Transesophageal echocardiographic identification of left upper pulmonary venous obstruction caused by compression by spontaneous pseudoaneurysm of the descending thoracic aorta.

Pseudoaneurysm of the aorta usually occurs as a complication of nonpenetrating trauma or deceleration injuries. Spontaneous pseudoaneurysm of the aorta is, however, extremely rare. Pulmonary veins can be affected in this situation because of the anatomic proximity. However, it is often overlooked during clinical examination, during routine echocardiography, and even at invasive angiography. This report describes the importance of transesophageal echocardiography in the detection of pulmonary vein compression, which is not suspected during other noninvasive and invasive diagnostic tests, in a patient with spontaneous pseudoaneurysm of the descending thoracic aorta.

Surgery for atrial fibrillation.

The observations made under controlled experimental conditions provided us with a clearer understanding of the mechanisms involved in the generation and perpetuation of atrial fibrillation. The magnitude and rapidity of change that occurs in the activation patterns during atrial fibrillation were not appreciated, however, until the arrhythmia was studied in similar detail in humans. These studies provided the scientific basis for devising a surgical treatment for atrial fibrillation that has been successful in three patients. By converting the atrial fibrillation to normal sinus rhythm, all three of the detrimental sequelae of atrial fibrillation have been alleviated in each of these patients. Despite the fact that these clinical results are preliminary at this point, our experience documents that atrial fibrillation can be cured by surgical means. In the absence of other effective forms of therapy and in view of the devastating complications of the arrhythmia, surgical intervention should be considered a viable option for the treatment of atrial fibrillation.