Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events

BackgroundFamilial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD).ObjectiveWe aimed to evaluate the prognostic impact of cascade screening for FH.MethodsWe retrospectively investigated the health records of 1050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened, who were referred to our institute. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiac events (MACE). The median period of follow-up evaluating MACE was 12.3 years (interquartile ranges [IQR] = 9.1–17.5 years), and MACE included death associated with ASCVD, or acute coronary syndrome.ResultsDuring the observation period, 113 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P < 0.0001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.67; 95%CI = 0.44 to 0.90; P = 0.0044) when compared with the probands, even after adjusting for those known risk factors, including age, and prior ASCVD.ConclusionsThe identification of patients with FH via cascade screening appeared to result in better prognosis.     

A multi-disciplinary distributed simulation environment for mechatronic system design enabling hardware-in-the-loop simulation based on HLA

This paper proposes a high-level architecture-based multi-disciplinary distributed simulation environment for designing mechatronic systems. In the system, commercial off-the-shelf simulators can communicate each other via real-time-infrastructure to realize software-in-the-loop simulation. Moreover, hardware prototypes can also participate in a part of the distributed simulation environment which enable us hardware-in-the-loop simulation. Effectiveness was verified by applying the environment to mechatronic system design of an automotive power-window and an omni-directional electric wheel chair.     

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection

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Role of the coronary sinus in maintenance of atrial fibrillation

INTRODUCTION: Bursts of tachycardia arising in the pulmonary veins may play an important role in perpetuating atrial fibrillation (AF). However, the role of the coronary sinus (CS) in the perpetuation of AF has been unclear. The aim of this study was to determine whether the CS plays a role in perpetuation of AF. METHODS AND RESULTS: Pulmonary vein isolation was performed by segmental ostial ablation with radiofrequency energy in 22 consecutive patients with paroxysmal AF. Bipolar and unipolar electrograms recorded in the left atrium and CS were analyzed during atrial pacing from the mitral annulus and during AF. There was a mean of 2.5 +/- 0.5 electrical connections between the CS and the left atrium. The electrical connections between the left atrium and CS were ablated with a mean of 6.2 +/- 2.7 minutes of radiofrequency energy applied along the atrial side of the inferior mitral annulus. During AF, episodes of intermittent tachycardia alternated between the left atrium and the CS. Among the 22 patients, sustained AF was still inducible in 9 after pulmonary vein isolation. After electrical disconnection of the CS from the left atrium, sustained AF was inducible in only 3 of these 9 patients. CONCLUSION: The CS may be a source of rapid repetitive electrical activity during AF. The lower probability of inducible sustained AF after electrical disconnection of the CS from the left atrium suggests that the CS may play a role in perpetuating AF.     

Squamous Cell Carcinoma after Endoscopic Injection Sclerotherapy for Esophageal Varices

We report two cases of squamous cell carcinoma of the esophagus following endoscopic injection sclerotherapy for esophageal varices. The interval between sclerotherapy and the development of carcinoma was 24 months in case 1 and 21 months in case 2. The sclerosant was 5% sodium morrhuate in case 1 (total dose, 10 ml) and 5% ethanolamine oleate in case 2 (45.5 ml). Although no recurrent variceal bleeding occurred after sclerotherapy, we could not perform any curative surgical treatment for esophageal cancer because of the advanced stage of the cancer and the severity of the accompanying liver dysfunction. It is difficult to determine the relationship between sclerotherapy and carcinoma; however, long-term surveillance is essential to avoid overlooking a neoplasm in the esophagus after endoscopic injection sclerotherapy.     

Identification of a Novel NDM Variant,NDM-13, from a Multidrug-Resistant Escherichia coli Clinical Isolate in Nepal

A novel New Delhi metallo-β-lactamase, NDM-13, was identified in a carbapenem-resistant Escherichia coli clinical isolate obtained from the urine of a patient in Nepal. The enzymatic activity of NDM-13 against β-lactams was similar to that of NDM-1. However, NDM-13 displayed significantly higher k_cat/K_m ratios for cefotaxime. The genetic environment of bla_NDM-13 was determined to be tnpA-IS30-bla_NDM-13-ble_MBL-trpF-dsbC-cutA-groES-groL, with bla_NDM-13 located within the chromosome.     

Effects of transjugular intrahepatic portosystemic shunt (TIPS) on esophageal motor function and gastroesophageal reflux

The effects of transjugular intrahepatic portosystemic shunt (TIPS) placement on esophageal motor function and gastroesophageal reflux were investigated in patients with esophageal varices. In six men with esophageal varices, esophageal manometry and upper gastrointestinal endoscopy were performed before and 15–20 days after TIPS placement. Intraesophageal pH monitoring was performed in the four patients with severe esophageal varices (defined as the largest sized varices) following TIPS placement. Findings were compared with those in six healthy men (controls) who underwent esophageal manometry and intraesophageal pH monitoring. The esophageal varices resolved or were reduced after TIPS placement. Resting lower esophageal sphincter (LES) pressures were similar in the study group before and after TIPS placement and in the control subjects. The incidence and progression of esophageal contractions were similar in the study group before and after TIPS placement and in the control subjects. At 3 cm above the LES, the amplitude of esophageal contraction after TIPS placement was significantly higher than that before TIPS placement. At 3 and 8 cm above the LES, the amplitude of esophageal contraction in the control subjects was significantly higher than that in the study group before and after TIPS placement. Esophageal acid exposure time after TIPS placement was similar to that in the controls. TIPS placement is a useful treatment that improves esophageal motor function without the occurrence of pathologic gastroesophageal reflux. (Received May 28, 1997; accepted Sept. 26, 1997)     

Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism

BACKGROUND: The D allele of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. METHODS: We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7+/-13.3 years) undergoing coronary angiography. RESULTS: The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. CONCLUSION: We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism.