Young woman with repeated late stent thrombosis: a case report

A 34-year-old woman with hypertension, obesity, and history of smoking presented with unstable angina and severe stenosis of the proximal left anterior descending artery. Percutaneous coronary intervention was performed with stent implantation resulting in adequate expansion. She was treated with aspirin and ticlopidine for 1 month, then only aspirin for 1 month. One year after stenting, she presented with acute myocardial infarction and total occlusion at the stent. Balloon angioplasty was performed. She took ticlopidine and aspirin for 9 months. Two months later, she presented with acute myocardial infarction with reocclusion at the stent. Blood examination showed no manifest collagen disease or thrombophilia. This case of repeated late stent thrombosis occurred in a young woman not treated by brachytherapy.     

Effects of right atrial pacing preference in prevention of paroxysmal atrial fibrillation: Atrial Pacing Preference study (APP study).

BACKGROUND: Several preliminary studies have indicated that atrial pacing can prevent atrial tachyarrhythmias. The suggested mechanisms by which pacing may be effective include suppression of premature atrial beats. METHODS AND RESULTS: The Atrial Pacing Preference (APP; Guidant, St Paul, MN, USA) algorithm allows the pacemaker to maintain a pacing rate slightly higher than the sinus rate. The preventive effects of APP on paroxysmal atrial fibrillation (AF) were studied in 51 patients (70+/-11 years). Nine patients did not complete the protocol. The pacemaker was programmed in random order to APP off and APP on at 3 different settings (ie, 8, 16 and 32 cycles) for 4 weeks each, using a cross-over design. Percentage atrial pacing was lower in APP off than at the other settings. Premature beat counts were greater in APP off than at the other settings. There was a significant difference in mode switch episode counts between APP off and the most effective setting (3,818+/-15,356 vs 596+/-1,719; p<0.01). CONCLUSIONS: The APP algorithm is a promising method for preventing atrial tachyarrhythmia in patients with an implanted pacemaker and AF. Optimizing the setting of the APP algorithm is an important issue in the prevention of AF.     

Exercise-induced changes of functional mitral regurgitation in asymptomatic or mildly symptomatic patients with idiopathic dilated cardiomyopathy

It has remained unclear why functional mitral regurgitation (MR), even if it is of a mild degree, has prognostic importance in patients with idiopathic dilated cardiomyopathy (IDC). Exercise-induced changes in functional MR, which might be a clue to this question, have not been fully clarified. Thus, in this study, semisupine exercise echocardiography was performed on 32 asymptomatic or mildly symptomatic patients with IDC (29 men, mean age 45 +/- 14 years). The mean ejection fraction was 28 +/- 10% (range 13% to 45%). The effective regurgitant orifice (ERO) area of MR was measured, as well as echocardiographic parameters including mitral valve geometry. ERO at rest was associated best with systolic mitral tenting area (r(S) = 0.85, p <0.001). Functional MR did not newly appear during exercise in 9 subjects without MR at rest. In the remaining 23 subjects with functional MR at rest, all showed exacerbations of MR, with a median ERO of 10.5 mm(2) (interquartile range 6.3 to 16.5) to 18.7 mm(2) (interquartile range 9.5 to 29.3) (p <0.001). An increase in ERO was correlated best with the enlargement of tenting area (r(S) = 0.90, p <0.001) and was the strongest independent determinant of exercise duration (beta = -0.55, p = 0.002, multiple R(2) = 0.46). In conclusion, functional MR complicated with IDC was significantly exacerbated during exercise, with mitral valve deformation, which was strongly related to exercise intolerance; thus, the clinical impact of functional MR in patients with IDC could be more serious than can be expected by its degree at rest.     

Tristetraprolin (TTP) gene polymorphisms in patients with rheumatoid arthritis and healthy individuals

Tristetraprolin (TTP) is an intracellular protein that modulates the production of cytokines, including TNFα, by binding to and destabilizing the mRNAs of these cytokines. Therefore, differences in TTP gene expression may affect the severity of inflammatory diseases, such as rheumatoid arthritis (RA). We searched for polymorphisms in the human TTP gene and for this purpose, we sequenced the entire TTP gene in 20 Japanese individuals (ten with RA and ten healthy volunteers) and found one single nucleotide polymorphism (SNP) in the promoter region. We analyzed this SNP (A/G) by restriction fragment length polymorphism method in 155 RA patients and 100 control subjects. While the frequency of A allele in this SNP was similar in RA patients (74.5%) and controls (76.0%), the disease duration in RA patients with genotype GG was shorter than that of patients with genotypes AA/AG and RA patients with genotype GG had a higher probability of being treated with infliximab. We studied the difference in promoter activity between the two alleles by luciferase assay and found that the promoter activity of TTP promoter region with allele A was around two-fold higher than that with allele G. We conclude that this SNP in the promoter region of the TTP gene mildly affects promoter activity, and thus, may influence the disease activity of inflammatory disorders including RA.     

Arteriosclerosis obliterans associated with anti-cardiolipin antibody/beta2-glycoprotein I antibodies as a strong risk factor for ischaemic heart disease in patients with systemic lupus erythematosus

Objective. The main objective of this study was to clarify therole of aPLs in the pathogenesis of arteriosclerosis obliterans(ASO), ischaemic heart disease (IHD) and cerebral vascular disorder(CVD) in patients with SLE. Methods. We evaluated 155 patients with SLE by using objectivetests for diagnosing ASO, IHD and CVD and laboratory tests includingELISA for aCL/β2-glycoprotein I antibodies (aCL/β2-GPI)and anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT). Results. Twenty-five (16.1%) of the 155 SLE patients were diagnosedwith ASO. Both aCL/β2-GPI and anti-PS/PT levels were significantlyhigher in SLE patients with ASO (mean ± S.E., 104.3 ±38.8 U/ml for aCL/β2-GPI, P < 0.01; 72.6 ± 48.9U/ml for anti-PS/PT, P < 0.05) than in SLE patients withoutASO (22.8 ± 9.9 U/ml for aCL/β2-GPI; 18.3 ±4.4 U/ml for anti-PS/PT). Multivariate logistic analysis includingaCL/β2-GPI, anti-PS/PT and traditional risk factors (hypercholesterolaemia,hypertension and diabetes mellitus) confirmed that the presenceof aCL/β2-GPI was the most significant risk factor forASO in SLE patients [odds ratio (OR) 3.45; 95% CI 1.40, 8.56;P < 0.01]. Furthermore, the prevalence of ASO was associatedstrongly with IHD (OR 11.8; 95% CI 3.45, 40.1; P < 0.0001)but not CVD (OR 1.84; 95% CI 0.65, 5.21; P = 0.25). Conclusions. The presence of aCL/β2-GPI contributes tothe risk of development of ASO, which may represent an importantmechanism for the pathogenesis of IHD in patients with SLE. KEY WORDS: Systemic lupus erythematosus, Anti-phospholipid antibodies, Arteriosclerosis obliterans, Ischaemic heart disease, Cerebral vascular disorder Submitted 12 December 2007; revised version accepted 22 February 2008.     

Plasma interleukin-6 and tumor necrosis factor-alpha can predict coronary endothelial dysfunction in hypertensive patients.

Coronary endothelial function is impaired in hypertension; however, the severity of this impairment varies among patients. We aimed to identify the predictors of coronary endothelial dysfunction among clinical variables related to hypertension and atherosclerosis. Twenty-seven untreated, uncomplicated essential hypertensive patients and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography (PET) at rest and during a cold pressor test (CPT). Coronary vascular resistance (CVR) during CPT was used as a marker of coronary endothelial function. Serum low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, malondialdehyde-LDL, homeostasis model assessment, high-sensitivity C-reactive protein (hs-CRP), and plasma interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were also measured. CVR during CPT was significantly higher in hypertensive patients than in healthy controls (114+/-26 vs. 94+/-12 mmHg/[mL/g/min]; p<0.05). By univariate analysis, CVR during CPT was correlated with LDL cholesterol (r=0.38, p<0.05), IL-6 (r=0.46, p<0.02), and TNF-alpha (r=0.39, p<0.05) in hypertensive patients. By multivariate analysis, IL-6 and TNF-alpha were significant independent predictors of CVR during CPT. Elevated plasma IL-6 and TNF-alpha levels were independent predictors of coronary endothelial dysfunction in hypertensive patients. These results suggest that plasma IL-6 and TNF-alpha might be useful for identifying the high risk subgroup of hypertensive patients with coronary endothelial dysfunction and provide an important clue to link systemic inflammation to the development of coronary atherosclerosis.     

Broad and specific caspase inhibitor-induced acute repression of apoptosis in atherosclerotic lesions evaluated by radiolabeled annexin A5 imaging.

OBJECTIVES: The purpose of this study was to evaluate the role of caspase inhibitors on acute resolution of apoptosis in atherosclerotic lesions as evaluated by imaging with annexin A5. BACKGROUND: Extensive apoptosis of macrophages has been reported at the site of plaque rupture in patients dying of acute coronary syndrome. METHODS: Of 31 New Zealand White atherosclerotic rabbits, 6 received broad caspase, 3 received caspase-1, 3 received caspase-3, 3 received caspase-8, and 4 received caspase-9 inhibitors; 12 animals did not receive any caspase inhibitors (treatment control group). Six unmanipulated rabbits were used for comparison (disease control group). Technetium-99m-labeled annexin A5 was used for imaging atherosclerotic lesions; 6 of the 12 uninhibited atherosclerotic rabbits received (99m)Tc-labeled mutant annexin A5 (radiotracer control group). Gamma images were obtained, and quantitative radiotracer uptake was compared with pathologic findings. RESULTS: Atherosclerotic lesions were best visible in untreated atherosclerotic rabbits. Quantitative annexin uptake, defined as the percent of injected dose per g of abdominal aorta tissue, was significantly higher in untreated atherosclerotic animals (mean +/- SD = 0.0515 +/- 0.0099) compared with the normal rabbits (0.0065 +/- 0.0008; p < 0.0001) or atherosclerotic rabbits receiving mutant annexin (0.014 +/- 0.0024; p < 0.0001). Among all caspase inhibitor-treated rabbits, uptake was 39% lower (0.0314 +/- 0.0151) than in untreated atherosclerotic animals (p < 0.01). Uptake was also significantly lower in rabbits receiving broad caspase (0.0206 +/- 0.0058; p < 0.0001) or caspase-1, -3, or -9 (0.0272 +/- 0.0088, p < 0.01; 0.0286 +/- 0.0095, p < 0.01; 0.0300 +/- 0.0021, p < 0.01, respectively) inhibitors. Caspase-8 inhibitor did not affect apoptosis (0.0618 +/- 0.0047; p = NS). Upon histologic characterization, a substantial decrease in macrophage apoptosis was observed in caspase-inhibited animals. CONCLUSIONS: Molecular imaging, using radiolabeled annexin A5, allows the detection of acute resolution of apoptosis as a result of caspase inhibition in experimental atherosclerosis. If proven clinically, this may allow development of novel intervention strategies in acute vascular events.     

The impact of visceral obesity on surgical outcomes of laparoscopic surgery for colon cancer

Purpose

Although obesity is considered as a risk factor for postoperative morbidity in abdominal surgery, its effect on the outcomes of laparoscopic-assisted colectomy (LAC) is still unclear. The technical difficulty and risk factor for postoperative complication in LAC are thought to be influenced by visceral obesity. The aim of this prospective study was to evaluate the impact of visceral fat on the surgical outcomes of LAC.

Methods

Between April 2005 and December 2010, consecutive patients with preoperatively diagnosed colon cancer, excluding medium and low rectal cancer, who underwent LAC, were enrolled. Their visceral fat area (VFA) and body mass index (BMI) were prospectively collected. The VFA was assessed by Fat Scan software. The patients were classified into two groups as follows: VFA nonobese with VFA <100 cm² (VNO) and VFA obese with VFA ≧100 cm² (VO). The predictive factors for surgical complications of LAC were evaluated by univariate and logistic regression analyses.

Results

A total of 338 consecutive patients were enrolled in this study. Of the 338 patients, 194 (57.4 %) and 138 (42.6 %) were classified into the VNO and VO groups, respectively. Logistic regression analysis showed that high BMI (≧25 kg/m²) and VO independently predicted the incidence of overall postoperative complications (p?=?0.040 and 0.007, respectively). VO was more highly related to the incidence of overall postoperative complications, anastomotic leakage (p?=?0.021), and surgical site infection (SSI) (p?=?0.013) than high BMI.

Conclusions

VFA is a more useful parameter than BMI in predicting surgical outcomes after LAC.     

Soluble interleukin-2 receptor level on day 7 as a predictor of graft-versus-host disease after HLA-haploidentical stem cell transplantation using reduced-intensity conditioning

In the present study, we analyzed the kinetics of serum soluble interleukin-2 receptor (sIL-2R) using data from 77 patients undergoing HLA-haploidentical transplantation using reduced-intensity conditioning (RIC), who were at an advanced stage or at high risk for relapse, to clarify the usefulness of sIL-2R as a biomarker of acute graft-versus-host disease (GVHD). Anti-T-lymphocyte globulin and methylprednisolone were used as GVHD prophylaxis. While the median sIL-2R in 38 patients not developing GVHD was suppressed at levels <740 U/ml, sIL-2R in 25 patients developing severe GVHD peaked on day 11 (1,663 U/ml), and thereafter decreased to <1,000 U/ml after day 30. The occurrence of GVHD was not limited to times of high sIL-2R level, but occurred at any time point on the sIL-2R curve. Most patients developing GVHD, however, experienced a higher sIL-2R level early in their transplant course. The combination of RIC and glucocorticoids sufficiently suppressed sIL-2R levels after HLA-haploidentical transplantation. In a multivariate analysis to identify factors associated with GVHD, day 7 sIL-2R >810 U/ml was the only factor significantly associated with the occurrence of severe GVHD (p = 0.0101).     

Clinicopathological differences of laterally spreading tumors arising in the colon and rectum

Purpose

Laterally spreading tumors (LST) have been recognized worldwide. The aim of our retrospective study was to evaluate the clinicopathological differences of LST arising in the colon and rectum.

Methods

We investigated the clinical records of consecutive patients with LST that were endoscopically or surgically resected at our hospital between February 2006 and March 2011. LST were classified into three types: granular-homogenous (LST-GH), granular-nodular mixed (LST-GM), and nongranular (LST-NG) types. We also defined the hardly elevated flat lesion with a dilated pit pattern that occurs at the margins of LST as the “skirt.” The clinicopathological characteristics of the LST arising in the colon and rectum, including the presence of the skirt, were compared.

Results

A total of 496 colorectal LST in 435 patients were examined. LST-GM was predominant in the rectum, whereas LST-NG was predominant in the colon (p?p?p?p?Conclusions A greater proportion of LST-GM, greater mean size, and lower incidence of low-grade dysplasia were found in rectal LST. The skirt was a novel and unique finding, primarily observed in rectal LST-GM cases.