Valve Excrescences: Prevalence, Evolution and Risk for Cardioembolism

AbstractObjectives. We sought to determine prospectively the prevalence, evolution and embolic risk of valve excrescences in normal subjects and patients with and without suspected cardioembolism.Background. Valve excrescences detected by transesophageal echocardiography (TEE) have been considered a cardioembolic substrate in selected patients.Methods. Ninety healthy volunteers (Group I) and 88 patients without suspected cardioembolism and a normal TEE (Group II) were studied and followed up clinically for 58 ± 21 and 48 ± 20 months, respectively. To assess the evolution of valve excrescences, 45 of these subjects underwent repeat TEE at 31 ± 13 months. The findings in Groups I and II were compared with those of Group III—49 patients referred for TEE for suspected cardioembolism.Results. Valve excrescences were detected in 34 subjects (38%) in Group I and in 41 patients (47%) in Group II. In Group III, 20 patients (41%) had excrescences, but 85% of them had other potential cardiac or vascular sources of embolism. In all groups, mitral valve excrescences were predominant (68% to 76%), followed by aortic (38% to 50%) and right-sided valves (<10%). Excrescences were equally frequent in men and women and between all age groups studied. During follow-up in Groups I and II, excrescences persisted unchanged, and 1 (1.4%) of 74 patients with and 2 (2%) of 99 subjects without excrescences had cerebral ischemic events (80% power to detect a clinically meaningful difference of 4%).Conclusions. Valve excrescences are common on the left-sided heart valves of normal subjects and patients regardless of gender and age; they persist unchanged over time and do not appear to be a primary source of cardioembolism

Altered splicing of CEACAM1 in breast cancer: Identification of regulatory sequences that control splicing of CEACAM1 into long or short cytoplasmic domain isoforms

<p>Abstract</p> <p>Background</p> <p>Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a cell adhesion molecule expressed in a variety of cell types is a putative tumor suppressor gene. Alternative splicing of CEACAM1 generates 11 different splice variants, which include 1–4 ectodomains with either short or long cytoplasmic domain generated by the exclusion (CEACAM1-S) or inclusion (CEACAM1-L) of exon 7. Studies in rodents indicate that optimal ratios of CEACAM1 splice variants are required to inhibit colonic tumor cell growth.</p> <p>Results</p> <p>We show that CEACAM1 is expressed in a tissue specific manner with significant differences in the ratios of its short (CEACAM1-S) and long (CEACAM1-L) cytoplasmic domain splice variants. Importantly, we find dramatic differences between the ratios of S:L isoforms in normal breast tissues versus breast cancer specimens, suggesting that altered splicing of CEACAM1 may play an important role in tumorogenesis. Furthermore, we have identified two regulatory <it>cis</it>-acting elements required for the alternative splicing of CEACAM1. Replacement of these regulatory elements by human β-globin exon sequences resulted in exon 7-skipped mRNA as the predominant product. Interestingly, while insertion of exon 7 in a β-globin reporter gene resulted in its skipping, exon 7 along with the flanking intron sequences recapitulated the alternative splicing of CEACAM1.</p> <p>Conclusion</p> <p>Our results indicate that a network of regulatory elements control the alternative splicing of CEACAM1. These findings may have important implications in therapeutic modalities of CEACAM1 linked human diseases.</p

Plasminogen activator levels are influenced by location and varicosity in greater saphenous vein

AbstractPurpose: The plasminogen system, which includes tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA), and their main inhibitor, plasminogen activator inhibitor type 1 (PAI-1), plays a major role in both fibrinolysis and tissue remodeling. This study compares the levels of tPA, uPA, and PAI-1 at the groin and ankle in normal and varicose greater saphenous vein (GSV).Methods: GSV was collected from patients undergoing varicose vein (VV) removal and from normal vein (NV) from arterial bypass procedures. Portions of the GSV at the groin and the ankle were minced and placed in serum-free media for 48 hours. Assays of the supernatants were obtained for tPA, uPA, and PAI-1 protein by enzyme-linked immunosorbent assay. Cyclohexamide and actinomycin D were also added to the media of the VV tissue explant supernatants to inhibit protein and RNA synthesis, respectively.Results: Levels of tPA were significantly higher at the groin (11 ± 2) than the ankle (5 ± 1) in the VV ( p < 0.005), and this trend was also seen in the NV (groin 10 ± 2 and ankle 7 ± 3). Levels of uPA were significantly higher in the groin VV (14 ± 4.3) than in NV (3.0 ± 0.8, p < 0.05). This difference, although not statistically significant, applied to the ankle as well (VV 14.5 ± 6.3 and NV 5.3 ± 2.7). No significant difference was seen between NV and VV for PAI-1 (NV, groin 155 ± 73 and ankle 113 ± 53, VV, groin 161 ± 20 and ankle 142 ± 38) or tPA. Inhibitor studies revealed no significant difference among control, cyclohexamide, and actinomycin D supernatants for tPA, suggesting release of protein rather than active synthesis. In contrast, inhibitor supernatants were significantly lower for uPA and PAI-1 than control supernatants ( p < 0.05), suggesting that uPA and PAI-1 were actively synthesized.Conclusions: In the tissue explant supernatant model uPA and PAI-1 are actively synthesized, but tPA is not. Levels of PAI-1 were comparable in all four groups. Levels of uPA in the varicose GSV were higher than in NV, suggesting a role for uPA in the pathologic makeup of VV. Levels of tPA were higher at the groin versus the ankle position, potentially explaining the previously described increased fibrinolytic activity seen at the groin. (J Vasc Surg 1996;24:719-24.

Appetite suppressants and valvular heart disease - a systematic review

Background Although appetite suppressants have been implicated in the development of valvular heart disease, the exact level of risk is still uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were affected, but subsequent research has yielded substantially different figures. Our objective was to systematically assess the risk of valvular heart disease with appetite suppressants. Methods We accepted studies involving obese patients treated with any of the following appetite suppressants: fenfluramine, dexfenfluramine, and phentermine. Three types of studies were reviewed: controlled and uncontrolled observational studies, and randomized controlled trials. Outcomes of interest were echocardiographically detectable aortic regurgitation of mild or greater severity, or mitral regurgitation of moderate or greater severity. Results Of the 1279 patients evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral regurgitation, respectively. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals 1.06 to 2.25, p = 0.02) with an attributable rate of 1.0%. Only one case of valvular heart disease was detected in 57 randomized controlled trials, but this was judged unrelated to drug therapy. Conclusions The risk of valvular heart disease is significantly increased by the appetite suppressants reviewed here. Nevertheless, when considering all the evidence, valvulopathy is much less common than suggested by the initial, less methodologically rigorous studies

Genomic Organization, Splice Variants and Expression of CGMl, a CD66-related Member of the Carcinoembryonic Antigen Gene Family

The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunogiobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGMI. a transmembrane member of the CEA family without immunoglobulin constant.like domains. CGM1a and CGM1c contain cytopiasmic domains of 71 and 31 amino acids, respectively, The cytoplasmic region of CGM1a is encoded by four exons (Cyt1-Cyt4). Differential splicing of the Cyt1 exon (53 bp)..

Ethnic Differences in Quality of Life in Persons with Heart Failure

Background Chronic illness burdens some groups more than others. In studies of ethnic/racial groups with chronic illness, some investigators have found differences in health-related quality of life (HRQL), whereas others have not. Few such comparisons have been performed in persons with heart failure. The purpose of this study was to compare HRQL in non-Hispanic white, black, and Hispanic adults with heart failure. Methods Data for this longitudinal comparative study were obtained from eight sites in the Southwest, Southeast, Northwest, Northeast, and Midwest United States. Enrollment and 3- and 6-month data on 1212 patients were used in this analysis. Propensity scores were used to adjust for sociodemographic and clinical differences among the ethnic/racial groups. Health-related quality of life was measured using the Minnesota Living with Heart Failure Questionnaire. Results Significant ethnic/racial effects were demonstrated, with more favorable Minnesota Living with Heart Failure Questionnaire total scores post-baseline for Hispanic patients compared with both black and white patients, even after adjusting for baseline scores, age, gender, education, severity of illness, and care setting (acute vs. chronic), and estimating the treatment effect (intervention vs. usual care). The models based on the physical and emotional subscale scores were similar, with post hoc comparisons indicating more positive outcomes for Hispanic patients than non-Hispanic white patients. Conclusion Cultural differences in the interpretation of and response to chronic illness may explain why HRQL improves more over time in Hispanic patients with heart failure compared with white and black patients

Why Primate Models Matter

Research involving nonhuman primates (NHPs) has played a vital role in many of the medical and scientific advances of the past century. NHPs are used because of their similarity to humans in physiology, neuroanatomy, reproduction, development, cognition, and social complexity – yet it is these very similarities that make the use of NHPs in biomedical research a considered decision. As primate researchers, we feel an obligation and responsibility to present the facts concerning why primates are used in various areas of biomedical research. Recent decisions in the United States, including the phasing out of chimpanzees in research by the National Institutes of Health and the pending closure of the New England Primate Research Center, illustrate to us the critical importance of conveying why continued research with primates is needed. Here we review key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research

A rare localization in right-sided endocarditis diagnosed by echocardiography: A case report

BACKGROUND: Right-sided endocarditis occurs predominantly in intravenous drug users, patients with pacemakers or central venous lines and with congenital heart diseases. The vast majority of cases involve the tricuspid valve. CASE PRESENTATION: A case of a 31-year-old woman with intravenous drug abuse who had a right-sided vegetation attached to the muscular bundle of the right ventricle is presented. Transthoracic echocardiography revealed a vegetation in the right ventricular outflow tract. Transesophageal echocardiography clearly showed that the 1.8 cm vegetation was not adherent to the pulmonary valve but attached to a muscular bundle. CONCLUSIONS: Our case points to an unusual location of right-sided endocarditis in intravenous drug users. It confirms that TTE remains an easy and highly sensitive first-line examination for the diagnosis of right-sided endocarditis