Cytomegalovirus Localization in Atherosclerotic Plaques is Associated with Acute Coronary Syndromes: Report of 105 Patients

It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical rele-vance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and poly-merase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.     

Comparative measurement of anti-factor VIII antibody by Bethesda assay and ELISA reveals restricted isotype profile and epitope specificity

Factor VIII (FVIII) inhibitor antibodies are produced against functional epitopes of FVIII in about 30% of severe hemophilia A patients leading to inhibition of its procoagulant activity. The Bethesda assay, the most commonly used method to measure FVIII inhibitors, based on inhibition of coagulant activity of FVIII, is neither able to detect noninhibitory antibodies nor their isotype. In this study we employed an indirect enzyme-linked immunosorbent assay (ELISA) to measure dif ferent isotypes and IgG subclasses of anti-FVIII anti body in the plasma of hemophiliacs (with and without inhibitor) and normal individuals using recombinant FVIII-coated microtiter plates. The results showed a predominance of IgG and IgG4, though IgA was slightly elevated in a few inhibitor-positive patients and IgM was hardly detectable. A highly significant correlation was found between the Bethesda titer and the optical density values of total Ig, IgG and IgG4 anti-FVIII antibodies obtained by ELISA (p<0.0001). These findings suggest a restricted specificity of anti-FVIII response in hemophiliacs towards functional epitopes of the molecule. Furthermore, high specificity and reasonable sensitivity of the ELISA, together with other technical advantages, suggest this method as a suitable supplementary technique for rapid large-scale screening of inhibitor-positive samples, though ELISA-negative samples need to be rechecked by the Bethesda assay to identify patients with a low inhibitor titer.     

The evolving practice of nuclear cardiology: Results from the 2011 ASNC member survey

Background

Today??s imaging laboratories face challenges including reimbursement, prior authorization, and accreditation standards. The impact on the practice of nuclear cardiology in the United States is unknown. We conducted a survey of ASNC members to provide a snapshot of nuclear cardiology imaging laboratories in 2011.

Methods and Results

The survey identified practice patterns including personnel, volumes, protocols used, and laboratory characteristics. We employed random sampling methodology stratified geographically. The response rate was 19.5% (73/374 laboratories). A non-random survey conducted in 2001 of 25 laboratories served as a comparator. A total of 73 laboratories, representing 202 physicians and 177 technologists responded. The reported median procedural volume was 1,225 studies annually; 88.9% of laboratories were accredited. Compared with 2001, dual isotope imaging protocol use dropped from 72% to 15.6%. Five markers of quality were surveyed. Half of laboratories use the American College of Cardiology??s Appropriate Use Criteria, 61% used segmental scoring, and 32% provided guidance on post-test therapeutic management. 89% perform catheterization correlations while only 33% implemented radiation dose tracking.

Conclusions

This survey of ASNC members provides critical information on nuclear cardiology practice to better target and service our members?? needs. These data can prove invaluable to target educational needs and inform healthcare policy of contemporary nuclear cardiology practice.     

Runx1 dose-dependently regulates endochondral ossification during skeletal development and fracture healing

Runx1 is expressed in skeletal elements, but its role in fracture repair has not been analyzed. We created mice with a hypomorphic Runx1 allele (Runx1(L148A) ) and generated Runx1(L148A/-) mice in which >50% of Runx1 activity was abrogated. Runx1(L148A/-) mice were viable but runted. Their growth plates had extended proliferating and hypertrophic zones, and the percentages of Sox9-, Runx2-, and Runx3-positive cells were decreased. Femoral fracture experiments revealed delayed cartilaginous callus formation, and the expression of chondrogenic markers was decreased. Conditional ablation of Runx1 in the mesenchymal progenitor cells of the limb with Prx1-Cre conferred no obvious limb phenotype; however, cartilaginous callus formation was delayed following fracture. Embryonic limb bud-derived mesenchymal cells showed delayed chondrogenesis when the Runx1 allele was deleted ex vivo with adenoviral-expressed Cre. Collectively, our data suggest that Runx1 is required for commitment and differentiation of chondroprogenitor cells into the chondrogenic lineage.     

Lectin histochemistry of the embryonic heart: Fucose-specific lectin binding sites in developing rats and chicks

Glycoconjugates, particularly their sugar side chains, play important roles in embryonic development. Changes in cell-surface-associated glyco-conjugates are known to affect cell differentiation, cellular interactions, and other developmental phenomena during embryogenesis. The embryonic heart goes through a series of complicated morphologic events during development. Of particular interest is morphogenesis of the outflow tract. This region of the embryonic heart originates from more than one cell population and undergoes a complex process of septation during formation of the great vessels. Histochemi-cal analysis with a series of fucose-specific lectins conjugated to horseradish peroxidase has revealed the presence of a fucosylated glycoconjugate in the outflow tract of the developing heart. The results reveal further that the expression of the fucosylated glycoconjugate is stage-dependent and thus probably genetically regulated. The timing and distribution of staining with the lectin OFA suggest that this fucosylated glycocoiyu-gate may play a role in directing the migration of neural crest cells into the heart and subsequent formation of the conus septum.     

Natural deaths in male prisoners: a 20-year mortality study

BACKGROUND: Although morbidity is high in prisoners compared with the general population, uncertainty exists over rates for natural causes of death. We investigated natural deaths in prisons in England and Wales over a 20-year period. METHODS: All men who died in English and Welsh prisons from 1978-1997 were identified. All deaths received a post-mortem. Death certificates were obtained to provide mortality information according to ICD-9. Standardised mortality ratios (SMRs) for major causes of natural death were calculated in those <60 years. RESULTS: 574 male prisoners died in custody from natural deaths, of which 307 (53%) deaths were from circulatory diseases and 91 (16%) from respiratory causes. Overall, SMRs for natural deaths were significantly lower than the general population (SMR = 0.70; 95% CI = 0.65-0.76). However, SMRs from respiratory pneumonia (SMR = 2.35; 1.75-3.16) and from other infectious causes were higher (SMR = 1.52; 1.03-2.23). CONCLUSION: There are important methodological challenges in calculating SMRs in prisoners. Bearing these in mind, we found increased mortality ratios for respiratory pneumonia and other infections. These findings highlight the need for the screening and effective treatment of infectious diseases in prisoners.