Heart rate control in patients with atrial fibrillation referred for exercise testing

Clinical practice guidelines for patients with atrial fibrillation (AF) recommended a heart rate (HR) of 60 to 80 beats/min at rest and 90 to 115 at moderate exercise. The degree to which HR control at rest and with exercise in patients with AF complies with these recommendations is unknown. HR at rest and at peak exercise was retrospectively examined in 1,097 consecutive patients with AF referred for exercise myocardial perfusion imaging. In a subgroup of 195 patients, HR was also measured at an intermediate "moderate" level. Median HR at rest was 80 beats/min, at the upper end of the recommended range of 60 to 80. Only patients administered a beta blocker (BB; 31%) had lower (p <0.001) median HRs at rest. Median HR at moderate exercise was 128 beats/min, higher than the range of 90 to 115 recommended by the guidelines. Only patients administered a BB had significantly reduced HRs (p <0.003) at moderate exercise. Median peak exercise HR was 147 beats/min. Forty-five percent of patients exceeded their age-predicted maximal HR. Patients administered BBs were significantly less likely (p <0.01) to exceed their age-predicted maximal HR. In conclusion, in patients with AF, HR control at rest and during exercise often did not comply with guideline recommendations. Regimens including a BB were more effective in achieving HR control.     

Apparent reduction of aortic and left heart chamber size in atrial septal defect

Although it is widely held that the size of the aorta and left atrium is diminished in patients with atrial septal defect, few data are available to support this contention. Therefore, aortic and left heart chamber dimensions in 24 patients with documentation of an atrial septal defect at cardiac catheterization were compared with those of 22 normal persons. The data were obtained using echocardiography, cineangiography and qualitative estimation of aortic size from chest X-ray films. Aortic size was similar in the patients with an atrial septal defect and normal subjects (1.7 cm/m² for both groups on angiography). Although the aortic diameter was estimated to be small in 12 of the 24 patients with an atrial defect on chest X-ray films, no difference existed in aortic measurements on echocardiography or angiography in patients judged to have normal as opposed to those judged to have reduced aortic size. Although the left atrial echographic dimension tended to be slightly greater in the patient group than in normal subjects (2.2 versus 1.9 cm/m²), this difference was not statistically significant. The echographic ratio of left atrial to aortic size was greater in the patient group (1.3 versus 1.1) (P < 0.02). Stroke index was similar in the two groups (37.5 versus 42.8 ml/m² with the dye-dilution technique and 35.1 versus 36.3 ml/m² on angiography). Although echocardiographic left ventricular diastolic dimension was slightly smaller in the patient group than in normal subjects (2.5 versus 3.0 cm/m²) (P < 0.02), diastolic volume index on angiography was similar in the two groups (50.1 versus 52.9 ml/m²). Thus, these data do not support the conventional belief that, because of a reduced stroke volume, the size of the aorta and left atrium is diminished in patients with an atrial septal defect.     

Insight into the molecular basis of pathogen abundance: group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells

Streptococcal inhibitor of complement (Sic) is a secreted protein made predominantly by serotype M1 Group A Streptococcus (GAS), which contributes to persistence in the mammalian upper respiratory tract and epidemics of human disease. Unexpectedly, an isogenic sic-negative mutant adhered to human epithelial cells significantly better than the wild-type parental strain. Purified Sic inhibited the adherence of a sic negative serotype M1 mutant and of non-Sic-producing GAS strains to human epithelial cells. Sic was rapidly internalized by human epithelial cells, inducing cell flattening and loss of microvilli. Ezrin and moesin, human proteins that functionally link the cytoskeleton to the plasma membrane, were identified as Sic-binding proteins by affinity chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Sic colocalized with ezrin inside epithelial cells and bound to the F-actin-binding site region located in the carboxyl terminus of ezrin and moesin. Synthetic peptides corresponding to two regions of Sic had GAS adherence-inhibitory activity equivalent to mature Sic and inhibited binding of Sic to ezrin. In addition, the sic mutant was phagocytosed and killed by human polymorphonuclear leukocytes significantly better than the wild-type strain, and Sic colocalized with ezrin in discrete regions of polymorphonuclear leukocytes. The data suggest that binding of Sic to ezrin alters cellular processes critical for efficient GAS contact, internalization, and killing. Sic enhances bacterial survival by enabling the pathogen to avoid the intracellular environment. This process contributes to the abundance of M1 GAS in human infections and their ability to cause epidemics.     

Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria

Antibiotic use is known to promote the development of antibiotic resistance, but substantial controversy exists about the impact of agricultural antibiotic use (AAU) on the subsequent emergence of antibiotic-resistant bacteria among humans. AAU for animal growth promotion or for treatment or control of animal diseases generates reservoirs of antibiotic-resistant (AR) bacteria that contaminate animal food products. Mathematical models are an important tool for understanding the potential medical consequences of this increased exposure. We have developed a mathematical model to evaluate factors affecting the prevalence of human commensal AR bacteria that cause opportunistic infections (e.g., enterococci). Our analysis suggests that AAU hastens the appearance of AR bacteria in humans. Our model indicates that the greatest impact occurs very early in the emergence of resistance, when AR bacteria are rare, possibly below the detection limits of current surveillance methods.     

Fujinami sarcoma virus: An avian RNA tumor virus with a unique transforming gene

The oncogenic properties and RNA of the Fujinami avian sarcoma virus (FSV) and the protein it encodes were investigated and compared to those of other avian tumor viruses with sarcomagenic properties such as Rous sarcoma virus and the acute leukemia viruses MC29 and erythroblastosis virus. Cloned stocks of FSV caused sarcomas in all chickens inoculated and were found to contain a 4.5-kilobase (kb) and an 8.5-kb RNA species. The 4.5-kb RNA was identified as the genome of defective FSV because it was absent from nondefective FSV-associated helper virus and because the titer of focus-forming units increased with the ratio of 4.5-kb to 8.5-kb RNA in virus preparations. This is, then, the smallest known tumor virus RNA with a transforming function. Comparisons with other viral RNAs, based on oligonucleotide mapping and molecular hybridization, indicated that 4.5-kb FSV RNA contains a 5' gag gene-related sequence of 1 kb, an internal specific sequence of about 3 kb that is unrelated to Rous sarcoma virus, MC29, and erythroblastosis virus, and a 3'-terminal sequence of about 0.5 kb related to the conserved C region of avian tumor viruses. The lack of some or all nucleotide sequences of the essential virion genes, gag, pol, and env, and the isolation of FSV-transformed nonproducer cell clones indicated that FSV is replication defective. A 140,000-dalton, gag-related non-structural protein was found in FSV-transformed producer and nonproducer cells and was translated in vitro from full-length FSV RNA. This protein is expected to have a transforming function both because its intracellular concentration showed a positive correlation with the percentage of transformed cells in a culture and because FSV is unlikely to code for major additional proteins since the genetic complexities of FSV RNA and the FSV protein are almost the same. It is concluded that the transforming onc gene of FSV is distinct from that of Rous sarcoma virus and other avian tumor viruses with sarcomagenic properties. Hence, multiple mechanisms exist for sarcomagenic transformation of avian cells.     

Headgroup interactions in mixed phospholipid bilayers

²H NMR methods have been used to study how bilayer-forming phospholipids interact with each other at the membrane surface. Aqueous dispersions of dimyristoyl-sn-phosphatidylcholine (Myr₂-PtdCho), dimyristoyl-sn-phosphatidylethanolamine (Myr₂-PtdEtn), and dimyristoyl-sn-phosphatidyl-3-glycerol, specifically deuterated at different positions in their headgroups, give well-resolved ²H NMR powder spectra. These spectra are characteristic of a lipid bilayer with quadrupole splittings that are sensitive to the amplitude of headgroup motion. In binary mixed bilayers of deuterated lipids with an unlabeled component, all parts of the deuterated headgroup monitor the presence of the second lipid from changes in the measured quadrupole splittings. The headgroups of the charged lipids, dimyristoyl-sn-phosphatidylserine and dimyristoyl-sn-phosphatidyl-3-glycerol, interact to the largest extent with the choline moiety of Myr₂-PtdCho and the ethanolamine moiety of Myr₂-PtdEtn, whereas a somewhat smaller but still marked alteration in headgroup motion was observed in Myr₂-PtdCho/Myr₂-PtdEtn mixtures. The large changes in the deuterium quadrupole splittings for the zwitterionic lipids after addition of a charged lipid suggest that either a strong perturbation in the hydrogen bonding occurs or changes take place in the water structure at the membrane surface, or possibly both.