Discordant atrial natriuretic peptide and brain natriuretic peptide levels in lone atrial fibrillation

OBJECTIVES: We sought to characterize natriuretic peptide levels in a cohort of rigorously characterized subjects with lone atrial fibrillation (AF). BACKGROUND: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are sensitive biomarkers of cardiac contractile dysfunction. Both peptides have been reported to be elevated in cohorts with AF, but previous studies have included subjects with underlying structural heart disease. We studied these hormones in 150 subjects with lone AF. METHODS: Study subjects had electrocardiographic evidence of at least one episode of AF and a structurally normal heart on echocardiography. Subjects were excluded if they had a history of a myocardial infarction, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension that preceded the onset of AF. Control subjects were obtained from a healthy outpatient primary care population. Plasma pro-ANP and N-terminal pro-BNP (nt-pro-BNP) levels were determined using commercially available immunoassays. RESULTS: A total of 150 serial subjects with lone AF were enrolled and studied, the majority during normal sinus rhythm. Median levels of nt-pro-BNP were significantly elevated in subjects with lone AF as compared with control subjects (166 vs. 133 fmol/ml, p=0.0003). There was no significant difference in pro-ANP levels between subjects with lone AF and control subjects (1,730 vs. 1,625 fmol/ml, p=0.90). CONCLUSIONS: Discordant natriuretic peptide levels were observed in this homogeneous population of subjects with lone AF. This biomarker pattern, which is present even in sinus rhythm, may represent an underlying subclinical predisposition to this common arrhythmia.     

Characterization of Campylobacter-like organisms isolated from homosexual men

Thirteen Campylobacter-like organisms (CLOs) isolated from rectal cultures from homosexual men were studied. Like catalase-positive Campylobacter species, CLOs were curved gram-negative rods that did not grow aerobically, were motile, were oxidase- and catalase-positive, and did not utilize glucose. However, CLOs could not be classified within any of the Campylobacter species because they grew slowly and had unusual colony morphology; did not grow at 25 C, hydrolyze hippurate, produce H2S in triple sugar-iron agar, or tolerate 2% NaCl; were inhibited by 30-micrograms disks of nalidixic acid; and tolerated 1% glycine and 0.04% triphenyltetrazolium chloride. Three groups of CLOs were identified based on differences in nitrate reduction, growth at 42 C, and sensitivity to cephalothin. By the colony hybridization technique, whole-cell DNA isolated from a strain in each CLO group hybridized with DNA from other strains in the same group, but not with strains in other groups or with reference strains of catalase-positive Campylobacter species.     

Familial protein S deficiency with a variant protein S molecule in plasma and platelets

A protein S deficient family presenting a variant protein S molecule in plasma and platelets is described. The propositus, age 20, and two brothers suffered from venous thrombotic disease. The propositus, the only family member studied while taking oral anticoagulants, had a protein S antigen (ag) level of 17% and undetectable activity. As demonstrated by immunoblotting both the propositus and one clinically affected brother (42% ag, 7% activity) presented variant protein S molecules of 65,000 molecular weight (mol wt) while the other clinically affected brother (64% ag, 11% activity) had only protein S with normal electrophoretic mobility of 70,000 mol wt. The mother had normal protein S levels (93% ag, 100% activity) but had both normal and variant protein S molecules and based on her functional protein S data a normal anticoagulant activity of the variant molecule is suggested. One asymptomatic but protein S deficient sister (68% ag, 9% activity) as well as the asymptomatic protein S deficient father (59% ag, 10% activity) had only protein S molecules of 70,000 mol wt. The variant protein S bound to C4b-binding protein in plasma, and differed from normal protein S in carbohydrate content. Platelets of each family member contained the same immunoblotting pattern of normal and variant protein S forms as found in plasma, consistent with the hypothesis that protein S gene expression involves codominant expression of two alleles that is similar in cells that control the synthesis of both platelet and plasma forms of protein S.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Pseudouridine formation in U2 small nuclear RNA.

U2 small nuclear RNA contains 13 pseudouridine (psi) nucleotides, of which 11 are clustered in 5' regions involved in base-pairing interactions with other RNAs in the spliceosome. As a first step toward understanding the psi formation pathway in U2 RNA, we investigated psi formation on unmodified human U2 RNA in a HeLa cell extract system. Psi formation was found to occur specifically within only those RNase T1 oligonucleotide fragments of U2 RNA known to contain psi in vivo. Using 5-fluorouridine (FUrd)-containing U2 RNAs as specific inhibitors of psi formation in non-FUrd-substituted substrate U2 RNA, we found that wild-type FUrd-containing U2 RNA as well as several FUrd-containing mutant U2 RNAs completely inhibited psi formation. In contrast, certain other mutant U2 RNAs containing FUrd displayed reduced inhibitory capacity. In these cases psi modifications occurred in specific RNase T1 fragments of the substrate U2 RNA only if the FUrd-containing competitor RNA was mutated at or near this site. Formation of psi at one site in U2 RNA appeared to be neither dependent on prior psi formation at another site or sites nor required for subsequent psi formation elsewhere in the molecule. This autonomous mode of psi formation may be driven by multiple psi synthase enzymes acting independently at different sites in U2 RNA.     

Novel Z Scores to Correct Biases Due to Ventricular Volume Indexing to Body Surface Area in Adolescents and Young Adults

BackgroundReference values for cardiac magnetic resonance imaging (cMRI) in children and young adults are scarce. This leads to risk stratification of patients with congenital heart diseases being based on volumes indexed to body surface area (BSA). We aimed to produce cMRI Z score equations for ventricular volumes in children and young adults and to test whether indexing to BSA resulted in an incorrect assessment of ventricular dilation according to sex, body composition, and growth.MethodsWe retrospectively included 372 subjects aged < 26 years with either normal hearts or conditions with no impact on ventricular volumes (reference group), and 205 subjects with repaired tetralogy of Fallot (TOF) aged < 26 years. We generated Z score equations by means of multivariable regression modelling. Right ventricular dilation was assessed with the use of Z scores and compared with indexing to BSA in TOF subjects.ResultsVentricular volume Z scores were independent from age, sex, and anthropometric measurements, although volumes indexed to BSA showed significant residual association with sex and body size. In TOF subjects, indexing overestimated dilation in growing children and underestimated dilation in female compared with male subjects, and in overweight compared with lean subjects.ConclusionsIndexed ventricular volumes measured with cMRI did not completely adjust for body size and resulted in a differential error in the assessment of ventricular dilation according to sex and body size. Our proposed Z score equations solved this problem. Future studies should evaluate if ventricular volumes expressed as Z scores have a better prognostic value than volumes indexed to BSA.     

Hemodynamic comparison of ventricular pacing, atrioventricular sequential pacing, and atrial synchronous ventricular pacing using radionuclide ventriculography

To assess the hemodynamic effects of physiologic pacing, 13 patients with DDD pacemakers who had varying degrees of atrioventricular (AV) block were studied with radionuclide ventriculography during VVI, DVI and VDD modes. Radionuclide ventriculography was performed with patient in the supine position at rest 5 to 10 minutes after the pacing mode and AV delay were changed. The AV delays selected were short (mean 147 +/- 4.8 ms) and long (mean 197 +/- 4.8 ms), with a constant difference of 50 ms. During VVI, 6 patients (group 1) had a left ventricular ejection fraction of 40% or less (mean 22 +/- 11) and 7 patients (group 2) had an ejection fraction of more than 40% (mean 59 +/- 11). Comparisons of ejection fraction, end-diastolic volume and cardiac index between VVI and both modes of AV pacing (VDD and DVI) and between long and short AV delays led to the following conclusions: DVI or VDD pacing produces more beneficial hemodynamic effects than VVI, and these effects are more pronounced in patients with low ejection fraction if longer AV delay is used. The VDD mode significantly improves ventricular function over the DVI mode in patients with an ejection fraction of more than 40% independent of heart rate. Longer AV delay is essential in patients with an ejection fraction of 40% or less to improve ventricular function with physiologic pacing.