Predictors of Coronary and Carotid Atherosclerosis in Patients with Severe Degenerative Aortic Stenosis

Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis.     

Cambridge Neuropsychological Test Automated Battery in assessment of cognitive parameters in patients with systemic lupus erythematosus in relation to autoantibody profile

Objectives

To relate the cognitive parameters of systemic lupus erythematosus (SLE) patients in remission to their profile of autoantibodies.

Material and methods

The study included 32 patients with SLE in remission, with mild disease activity as indicated by SELENA-SLEDAI < 6. For neuropsychological assessment, the Cambridge Neuropsychological Test Automated Battery (CANTAB) was applied, using motor screening (MOT), big little circle (BLC), paired associated learning (PAL), stockings of Cambridge (SOC), and graded naming tests (GNT). Detection of autoantibodies against dsDNA, nucleosome (aNuc), Sm, and anticardiolipin (aCL: IgG and IgM) was performed with immunoassays.

Results

The SLE patients demonstrated standard scores below norms, matched according to age and gender, in the following tests: GNT (–0.87 ±0.85), SOC PSMM (–0.47 ±0.97), PAL (–1.88 ±3.58), and BLC (–0.31 ±1.90). GNT scores under –0.5 were found significantly more frequently in SLE patients, seen in roughly 66% of test subjects. Values for PAL and mean subsequent thinking time of stockings of Cambridge (SOC MSTT) were found to be lower than –0.5 in approximately half of the patients. Mean error of motor screening (MOT ME) was found to negatively correlate with mean latency of motor screening (MOT ML) (r = –0.55). PAL significantly correlated with SOC MSTT (r = 0.38) and with GNT (r = 0.36). Anti-dsDNA antibody level correlated negatively with MOT ME (r = –0.46). Anti-Nuc antibodies correlated with MOT ML (r = 0.41) but negatively correlated with MOT ME (r = –0.58). The levels of anti-Sm, anti-CL IgM and IgG did not correlate significantly with the outcomes of CANTAB. The age of the patients correlated negatively with MOT ME (r = –0.36), positively with BLC (r = 0.53) and negatively with SOC MSTT (r = –0.43). The level of anti-Nuc antibodies correlated with anti-dsDNA level (r = 0.62) and of anti-CL IgM with anti-Sm (r = 0.39) and anti-CL IgG (r = 0.87).

Conclusions

CANTAB reveals a decrease in selected cognitive functions in patients with SLE. ACL IgG and anti-dsDNA antibodies indicated SLE patients prone to develop a decrease in cognitive functions.     

Torsion dynamics in the evolution from acute to chronic mitral regurgitation

BACKGROUND AND AIM OF STUDY: Left ventricular (LV) torsion reduces transmural fiber strain gradients during systole, and torsional recoil in early diastole is thought to assist LV filling. To test the hypothesis that deterioration of torsional dynamics accompanied LV dysfunction during the evolution of mitral regurgitation (MR), torsion was measured during the progression from acute to chronic MR in a canine model. METHODS: Seven dogs underwent cardiopulmonary bypass for LV marker placement and creation of MR by disrupting the posterior leaflet. After 7-10 days, three-dimensional marker coordinates were measured with biplane videofluoroscopy to study LV geometry, size and function, plus maximal torsional deformation, time of maximal torsion relative to end-ejection, and early diastolic torsional recoil during the first 5% of filling. After three months, the animals were re-studied. RESULTS: Progression from acute to chronic MR was associated with a significant decrease in maximum LV dP/dt (1,574+/-213 to 1,300+/-252 mmHg/s, p <0.01) and an increase in LVEDP from 11+/-5 to 15+/-5 mmHg (p <0.01). After three months of MR, maximum torsional deformation decreased from 6.3+/-1.9 to 4.7+/-2.0 degrees (p = 0.04), as did early diastolic recoil (-3.8+/-1.0 to -1.5+/-1.7 degrees, p = 0.03). CONCLUSION: Progression from acute to chronic MR is accompanied by decreased and delayed systolic LV torsional deformation and a decline in early diastolic recoil, which may contribute to LV dysfunction by increasing transmural strain gradients during systole and impairing diastolic filling. As torsional deformation and recoil can be measured non-invasively with MRI in humans, such measurements might prove useful in patients with progressive MR as an adjunct to determine the timing of surgical repair.     

LPS alters pattern of sickness behavior but does not affect glutathione level in aged male rats

Behavioral symptoms of sickness, such as fever and motor activity are a coordinated set of changes that develop during infection. The aim of study was to compare the sickness behaviour (SB) in healthy old and young rats treated with pyrogenic dose of endotoxin and to check their glutathione level. Before experimentation male Wistar rats were selected according to standard body mass, motor activity, and white blood cells count. Intraperitoneal injection of lipopolysaccharide (LPS) from E. coli was used to provoke SB. The level of liver glutathione, interleukin (IL) -6, deep body temperature (Tb) and motor activity were measured. Glutathione level in old and young rats did not differ significantly. In both young and old rats LPS administration provoked fever (the mean value of Tb was 38.06 ± 0.01 °C in old rats, and 38.19 ± 0.06 °C in young rats). LPS injection affected night-time activity in both groups (12 h averages were 1.56 ± 0.40 counts in old LPS-treated rats vs 2.74 ± 0.53 counts in not-treated old rats and 3.44 ± 0.60 counts for young LPS-treated vs 4.28 ± 0.57 counts for young not-treated rats). The injection of LPS provoked an elevation of plasma IL-6 concentration (from values below the lowest detectable standard in not-treated groups of animals to 6322.82 ± 537.00 pg/mL in old LPS-treated rats and 7415.62 ± 451.88 pg/mL in young LPS-treated rats). Based on these data, we conclude that good health of aged rats prevents decrease in the glutathione level. Old rats are still able to develop SB in response to pyrogenic dose of LPS, although its components have changed pattern compared to young animals.     

Penicillin tolerance in multiply drug-resistant natural isolates of Streptococcus pneumoniae

Five of six multiply drug-resistant clinical isolates of Streptococcus pneumoniae from South Africa demonstrated penicillin tolerance. In contrast to the common wild-type strains of pneumococci, treatment of the tolerant strains with penicillin above the minimum inhibitory concentration did not induce cell wall degradation, lysis, or leakage of intracellular components, and the rate of loss of viability was reduced compared with that of nontolerant strains. While these South African strains contained lower specific activity of autolytic enzyme than did nontolerant strains, the residual autolytic activity (15%-26% of the nontolerant wild type) was much more than that found in lysis-defective laboratory mutants of pneumococci (less than or equal to 1%); the rate of penicillin-induced lysis did not correlate with the specific activity of residual autolysin. Also, in contrast to the complete lysis resistance of lysis-defective mutants to all lytic agents, the tolerant South African strains were resistant primarily to lysis by beta-lactam antibiotics but could still be lysed by other cell wall inhibitors (e.g., cycloserine) and detergents. The penicillin resistance and penicillin tolerance traits could be separated by genetic transformation. We suggest that the drug-specific tolerance of the South African pneumococcal strains is related to some alteration in the control of autolysin activity.