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.     

Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK.

The products of the Escherichia coli dnaK, dnaJ, and grpE heat shock genes have been previously shown to be essential for bacteriophage lambda DNA replication at all temperatures and for bacterial survival under certain conditions. DnaK, the bacterial heat shock protein hsp70 analogue and putative chaperonin, possesses a weak ATPase activity. Previous work has shown that ATP hydrolysis allows the release of various polypeptides complexed with DnaK. Here we demonstrate that the ATPase activity of DnaK can be greatly stimulated, up to 50-fold, in the simultaneous presence of the DnaJ and GrpE heat shock proteins. The presence of either DnaJ or GrpE alone results in a slight stimulation of the ATPase activity of DnaK. The action of the DnaJ and GrpE proteins may be sequential, since the presence of DnaJ alone leads to an acceleration in the rate of hydrolysis of the DnaK-bound ATP. The presence of GrpE alone increases the rate of release of bound ATP or ADP without affecting the rate of hydrolysis. The stimulation of the ATPase activity of DnaK may contribute to its more efficient recycling, and it helps explain why mutations in dnaK, dnaJ, or grpE genes often exhibit similar pleiotropic phenotypes.     

Attempt to eliminate health inequalities in Poland arising at the time of political and economic transformation: Polish 400 Cities Project.

AIM: Epidemiological data show that citizens of small towns and villages have presented worse trends in cardiovascular mortality during the political, social and economic transformation in Poland during past 15 years than citizens of large towns. To try to eliminate these inequalities the Polish 400 Cities Project (P400CP), a large educational and interventional project, was prepared. The project consists of two arms: medical and social interventions. MATERIAL AND METHODS: The main aim of the medical screening intervention in P400CP is to increase detection and control of cardiovascular risk factors in inhabitants of 418 small cities (<8000 inhabitants) and surrounding villages, particularly in men and people of lower education. In 2003 and 2004 the P400CP covered 123 cities. All together, 36 696 subjects aged between 18 and 98 years were examined. In all participants, blood pressure (BP), anthropometric measurements, laboratory tests and questionnaire interviews were performed. The social arm of P400CP is one of multi-level educational intervention. Modern techniques of social psychology and marketing were involved to increase participation in interventions. RESULTS: Only 12.5% of all subjects had normal BP, cholesterol (<190 mg/dl) and glucose (<100 mg/dl in whole capillary blood) levels. During the first screening visit 65.5% of all examined subjects had BP>/=140 mmHg or >/=90 mmHg. The fasting glucose level was increased in 19% of women and 26% of men. Almost two-third of all subjects had a total cholesterol level above the norm. CONCLUSIONS: The prevalence of cardiovascular risk factors in participants of the screening programme P400CP in small towns in Poland was very high. High prevalence and low control of risk factors in participants of the P400CP confirm the decision to target this programme at citizens of small towns and villages.     

Hemorrhagic stroke in a patient requiring long-term anticoagulant treatment

Hemorrhagic stroke is a frequent cause of morbidity and mortality in Poland. It results from disruption of intracranial vessel wall continuity. We report a case of 66-years-old man with prosthetic aortic valve after three ischemic strokes treated with acenocoumarol who was admitted to hospital with vertigo and motoric aphasia. Computed tomography confirmed a hemorrhagic stroke related to anticoagulant treatment. We discussed the principles of management and therapeutic options in patients requiring long-term anticoagulation suffering from severe hemorrhagic complications.     

Percutaneous peripheral interventions in patients with non-ST elevation acute coronary syndromes performed by interventional cardiologists: rationale and results

BACKGROUND: The coexistence of peripheral artery disease (PAD) and multilevel atherosclerosis increases death and stroke rates in patients with coronary artery disease (CAD). Due to many comorbidities these patients are often treated conservatively without revascularisation. AIM: To investigate whether complex percutaneous cardiovascular interventions for CAD and PAD may improve prognosis and long-term outcome in this group of patients. METHODS: We studied consecutive patients treated for symptomatic CAD who also had chronic PAD. The primary cause of hospital admission for all our patients was non-ST elevation acute coronary syndrome (NSTE ACS). All percutaneous peripheral interventions were performed during one hospital stay (index hospitalisation). Major adverse cardio- and cerebrovascular events (MACCE) during follow-up were defined as follows: death (cardiac and non-cardiac), myocardial infarction (MI), urgent revascularisation (surgical or repeat PCI, peripheral percutaneous intervention), stroke/TIA or amputation. RESULTS: We performed 109 interventions in 78 consecutive patients with chronic peripheral artery stenoses and occlusions. The average age was 61.5+/-8.6 years and the majority were males (80%). Preinterventional angiography showed occlusions that involved the common iliac artery in 28 (36%) patients, the external iliac artery in 16 (21%) patients, internal iliac artery in 2 (3%) patients, and superficial femoral artery in 63 (81%) patients. Stenting was performed in half of the patients with a mean stent length of 69.6+/-50.3 mm. An average number of 1.24+/-0.55 stents was used for each lesion. During a mean follow-up of 18 months (range 4 to 42), there were 4 deaths, 3 MIs, 13 repeated percutaneous peripheral interventions due to restenosis in previously treated peripheral lesions, two urgent coronary interventions, two ischaemic strokes, two TIAs and one amputation. The combined follow--up MACCE end-point occurred in 32% of patients. CONCLUSIONS: Patients with concomitant CAD and PAD could safely undergo percutaneous cardiovascular and peripheral interventions. Multilevel intervention is associated with a promising long-term follow-up.