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Biomedical subjects

A Czlonkowska

Publications and source records attributed to A Czlonkowska.

At least 19 recordsLinked to original sources

IL1RN intron 2 polymorphism caused by variable number tandem repeats is associated with 1-year outcome in patients with ischaemic stroke.

BACKGROUND: Results of experimental and clinical studies suggest that recombinant human interleukin 1 receptor antagonist (rhIL1ra) may be a good new therapeutic agent for acute stroke. In humans, IL1ra is encoded by the IL1RN gene located on chromosome 2. OBJECTIVES: To report on the association between different genotypes of the variable number tandem repeat (VNTR) polymorphism within IL1RN, and disease severity and 1-year outcome in patients with ischaemic stroke. METHODS: IL1RN genotypes were evaluated using polymerase chain reaction in 391 patients with ischaemic stroke diagnosed according to the World Health Organization definition. The effects of IL1RN genotypes on severity of stroke at maximum impairment, and on the survival status and neurological and functional condition of patients at 7 days, 1 month, 3 months and 1 year after the onset, were evaluated. RESULTS: No relationship was found between IL1RN genotypes and severity of symptoms at the time of maximum impairment. Homozygotes for the IL1RN*2 allele showed less severe neurological and functional impairments when assessed after the time period between 7 days and 1 year after stroke compared with carriers of the other two IL1RN genotypes. Patients with at least one copy of the IL1RN*2 allele had increased risk of death during the first week, and patients homozygotic for this allele had increased risk of death within the first month after stroke. CONCLUSION: IL1RN intron 2 variable number tandem repeats polymorphism influences the clinical outcome in patients with ischaemic stroke. It may possibly modify effects of treatment with rhIL1ra in patients with acute stroke.

Brain Ischemia↗

Sonographic detection of basal ganglia lesions in asymptomatic and symptomatic Wilson disease.

OBJECTIVE: To investigate whether transcranial brain parenchyma sonography (TCS) detects basal ganglia abnormalities in asymptomatic and symptomatic patients with Wilson disease (WD) and whether findings correlate with disease severity. METHODS: Twenty-one patients with WD with (n = 18) or without (n = 3) neurologic symptoms were investigated. Disease severity was assessed by three independent neurologists using a WD rating scale (WDRS) with the items dysarthria, akinesia, ataxia, tremor, and dystonia; the raters' median score was used for further analysis. Basal ganglia TCS was performed according to a standardized protocol. RESULTS: TCS revealed lenticular nucleus (LN) hyperechogenicity in all assessable neurologically symptomatic and in two of the three asymptomatic patients. Size of LN hyperechogenic area correlated with the WDRS score (Spearman correlation, rho = 0.604, p = 0.006), as did the size of thalamus hyperechogenic area (n = 7, rho = 0.891, p = 0.007), the width of third ventricle (n = 21, rho = 0.613, p = 0.003), and the width of lateral ventricles (n = 20, rho = 0.642, p < 0.001). Substantia nigra hyperechogenicity, detected in 10 patients, did not correlate with disease severity. There was no correlation between age at disease onset or disease duration and any TCS finding. Of the 19 patients with LN hyperechogenicity, only 12 showed abnormal LN on MRI. CONCLUSIONS: Transcranial brain parenchyma sonography (TCS) detects lenticular nucleus hyperechogenicity, likely to be caused by copper accumulation, in neurologically symptomatic and asymptomatic Wilson disease (WD). TCS findings correlate with disease severity. TCS appears a promising tool for disease monitoring in WD.

Adult↗

A prospective study of the financial costs of multiple sclerosis at different stages of the disease.

The aim of our study was to estimate the costs of multiple sclerosis (MS) in Poland according to severity of disease. Total, direct and indirect costs were compared in 148 patients divided into three groups categorized by disease severity: stage I Expanded Disability Status Scale (EDSS <3.5), stage II (EDSS 4.0-6.0) and stage III (EDSS >6.5). Cost evaluation was performed from the societal perspective and covered the 5-month period. Simple sensitivity analysis was performed by varying the tariffs and valuing caregiving at 40% of the average wage. The mean total cost/patient for 5 months was estimated at 10,955, 15, 603 and 18, 464 PLN for stage I, II and III, respectively [exchange rate: 4 PLN=1 EUR; purchasing power pariety: 1 EUR=2.05 PLN] (P <0.0001). Regardless of EDSS stage indirect costs exceeded direct costs. Both direct and indirect costs increased with MS progression. For indirect cost the main item was productivity loss. This study confirms that MS represents a high economic burden, with indirect costs greatly exceeding direct costs. As costs increase with disease progression, treatment efforts should focus on patients in the early stages of MS.

Adult↗

Estrogen and cytokines production - the possible cause of gender differences in neurological diseases.

Naturally occurring sexual dimorphism has been implicated in the risk, progression and recovery from numerous neurological disorders. These include head injury, multiple sclerosis (MS), stroke, and neurodegenerative diseases (Parkinson's disease (PD), Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). Accumulating evidence suggests that observed differences between men and women could result from estrogen's wide range of effects within the mammalian central nervous system (CNS), with it's neuroprotective effect being one of the most important. It seems possible that neuroprotective activity of estrogen could be partially a result of it's anti-inflammatory action. It has been well established that inflammation plays an important role in the etiopathogenesis and manifestation of brain pathological changes. In this regard, an important role has been suggested for pro-inflammatory cytokines produced by activated glial cells, neurons and immune cells that invade brain tissue. Within the CNS, cytokines stimulate inflammatory processes that may impair blood-brain barrier permeability as well as promote apoptosis of neurons, oligodendrocytes and induce myelin damage. Given that estrogen may modulate cytokine expression, coupled with the fact that gender differences of cytokine production are apparent in animal models of PD and MS, suggests an important connection between hormonal-cytokine link in neurodegeneration. Indeed, while MS patients and mice subjected to experimental autoimmune encephalomyelitis (EAE) display gender specific alterations of IFN-gamma and IL-12, variations of TNF and IL-6 were associated with PD. Also in case of more acute neurodegenerative conditions, such as stroke, the effect of IL-6 gene G-174C polymorphism was different in males and females. Given that our understanding of the role of estrogen on cytokine production and accompanying CNS pathological conditions is limited, the present reviews aims to present some of our recent findings in this area and further evaluate the evidence that may be relevant to the design of new hormonal anti-inflammatory treatment strategies for neurodegenerative diseases.

Animals↗

Increase of matrix metalloproteinase-9 in peripheral blood of multiple sclerosis patients treated with high doses of methylprednisolone.

Matrix metalloproteinases (MMPs) are believed to play a role in the pathogenesis of multiple sclerosis (MS). As methylprednisolone is the treatment of choice for a relapse, we investigated the effect of methylprednisolone on blood levels of MMPs. Baseline TIMP-1 and MMP-2 levels were lower in MS patients than in healthy controls. MMP-9 levels tended to be elevated. During therapy, MMP-9 levels demonstrate a dose-dependent increase. No effect was noted on TIMP-1 and MMP-2 levels. The short-lived increase of MMP-9 plasma levels may be at least in part due to an activation and an increase of granulocytes and monocytes by methylprednisolone.

Adult↗

Factors predicting early stroke fatality in Poland. Preliminary report of the Polish National Stroke Registry.

Poland has one of the highest rates of death due to stroke in Europe, which, in contrast to many industrialized countries, has not changed since at least 1984. To improve this unfavorable situation, the entire approach to stroke management needs to be recognized. For this purpose, an analysis of stroke epidemiology regarding regional differences was one of the the strategic points of the Polish National Project of Stroke Prevention and Treatment. The Polish National Stroke Registry was maintained from 1 January to 31 December 2000 in 59 Neurological Department in all 16 districts of Poland. In total 11,107 patients were included: 11% with intracerebral hemorrhage, 63.4% with ischemic stroke, and 25.6% with unclassified stroke. Computed tomography (CT) was performed in 73.6% of patients. Analysis of in-hospital deaths showed great differences between the centers (from 8% to 36%). According to multifactorial analysis, not only well-known predictors of early death (decrease in consciousness at the onset of stroke, decrease in functional state prior to stroke, and severity of stroke) influence the prognosis. In centers with high risk of death, CT, especially CT on admission, was performed significantly less often (4.2% vs. 62.6%), early rehabilitation was delayed (38.3% vs. 73.4%), and secondary prevention treatment was prescribed to fewer patients (antiplatelettherapy 36.4% vs. 77.4%; antithrombotic therapy 4.9% vs. 13%).

Aged↗

Variation in the management of acute physiological parameters after ischaemic stroke: a European perspective.

Studies have shown significant variation in stroke case fatality across Europe. These variations suggest the need to explore whether differences in physiological support in acute stroke exist across Europe. Data were collected in four European centres over 6 months. These included clinical status and management of acute physiology (hydration, oxygenation, nutrition, hypertension, hyperglycaemia and temperature in the first week of ischaemic stroke) and survival at 3 months. Differences in acute supportive care between centres were adjusted for case mix. Patients admitted to centres in London (n = 106), Dijon (n = 95), Erlangen (n = 91) and Warsaw (n = 72) were studied. There were significant differences in incontinence, dysphasia, dysphagia, conscious level, pyrexia, hyperglycaemia and comorbidity between centres. After adjusting for case mix, there were significant differences in intravenous fluid use (P = 0.04), enteral feeding (P = 0.003), initiation of new antihypertensive therapy (P = 0.0006) and insulin therapy (P = 0.004) between centres, with the London centre having the lowest uptake of interventions. Three-month case fatality rates varied from 10 to 28%. This pilot study shows significant variation in acute physiological support in acute stroke across four European centres, which remains unexplained by case mix. Further research is required to link variation in acute care with stroke outcome, to identify which interventions appear to be the most effective.

Acute Disease↗

Factor V Leiden, prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase C677T genotype in young adults with ischemic stroke.

Ischemic stroke in young adults is a well-known disease, but despite extensive clinical and laboratory investigations, its etiology remains unclear in approximately half of the cases. We examined the prevalence of factor V Leiden, the prothrombin G20210A genotype, and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in 100 patients (51 males and 49 females) who survived an ischemic stroke without a cardiac embolic source at an age < or = 45 years, and in 238 healthy control subjects from the same geographic area. The patients were selected for study only if the diagnosis of stroke was documented by computed tomography scan or nuclear magnetic resonance (NMR) of the brain, or both. Heterozygosity for the FV Leiden mutation was found in 3 patients (3.0%) and in 10 control subjects (4.2%). Two patients (2.0%) and five control subjects (2.1%) were heterozygous for the prothrombin G20210A mutation. The frequencies of the MTHFR 677TT, CT, and CC genotypes in the patient group were 12%, 37%, and 51%, respectively, and were not significantly different from those in control subjects (11%, 40%, and 49%, respectively). In conclusion, our results indicate that FV Leiden mutation, prothrombin G20210A genotype, and homozygosity for the C677T mutation in the MTHFR gene are not associated with an increased risk for ischemic stroke in young adults.

Adolescent↗

Ischemic strokes are more severe in Poland than in the United States.

Case fatality rates for stroke were ascertained prospectively in two regional catchment hospitals in Poland and 36 teaching hospitals in the US University Hospital Consortium. Case fatality rates in Poland (23.9%) were higher than in the United States (7.5%). Angina, atrial fibrillation, and congestive heart failure were more frequent in Polish stroke patients (40%, 26%, and 25%, respectively) than in US patients (17%, 12%, and 10%). Stroke severity as indicated by higher frequencies of hemiplegia, disordered consciousness, dysphagia, and aphasia was greater in Poland (19%, 39%, 28%, and 42%, respectively) than the United States (11%, 13%, 14%, and 26%).

Adolescent↗

Anticardiolipin antibodies are an independent risk factor for ischemic stroke.

Our aim was to determine if anticardiolipin antibodies are an independent risk factor for ischemic stroke and to determine their influence on stroke type and clinical outcome. We prospectively studied 194 consecutive patients with ischemic stroke admitted within 48 h of stroke. A control group consisted of 100, age and sex matched, healthy individuals. Neurological and functional status was assessed on admission, at 30 days, and at 1 year. IgG anticardiolipin antibodies were significantly more frequent in stroke patients (25.3%) than controls (6%, p < 0.05). A multivariate analysis suggested that anticardiolipin antibodies are an independent risk factor for ischemic stroke in addition to hypertension and atrial fibrillation (RR = 2.94, p < 0.05). Elevated IgG anticardiolipin antibodies were associated with cognitive impairment as measured by the Mini Mental State Examination at 30 days and at 1 year. IgG anticardiolipin antibodies did not correlate with stroke recurrence, or mortality at 30 days or 1 year.

Adult↗

Stroke recurrence among 30 days survivors of ischemic stroke in a prospective community-based study.

A cohort of 209 patients (105 men and 104 women), who survived 30 days after 'first ever-in-lifetime ischemic stroke' were followed for one year. Predictors of survival were examined by log-rank test and Cox proportional hazards method. Twenty-four patients had a stroke recurrence (11.4%). Thirteen of the patients with recurrent stroke (54%) died because of the sequelae of the second stroke. Stroke recurred in 16% of patients with stroke due to atherosclerosis, in 12.5% of patients with cardioembolic stroke, and in 4.4% of patients with lacunar stroke. The life table cumulative risk of death at 6 and 12 months for patients with recurrent stroke was statistically higher (22% and 57%) than patients without recurrent stroke (13% and 29% respectively). History of untreated hypertension prior to the initial stroke (RR = 1.7, 95% Cl 1.2-4.1, p < 0.05) was an independent predictor of recurrence. In 134 patients (64.9%) aspirin was initiated during the first month after stroke. Only 81 patients (39.8%) continued aspirin treatment for the whole year. Life table cumulative risk of mortality among the patients treated with aspirin was 8% at 6 months and 12% at 1 year compared to 19% at 6 months and 45% at 12 months for those untreated with aspirin. We conclude that the high risk of recurrent stroke in Poland could be redaced by increased use of anti-platelets therapy and anti-hypertensive therapy after ischemic stroke.

Aged↗

Effects of long-term treatment in Wilson's disease with D-penicillamine and zinc sulphate.

The results of treatment with D-penicillamine (D-P) or zinc sulphate (Zn) in 67 newly diagnosed cases of Wilson's disease have been compared. All patients (7 with hepatic, 1 with psychiatric and 59 with neurological or preclinical forms) were fully compliant. During 12 years of observation, 34 patients received d-P and 33 Zn as the primary treatment. Fifteen patients (44%) discontinued D-P, in 10 cases owing to side effects. Four (12%) patients discontinued Zn, in 2 cases because of side-effects. One patient who received Zn deteriorated during the first few months after the initiation of therapy. The effectiveness of long-term treatment with D-P and Zn was similar in those patients who were able to continue the initial therapy. Zn was tolerated better than D-P; we suggest, therefore, that it may be recommended as an initial therapy for patients in the preclinical stage of Wilson's disease or with neurological presentation of the disease. More observation is needed for patients with the hepatic and psychiatric forms of the disease.

Adult↗

Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-alpha by HLA-DR2+ T cells.

Lymphotoxin (LT) and tumor necrosis factor-alpha (TNF-alpha) play an important role in the pathogenesis of multiple sclerosis (MS). MS is associated with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. Because both LT and TNF-alpha are encoded in the HLA region, the HLA association of MS may be related to the production of these cytokines. To test this hypothesis, we investigated the production of LT, TNF-alpha, and interferon-gamma (IFN-gamma) by CD4+ T-cell lines (TCLs) specific for myelin basic protein (MBP) or tetanus toxoid (TT) isolated from MS patients and normal controls. After stimulation with specific antigen but not mitogen, TCLs from HLA-DR2+ donors produced significantly more LT and TNF-alpha than TCLs from DR2- donors. In contrast, HLA-DR2+ and DR2- TCLs did not differ in the production of IFN-gamma, a cytokine also produced by T cells but not encoded in the HLA region. Increased secretion of LT and TNF-alpha was unrelated to the specificity (MBP vs TT), MHC restriction (HLA-DR2 vs other DR molecules), or source (MS vs normal) of the TCLs. There was no significant association of the cytokine production with individual LT or TNF-alpha alleles, indicating that the increased production of these cytokines may be linked to other polymorphic genes in this region. The results suggest that the association of MS with HLA-DR2 implies a genetically determined propensity of T cells to produce increased amounts of LT and TNF-alpha.

Animals↗

A prospective community-based study of stroke in Warsaw, Poland.

BACKGROUND AND PURPOSE: Poland is a country with high morbidity and mortality rates from cardiovascular diseases. No recent studies have evaluated the contribution of cerebrovascular diseases to this morbidity and mortality. Our aim was to accurately determine stroke incidence rates in Warsaw, Poland. METHODS: A 2-year prospective and population-based stroke registry was maintained for health care units 2 and 3 in Warsaw, Poland (population, 182,285). Case subjects were ascertained by surveying hospital admissions, outpatient visits, and death certificates. RESULTS: During the 2 years of the study (1991 to 1992), 633 cases of first-event strokes were registered, 462 of which were first ever in a lifetime. Computed tomography or necropsy was performed in 72% of first-ever stroke cases. The crude annual incidence rate for first-ever stroke was 127/100,000 (95% confidence intervals, 111 to 145); the rate standardized to the European population was 111 (95% confidence intervals, 96 to 128). Our incidence rates for first-event strokes were found to be in the middle of the range among other first-event studies. When comparing our first-ever stroke incidence rates with those of comparable studies performed throughout Europe, they were found to be similar for groups aged younger than 65 years but lower in the older age groups. The distribution of ischemic and hemorrhagic stroke subtypes was similar to that of other countries. CONCLUSIONS: This first population-based prospective stroke registry in Poland showed that incidence rates were not high compared with other studies throughout Europe and the world. These stroke incidence rates are not a large contributing factor to high cardiovascular morbidity rates in Poland.

Adult↗