Wojciech Kozubski

Poznan University of Medical Sciences, Posen, Greater Poland Voivodeship, Poland

Are you Wojciech Kozubski?

Claim your profile

Publications (158)296.5 Total impact

  • Source

    Full-text · Dataset · Nov 2015

  • No preview · Article · Jul 2015
  • Piotr Iwanowski · Wojciech Kozubski · Jacek Losy

    No preview · Article · Jun 2015 · Journal of the neurological sciences
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time. MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found. This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS.
    Full-text · Article · May 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the prevalence of considerable burden among caregivers of stroke survivors at 6 months (Time 1) and 5 years after stroke (Time 2), to analyse changes in burden severity over time and to identify factors associated with the burden. Eighty eight patient/caregiver pairs were assessed. Caregiver burden was measured with the Caregiver Burden Scale. Socio-demographic, stroke-related and psychological characteristics were analysed as potential determinants of the burden. Exact multiple logistic regression was used to identify the predictive factors. Considerable burden was reported by 44% of the caregivers at Time 1 and 30% at Time 2. The burden was independently associated with caregivers' sense of coherence and amount of time spent caregiving at Time 1, and with caregivers' anxiety at Time 2. A significant proportion of the caregivers experienced considerable burden in the post-acute and chronic phases of stroke, although this proportion declined over time. Several characteristics were associated with the increased burden at different time points. All the independent predictors related to aspects of the carers. Programmes including education about coping strategies and time management, as well as respite care provision, could be beneficial and might help to reduce the burden of caregiving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · Patient Education and Counseling
  • [Show abstract] [Hide abstract]
    ABSTRACT: The etiology of Parkinson’s disease (PD) is still unclear, but mutations in PRKN have provided some biological insights. The role of PRKN mutations and other genetic variation in determining the clinical features of PD remains unresolved. The aim of the study was to analyze PRKN mutations in PD and controls in the Polish population and to try to correlate between the presence of genetic variants and clinical features. We screened for PRKN mutations in 90 PD patients and 113 controls and evaluated clinical features in these patients. We showed that in the Polish population 4% of PD patients had PRKN mutations (single or with additional polymorphism) while single heterozygous polymorphisms (S167N, E310D, D394N) of PRKN were present in 21% of sporadic PD. Moreover, 5% PD patients had more than one PRKN change (polymorphisms and mutations). Detected PRKN variants moderately correlated with PD course and response to L-dopa. It also showed that other PARK genes (SNCA, HTRA2, SPR) mutations probably may additionally influence PD risk and clinical features. PRKN variants are relatively common in our Polish series of patients with PD. Analysis of the PRKN gene may be useful in determining clinical phenotype, and helping with diagnostic and prognostic procedures in the future.
    No preview · Article · Mar 2015 · Current Genomics
  • Justyna Rosińska · Maria Łukasik · Wojciech Kozubski
    [Show abstract] [Hide abstract]
    ABSTRACT: The diver's nervous system is extremely sensitive to high ambient pressure, which is the sum of atmospheric and hydrostatic pressure. Neurological complications associated with diving are a difficult diagnostic and therapeutic challenge. They occur in both commercial and recreational diving and are connected with increasing interest in the sport of diving. Hence it is very important to know the possible complications associated with this kind of sport. Complications of the nervous system may result from decompression sickness, pulmonary barotrauma associated with cerebral arterial air embolism (AGE), otic and sinus barotrauma, high pressure neurological syndrome (HPNS) and undesirable effect of gases used for breathing. The purpose of this review is to discuss the range of neurological symptoms that can occur during diving accidents and also the role of patent foramen ovale (PFO) and internal carotid artery (ICA) dissection in pathogenesis of stroke in divers. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
    No preview · Article · Feb 2015 · Neurologia i neurochirurgia polska
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this case-control study was to evaluate carotid hemodynamic variables and traditional cardiovascular risk factors in women with Hashimoto thyroiditis (HT). The study group consisted of 31 females with HT on levothyroxine (L-T4) and 26 euthyroid women with HT without L-T4 matched for age and body mass index (BMI) as controls. Carotid intima-media thickness (CIMT), carotid extra-media thickness (CEMT), and pulsatility indexes in common carotid artery (PI CCA) and in internal carotid artery (PI ICA) were measured. BMI, waist circumference, lipid profile, fasting glucose and insulin levels, and parameters of thyroid function [TSH, free thyroxine (FT4) and antithyroperoxidase antibodies (TPOAbs)] were assessed. The study and the control groups did not differ in age, BMI, waist circumference, lipid profile, fasting glucose, and insulin levels. Results are expressed as median (IQR). Treated HT group had higher FT4 levels than nontreated [17.13 (5.11) pmol/l vs. 14.7 (2.27) pmol/l; p=0.0011] and similar TSH [1.64 (2.08) IU/ml vs. 2.07 (3.14) IU/ml; p=0.5915]. PI CCA and PI ICA were higher in the study group than in controls (p=0.0224 and p=0.0477, respectively). The difference remained statistically significant for PI ICA and PI CCA after adjustment for other variables (coefficient=0.09487; standard error=0.04438; p=0.037 and coefficient=0.1786; standard error=0.0870; p=0.0449, respectively). CIMT and CEMT were similar in both groups (p=0.8746 and p=0.0712, respectively). Women with HT on L-T4 replacement therapy have increased PI in common and internal carotid arteries than nontreated euthyroid HT patients. Therefore, it seems that hypothyroidism, but not autoimmune thyroiditis per se, influences arterial stiffness. © Georg Thieme Verlag KG Stuttgart · New York.
    No preview · Article · Feb 2015 · Hormone and Metabolic Research
  • Source
    Dataset: mutations

    Full-text · Dataset · Feb 2015
  • Source

    Full-text · Dataset · Jan 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Osteopontin (OPN) is a key cytokine involved in T-cell activation in multiple sclerosis (MS). We investigated whether polymorphism of the osteopontin gene affects MS occurrence and clinical course in a Polish population. Disability in 100 MS patients was evaluated using the Expanded Disability Status Scale (EDSS). Genotype and allele frequencies at exons 6 and 7 were examined by PCR. Using appropriate statistical tests, the distribution of variables was tested and means ± SD compared. Genotype distribution and allele frequency differences between patients and control individuals were not statistically significant. No association of OPN with susceptibility to MS was found in the Polish population. The EDSS score was higher in 8090 T/T + 9250 C/C patients than in 8090 C/C + 9250 C/C MS patients (p = 0.0120), and the disability in 8090 C/C + 9250 C/T MS patients was higher than in 8090 C/C + 9250 C/C MS patients (p = 0.0137). Logistic regression analysis revealed age to be an independent factor influencing disability. The polymorphisms of the OPN gene in positions 8090 T/T + 9250 C/C, 8090 C/C + 9250 C/T, and 8090 C/T + 9250 C/T were linked with higher levels of disability in MS patients.
    No preview · Article · Jan 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Despite the growing body of literature on the consequences of providing non-professional care to stroke survivors, the determinants of caregiving burden are still not fully recognized. Identification of significant determinants can facilitate caregiver intervention programs. The aim of this study was to evaluate the level of burden borne by caregivers of stroke patients and to identify the most important determinants of burden at 6 months after hospitalization. Material and methods Data were collected from 150 pairs of stroke patients/caregivers. Caregiver burden was assessed on the Caregiver Burden scale (CB). Several characteristics were measured as potential predictors of the burden. Special attention was paid to the caregiver's sense of coherence (SOC) and anxiety. Regression analysis was employed to test the hypothesized relationships between these variables and the burden. Results Forty-seven percentage of the caregivers reported a substantial burden (severe or moderate). Caregiver SOC (p < 0.001), anxiety (p < 0.001) and the patients’ functional status (p < 0.001) were the most important predictors of the overall burden and the most consistent predictors of the majority of aspects included in the CB scale. Caregiver health, patient's gender, time spent caregiving and social support were also factors related to the burden. The identified predictors explained 67% of the variance in the overall burden. Conclusions Clinicians and other professionals should focus on the coping abilities of caregivers, their emotional state and the level of patients’ dependency, as these are the vital and modifiable factors affecting caregiver burden following stroke.
    Full-text · Article · Oct 2014 · Archives of Medical Science
  • [Show abstract] [Hide abstract]
    ABSTRACT: Polimorfizm promotora genu G-308A TNFα a ryzyko udaru niedokrwiennego. Czynnik martwicy nowotworu alfa (TNFα) jest ważnym mediatorem immunologicznym i może współdziałać w zapoczątkowaniu i postępie udaru niedokrwiennego. Genetyka cząsteczki TNFα może mieć ważną rolę w ryzyku udaru. Najbardziej interesujący aspekt polimorfizmu G-308 A pozostaje niewyjaśniony, z powodu wielu różnic w wynikach badań. Różnice etniczne w badanych kohortach mogą stanowić jedną z przyczyn wystąpienia udaru niedokrwiennego. Nasz badany materiał dotyczył 101 chorych z udarem niedokrwiennym, w tym 30% zdiagnozowano jako udar lakunarny. Rozpoznanie było oparte na nagłym występowaniu objawów neurologicznych, trwających dłużej niż 24 godziny i potwierdzonych przez metody neuroobrazowania. Wszyscy badani byli Polakami rasy kaukaskiej. 100 przypadkowo wybranych osób bez objawów choroby naczyniowej ośrodkowego układu nerwowego stanowiło materiał kontrolny. Częstość występowania polimorfizmu G-308A genu TNFα była określana jak opisano przez Rubattu i wsp. /2005/ [11]. Rozdział genotypów w naszym materiale był podobny i nieistotny statystycznie pomiędzy chorymi i grupą kontrolną. Heterozygoty G/A były stwierdzone u 9% chorych i w 15% przypadków grupy kontrolnej, homozygoty A/A były stwierdzone u 5% chorych i tylko u 1 osoby kontrolnej, a G/G u 87% chorych i u 84% osobników kontrolnych. Nasze wyniki są więc negatywne odnośnie możliwego znaczenia polimorfizmu G-308A TNFα w ryzyku udaru niedokrwiennego u osób rasy kaukaskiej, żyjących w Polsce.
    No preview · Article · Oct 2014 · Neurologia i neurochirurgia polska
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperechogenicity of the substantia nigra (SN) measured by transcranial sonography (TCS) is a characteristic feature observed in patients with Parkinson's disease (PD). To our knowledge, no SN hyperechogenicity data are available for Polish population. Moreover most of studies come from few centres, which used the one type of ultrasound device. The main aim of the study was to investigate the association between PD and SN hyperechogenicity measured by sonographic machine, not assessed so far. In this study cross-sectional study SN hyperechogenicity was evaluated in 102 PD patients and 95 control subjects. Midbrain was visualised by Aloka Prosound 7 ultrasound device. SN area measurement, the relation to the clinical features of PD, inter- and intra-observer reliability were evaluated. We confirmed that SN echogenicity is significantly increased in PD patients compared to control subjects (p < 0.001). The area under curve for PD patients vs. controls was 0.93. Receiver operating characteristic analysis indicated a cut-offs for SN echogenicity at 0.19 cm² with accuracy equal to 90%, specificity - 86% and sensitivity - 93.7%. The SN hyperechogenicity was not related to PD clinical findings. Reliability was good if an experienced sonographer performed the SN measurements. This study shows that the SN abnormality observed by TCS isa specific feature, which can be helpful in the process of PD diagnosing.
    Preview · Article · Sep 2014 · Folia morphologica

  • No preview · Conference Paper · Sep 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite a significant progress in prevention, treatment and management in the past decades, stroke remains the most common disabling chronic condition in adult population. It may be a source of serious temporary or permanent consequences. These consequences should be recognised and measured for defining and implementation of remedial interventions and for optimum utilisation of health care resources. The aim of this work was to present sequels of stroke, taking into account objective and subjective indices, as documented in the recent literature of the subject. Selected data on mortality and survival following stroke were presented, the up-to-date literature was reviewed and register-based prospective studies were presented on quality of life (QoL) in post-stroke patients. Systematic reviews and meta-analyses of randomised controlled trials (RCTs) were summed up, related to efficacy of interventions aimed at improving QoL of the patients. Moreover, the studies were reviewed on burden and QoL experienced by caregivers of post-stroke patients and results were summed up of RCT synthesis aimed at reducing the burden and at improving QoL in the caregivers. The analysed studies indicated that stroke exerts a long-term, negative effect on patients’ QoL, promoting a decrease in this measure and burdening a significant proportion of the family caregivers. The applied till now different interventions and programmes targeted at the patients and at their carers analysed in RCTs showed no or modest effects on improving of QoL or reducing the caregiver's burden.
    Full-text · Article · Jul 2014 · Neurologia i neurochirurgia polska
  • Source

    Full-text · Article · Jul 2014 · Alzheimer's and Dementia
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease (AD), a progressive neurodegenerative disorder leads to production of β‐amyloid (Aβ) which accumulation, facilitated in apolipoprotein E (APOE) ε‐4 carriers, results in brain degeneration by apoptosis, which may arise from oxidative damage generated by Aβ and checkpoint proteins deregulation, such as p53. The aim of the study was to analyze the mutation status in highly conservative exon 7 of TP53 and APOE allele, as well as p53 protein level in AD patients and control subjects. The study on TP53 and APOE was performed on 29 AD patients and 16 control subjects. The TP53 exon 7 was analyzed in DNA extracted from blood by sequencing and APOE allele was determined by RT‐PCR mismatchprimer technique. The p53 protein level was determined in peripheral lymphocytes by Western Blotting. The sequencing of exon 7 of TP53 revealed the presence of two various mutations only in AD patients: a missense mutation C748A (P250T, 3.4%) present in an APOE ε‐3/ε‐4 allele carrier and a silent mutation C708T (Y236Y), found in 6 (20.1%) AD patients with various APOE genotypes (ε‐2/ε‐3, ε‐3/ε‐3 and ε‐3/ε‐4). The analysis of APOE showed ε‐3/ε‐3 genotype to be more common in control group (62.5%) than in AD patients (37.9%). The ε‐3/ε‐4 variant was more abundant in AD group (44.8%) as compared to controls (31.3%). Variant ε‐4/ε‐4 occurred in a single AD patient, whereas ε‐2/ε‐2 genotype was found only in a control subject. Our results indicated that in the AD group the p53 level was highest in APOE ε‐4 carriers and did not change significantly in control group. It is most likely that both: mutations in the TP53 gene and APOE status participate in the pathogenesis of AD.
    No preview · Conference Paper · Jun 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurodegeneration with brain iron accumulation (NBIA) defines a heterogeneous group of progressive neurodegenerative disorders characterized by excessive iron accumulation in the brain, particularly affecting the basal ganglia. In the recent years considerable development in the field of neurodegenerative disorders has been observed. Novel genetic methods such as autozygosity mapping have recently identified several genetic causes of NBIA. Our knowledge about clinical spectrum has broadened and we are now more aware of an overlap between the different NBIA disorders as well as with other diseases. Neuropathologic point of view has also been changed. It has been postulated that pantothenate kinase-associated neurodegeneration (PKAN) is not synucleinopathy. However, exact pathologic mechanism of NBIA remains unknown. The situation implicates a development of new therapies, which still are symptomatic and often unsatisfactory. In the present review, some of the main clinical presentations, investigational findings and therapeutic results of the different NBIA disorders will be presented.
    No preview · Article · May 2014 · Neurologia i neurochirurgia polska
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease (AD) leads to generation of β-amyloid (Aβ) in the brain. Alzheimer’s disease model PS/APP mice show a markedly accelerated accumulation of Aβ, which may lead to apoptosis induction e.g. in cells expressing wild-type p53. The TP53 gene is found to be the most frequently mutated gene in human tumour cells. There is accumulating evidence pointing out to the contribution of oxidative stress and chronic inflammation in both AD and cancer. The purpose of this study was to analyze exon 7 mutations of the murine Trp53 gene and Aβ/A4 and p53 protein levels in PS/APP and control mice. The studies were performed on female double transgenic PS/APP mice and young adults (8-12 weeks old) and agematched control mice. The Trp53 mutation analysis was carried out with the use of PCR and DNA sequencing. The Aβ/A4 and p53 levels were analyzed by Western blotting. The frequency of mutations was almost quadrupled in PS/APP mice (44%), compared to controls (14%). PS/APP mice with the A929T and A857G mutations had a similar p53 level. In cerebral gray matter of PS/APP mice the level of p53 positive correlated with the level of Aβ protein (RS = +0.700, p < 0.05). In younger control animals, the T854G mutation was related to p53 down-regulation, while in aging ones, G859A substitution was most likely associated with over-expression of p53. In silico protein analysis revealed a possibly substantial impact of all four mutations on p53 activity. Three mutations were in close proximity to zinc-coordinating cysteine residues. It seems that in PS/APP mice missense Trp53 exon 7 mutations may be associated with the degenerative process by changes of p53 protein function.
    Full-text · Article · Apr 2014 · Folia Neuropathologica

Publication Stats

714 Citations
296.50 Total Impact Points

Institutions

  • 1998-2015
    • Poznan University of Medical Sciences
      • • Department of Neurology
      • • Department of Metabolism Endocrinology and Internal Medicine
      Posen, Greater Poland Voivodeship, Poland
  • 2006-2012
    • Uniwersytet Medyczny im.Karola Marcinkowskiego w Poznaniu
      Posen, Greater Poland Voivodeship, Poland
  • 2005
    • University of Lodz
      Łódź, Łódź Voivodeship, Poland
  • 2002
    • Polish Academy of Sciences
      • Institute of Human Genetics
      Warszawa, Masovian Voivodeship, Poland