Design and evaluation of devices for the treatment of intervertebral disorders

The a1m of this thesis was to design and evaluate implants used m the treatment of intervertebral disc disorders. A new cervical PEEK-on-PEEK disc device, combining a ball-on-socket mechanism with an elastomeric core, was designed. To find a material for the core, quasi-static compression tests were performed; on the basis of which an elastomer MED 4780 was selected for further testing. Finite element analysis (FEA) was used to investigate the maximum stresses in the device during static compression. The results showed that maximum stresses did not exceed PEEK's compressive or fatigue strength. The comparison of the mechanical properties of pedicle screws (cylindrical and dual-core), used as an integral part of the posterior lumbar stabilisation system, was performed. The screws were tested in axial pullout, quasi-static and dynamic bending, as well as subjected to the static bending, using FEA. The results of the pullout tests, performed using three polyurethane foams (0.16, 0.32 and 0.64 g/cm\ showed no significant difference between pullout strength values. However, dual-core screws had significantly higher bending strength and a longer fatigue life. The FEA showed lower stress values for the dual-core screw. Furthermore, a critical assessment of explanted screws has shown that fatigue bending was the cause of failure in vivo

Primary myelofibrosis with normal karyotype and cryptic aberrations detected by FISH: case report

Introduction. Myeloproliferative neoplasms (MPNs) are the result of clonal haematopoietic stem cell disorders. The most common cytogenetic aberrations are: partial trisomy 1q, 13q–, 20q–, trisomy 8 and abnormalities of chromosomes 1, 7 and 9. Conventional karyotyping is a routinely used method. Fluorescent in situ hybridisation (FISH) analysis however may also be an integral component of the diagnostic evaluation, especially when the abnormality is cryptic. Subject and methods. A 70-year-old woman was admitted to the Department of Haematology in September 2013 with suspected acute myeloid leukemia (AML). The final diagnosis was primary myelofibrosis and NYHA class III heart failure. Bone marrow (BM) was used for karyotyping and FISH. Peripheral blood (PB) was used for PCR. Results. Cytogenetic GTG analysis revealed normal female karyotype — 46,XX [22]. The result of analysis of JAK2 V617F mutation was negative. Analysis using LSI BCR/ABL Dual Fusion Probe, JAK2 Break Probe and RB1 Deletion Probe showed abnormal cells, of which the numbers were beyond the normal cutoffs. FISH examinations using p53 Deletion Probe and LSI CDKN2A/CEP 9 showed normal cells. Conclusion. The diagnosis of primary myelofibrosis may pose a problem. We still do not know the specific abnormalities (i.e. genomic and chromosomal aberrations or gene mutations), the occurrence of which may help to diagnose and assess a probable time of survival of patients with PMF. Further examinations are needed (e.g. using aCGH) to find out more about myeloproliferative neoplasms

Znaczenie prognostyczne rearanżacji BCR-ABL w ostrej białaczce limfoblastycznej u dzieci

B a c k g r o u n d . Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. Presence of adverse risk factors determines risk group stratification in this disease.O b j e c t i v e . The aim of study was the analysis of results of therapy and role of prognostic risk factors in treatment of childhood ALL in kujawsko-pomorskie region in 1995-2010.P a t i e n t s a n d m e t h o d s . During this period, ALL was diagnosed in 223 patients. With respect to time period and therapy protocol, the patients were divided into two groups: group 1 A/B (1995-2002) and group 2 (2002- 2010). Probability of overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were analyzed. Uni- and multivariate analyzes for risk factors were performed.R e s u l t s . Over the analyzed 17-year period, OS has increased from 77.9% in group 1A and 73.7% in group 1B to 86.2% in group 2. Results of RFS and EFS have also increased during this time. The death rate has decreased from 26% in group 1A and 26.3% in group 1B to 10.2% in group 2. The most important adverse prognostic risk factors during the first period included involvement of liver, spleen, lymph nodes as well as poor response to initial therapy, while during the second period the most important independent risk factor was BCR-ABL rearrangement in lymphoblasts.C o n c l u s i o n s . The most important independent prognostic risk factors in pediatric ALL include advanced disease, BCR-ABL rearrangement, and initial response to therapy. These factors are used for stratification to treatment groups, intensification of therapy and hematopoietic stem cell transplantation.W s t ę p . Ostra białaczka limfoblastyczna (ALL) jest najczęstszym nowotworem wieku dziecięcego. W tej chorobie obecność czynników ryzyka decyduje o stratyfikacji pacjentów do grup ryzyka.C e l p r a c y . Analiza wyników terapii i roli czynników prognostycznych w ALL u dzieci w regionie kujawsko-pomorskim w latach 1995-2010.P a c j e n c i  i  m e t o d y k a . Analizą objęto 223 dzieci, które podzielono na 2 grupy w zależności od okresu terapii i stosowanych protokołów leczenia: grupa 1A/B (1995-2002) i grupa 2 (2002-2010). Wyznaczono prawdopodobieństwo przeżycia wolnego od zdarzeń (pEFS), prawdopodobieństwo przeżycia (pOS) i prawdopodobieństwa przeżycia wolnego od wznowy (pRFS). Przeprowadzono analizę jedno- i wielowariantową czynników ryzyka niepowodzenia terapii.Wy n i k i . W analizowanym okresie 17 lat, OS wzrosło od 77,9% w grupie 1A i 73,7% w grupie 1B do 86,2% w grupie 2. Wyniki RFS i EFS również uległy poprawie. W tym czasie odsetek zgonów obniżył się z 26% w grupie 1A i 26,3% w grupie 1B do 10,2% w grupie 2. W analizie czynników ryzyka wykazano, że w pierwszym analizowanym okresie zajęcie wątroby, śledziony i węzłów chłonnych oraz niekorzystna początkowa odpowiedź na terapię były związane z gorszymi ostatecznymi wynikami terapii, natomiast w drugim okresie czasu najsilniejszym niezależnym niekorzystnym czynnikiem rokowniczym była obecność rearanżacji BCR-ABL w limfoblastach.Wn i o s k i . Najważniejszymi czynnikami prognostycznymi w ALL u dzieci są: zaawansowanie choroby, odpowiedź na leczenie oraz obecność rearanżacji BCR-ABL, które są podstawą stratyfikacji do grup ryzyka, intensyfikacji leczenia w grupach wysokiego ryzyka oraz kwalifikacji do przeszczepiania komórek krwiotwórczych

Prognostic significance of BCR-ABL rearrangement in childhood acute lymphoblastic leukemia

B a c k g r o u n d. Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. Presence of adverse risk factors determines risk group stratification in this disease. O b j e c t i v e. The aim of study was the analysis of results of therapy and role of prognostic risk factors in treatment of childhood ALL in kujawsko-pomorskie region in 1995-2010. P a t i e n t s a n d m e t h o d s. During this period, ALL was diagnosed in 223 patients. With respect to time period and therapy protocol, the patients were divided into two groups: group 1 A/B (1995-2002) and group 2 (2002- 2010). Probability of overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were analyzed. Uni- and multivariate analyzes for risk factors were performed. R e s u l t s. Over the analyzed 17-year period, OS has increased from 77.9% in group 1A and 73.7% in group 1B to 86.2% in group 2. Results of RFS and EFS have also increased during this time. The death rate has decreased from 26% in group 1A and 26.3% in group 1B to 10.2% in group 2. The most important adverse prognostic risk factors during the first period included involvement of liver, spleen, lymph nodes as well as poor response to initial therapy, while during the second period the most important independent risk factor was BCR-ABL rearrangement in lymphoblasts. C o n c l u s i o n s. The most important independent prognostic risk factors in pediatric ALL include advanced disease, BCR-ABL rearrangement, and initial response to therapy. These factors are used for stratification to treatment groups, intensification of therapy and hematopoietic stem cell transplantation.W s t ę p. Ostra białaczka limfoblastyczna (ALL) jest najczęstszym nowotworem wieku dziecięcego. W tej chorobie obecność czynników ryzyka decyduje o stratyfikacji pacjentów do grup ryzyka. C e l p r a c y. Analiza wyników terapii i roli czynników prognostycznych w ALL u dzieci w regionie kujawsko-pomorskim w latach 1995-2010. P a c j e n c i  i  m e t o d y k a. Analizą objęto 223 dzieci, które podzielono na 2 grupy w zależności od okresu terapii i stosowanych protokołów leczenia: grupa 1A/B (1995-2002) i grupa 2 (2002-2010). Wyznaczono prawdopodobieństwo przeżycia wolnego od zdarzeń (pEFS), prawdopodobieństwo przeżycia (pOS) i prawdopodobieństwa przeżycia wolnego od wznowy (pRFS). Przeprowadzono analizę jedno- i wielowariantową czynników ryzyka niepowodzenia terapii. Wy n i k i. W analizowanym okresie 17 lat, OS wzrosło od 77,9% w grupie 1A i 73,7% w grupie 1B do 86,2% w grupie 2. Wyniki RFS i EFS również uległy poprawie. W tym czasie odsetek zgonów obniżył się z 26% w grupie 1A i 26,3% w grupie 1B do 10,2% w grupie 2. W analizie czynników ryzyka wykazano, że w pierwszym analizowanym okresie zajęcie wątroby, śledziony i węzłów chłonnych oraz niekorzystna początkowa odpowiedź na terapię były związane z gorszymi ostatecznymi wynikami terapii, natomiast w drugim okresie czasu najsilniejszym niezależnym niekorzystnym czynnikiem rokowniczym była obecność rearanżacji BCR-ABL w limfoblastach. Wn i o s k i. Najważniejszymi czynnikami prognostycznymi w ALL u dzieci są: zaawansowanie choroby, odpowiedź na leczenie oraz obecność rearanżacji BCR-ABL, które są podstawą stratyfikacji do grup ryzyka, intensyfikacji leczenia w grupach wysokiego ryzyka oraz kwalifikacji do przeszczepiania komórek krwiotwórczych

Coexistance of lung cancer and chronic obstructive pulmonary disease

Wstęp. Celem niniejszego opracowania było określenie częstości występowania przewlekłej obturacyjnej choroby płuc (POChP) u chorych na zaawansowanego raka płuca. Materiał i metody. Badaniem objęto kolejnych 51 chorych na zaawansowanego (stopień IIIB i IV) raka płuca - 13 kobiet (25%) i 38 mężczyzn (75%) w wieku 40-80 lat (średnia wieku: 63 lata). Wyniki. Wśród 51 chorych na zaawansowanego raka płuca w 18 przypadkach (35%) rozpoznano POChP. W tej grupie u niemal 3/4 osób (72%) występowała umiarkowana, a u 28% ciężka i bardzo ciężka postać choroby. Związek między POChP a rakiem płuca był najsilniejszy u chorych na raka płaskonabłonkowego (współczynnik korelacji Spearmana: r = 0,43; różnica w porównaniu z pozostałymi typami: p = 0,002). Wykazano, że współwystępowanie raka płuca i POChP wiązało się z większym narażeniem na dym tytoniowy, jednak zależność ta nie osiągnęła znamienności statystycznej (p = 0,072). Nie stwierdzono korelacji między obecnością POChP w badanej grupie a innymi klinicznymi cechami, takimi jak wiek, płeć i zaawansowanie choroby nowotworowej. Wnioski. Współwystępowanie raka płuca i POChP jest częste. Wydaje się, że uwzględnienie współistniejących pneumonologicznych schorzeń w opiece paliatywnej nad chorymi w końcowej fazie choroby nowotworowej pozwoliłoby poprawić jakość ich życia.Background. The aim of the study was to evaluate the frequency of coexistance of lung cancer and chronic obstructive pulmonary disease. Material and methods. Fifty one patients (13 women and 38 men, aged from 40 to 80 years, range: 63 years) with diagnosed advanced lung cancer (stage IIIB and IV) were included into the study. Results. The chronic obstructive pulmonary disease was diagnosed in 18 cases (35%), including 72% moderate and 28% with severe and very severe disease. The chronic obstructive pulmonary disease was significantly more frequent in squamous cell lung carcinoma in comparison to other subtypes (p = 0.002). There was also a tendency to coexistence of lung cancer and the chronic obstructive pulmonary disease in patients with higher exposure to cigarette smoke (p = 0.072).Conclusion. Coexistence of lung cancer and the chronic obstructive pulmonary disease is frequent, thus it is important to include treatment for the chronic obstructive pulmonary disease in palliative care of advanced lung cancer patients

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Księga poświęcona Profesorowi Hieronimowi Kubiakowi w 75. rocznicę urodzin. Tom ofiarowany przez przyjaciół i uczniów

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research

Novel vitamin D3-hydroxyderivatives as candidates for the therapy against skin-aging and photo-aging: bioinformatical analysis

Vitamin D3 acts through its most active form, calcitriol, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] as agonist of one of the receptors involved in this ligand action, vitamin D receptor (VDR), which is also a transcription factor. Numerous modifications of calcitriol at its side-chain, C-ring, A-ring, triene system, alone or in combination, as well as nonsteroidal mimics provided new VDR agonists and some antagonists with biological activity and possible therapeutical potential. Some of the D3 metabolites, including 20,23(OH)2D3 and 20(OH)D3 are able to inhibit RORE-mediated transactivation, as well as the interaction between the RORα/γ ligand-binding domain (LBD) with an LXXLL coactivator peptide. Our analysis of recently reported microarray data on vitamin D3 (D3) induced changes in cultured human keratinocytes indicated that D3 hydroxyderivatives stimulate the expression of genes involved in anti-aging activities. Furthermore, we noted upregulation of the kallikrein gene family by 1,25(OH)2D3 after 24-hour treatment, including stimulation of KLK6, KLK13, KLK3, KLK9, KLK5, KLK7, and KLK10. Also, after 6-hour incubation with 1,25(OH)2D3, the upregulation of KLK6, KLK13, and KLK3 was seen.  Interestingly, ACEIs administered to hypertensive rats doubled the lifespan of these animals. In humans, ACEIs prevent hallmarks of aging, such as organ fibrosis and cardiac hypertrophy. We noted also that vitamin D3-hydroxyderivatives act against oxidative stress through upregulation of thioredoxin reductase (TXNRD1) and heme reductase-1 (HMOX-1) gene expression in keratinocytes treated for 24h. Another mechanism of anti-aging properties of inverse agonist RORa/γ is the resolution of inflammation caused by T helper (Th17) lymphocytes and switching the immune response into T regulatory (Treg) lymphocytes activation, with silencing of the inflammation state and reducing the inflammation process. The gene connected with inflammatory response, AKR1C3 (which encodes prostaglandin F synthase) is also strongly downregulated by 20,23(OH)2D3 in keratinocytes after incubation for 24 h. We suggest that vitamin D3 analogs, such as 20,23(OH)2D3, 1,25(OH)2D3, and 20(OH)D3 may have anti-aging properties through action on different pathways connected with DNA repair