Browsing by Author "Kalējs, Mārtiņš"

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    Anaesthesia management with deep hypothermia and circulatory arrest during surgery for chronic thromboembolic pulmonary hypertension
    (2014-12-01) Leibuss, Roberts; Kalējs, Mārtiņš; Skride, Andris; Bekkers, Mihails; Ozoliņa, Agnese; Stradiņš, Pēteris; Strīķe, Eva; Lācis, Romans; Rīga Stradiņš University
    Chronic thromboembolic pulmonary hypertension (CTEPH) occurs in 1 to 4% after acute pulmonary embolism. CTEPH can be cured by pulmonary endarterectomy (PEA), which is approved golden standard in chronic condition. There were performed three cases of PEA in Latvian Cardiology Centre during 2013-2014. General anaesthesia under cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrests was provided. The core issue is correct patient selection (in terms of central PA obstruction by thrombus) as well as pulmonary circulation recovery capacity. Neuroprotection was provided by deep hypothermia, topical cooling of the head, Trendelenburg position, mild hypocapnia, Hb 9-10 g/L and pharmacological agents. For screening postoperative cognitive function the mini mental state examination (MMSE) was used before and after the surgery. Postoperative pulmonary vascular resistance index decreased by 56.3% (right ventricular systolic pressure decreased from 93.3 ± 25.7 to 44.5 ± 11.2 mmHg). Before the surgery three patients had NYHA functional class III or IV, at the time of discharge - I or II. In one case moderate (MMSE 18) cognitive disorders was observed at discharge from the ICU. No one died neither in the hospital nor within 30 days of discharge. The surgery improved RV function and pulmonary perfusion with no considerable organ failure, except mild cognitive disorders.
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    The cancer aneuploidy paradox : In the light of evolution
    (2019-01-01) Salmina, Kristine; Huna, Anda; Kalējs, Mārtiņš; Pjanova, Dace; Scherthan, Harry; Cragg, Mark S.; Ērenpreisa, Jekaterina; Biomehānikas zinātniskā laboratorija
    Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform the segregation of two parental groups of end-to-end linked dyads by pseudo-mitosis creating tetraploid cells through a dysfunctional spindle. This is followed by autokaryogamy and a homologous pairing preceding a bi-looped endo-prophase. The associated RAD51 and DMC1/γ- H2AX double-strand break repair foci are tandemly situated on the AURKB/REC8/kinetochore doublets along replicated chromosome loops, indicative of recombination events. MOS-associated REC8-positive peri-nucleolar centromere cluster organises a monopolar spindle. The process is completed by reduction divisions (bi-polar or by radial cytotomy including pedogamic exchanges) and by the release of secondary cells and/or the formation of an embryoid. Together this process preserves genomic integrity and chromosome pairing, while tolerating aneuploidy by by-passing the mitotic spindle checkpoint. Concurrently, it reduces the chromosome number and facilitates recombination that decreases the mutation load of aneuploidy and lethality in the chemo-resistant tumour cells. This cancer life-cycle has parallels both within the cycling polyploidy of the asexual life cycles of ancient unicellular protists and cleavage embryos of early multicellulars, supporting the atavistic theory of cancer.
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    Cancer/testis antigens and gametogenesis : A review and "brain-storming" session
    (2005-02-16) Kalējs, Mārtiņš; Ērenpreisa, Jekaterina
    Genes expressed both in normal testis and in malignancies (Cancer/ Testis associated genes - CTA) have become the most extensively studied antigen group in the field of tumour immunology. Despite this, many fundamentally important questions remain unanswered: what is the connection between germ-cell specific genes and tumours? Is the expression of these genes yet another proof for the importance of genome destabilisation in the process of tumorigenesis?, or maybe activation of these genes is not quite random but instead related to some programme giving tumours a survival advantage? This review collates most of the recent information available about CTAs expression, function, and regulation. The data suggests a programme related to ontogenesis, mostly to gametogenesis. In the "brain-storming" part, facts in conflict with the hypothesis of random CTA gene activation are discussed. We propose a programme borrowed from organisms phylogenetically much older than humans, which existed before the differentiation of sexes. It is a programme that has served as a life cycle with prominent ploidy changes, and from which, as we know, the germ-cell ploidy cycle - meiosis - has evolved. Further work may show whether this hypothesis can lead to a novel antitumour strategy.
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    From Biomechanical Properties to Morphological Variations : Exploring the Interplay between Aortic Valve Cuspidity and Ascending Aortic Aneurysm
    (2024-07-19) Brečs, Ivars; Skuja, Sandra; Kasyanov, Vladimir; Groma, Valērija; Kalējs, Mārtiņš; Svirskis, Šimons; Ozolanta, Iveta; Stradiņš, Pēteris; Joint Laboratory of Electron Microscopy; Joint Laboratory of Traumatology and Orthopaedics; Faculty of Medicine; Institute of Microbiology and Virology
    Background: This research explores the biomechanical and structural characteristics of ascending thoracic aortic aneurysms (ATAAs), focusing on the differences between bicuspid aortic valve aneurysms (BAV-As) and tricuspid aortic valve aneurysms (TAV-As) with non-dilated aortas to identify specific traits of ATAAs. Methods: Clinical characteristics, laboratory indices, and imaging data from 26 adult patients operated on for aneurysms (BAV-A: n = 12; TAV-A: n = 14) and 13 controls were analyzed. Biomechanical parameters (maximal aortic diameter, strain, and stress) and structural analyses (collagen fiber organization, density, fragmentation, adipocyte deposits, and immune cell infiltration) were assessed. Results: Significant differences in biomechanical parameters were observed. Median maximal strain was 40.0% (control), 63.4% (BAV-A), and 45.3% (TAV-A); median maximal stress was 0.59 MPa (control), 0.78 MPa (BAV-A), and 0.48 MPa (TAV-A). BAV-A showed higher tangential modulus and smaller diameter, with substantial collagen fragmentation ( p < 0.001 vs. TAV and controls). TAV-A exhibited increased collagen density ( p = 0.025), thickening between media and adventitia layers, and disorganized fibers ( p = 0.036). BAV-A patients had elevated adipocyte deposits and immune cell infiltration. Conclusions: This study highlights distinct pathological profiles associated with different valve anatomies. BAV-A is characterized by smaller diameters, higher biomechanical stress, and significant collagen deterioration, underscoring the necessity for tailored clinical strategies for effective management of thoracic aortic aneurysm.
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    Incidence of permanent pacemaker implantation after cardiac surgery : A single centre experience
    (2019-08-01) Kalējs, Mārtiņš; Prozorovskis, Edgars; Kupics, Kaspars; Brečs, Ivars; Strazdiņš, Uldis; Stradiņš, Peteris; Biomehānikas zinātniskā laboratorija; Rīga Stradiņš University
    Permanent pacemaker implantation (PPI) after open heart surgery is required in 0.4-8.5% of patients. The aim of our study was to determine the incidence of PPI after cardiac surgery at Pauls Stradiņš Clinical University Hospital and to assess its influence on intrahospital outcomes. This was a single-centre retrospective study. We reviewed all patients who underwent either open heart surgery or transcatheter aortic valve implantation (TAVI) between the years 2015 and 2017. Included were all patients with PPI postoperatively before discharge. We compared the patient demographics, and perioperative state, incidence of PPI and intrahospital stay among groups. After cardiac surgery a total of 135 (4.2%) patients received a PPI. The PPI incidence was highest in the tricuspid valve intervention group - 8.8% followed by aortic valve replacement (AVR) patients with 3.3%. After TAVI incidence of PPI was 4.0% after Sapien valve and 8% after CoreValve implantations, respectively. Incidence of PPI after TAVI with the Sapien valve was not significantly higher when compared to conventional AVR, but it was significantly higher after TAVI with CoreValve. Regardless of the initial procedure a need for PPI significantly increased the total length of hospital stay.
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    Long-term complications evidenced studying the explanted Gore® HELEX® atrial septal defect occluder seven years after implantation : a case report
    (2017-09-18) Sekretarjovs, Jurijs; Kalējs, Mārtiņš; Rudzītis, Ainārs; Brečs, Ivars; Sorokins, Hermanis; Skuja, Sandra; Stradiņš, Pēteris; Groma, Valērija; Institute of Anatomy and Anthropology
    We present the results of the first morphological study of a Gore® HELEX® Septal Occluder 30 mm that was explanted seven years after interventional implantation due to a significant left-to-right shunt (7 mm) which resulted from the stretching of the concomitant patent foramen ovale by the occluder after atrial septal defect closure. Complete endothelialization of the surface of the device, the formation of the connective tissue around the implant, minor chronic inflammation, the appearance of foreign body giant cells and weakened myocardial cells adjacent to the implant as well as enhanced expression of matrix metalloproteinases were demonstrated.
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    Optimāli sirds vārstuļu struktūrkomponentu mehāniskie parametri un atbilstoša aizvietotājmateriāla izvēle. Promocijas darbs
    (Rīgas Stradiņa universitāte, 2014) Kalējs, Mārtiņš; Stradiņš, Pēteris
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    Upregulation of meiosis-specific genes in lymphoma cell lines following genotoxic insult and induction of mitotic catastrophe
    (2006-01-09) Kalējs, Mārtiņš; Ivanov, Andrey; Plakhins, Gregory; Cragg, Mark S.; Emzinsh, Dzintars; Lllidge, Timothy M.; Ērenpreisa, Jekaterina
    Background: We have previously reported that p53 mutated radioresistant lymphoma cell lines undergo mitotic catastrophe after irradiation, resulting in metaphase arrest and the generation of endopolyploid cells. A proportion of these endopolyploid cells then undergo a process of de-polyploidisation, stages of which are partially reminiscent of meiotic prophase. Furthermore, expression of meiosis-specific proteins of the cancer/testis antigens group of genes has previously been reported in tumours. We therefore investigated whether expression of meiosis-specific genes was associated with the polyploidy response in our tumour model. Methods: Three lymphoma cell lines, Namalwa, WI-L2-NS and TK6, of varying p53 status were exposed to a single 10 Gy dose of gamma radiation and their responses assessed over an extended time course. DNA flow cytometry and mitotic counts were used to assess the kinetics and extent of polyploidisation and mitotic progression. Expression of meiotic genes was analysed using RT-PCR and western blotting. In addition, localisation of the meiotic cohesin REC8 and its relation to centromeres was analysed by immunofluorescence. Results: The principal meiotic regulator MOS was found to be significantly post-transcriptionally up-regulated after irradiation in p53 mutated but not p53 wild-type lymphoma cells. The maximum expression of MOS coincided with the maximal fraction of metaphase arrested cells and was directly proportional to both the extent of the arrest and the number of endopolyploid cells that subsequently emerged. The meiotic cohesin REC8 was also found to be up-regulated after irradiation, linking sister chromatid centromeres in the metaphase-arrested and subsequent giant cells. Finally, RT-PCR revealed expression of the meiosis-prophase genes, DMCI, STAG3, SYCP3 and SYCP1. Conclusions: We conclude that multiple meiotic genes are aberrantly activated during mitotic catastrophe in p53 mutated lymphoma cells after irradiation. Furthermore, we suggest that the coordinated expression of MOS and REC8 regulate the extent of arrested mitoses and polyploidy.