Browsing by Author "Doniņa, Simona"

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    Biomarķieri olnīcu vēža diagnostikā, to jutība un specifiskums kombinācijā ar ultrasonogrāfisko atradi un klīniskiem simptomiem. Promocijas darba kopsavilkums
    (Rīgas Stradiņa universitāte, 2012) Mačuks, Ronalds; Doniņa, Simona
    Latvijā saslimstības struktūrā ar ļaundabīgajiem ginekoloģiskajiem audzējiem saslimstība ar olnīcu vēzi ieņem otro vietu. Laikā no 2003. līdz 2009.gadam Latvijā katru gadu diagnosticēti 283 līdz 340 saslimšanas gadījumi ar olnīcu vēzi, savukārt mirstība bija 58,6-70,7% no katrā attiecīgajā gadā reģistrēto gadījumu skaita. Diagnosticējot olnīcu vēzi slimības agrīnajās stadijās, piecu gadu dzīvildze ir 80%, bet atklājot saslimšanu vēlīnās stadijās, piecu gadu dzīvildze ir sagaidāma tikai 30% gadījumu. Ir pierādīts, ka labāki olnīcu vēža ārstēšanas rezultāti sasniedzami, ja pacientes ārstē onkoloģijas ginekologi, tāpēc svarīgi ir izstrādāt ģimenes ārstiem un ginekologiem paredzētas rekomendācijas olnīcu audzēju diferenciāldiagnostikā. Pētījuma mērķis ir izveidot olnīcu vēža diagnostikas algoritmu, izmantojot jutīgākos un specifiskākos biomarķierus kombinācijā ar klīniskajiem simptomiem un ultrasonogrāfisko atradi. Pētījumā tika iekļautas 83 pacientes ar ļaundabīgiem un 77 pacientes ar labdabīgiem olnīcu audzējiem, kā arī 82 veselas atbilstoša vecuma sievietes kontroles grupā. Pētījumā tika analizēta olnīcu vēža simptomu indeksa jutība un specifiskums atsevišķi un saistībā ar biomarķieriem; dažādu malignitātes riska indeksa aprēķināšanas metožu jutība un specifiskums, apolipoproteīna A1, transtiretīna, transferīna, beta-2-mikroglobulīna, cilvēka epidydimis sekretorā proteīna-4 (HE4) un ar audzēju asociētā antigēna CA125 jutība un specifiskums olnīcu vēža diagnostikā. Pētījumā tika izstrādāts jauns olnīcu vēža diagnostikas algoritms, kurš nodrošina augstāku diagnostisko jutību un specifiskumu nekā līdz šim olnīcu vēža diagnostikā lietotie testi un to kombinācijas. Pētījumā izstrādātais olnīcu vēža diagnostikas algoritms ir pārbaudīts divās neatkarīgās pacientu populācijās „Danish Pelvic Mass Project” un Āzijas Klusā okeāna valstu olnīcu vēža biomarķieru izpētes grupas pētījumā. Tika izstrādātas arī rekomendācijas olnīcu vēža simptomu indeksa, malignitātes riska indeksa un jaunizveidotā olnīcu vēža diagnostikas algoritma izmantošanai klīniskajā praksē.
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    Biomarķieri olnīcu vēža diagnostikā, to jutība un specifiskums kombinācijā ar ultrasonogrāfisko atradi un klīniskiem simptomiem. Promocijas darbs
    (Rīgas Stradiņa universitāte, 2012) Mačuks, Ronalds; Doniņa, Simona
    Latvijā saslimstības struktūrā ar ļaundabīgajiem ginekoloģiskajiem audzējiem saslimstība ar olnīcu vēzi ieņem otro vietu. Laikā no 2003. līdz 2009.gadam Latvijā katru gadu diagnosticēti 283 līdz 340 saslimšanas gadījumi ar olnīcu vēzi, savukārt mirstība bija 58,6-70,7% no katrā attiecīgajā gadā reģistrēto gadījumu skaita. Diagnosticējot olnīcu vēzi slimības agrīnajās stadijās, piecu gadu dzīvildze ir 80%, bet atklājot saslimšanu vēlīnās stadijās, piecu gadu dzīvildze ir sagaidāma tikai 30% gadījumu. Ir pierādīts, ka labāki olnīcu vēža ārstēšanas rezultāti sasniedzami, ja pacientes ārstē onkoloģijas ginekologi, tāpēc svarīgi ir izstrādāt ģimenes ārstiem un ginekologiem paredzētas rekomendācijas olnīcu audzēju diferenciāldiagnostikā. Pētījuma mērķis ir izveidot olnīcu vēža diagnostikas algoritmu, izmantojot jutīgākos un specifiskākos biomarķierus kombinācijā ar klīniskajiem simptomiem un ultrasonogrāfisko atradi. Pētījumā tika iekļautas 83 pacientes ar ļaundabīgiem un 77 pacientes ar labdabīgiem olnīcu audzējiem, kā arī 82 veselas atbilstoša vecuma sievietes kontroles grupā. Pētījumā tika analizēta olnīcu vēža simptomu indeksa jutība un specifiskums atsevišķi un saistībā ar biomarķieriem; dažādu malignitātes riska indeksa aprēķināšanas metožu jutība un specifiskums, apolipoproteīna A1, transtiretīna, transferīna, beta-2-mikroglobulīna, cilvēka epidydimis sekretorā proteīna-4 (HE4) un ar audzēju asociētā antigēna CA125 jutība un specifiskums olnīcu vēža diagnostikā. Pētījumā tika izstrādāts jauns olnīcu vēža diagnostikas algoritms, kurš nodrošina augstāku diagnostisko jutību un specifiskumu nekā līdz šim olnīcu vēža diagnostikā lietotie testi un to kombinācijas. Pētījumā izstrādātais olnīcu vēža diagnostikas algoritms ir pārbaudīts divās neatkarīgās pacientu populācijās „Danish Pelvic Mass Project” un Āzijas Klusā okeāna valstu olnīcu vēža biomarķieru izpētes grupas pētījumā. Tika izstrādātas arī rekomendācijas olnīcu vēža simptomu indeksa, malignitātes riska indeksa un jaunizveidotā olnīcu vēža diagnostikas algoritma izmantošanai klīniskajā praksē.
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    Cells and Cytokines in Milk of Subclinically Infected Bovine Mammary Glands after the Use of Immunomodulatory Composition GLP 810
    (2020-03-10) Gulbe, Gundega; Pilmane, Māra; Saulīte, Vaira; Doniņa, Simona; Jermolajevs, Jevgenijs; Peškova, Lilija; Valdovska, Anda
    The aim of this study was to investigate the effect of intramammary infusions of natural composition GLP 810 with immunomodulating properties on the local nonspecific cellular and humoral immune response in cows with subclinical mastitis. The composition GLP 810 consists of lactic acid, lysozyme, glycopeptides, and 0.9% solution of NaCl. The following parameters were studied: (1) leukocyte differential distribution in milk, (2) expression of cytokines in milk leukocytes, (3) antibacterial activity, and (4) milk quality. Nineteen mammary glands in five lactating cows were infused with 10 mL of GLP 810, and nineteen other glands from five control cows were treated with 10 mL 0.9% NaCl. The results showed that after intramammary administration of the composition GLP 810 three times with 48 h intervals, the following effects on leukocyte populations in milk were observed: (1) an increase in the number of polymorphonuclear leukocytes and lymphocytes and (2) a decrease in the number of macrophages. A reduction in the number of pathogenic bacteria was also detected. The analyses of tumour necrosis factor-alpha, interleukin-10, and beta-defensin-2 revealed that the production of the aforementioned cytokines significantly increased, whereas no significant effects on interleukin-1 and caspase-6 expression in milk leukocytes were recorded. However, there were significant differences between mammary glands with high and low milk somatic cell count. The results suggest that the composition GLP 810 has an immunomodulatory effect on mammary glands and it could be used for improving the immune response in cows with subclinical mastitis during lactation.
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    Cells and Cytokines in Milk of Subclinically Infected Bovine Mammary Glands after the Use of Immunomodulatory Composition GLP 810
    (2020-03-10) Gulbe, Gundega; Pilmane, Māra; Saulīte, Vaira; Doniņa, Simona; Jermolajevs, Jevgenijs; Peškova, Lilija; Valdovska, Anda; Institute of Microbiology and Virology; Institute of Anatomy and Anthropology; Faculty of Medicine
    The aim of this study was to investigate the effect of intramammary infusions of natural composition GLP 810 with immunomodulating properties on the local nonspecific cellular and humoral immune response in cows with subclinical mastitis. The composition GLP 810 consists of lactic acid, lysozyme, glycopeptides, and 0.9% solution of NaCl. The following parameters were studied: (1) leukocyte differential distribution in milk, (2) expression of cytokines in milk leukocytes, (3) antibacterial activity, and (4) milk quality. Nineteen mammary glands in five lactating cows were infused with 10 mL of GLP 810, and nineteen other glands from five control cows were treated with 10 mL 0.9% NaCl. The results showed that after intramammary administration of the composition GLP 810 three times with 48 h intervals, the following effects on leukocyte populations in milk were observed: (1) an increase in the number of polymorphonuclear leukocytes and lymphocytes and (2) a decrease in the number of macrophages. A reduction in the number of pathogenic bacteria was also detected. The analyses of tumour necrosis factor-alpha, interleukin-10, and beta-defensin-2 revealed that the production of the aforementioned cytokines significantly increased, whereas no significant effects on interleukin-1 and caspase-6 expression in milk leukocytes were recorded. However, there were significant differences between mammary glands with high and low milk somatic cell count. The results suggest that the composition GLP 810 has an immunomodulatory effect on mammary glands and it could be used for improving the immune response in cows with subclinical mastitis during lactation.
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    Cellular immunity in human herpes viruses 6 and 7 infected gastrointestinal cancer patients
    (2009) Jaunalksne, Inta; Doniņa, Simona; Čapenko, Svetlana; Čistjakovs, Maksims; Murovska, Modra; Institute of Microbiology and Virology
    CD4+ T lymphocytes appear to be the preferential target for replication of HHV-6 (human herpes virus) as well as HHV-7 viruses in vivo. In addition, CD8+ T cells, monocytes/macrophages, natural killer cells, epithelial, endothelial, neural cells and fibroblasts may be infected. By definition, however, even a tumour designated by pathologists to be early stage may be late stage when considered by the immune system. Certainly, even early stage tumours have evaded immune control, suggesting that they have acquired many immunosuppressive characteristics. The aim of the study was to clarify the influence of beta-herpes viruses on cellular immune response. In 95 gastrointestinal cancer patients we determined the immunocompetent cell level CD3, CD4, CD8, CD19, CD38, CD95, CD25 using laser flow cytofluorimeter and B- herpes viruses HHV-6, HHV-7 presence using a nested polymerase chain reaction method. Our data showed no statistically significant difference in immunocompetent cell level between negative, latent and active HHV-6, HHV-7 infection. Patients with immunocompromised immune status (lymphopenia) had a tendency to decreased CD4+, CD19+ absolute count. It may be suggested that virus-mediated immune response inhibition seems to be similar to cancer mediated, but differences in immune response among the same group of individuals had no influence on the average number of the immunocompetent cells in the group. Therefore, to characterise host-virus-tumour interactions, individual interpretation of each case is needed.
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    Diagnostic Sensitivity and Specificity of Biomarkers in Combination with Ultrasonographic Findings and Clinical Symptoms in Ovarian Cancer. Summary of the Doctoral Thesis
    (Rīga Stradiņš University, 2012) Mačuks, Ronalds; Doniņa, Simona
    Ovarian cancer is the second most common morbidity among gynecological cancers. In the period from 2003 to 2009 in Latvia there were 283-340 ovarian cancer patients diagnosed each year with mortality rates of 58,6-70,7%. Five year survival rate reaches 80% when disease is diagnosed in the early stages, but only 30%, when detected in the late stages. It has been proven that better treatment results can be achieved when ovarian cancer patients are centralised and treated by gynecological oncologists, therefore it is important to establish recommendations for gynecologists and physicians in ovarian tumor differentialdiagnosis. Aim of the study is to develop ovarian cancer detection algorithm with the most sensitive and specific biomarker combination together with clinical symptoms and ultrasonographic findings. In the prospective case-control study 83 patients with ovarian cancer, 77 patients with benigh ovarian tumors and 82 healthy, age-matched women in the control group were involved. Sensitivity and specificity of ovarian cancer symptom index were analyzed separately and in the conjuction with the biomarker concentrations. Also sensitvity and specificity for different methodologies of malignancy risk index calculations and diagnostic accuracy of single biomarkers (apolipoprotein A1, transthyretin, transferrin, beta-2-microglobulin, human epidydimis secretory protein 4 (HE4) and ovarian cancer associated antigen CA125) and their combinations were analyzed. A new diagnostic algorithm for patients with ovarian tumors was developed. Newly established ovarian cancer detection algorithm is more sensitive and specific in comparison to conventional diagnostic tests and has been evaluated in independent patient populations from „Danish Pelvic Mass Project” and Asia Pacific Ovarian cancer biomarker research group study. Recommendations on ovarian cancer symptom index, malignancy risk index and novel ovarian cancer diagnostic algorithm application in clinical practice were developed.
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    Management of a primary malignant melanoma of uterine cervix stage IVA patient with radical surgery and adjuvant oncolytic virus Rigvir(R) therapy: A case report.
    (2020-05-22) Pumpure, Elizabete; Dručka, Eva; Kigitoviča, Dana; Meškauskas, Raimundas; Isajevs, Sergejs; Nemiro, Ineta; Rasa, Agnija; Olmane, Evija; Zablocka, Tatjana; Alberts, Pēteris; Doniņa, Simona
    Primary malignant melanoma of the uterine cervix is a rare disease with poor prognosis and high recurrence rate. We used Rigvir® as adjuvant therapy for a stage IVA patient. Tolerability, overall and progression-free survival are good.
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    Novel Challenges and Opportunities for Anesthesia and Perioperative Care in Microvascular Flap Surgery : A Narrative Review
    (2024-10-18) Ojuva, Aleksi Matias; Rocans, Rihards Peteris; Zariņš, Jānis; Bine, Evita; Mahauri, Insana; Doniņa, Simona; Mamaja, Biruta; Vanags, Indulis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Institute of Microbiology and Virology
    Complex microvascular techniques and in-depth knowledge of blood rheology and microanastomosis function are required for success in microvascular flap surgery. Substantial progress has been achieved in preventing complications, but the rate of flap loss is still significant and can have significant adverse effects on the patient. Flap thrombosis, flap hematoma, and flap loss are the most frequent and severe major surgical complications. Advances in understanding the pathophysiology of different flap complications, the use of preoperative risk assessment and new treatment concepts could improve the perioperative care of microvascular flap surgery patients. Our aim was to outline novel avenues for best practice and provide an outlook for further research of anesthesia and perioperative care concepts in microvascular flap surgery
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    Potential effect of two different anaesthesia techniques on the activation of hhv-6 and hhv-7 infection in relation to changes in total lymphocyte count and peripheral immune cell distribution after prolonged microvascular free flap surgery
    (2014-12-01) Vilks, Arnis; Rasa, Santa; Doniņa, Simona; Murovska, Modra; Mamaja, Biruta; Department of Doctoral Studies; Institute of Microbiology and Virology; Department of Anaesthesiology, Intensive Care and Clinical simulations
    Microvascular free flap surgery is a complex method of wound closure for large wounds. Tissue trauma, surgical stress and general anaesthesia are known immunosuppressors that may exacerbate postoperative infections. Beta-herpesviruses HHV-6 and HHV-7 are immunomodulating viruses highly prevalent in the population of healthy individuals, which can interfere with the function of the host immune system. These viruses can be reactivated in immunosuppressed conditions. The aim of this study was to monitor the potential effects of two different anaesthesia techniques - general anaesthesia (GA) and regional anaesthesia (RA) - on the activation of HHV-6 and HHV-7 infection in relation to changes in the total lymphocyte count and peripheral immune cell distribution after microvascular free flap surgery. We found significant increase in the frequency of active HHV-7 infection after surgery (p < 0.05) in the GA group. In the RA group changes were not significant. The activation of HHV-7 infection was associated with decrease in the total lymphocyte count post-operatively in patients from the GA group. The data of our study show that reconstructive flap surgery under GA is linked with more frequent postoperative lymphopenia, which is a potential post-operative immunosuppressor that probably triggers the activation of HHV-6 and HHV-7 infection.
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    Seruma šķīstošā interleikīna 2 receptora alfa (sIL-R2α) un CA-125 kombinētais tests olnīcu vēža diagnostikai
    (2011-01-01) Mačuks, Ronalds; Baidekalna, Ieva; Nuķe, Inta; Doniņa, Simona; Rīga Stradiņš University; Institute of Microbiology and Virology
    Detection of ovarian cancer can be improved using a combined diagnostic test consisting of Ca-125 and serum interleukine-2 receptor alpha (sIL-R2α) at a particular threshold. The objective of the study was to evaluate the accuracy of a diagnostic marker assay that combined Ca-125 and serum interleukine-2 receptor alpha. A case-control study of 38 patients with ovarian cancer, 40 patients with benign ovarian diseases and 31 age-matched healthy controls was designed. Ca-125 and sIL-2Rα were detected in patients' serum by standardized chemiluminescent immunometric assays. For Ca-125, a standard cutoff level of 21 U/ml was applied and for sIL-R2α - two cutoff levels were calculated from women included in the control group - one as a mean concentration and the other as an upper limit of a 95% confidence interval. Mean serum concentrations among ovarian cancer patients for CA125 and sIL-2Rα were 265.9 ± 40.2 U/ml and 651.0 ± 50.5 U/ml, respectively. The upper limit of the 95% confidence interval for a healthy control group of women was 304.5 U/ml for sIL-2Rα. Sensitivity and specificity of 89.4% and 85.9% was achieved when CA125 was combined together with sIL-2Rα at a threshold of 304.5U/ml with the condition that both markers are elevated. Sensitivity and specificity of 92.5% and 88.4% was observed when both biomarkers were applied to menopausal women. Serum sIL-2Rα in combination with CA125 can be used as a differential diagnostic test for ovarian cancer at a specific threshold, especially among menopausal women.
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    Stage IIA Skin Melanoma Treatment With ECHO-7 Oncolytic Virus Rigvir
    (2022-09-14) Čēma, Ingrīda; Kleina, Regīna; Doniņa, Simona; Isajevs, Sergejs; Zablocka, Tatjana; Rasa, Agnija; Alberts, Pēteris; Rīga Stradiņš University; Faculty of Medicine; Institute of Microbiology and Virology
    Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma recommend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a brown spot on the right cheek, surgery was indicated because the mass had started to ulcerate. Rigvir virotherapy was applied both before and after surgery. Observations made more than 7 years after surgery indicated no signs of disease progression. This case report illustrates an early treatment approach. Neoadjuvant treatment for early-stage melanoma is gaining more interest in both scientific and medical communities; therefore, the authors believe it is relevant to share their observations.
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    Urinary concentrations of human epidydimis secretory protein 4 (He4) in the diagnosis of ovarian cancer : A case-control study
    (2012) Macuks, Ronalds; Baidekalna, Ieva; Doniņa, Simona; Institute of Microbiology and Virology
    Objective: To analyze differential diagnostic accuracy of urinary human epidydimis secretory protein 4 (HE4)in patients with ovarian tumors. Materials and methods: In the case-control study 23 patients with ovarian cancer, 37 patients with benign ovarian tumors and 18 women in the control group were included. Serum CA125 values and urinary concentrations of HE4were assessed quantitatively. Urinary creatinine concentrations and glomerular filtration rate were also determined and used to calculate ratios to HE4. Results: Higher urinary HE4 concentrations were observed in patients with late stage ovarian cancer (p=0.001) and also in patients with early stage ovarian cancer when compared to patients with benign ovarian tumors (p=0.044). On analysis where all ovarian cancer patients were included, higher diagnostic accuracy was observed with calculated ratio of HE4 to glomerular filtration rate (GFR) to unchanged urinary HE4 concentrations -AUC 0.861 vs. 0.858. When discriminatory accuracy was calculated for urinary HE4/GFR ratio and unchanged urinary HE4 concentrations, the last demonstrated a higher area under the curve - 0.701 vs. 0.602. The urinary HE4/creatinine ratio had lower discriminatory characteristics than unchanged concentrations of urinary HE4. However, HE4 serum concentration was more accurate for discrimination of patients with benign and malignant ovarian tumors when compared to urinary HE4 and CA125 in sera (AUCs were 0.868 for serum HE4 and 0.856 and 0.653 for urinary HE4 and CA125, respectively). Conclusions: Ovarian cancer patients have higher urinary concentrations of human epidydimis secretory protein 4 than patients with benign ovarian tumors. Urinary HE4 has comparable discriminatory accuracy with serum HE4 for benign and malignant ovarian tumors and can be recommended as a non-invasive ovarian cancer riskassessment method.