A5040183274- Lung Cancer Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Antibiotics Pharmacokinetics and Efficacy
- Cancer Immunotherapy and Biomarkers
- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Neutropenia and Cancer Infections
- Cancer Genomics and Diagnostics
- Sepsis Diagnosis and Treatment
- Myasthenia Gravis and Thymoma
- Neonatal Health and Biochemistry
- Acute Lymphoblastic Leukemia research
- Hemoglobinopathies and Related Disorders
- Neonatal and Maternal Infections
- Heart Failure Treatment and Management
- Gastric Cancer Management and Outcomes
- Pneumonia and Respiratory Infections
- Pharmaceutical Practices and Patient Outcomes
- Pharmacogenetics and Drug Metabolism
- Palliative Care and End-of-Life Issues
- Radiomics and Machine Learning in Medical Imaging
- Pharmaceutical studies and practices
- Colorectal and Anal Carcinomas
- Cancer survivorship and care
- Antimicrobial Resistance in Staphylococcus
North Estonia Medical Centre
2016-2024
Tartu University Hospital
2012-2021
University of Tartu
1999-2015
Institute of Pharmacology
2007
Humboldt-Universität zu Berlin
2002-2003
Charité - Universitätsmedizin Berlin
2002-2003
Humboldt State University
2003
Aims A noncoding single nucleotide polymorphism (SNP) in exon 26 3435C > T of the highly polymorphic MDR1 gene has been demonstrated to alter digoxin absorption after induction product P‐glycoprotein by rifampicin or multiple oral dosing. The aim study was investigate effects major known SNPs on a dose large sample without drug pretreatment. Methods Fifty healthy white male subjects between age 18 and 40 years were enrolled. Following an overnight fast, all received 1 mg digoxin. Venous...
Abstract Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guidance. We present data from cohort thoracic tumors. Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin-embedded (FFPE) plasma samples. EORTC board (MTB) advised...
The standard definition of 'rare cancer' is a malignant disorder with an incidence <6 per 100 000 year according to the Surveillance Rare Cancers in Europe (RARECARE), wide variety for different rare cancers.
Our objective was to describe the pharmacokinetics of meropenem in peritoneal fluid (PF) six patients with severe peritonitis and septic shock relate measured concentrations minimum inhibitory concentration bacteria. Microdialysis catheters were placed into space during surgery. Meropenem plasma PF analyzed using compartmental modeling. areas under concentration–time curve lower than (average ratio, 73.8±15%) because degradation confirmed ex vivo. Compartment modeling elimination from a...
Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but not tested neonates. We compared the steady-state pharmacokinetics (PK) given as a short (30-min) or prolonged (4-h) to very-low-birth-weight (gestational age, <32 weeks; birth weight, <1,200 g) neonates define appropriate dosing regimen for phase 3 efficacy study. Short (n = 9) 10) infusions were at dose 20 mg/kg every 12 h. Immediately before and 0.5, 1.5, 4, 8, h after 4th 7th doses...
Abstract P‐glycoprotein (Pgp) is a member of the ABC‐transporter family, and in humans, encoded by MDR1 gene. Recently, several single‐nucleotide polymorphisms gene were identified. The aim present study was to evaluate effect genetic G2677T C3435T on Pgp activity CD56 + CD4 peripheral blood cells. Using flow cytometry, rhodamine 123 (Rh123) efflux determined 46 male healthy volunteers. Median Rh123 fluorescence control sample, after baseline dye uptake, set as 100%. samples, exposed...
Despite differences in types of infection and causative organisms, pharmacokinetic-pharmacodynamic (PKPD) targets vancomycin therapy derived from adult studies are suggested for neonates. We aimed to identify doses needed the attainment AUC/MIC > 400 300 neonates with sepsis correlate these recommended treatment outcome. Neonates who had Vancomycin therapeutic drug monitoring (TDM) performed between January 1, 2010 December 31, 2012 were studied. Clinical characteristics, episodes...
8512 Background: At the second interim analysis (IA2) of triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), pembrolizumab significantly improved DFS compared with placebo in patients (pts) completely resected stage IB (T ≥4 cm) to IIIA NSCLC per AJCC v7, regardless PD-L1 expression (N = 1177, HR 0.76, 95% CI 0.63-0.91, P 0.0014). We present subgroups related surgery, disease burden, and adjuvant chemotherapy use. Methods: Pts had pathologically confirmed, any ECOG PS 0-1....
8520 Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), at second interim analysis, pembrolizumab (pembro) significantly prolonged DFS vs placebo (pbo) in overall population of patients (pts) with completely resected stage IB–IIIA NSCLC per AJCC v7 who may or not have received adjuvant chemotherapy (chemo; up to 4 cycles) as recommended local guidelines (n = 1177; HR, 0.76 [95% CI, 0.63–0.91]; P 0.0014). Here we present outcomes for those pts 1–4...
Abstract Background P‐glycoprotein is a transmembrane efflux pump that extrudes wide variety of drugs, thereby reducing their intracellular access. In humans, encoded by the MDR1 gene. Recently, several single nucleotide polymorphisms in gene were identified. Moreover, it was postulated that, addition to full‐length P‐glycoprotein, ‘mini’ also present lymphocytes. Materials and methods We investigated effect genetic G2677T C3435T on mRNA expression FACS‐sorted peripheral blood CD4 + , CD8...
At second interim analysis (IA2) of the phase 3 PEARLS/KEYNOTE-091 study completely resected stage IB–IIIA NSCLC per AJCC v7 (NCT02504372), pembrolizumab (pembro) as adjuvant therapy significantly improved DFS vs placebo (pbo) in ITT population (HR, 0.76; 95% CI, 0.63–0.91; P = 0.0014); significance was not achieved PD-L1 TPS ≥50% (0.82; 0.57–1.18; 0.14). We report results from IA3, final analysis. Eligible pts aged ≥18 y with IB (T ≥4 cm), II, or IIIA (AJCC v7), ECOG PS 0 1, and tumor...
Abstract: Objectives: ATP‐binding cassette (ABC) transporters extrude a wide variety of endogenous and exogenous compounds. In cancer cells, they are known to confer multidrug resistance. The aim the present study was determine expression resistance‐associated protein 1 (MRP1) 2 (MRP2), which members subfamily C ABC family, in human hematopoietic cells. Methods: CD4 + , CD8 CD19 CD56 cells were isolated from whole blood by FACS‐sort 20 healthy volunteers. MRP1 MRP2 mRNA levels quantified...
ABSTRACT Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described extremely preterm neonates but poorly late-preterm and term neonates. Thus, evidence-based dosing recommendations lacking. We describe the PK in with a gestational age (GA) ≥32 weeks postnatal <72 h. Penicillin was administered intravenously at dose 25,000 or 50,000 IU/kg body weight every 12 h (q12h). At steady state, blood samples...
Thiopurine <i>S</i>-methyltransferase (TPMT) is a biotransformation phase II enzyme responsible for the metabolic inactivation of thiopurine drugs. The present study was carried out to investigate inhibitory potential 15 nonsteroidal anti-inflammatory drugs (NSAIDs) on human TPMT activity in vitro. measured pooled erythrocytes absence and presence various NSAIDs using previously published high-performance liquid chromatography-UV method. To determine inhibition type <i>K</i><sub>i</sub>...
Background: Lung cancer (LC) remains the most frequent cause of death worldwide. We aimed to examine long-term trends in LC survival Estonia by age, gender, histologic type and stage, with specific focus on surgical treatment.Material methods: Data all incident cases diagnosed from 1996 2016 were obtained Estonian Cancer Registry. Logistic regression was used receipt treatment localized LC. Relative ratios (RSR) calculated, excess hazard (EHR) estimated stage histology period diagnosis as...
Background The purpose of the study was to evaluate pharmacokinetics ( PK ) and pharmacodynamics PD piperacillin tazobactam during high‐volume haemodiafiltration HVHDF ). Methods A single dose piperacillin/tazobactam (4/0.5 g) administered as 30 minute infusion 10 patients with acute kidney injury due septic shock. Arterial blood samples were collected before at or 60 min intervals over 8 h (12 samples) after drug administration. Concentrations determined by HPLC ‐ MS / . R software used for...
Data on the pharmacokinetics (PKs) of penicillin G (PEN) in neonates date back to 1970s and do not include data for very-low-birth-weight (VLBW) neonates. The aim this study was describe steady-state PKs establish an optimal regimen dosing PEN with gestational ages less than 28 weeks birth weights 1,200 g. Two regimens were studied: 50,000 IU (30 mg)/kg body weight every 12 h (q12h) (group 1; n = 9) 25,000 (15 q12h 2; 9). Samples PK analysis drawn before injection at 2 30 min 1.5, 4, 8,...
Background : Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme involved in the metabolism of thiopurine drugs. To date, at least 25 single nucleotide polymorphisms have been reported TPMT gene, 23 these are associated with reduced activity. Methods The aim present study was to sequence whole coding region (exons 3–10) identify known and novel variants amongst healthy Estonians. Erythrocyte activity also measured carry out genotype-phenotype comparison. Results A total 21 subjects...
33-70% of lung cancer (LC) patients develop recurrence after radical treatment. Previous studies have shown the importance clinical-pathological characteristics for risk recurrence. The role molecular mechanisms remains unclear. aim was analyzing genomic features in LC with local (LR) versus distant (DR) to predict and type recurrence.Patients previously curatively treated recurrences from 2015 2017 were retrospectively enrolled. Histological specimens collected at time diagnosis sent whole...