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    RESEARCH ON THE INFLUENCE OF DIFFERENT TYPES OF ANION-EXCHANGE CARTRIDGES ON THE QUALITY OF [18F]NAF RADIOPHARMACEUTICAL AS PART OF PRODUCTION PROCESS DEVELOPMENT
    (Institute of Knowledge Management (Publications), 2022-09-30)
    Atanasova Lazareva, Marija
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    Janevikj Ivanovska, Emilija
    [18F]Sodium Fluoride radiopharmaceutical is a sterile solution for intravenous administration, intended for skeletal visualization by positron emission tomography (PET). [18F]Sodium Fluoride for bone imaging was introduced in early 1960's, but with the increased availability of PET scanners in the last two decades, this radiopharmaceutical has growing use in clinical practice for the detection of bone metastases. The production process of [18F] NaF includes production of the radioisotope [18F]F- and purification and formulation of the [18F]NaF radiopharmaceutical. The radioisotope [18F]F- is produced by a cyclotron via the 18O(p,n)18F nuclear reaction, followed by recovery of [18F]F- from [18O] proton-irradiated water by adsorption and desorption from anion exchange resins. The fluoride anions are trapped on the anion-exchange SPE (solid-phase extraction) cartridge, and all other cationic and water-soluble radionuclide impurities present in irradiated enriched water are collected in the waste vial. Next step is desorption of the fluoride anions from the cartridge by elution with saline solution (0.9%NaCl). This study aimed to define the most appropriate type of anion-exchange SPE cartridge which could be used for routine production [18F]Sodium fluoride radiopharmaceutical which meets the quality requirements defined in European pharmacopeia monograph. For that purpose, as part of development of in-house production method, manual productions with four different types of anion-exchange cartridges were performed. The influence of sorbent substrate and counter-ion of the cartridge on the final yield and the quality of the produced radiopharmaceutical was investigated. The study also aimed to define the minimum volume of physiological solution required for the pH parameter to be within limits. The results have shown that the quality parameters: appearance, chemical purity, radiochemical purity and radionuclide purity were in defined acceptance criteria and did not differ when using different anion-exchange cartridges. The pH analyses have demonstrated that the type of cartridge and counter-ion influence the final pH of[18F]NaF solution. This study confirmed that the three types of anion-exchange resins (QMA-Cl-, QMA-CO32- and PS-OH-) could be used for production. In the experiments where QMA-Cl- was used, the required pH level was obtained even without dilution. The other cartridges could be used in the [18F] NaF production process, but further dilution is necessary in order to obtain the pH value in acceptance criteria. On the basis of this study, the QMA-Cl- is chosen as a cartridge to be used in the further development of the in-house method for [18F] NaF radiopharmaceutical production.
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    Schoolchildren thyroid volume in North Macedonia: data from a national survey in an iodine-sufficient country
    (Springer Science and Business Media LLC, 2020-02-04)
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    Ittermann, T
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    North Macedonia is historically iodine deficient, but due to the longstanding and effective preventive measures, it has been considered iodine replete since 2003. The aim of the recent national survey was to re-evaluate iodine status and to measure thyroid volume (TVol) by ultrasound in schoolchildren as a representative of the general population.
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    THYROID FUNCTION TESTS DURING PREGNANCY: THE IMPORTANCE OF REFERENCE RANGE ESTABLISHMENT
    (Balkan Clinical Laboratory Federation, 2018-10)
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    Insulin, insulin resistance and antropometric parameters in overweight and obese women
    (Macedonian Association of Anatomists and Morphologists, 2013)
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    Item type:Publication,
    Perspectives from the Balkans
    (IOP Publishing, 2022-06)
    Ziberi, Bashkim
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    Nafezi, Gazmend
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    Ismaeli, Ilir
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    Manxhuka-Këliu, Suzana
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    Relationship of circulating adiponectin levels to subcutaneous and visceral fat tissue in overweight obese women
    (Macedonian association of physiologists and anthropologists, 2012)
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    Novel Ret Mutations in Macedonian Patients with Medullary Thyroid Carcinoma: Genotype-Phenotype Correlations
    (Walter de Gruyter GmbH / MANU, 2015-05-01)
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    Bogoeva, Biljana
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    Medullary thyroid carcinomas (MTCs) are rare neoplasms comprising 2-10% of all thyroid malignnancies. More than 75% are sporadic tumors and the remainder is familial and MEN2 related. Both sporadic and syndromic MTCs frequently show mutations in the RET proto-oncogene. It has been noted that some MTC cases present an indolent, and some an aggressive clinical course. Ki-67 expression is generally low, with documented exceptions, whereas high expression of Bcl-2 has been reported in majority of the cases. Some studies have shown that Ki-67 and Bcl-2 expressions have prognostic value, as well as RET mutational status. We analyzed 20 unrelated MTC cases for Ki-67, Bcl-2 expression and RET mutations and tested their intercorrelations, correlations to the morphologic features and stage of the tumors, as well as their influence on survival. In 13 of the 20 analyzed cases we found 23 sequence changes distributed in exons 8, 10-13 and 16. There were 11 different missense mutations, single nucleotide deletion with frameshift, and 8 different synonymous mutations. Only 4 of the sequence changes have been previously published. Twelve patients (60%) had tumors expressing one or more missense mutations or single nucleotide deletion and 7 of them (35%) had at least one damaging or possibly damaging RET mutation. Most of the tumors had low Ki-67 expression (mean 6.48% of cells) and high Bcl-2 expression (mean 68.3%). Significantly better survival was observed in cases with low Ki-67 (< 6.5%; p < 0.05), high Bcl-2 expression (> 68.3%; p < 0.01) and younger age at diagnosis (< 51 years; p < 0.05).
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    ADRENAL GLAND TLR EXPRESSION IN ApoE DEFICIENT HOMOZYGOUS (ApoE KO-/-) MICE WITH IMPAIRED THYROID FUNCTION
    (Macedonian Association of Anatomists and Morphologists, 2023-12)
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    Josifovska, Slavica
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    The main aim of our study was to investigate the expression of TLR receptors in the adrenal gland of ApoE knockout mice in context of ApoE deficiency as well as impaired thyroid function (hypo- and hyperthyroidism). The study was conducted on two following experimental animal groups: hypothyroid homozygous mice (ApoE KO-/-) treated with PTU; hyperthyroid homozygous mice (ApoE KO-/-) treated with L-thyroxine (T4) and two control groups: euthyroid homozygous mice (ApoE KO-/-) and euthyroid wild-type C57BL/6 mice (Bb). Determination of TLR gene expression in the adrenal gland was performed by RT-PCR reaction with semi-quantitative detection of populations of mRNA molecules transcribed from the TLR2, TLR4 and TLR9 genes in the adrenal gland in the treated experimental groups and the two untreated control groups. The results of our study are in support of the hypothesis that both conditions of impaired thyroid function produce TLR agonists that increase the expression of TLR in the adrenal gland (p<0,05). Also, in the untreated/control group of mice (ApoE KO-/-), an increased expression of TLR was found compared to the wild strain C57BL/6 mice (Bb) as a control group (p<0.001).
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    Skeletal metastasis detection with 99mTc-MDP bone scan and 18-F-FDG PET/CT scan in breast cancer patients
    (Springer Science and Business Media LLC, 2021)
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    Besliev S.
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    Bozinovska N.
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    Aim/Introduction: Breast cancer is the most commonly- diagnosed cancer worldwide in females. Skeleton is the most common site of metastasis spread (for breast cancer). Bone scan (BS) is a widely used, non-invasive nuclear medicine diagnostic tool for detecting bone metastasis (BM) in the early phase of the disease as well as after therapy. Although hybrid PET/CT imaging are more considered for staging and restaging the disease as well as evaluating treatment response, BS is still keeping its position as a highly sensitive method in detecting bone metastasis. The aim of our study was to compare the findings of bone scan and FDG-PET/ CT scan for detection of BM in breast cancer patients at initial staging of the disease. Materials and Methods: We retrospectively analyzed 25 patients with breast cancer who underwent both BS and PET/CT scan for detecting BM in the period 2019-2020. Whole body BS was performed 3 hours after iv injection of 740 MBq 99mTc-MDP. PET/CT was performed after 60 minutes of iv injection of 18F-FDG in accordance with standard protocols. Results: 25 patients were included in the study (age 53,56±11,55 years). BM affected both axial and appendicular skeleton in (n=7, 38,88%), axial skeleton only was affected in 8pts, while appendicular only in (n=4, 22,2%). Solitary metastases were detected in 5 pts, 3pts had 2 BM, 10pts had three or more BM. From all 25 patients, 7 pts (41,17%) had negative findings for BM with both methods, while 18 patients had positive findings with both methods. Among these positive findings, 10 patients (n=10/18; 55,55%) had identical metastatic bone foci detected with both methods. On the other hand, PET/CT scan revealed more foci of bone metastasis than BS in (n=7/18 patients; 38,88%), depicting BM in scapula, spine, sternum and iliac bones in different patients, that were not seen on bone scan. Bone scan presented more BM foci in only (n=2/18 patients; 11,1%). Patients with normal findings on BS did not reveal BM on PET/ CT scan which means there is a good correlation regarding false negative findings with both methods. Conclusion: BS and 18F-FDG-PET/CT are complementary modalities that are highly sensitive in evaluating BM in breast cancer patients. Hybrid imaging (SPECT/CT and PET/CT) because of the complementary value of CT may contribute to the diagnosis of BM. Bone scan is widely used, low cost, easy to perform diagnostic modality and remains the method of choice for detection of bone metastasis.
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    Thyroid cancer detection rate and associated risk factors in patients with thyroid nodules classified as Bethesda category III
    (Walter de Gruyter GmbH, 2018)
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    Background Ultrasound guided fine-needle aspiration (FNA) is a standard procedure for thyroid nodules management and selecting patients for surgical treatment. Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), as stated by The Bethesda System for Reporting Thyroid Cytopathology, is a diagnostic category with an implied malignancy risk of 5-15%. The aim of our study was to review cytology and histopathology reports, as well as clinical and ultrasound data, for thyroid nodules reported as AUS/FLUS, in order to evaluate the malignancy rate and to assess factors associated with malignant outcome. Patients and methods A total of 112 AUS/FLUS thyroid nodules in 105 patients were evaluated, of which 85 (75.9%) were referred to surgery, 21 (18.8%) were followed-up by repeat FNA and 6 nodules (5.3%) were clinically observed. Each was categorized in two final diagnostic groups - benign or malignant, which were further compared to clinical data of patients and ultrasonographic features of the nodules. Results Final diagnosis of malignancy was reached in 35 cases (31.2%) and 77 (68.8%) had benign lesions. The most frequent type of cancer was papillary thyroid carcinoma (PTC) - 58.1% PTC and 25.8% had follicular variant of PTC. Patients' younger age, smaller nodule size, hypoechoic nodule and presence of calcifications were shown to be statistically significant risk factors for malignancy. Conclusions The rate of malignancy for the AUS/FLUS diagnostic category in our study was higher than estimated by the Bethesda System. Clinical and ultrasound factors should be considered when decision for patient treatment is being made.