Macroprolactinaemia is a well-known analytical problem in diagnostics of hyperprolactinaemia usually detected with polyethylene glycol (PEG) precipitation method. Since there is no harmonization in ...macroprolactin detection and reporting results, this study proposes and evaluates the usefulness of in-house developed algorithm. The aims were to determine the most suitable way of reporting results after PEG treatment and the possibilities of rationalizing the precipitation procedure.
This is a retrospective study based on extracted data for 1136 patients. Prolactin concentrations were measured before and after PEG precipitation on Roche cobas e601. Macroprolactinaemia was defined by percentage recovery and post-PEG prolactin concentrations.
Prevalence of macroprolactinaemia using recovery criteria of ≤ 40%, ≤ 60%, and post-PEG prolactin concentrations was 3.3%, 8.8% and 7.8%, respectively. Raising the cut-off value from the upper limit of the manufacturer's reference interval to 32.9 µg/L does not drastically change detected macroprolactinaemia with recovery criteria. Post-PEG prolactin concentrations showed more than half of the patients with macroprolactinaemia would be overlooked. Regardless of the criteria, a cut-off of 47.0 µg/L would miss most of the macroprolactinaemic patients. Repeated recovery measurements of follow-up patients showed there is a significant difference with mean absolute bias of 9%.
Post-PEG prolactin concentration with corresponding reference interval is the most suitable way of reporting results. All samples with prolactin concentration above the upper limit of the manufacturer's reference interval should be submitted to PEG precipitation. Follow-up period could be prolonged since the difference between the recoveries of repeated measurements is not clinically significant.
Immunoassays are the most common method in routine practice for measuring androgens in women. Study's aim was to establish new population specific indirect reference intervals (RI) for ...dehydroepiandrostenedione sulphate (DHEAS) and for new androstenedione test available on automated Roche Cobas electrochemiluminescent immunoassay method.
From extracted laboratory records, testosterone, sex hormone binding globulin and follicle-stimulating hormone were used as reference tests to exclude possibly diseased women. After the data selection steps, the study included 3500 subjects for DHEAS and 520 for androstenedione aged 20-45 years. To evaluate the need for age partitioning, we calculated standard deviation ratio and bias ratio. For each hormone, 90% and 95% RIs were calculated with appropriate statistical method.
Total age group (20-45 years) 95% RIs were: 2.77-11.50 µmol/L for DHEAS and 2.48-8.89 nmol/L for androstenedione. Age-stratified 95% RIs for DHEAS were: 3.65-12.76 µmol/L (20-25 years); 2.97-11.50 µmol/L (25-35 years) and 2.30-9.83 µmol/L (35-45 years). Age-stratified 95% RIs for androstenedione were: 3.02-9.43 nmol/L (20-30 years) and 2.23-7.75 nmol/L (30-45 years).
New RIs for DHEAS were slightly wider for age group 20-25 and 35-45, while the differences in the age group 25-35 years were more pronounced. Androstenedione RI showed significantly higher concentrations than the manufacturer's. Age-related decrease of androgens should be considered when calculating RIs. We propose population specific, age-stratified RIs for DHEAS and androstenedione on electrochemiluminescent method, which should improve test interpretation in women of reproductive age.
IntroductionLaboratory plays important part in screening, diagnosis, and management of thyroid disorders. The aim of this study was to estimate current laboratory preanalytical, analytical and ...postanalytical practices and policies in Croatia.
Materials and methodsWorking Group for Laboratory Endocrinology of the Croatian Society of Medical Biochemistry and Laboratory Medicine designed a questionnaire with 27 questions and statements regarding practices and protocols in measuring thyroid function tests. The survey was sent to 111 medical biochemistry laboratories participating in external quality assurance scheme for thyroid hormones organized by Croatian Centre for Quality Assessment in Laboratory Medicine. Data is presented as absolute numbers and proportions.
ResultsFifty-three participants returned the questionnaire. Response rate varied depending on question, yielding a total survey response rate of 46-48%. All respondents perform thyroid stimulating hormone (TSH). From all other thyroid tests, most performed is free thyroxine (37/53) and least TSH-stimulating immunoglobulin (1/53). Laboratories are using nine different immunoassay methods. One tenth of laboratories is verifying manufacturer’s declared limit of quantification for TSH and one third is verifying implemented reference intervals for all performed tests. Most of laboratories (91%) adopt the manufacturer’s reference interval for adult population. Reference intervals for TSH are reported with different percentiles (90, 95 or 99 percentiles).
ConclusionThis survey showed current practices and policies in Croatian laboratories regarding thyroid testing. The results identified some critical spots and will serve as a foundation in creating national guidelines in order to harmonize laboratory procedures in thyroid testing in Croatia.
Long-term infection with high-risk human papillomavirus (HPV) is a major contributing factor in the development of premalignant and malignant cervical lesions. Effective disease prevention and ...control requires knowledge of the epidemiological characteristics of population, implementation of screening method, and detection of the disease at the early or at pre-stage of invasive disease. Screening methods include cytological methods – Pap smear, microbiological testing, HPV testing, HPV genotyping, and colposcopy. The use of new diagnostic tests necessitates a re-evaluation of all methods at all levels of screening or diagnosis. By comparing the guidelines of various professional societies for the screening and diagnosis of premalignant and malignant cervical lesions, colposcopy is a method that indicates further direction. The aim of this paper is to evaluate the importance and the role of colposcopy in diagnosis of premalignant and malignant changes of the cervix, in synergy with other diagnostic methods.
Dugotrajna infekcija visokorizičnim tipovima humanog papiloma virusa (HPV-a) glavni je čimbenik nastajanja premalignih i malignih lezija vrata maternice. Učinkovita prevencija i kontrola bolesti ...zahtijeva poznavanje epidemioloških karakteristika populacije, provođenje metoda probira te otkrivanja bolesti u što ranijem stadiju odnosno predstadiju invazivne bolesti. Dijagnostičke metode koje se koriste u cilju probira uključuju citološke metode – PAPA test, mikrobiološka testiranja, HPV testiranje, HPV genotipizaciju i kolposkopiju. Korištenje novih dijagnostičkih testova zahtijeva preispitivanje uloge svih razina probira odnosno dijagnosticiranja. Usporedom smjernica različitih stručnih društava za probir i dijagnosticiranje premalignih i malignih lezija vrata maternice, kolposkopija je metoda koja određuje daljnji smjer. Cilj je ovog rada propitati važnost i ulogu kolposkopije u dijagnostici i praćenju premalignih i malignih promjena vrata maternice u sinergiji s drugim dijagnostičkim metodama.
Evaluation of thyroid function is often requested and therefore defining paediatric reference intervals (RIs) is of vital importance. Currently, there is a distinct lack of paediatric RIs for thyroid ...function tests in Croatia. Thus, we established RIs for thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) in the Croatian paediatric population.
Reference intervals were calculated from 397 apparently healthy children, aged from 2 days to < 19 years. Serum samples were analysed for thyroid function tests on the Abbott Architect i2000. Age- and sex-specific 95% RIs with 90% confidence intervals were established according to Clinical and Laboratory Standards Institute guidelines. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using two-level nested ANOVA. The criterion for considering partitioning reference values was set to SDR > 0.3.
All thyroid function tests required age partitioning, confirmed by SDR above 0.3. There was no need for sex partitioning, confirmed by SDR below 0.3. Still, FT3 was partitioned due to visually noticeable sex related difference for the oldest group (12 years to < 19 years).
This is the first study to establish RIs for thyroid function tests in the Croatian paediatric population. We propose RIs for widely used Abbott platform, thus giving laboratories method- and population-specific paediatric RIs for thyroid function tests that should improve clinical test interpretation.
The aim of this study was to screen practices used in verification procedures for methods/analysers among medical biochemistry laboratories (MBLs) in Croatia. We hypothesized that these procedures ...differ widely from laboratory to laboratory and wanted to gather specific data on steps used in the verification workflow.
In order to obtain data, an online survey was conducted. The survey, divided in two sections, contained 29 questions and statements addressing general characteristics and specific steps of the verification workflow of each individual MBL. The survey was disseminated among managers of all MBLs in Croatia.
A total of 108/196 (55%) laboratories participated in the survey. Forty nine MBLs were excluded from the second part of the survey: 14 have not implemented verification procedures, and 35 MBLs due to the absence of answers. The most relevant results of the second part of the survey showed that: 18/59 (0.31) of the responding MBLs have difficulties when defining acceptance criteria, 27/59 (0.46) used the Clinical and Laboratory Standards Institute protocol for precision estimation; the majority of MBLs used a median of 20 samples for method/analyser comparisons and estimated bias using internal quality control samples; reference intervals provided by external sources are mainly adopted; 60% of MBLs do not include linearity verification in their protocol and do not use the national document for the estimation of measurement uncertainty.
Heterogeneous verification protocols are routinely utilized across Croatian MBLs which clearly confirms that a national document might help in the harmonization of verification procedures.
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The human histone demethylases of the KDM4 family have been related to diseases such as prostate and breast cancer. Majority of currently known inhibitors suffer from the low ...permeability and low selectivity between the enzyme isoforms. In this study, toxoflavin motif was used to design and synthesize new KDM4C inhibitors with improved biological activity and in vitro ADME properties. Inhibitors displayed good passive cellular permeability and metabolic stability. However, diminishing of redox liability and consequently non-specific influence on cell viability still remains a challenge.
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