Promene biokemijskih parametara u menopauzi

Physiological changes in menopause are the reflection of changes of circulating steroid hormone concentrations. The changes of menstrual cycles occurring just before menopause may be recorded best by higher FHS, normal LH concentrations and slightly increased estradiol level. Cessation of menstruation usually occurs when FSH concentration exceeds 40 IU/L in two separate measurements. In menopause, an altered hormonal status results in metabolic changes of various tissues and organs. Menopause in women carries higher risk of cardiovascular diseases, osteoporosis, thromboembolic disorders, impairments of cognitive functions and autoimmune diseases, etc. Termination of ovarian synthesis of estrogen, on one hand, and increased production of proinflammatory cytokines (TNF, IL-1, IL-6), on the other, provide conditions for inflammatory response which underlies many pathological processes. During and after menopause, lipid status is changed in women, as follows: higher concentrations of cholesterol, triglycerides, apo-B and LDL cholesterol and reduced HDL cholesterol. Bone density becomes lower with aging and depends upon duration of estrogen deficit in women after menopause, what increases the risk of osteoporosis. Menopause is also characterized by prothrombotic effects manifested by higher activity of FVII, FVIII and fibrinogen. The changes of hormone production of hypothalamus-hypophysis-ovarium axis in menopause, and responses of different non-productive somatic and nervous tissue to these respective have been the issue of many investigations.Fiziološke promene u menopauzi odraz su promena u cirkulišućim koncentracijama steroidnih hormona. Promene u menstrualnom ciklusu koje nastaju neposredno pre menopauze najbolje se mogu registrovati kroz povišene koncentracije FSH, normalne vrednosti LH i blago povišeni estradiol. Potpuni gubitak menstrualnog ciklusa obično se dešava kada koncentracija FSH premaši 40 IU/L u dva pojedinačna određivanja. U menopauzi se kao posledica izmenjenog hormonskog statusa dešavaju metaboličke promene u različitim tkivima i organima. Menopauza donosi ženi veći rizik za nastanak kardiovaskularne bolesti, osteoporoze, tromboembolijskih poremećaja, poremećaja kognitivnih funkcija, autoimunih bolesti i dr. Prestanak ovarijalne sinteze estrogena s jedne, a povećana produkcija proinflamatornih citokina (TNF, IL-1, IL-6) sa druge strane stvaraju uslove za razvoj inflamatornog odgovora koji se nalazi u osnovi mnogih patoloških procesa. U menopauzi i posle menopauze žene imaju izmenjen lipidni status: povećane koncentracije holesterola, triglicerida, apo-B i LDL holesterola i smanjen HDL-holesterol. Koštana gustina se smanjuje sa starošću i zavisi od trajanja estrogenskog deficita kod žena posle menopauze što povećava rizik od nastanka osteoporoze. Menopauzu takođe karakterišu protrombotički efekti koji se manifestuju porastom aktivnosti FVII, FVIII i fibrinogena. Promene u produkciji hormona duž hipotalamus-hipofiza-ovarijum ose u menopauzi, i odgovori različitih nereproduktivnih somatskih tkiva i nervnog tkiva na te promene predmet su velikog broja istraživanja

Uncertainty of Measurement in Laboratory Medicine

An adequate assessment of the measurement uncertainty in a laboratory medicine is one of the most important factors for a reliable interpretation of the results. A large number of standards and guidelines indicate the need for a proper assessment of the uncertainty of measurement results in routine laboratory practice. The available documents gene rally recommend participation in the proficiency schemes/external quality control, as well as the internal quality control, in order to primarily verify the quality performance of the method. Although all documents meet the requirements of the International Standard, ISO 15189, the standard itself does not clearly define the method by which the measurement results need to be assessed and there is no harmonization in practice regarding to this. Also, the uncertainty of measurement results is the data relating to the measured result itself, but all factors that influence the interpretation of the measured value, which is ultimately used for diagnosis and monitoring of the patient's treatment, should be taken into account. So in laboratory medicine, an appropriate assessment of the uncertainty of the measurement results should have the ultimate goal of reducing diagnostic uncertainty. However, good professional laboratory practice and understanding analytical aspects of the test for each individual laboratory is necessary to adequately define the uncertainty of measurement results for specific laboratory tests, which helps to implement good clinical practice. Also, setting diagnoses in medicine is a decision with a certain degree of uncertainty, rather than statistically and mathematically calculated conclusion

Immunoglobulin heavy chain gene rearrangements in patients with Gaucher disease

Uvod: Nekoliko studija u literaturi navode dokaze o povećanoj incidenci hematoloških komplikacija u bolesnika sa Gošeovom bolešću, uključujući monoklonsku i poliklonsku gamapatiju i hematološke malignitete, a posebno multipli mijelom. Metode: Određivana je serumska koncentracija imunoglobulina kao i rearanžman gena za teški lanac imunoglobulina - IGH, PCR analizom. Klonalni PCR produkti su direktno sekvencirani i analizirani koristeći adekvatne alate i baze podataka. Monoklonski proteini seruma su detektovani i identifikovani metodom elektroforeze. Rezultati: Među 27 bolesnika, klonalni IGH rearanžman je otkriven kod osmoro, od kojih je petoro imalo i monot klonski protein u serumu. Hipergamaglobulinemija je otkrivena u 9/27 bolesnika. Podaci o praćenju za 17 bolesnika su pokazali da je klonalni rearanžman ostao isti u četiri bolesnika, dok je u jednog bolesnika iščezao tokom perioda praćenja. Preostalih 12/17 bolesnika nisu imali klonalni IGH rearanžman niti su ga stekli nakon perioda praćenja. Zaključak: Iako klonska ekspanzija može da nastane relativno rano u toku Gošeove bolesti, barem sudeći prema rearanžmanu IGH gena, detektovani klonovi mogu biti tranzitorni. Pažljivo kliničko praćenje ovih bolesnika je obavezno, uključujući i nadzor nad limfoidnim neoplazmama, posebno multiplim mijelomom.Background: Several studies support the evidence of increased incidence of hematological complications in Gaucher disease including monoclonal and polyclonal gammopathies and blood malignancies, especially multiple myeloma. Methods: Serum concentrations of immunoglobulins and PCR analysis of the IGH gene rearrangements were performed. The clonal PCR products were directly sequenced and analyzed with the appropriate database and tools. Serum monoclonal proteins were detected and identified by electrophoresis. Results: Among 27 Gaucher patients, clonal IGH rearrangement was discovered in eight, with 5/8 having also serum monoclonal protein. Elevated immunoglobulins were detected in 9/27 patients. Follow-up data for 17 patients showed that the clonal rearrangement remained the same in four of them, however, in one patient it disappeared after the follow-up period. The remaining 12/17 patients were without previous IGH clonal rearrangement and remained so after the follow-up. Conclusions: Although clonal expansion may occur relatively early in the disease course, at least judging by the IGH gene rearrangements in Gaucher patients, the detected clones may be transient. A careful clinical follow-up in these patients is mandatory, including monitoring for lymphoid neoplasms, especially multiple myeloma

Verifying Sarcoidosis Activity: Chitotriosidase Versus ACE in Sarcoidosis - A Case-Control Study

Background: Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme - ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls. Methods: Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (F-18-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis. Results: Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of 82.5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on F-18-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P lt 0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (rho=0.272, P=0.001). Conclusions: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity

Soluble sPD-L1 and serum amyloid A1 as potential biomarkers for lung cancer

Background: The objective of this prospective study was to evaluate whether soluble programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) and serum amyloid A1 (SAA1) are potential diagnostic, predictive or prognostic biomarkers in lung cancer. Methods: Lung cancer patients (n=115) with advanced metastatic disease, 101 with non-small cell lung cancer, NSCLC (77 EGFR wild-type NSCLC patients on chemotherapy, 15 EGFR mutation positive adenocarcinoma patients, 9 patients with mPD-L1 Expression >= 50% NSCLC - responders to immunotherapy), and 14 patients with small cell lung cancer (SCLC) were examined. ELISA method was used to determine sPD-L1 and SAA1 concentrations in patients' plasma. Results: Significantly higher blood concentrations of sPD-L1 and SAA1 were noted in lung cancer patients compared with a healthy control group. In PD-L1 + NSCLC patients, a significantly higher sPD-L1 level was noticed compared to any other lung cancer subgroup, as well as the highest average SAA1 value compared to other subgroups. Conclusions: It seems that sPD-1/PD-L1 might be a potential biomarker, prognostic and/or predictive, particularly in patients treated with immunotherapy. Serum amyloid A1 has potential to act as a good predictor of patients' survival, as well as a biomarker of a more advanced disease, with possibly good capability to predict the course of disease measured at different time points

Laboratorijska dijagnostika hroničnih oštećenja jetre

Chronic liver diseases are conditions that are clinically manifested by duration longer than six months. According to etiological factors, they are classified as follows: infectious (chronic viral hepatitis), toxic (alcoholic hepatitis, drug- and toxin-associated), hereditary metabolic diseases, autoimmune and neoplastic diseases. Pathological changes include: hepatitis, cirrhosis and cholestasis. Diagnosis of these diseases is based on clinical picture, results of medical-biochemical and serological analyses, liver biopsy and other diagnostic methods, such as: ultrasonography, computerized tomography, esophagoduodenoscopy and endoscopic retrograde cholangiopancreatography. Chronic hepatitis is a clinical syndrome of heterogenous etiology, i.e., a group of diseases with necroinflammatory process in the liver, often followed by fibrosis and duration of more than six months. The impairment may progress to cirrhosis and hepatocellular cancer. Etiologically, chronic hepatitis is classified into several groups, such as: viral (hepatitis B and hepatitis C), autoimmune hepatitis (types 1, 2 and 3), autoimmune cholestatic diseases (primary biliary cirrhosis-PBC, and primary sclerosing cholangitis-PSC), drug-associated hepatitis, Wilson's disease, α 1 -antitripsine deficit, primary idiopathic hemochromatosis, cryptogenic hepatitis and non-alcoholic steatohepatitis. For differential diagnosis of these diseases, it is essential that initial evaluation includes the complete history of drug usage, alcohol consumption and ALT, AST, HBsAG and anti-HCV measurements. In persons with increased catalytic ALT activity and negative HBsAg and anti-HCV, it is necessary to determine the auto antibodies, Fe, TIBC and UIBC, ceruloplasmin, and α 1 -antitripsine phenotype. The diagnosis of chronic viral hepatitis requires determination of catalytic activity of ALT and specific serological tests: HBsAG, anti-HBs, HBeAg, anti-HBe, HBV-DNA, anti-HCV and HCV-RNA. Alcoholic liver disease is developed in several phases: from normal liver, through steatosis, alcoholic hepatitis to cirrhosis. In patients with verified history of alcohol consumption, it is necessary to determine the catalytic activity of γ-GT, AST, ALT, MCV and CDT. Determination of CDT and γ-GT is needed for monitoring of therapeutical effects, while liver biopsy is required for definite diagnosis. Cirrhosis is the end-stage of chronic liver diseases, and the most frequent causes are: acute and viral hepatitis, long-term and excessive alcohol consumption, metabolic and biliary diseases, autoimmune hepatitis, effects of drugs, chemical agents, etc. Chronic hepatitis developing to cirrhosis is characterized by two basic processes: necroinflammatory impairment and fibrosis. Necrotic inflammation is characterized by higher De Ritis coefficient with considerably higher activity of γ-GT and LDH. Reduced synthetic function is indicated by: lower ChE activity, decreased albumin concentration with predominant serum gamma-globulin and high IgG and IgA concentrations, lower concentrations of haptoglobin and transferrin as well as longer prothrombin time. Although liver biopsy is considered the method of choice for diagnosis of hepatic cirrhosis, determination of PGA index or Fibro test-Acti test (α 2 - macroglobulin, haptoglobin, γ-GT, total bilirubin, Apo-A I and ALT) is recommended as the alternative to biopsy, which exhibits the highest sensitivity, specificity as well as best predictive value for diagnosis of cirrhosis. HCC is the most common form of malignant liver tumors and may be the result of hepatic cirrhosis due to effects of hepatitis B and C, some toxins, α 1 AT deficit or hemochromatosis. Diagnosis is based on clinical picture, US, CT and MR imaging, liver biopsy and values of tumor markers, primarily: α-fetoprotein, carcinoembryonic antibody, and des-γ-carboxy prothrombin. The changes of biochemical parameters are not specific for tumor, but may serve to substantiate the diagnosis. In patients who are not alcohol consumers, chronic disease similar to alcoholic hepatitis, followed by steatosis, parenchymal inflammation and different forms of fibrosis is defined as non-alcoholic steatohepatitis (NASH). Liver biopsy is crucial for verification of NASH diagnosis. Metabolic liver diseases include: familial hyperbilirubinemia, primary hereditary hemochromatosis, Wilson's diseases, alpha-1-antitripsin deficiency, Reye's syndrome, etc. Diagnostic guidelines for differential diagnosis of familial hyperbilirubinemia are based on measurement of total and direct bilirubin concentrations. Primary hereditary hemochromatosis is an autosomal, recessive disorder where the iron is absorbed in larger quantities and deposited in parenchymal organs. The initial evaluation of hemochromatosis is grounded on verified higher saturation of transferrin (>45%) and unsaturated capacity of iron binding (<28 μmol/L). Genetic analysis is needed for definite diagnosis. Wilson's disease is hereditary disorder of copper metabolism characterized by deposition of toxic copper concentrations in tissues and organs. The most common diagnostic finding is low level of blood ceruloplasmin (< 0.17 g/L), higher concentration of free serum copper (>7 μmol/L), lower concentration of total copper, increased copper excretion via urine (up to 20 μmol/24h) and higher concentration of copper in liver tissue. α 1 AT deficit is an autosomal, recessive disorder with significantly lower α 1 -antitripsin values, giving rise to pulmonary emphysema, chronic liver diseases, cirrhosis and hepatocellular cancer. For making a diagnosis, it is necessary to measure serum α 1 AT concentration, phenotyping and genotyping. Reye's syndrome is a disease defined as acute, non-inflammatory encephalopathy associated with fat degeneration of the liver, with unknown etiology, and followed by general mitochondrial dysfunction. Differential diagnosis is necessary to rule out congenital metabolic defects, and determination of aminotransferases, glucose, PT, ammonia and free fat acids along with liver biopsy are crucial for verification of diagnosis. Autoimmune hepatic diseases include: autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Differential diagnosis involves the following measurements: anti-nuclear At, smooth muscle At, At to hepatic-renal-microsomal Ag, At to soluble-hepatic Ag, anti-mitochondrial At and perinuclear anti-neutrophil-cytoplasmic At, as well as utilization of endoscopic retrograde cholangiopancreatography