bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Markers - Their Nature and Clinical Use
Authors: Theis Manfred 
Published: May 2008

Bone Markers - Their Nature and Clinical UseBone remodeling units are the centerpiece of bone metabolism. They are fueled by a synchronized and well balanced interaction of osteoclasts and osteoblasts, the activity of which releases specific substances known as bone markers into the blood. Resorption markers result from osteoclastic activity, formation markers from osteoblastic activity, and turnover markers from both cell types. In clinical practice, bone markers are today widely used for monitoring of antiresorptive therapy and patient compliance. There is strong evidence that they are also useful for risk assessment with respect to osteoporosis, here complementing established imaging methods. Other possible and partly not yet investigated indications include monitoring of side-effects of certain therapeutic drugs and oncology. In particular the combination of resorption and formation markers may open up a more differentiated insight into the metabolic situation of a patient's bone. The activity of osteoclasts and osteoblasts is triggered and modulated by numerous factors, some of which are of endocrine nature. Easily measurable in today's laboratory are for instance PTH, calcitonin and vitamin D. While calcitonin is not widely used in osteology, PTH and vitamin D define risk factors for an accelerated loss of bone and impaired mineralization of osteoid with the related diseases of osteoporosis, ricketts and osteomalacia. Recent developments in lab diagnosis of bone diseases focus on rheumatic diseases like rheumatoid arthritis, where anti-CCP is a much more specific marker than the common rheuma factors.
Advances in the Genetic Basis of Ischemic Stroke
Authors: Stanković Sanja , Majkić-Singh Nada 
Published: May 2008

Advances in the Genetic Basis of Ischemic StrokeAs one of the leading causes of death within both the developed and developing world, stroke is a world-wide problem. About 80% of strokes are ischemic. It is caused by multiple genetic factors, environmental factors, and interactions among these factors. There is a long list of candidate genes that have been studied for a possible association with ischemic stroke. Among the most widely investigated genes are those involved in haemostasis, inflammation, nitric oxide production, homocysteine and lipid metabolism, renin-angiotensin-aldosterone system. Combined link-age/association studies have demonstrated that genes encoding PDE4D and ALOX5AP confer risk for stroke. We review the studies of these genes which may have potential application on the early diagnosis, prevention and treatment ischemic stroke patients.
Certainty in an Uncertain World - A Clinicians' Viewpoint of Sensitivity and Precision
Authors: Twomey Patrick 
Published: May 2008

Certainty in an Uncertain World - A Clinicians' Viewpoint of Sensitivity and PrecisionClinical practice is evolving as research evolves from the bench to the bedside. Similarly, analytical technologies are improving on an annual basis. Rightly or wrongly, increased emphasis is now placed by clinicians on such investigations to the detriment of clinical history and examination. As people live longer, the prevalence of long-term conditions such as thyroid disease, cardiovascular disease and malignancies is increasing. Clinical biochemistry assays play an important part in the management (screening, diagnosis, prognosis and monitoring) of such conditions. This is reflected in the UK since 2004 by the primary care contract where over 100 of the 550 clinical points depend on clinical biochemistry assay results. Inter-assay results may differ due to bias, precision, assay specificity and assay sensitivity. To date, little emphasis has been placed on the potential clinical effect of precision. This presentation will explore the effect that assay precision can have on the management of important long-term conditions such as thyroid disease, cardiovascular disease and malignancies.
Dilemmas and Controversies in the Interpretation of Laboratory Results
Authors: Popović Danica , Popović Mirko 
Published: May 2008

Dilemmas and Controversies in the Interpretation of Laboratory ResultsConcentration of many substances in blood is a good indicator of the physiologic state of a patient. It is usual that results obtained represent the real concentration of tested substances in a patient, that is, represent his physiological state. The influence of some factors indicates that this assumption is not always true. Mistakes owing to analytic factors are reduced to the least possible rate by using the quality control. Also, many nonanalytic factors can change the concentration of one or more substances in the sample, so the results obtained are not an indicator of the physiological state of the patient. Results of clinical-biochemical determination are interpreted by comparing with the reference values and so the conclusion is made by a comparison method. In order to perform this process properly, reference values for each specific parameter are necessary. Cyclic variations, physical activity, stress, and other factors significantly affect the obtained result analysis. In the interpretation of results, these specificities have to be considered, otherwise they will be interpreted as pathologic, which leads to wrong conclusions. Inadequate preparation of a patient for a certain analysis and disrespect for rules regarding preparation and sample analyzing can lead to drastic deviation of results from the real values. For those reasons there are certain dilemmas and controversies in the result interpretation.
Status of Development and Implementation of Medical Laboratories Accreditation in Serbia
Authors: Gligić Ljubinka 
Published: May 2008

Status of Development and Implementation of Medical Laboratories Accreditation in SerbiaThrough the release of the SRPS ISO 15189:2008 standard entitled >>Medicinske laboratorije: posebni zahtevi za kvalitet i kompetentnost<< conditions have been created for medical laboratory accreditation in Serbia. The application of the ISO 15189:2007 standard is an accepted mechanism for improvement of the quality of medical laboratory services throughout EU today. In that way, different approaches to the quality improvement of medical laboratories have been harmonized. Functional organisation of the accreditation process of medical laboratories in most European countries is mainly carried out in cooperation with national accreditation bodies, medical experts appointed by scientist associations and health departments. This type of collaboration has proven successful in the United Kingdom, Germany, Hungary, France, Finland, Croatia, etc. The experiences of the Accreditation Board of Serbia (ABS) in medical laboratory accreditation according to the SRPS ISO/IEC 17025:2006 standard (5 laboratories have been accredited) and the positive experiences of European countries in accreditation process constitute the basis for the development of the program for medical laboratory accreditation in Serbia. The first step in this direction is the set-up of the Committee consisting of experts from different medical fields, ABS experts and representatives of the competent Ministry, as well as the definition of their tasks, such as: preparation of the necessary documentation, set-up and preparation of qualification criteria and training programs for assessors, participation in the development of the external quality assessment scheme through interlaboratory testing, liaison with the European organisations for accreditation, organisation of mutual assessments with national and international assessors, participation in decision making on accreditation and accreditation maintenance.
Biochemical Markers of Atherosclerosis
Authors: Đerić Mirjana , Kojić-Damjanov Sunčica , Čabarkapa Velibor , Eremić Nevena 
Published: May 2008

Biochemical Markers of AtherosclerosisThis paper is a brief review of some lipid parameters and serum markers of inflammation in a view of their predictive relevance for the atherosclerotic disease. A discourse on the importance of measuring different lipids and lipoproteins, concentration of LDL particles and apolipoprotein levels is still underway. Also, the recommendations for apolipoprotein (a), phenotypization and other lipid markers have not yet been established. In recent years the recommendations imply simultaneous measuring of multiple markers and calculating the lipid index values such as lipid tetrad index (LTI), lipid pentad index (LPI) and atherogenic index of plasma (AIP). Several circulating markers of inflammation such as C-reactive protein, serum fibrinogen and elevated leukocyte number, are consistently associated with atherosclerosis. In spite of a lack of evidence on measuring the C-reactive protein in a wide population, the guidelines for its application in diagnostics and therapy of coronary heart disease were developed. Some proinflammatory cytokines, adhesion molecules and markers of leukocyte activation are promising markers, requiring, however, more detailed prospective evaluation. The question to be elucidated is if these inflammatory markers are directly involved in the pathogenic process.
Inflammatory and Apoptotic Markers in Ischemic Heart Disease Patients
Authors: Đorđević Vidosava , Ristić Tatjana , Ćosić Vladan , Vlahović Predrag , Zvezdanović Lilika , Đorđević Gordana 
Published: May 2008

Inflammatory and Apoptotic Markers in Ischemic Heart Disease PatientsIschemic heart disease is the most frequent cause of cardiovascular morbidity and mortality. It is developed on the basis of atherosclerosis which is today considered a chronic inflammatory disease. It is documented by an increase in inflammatory and immune biomarkers, such as C-reactive protein, fibrinogen, neopterin, leukocytes, lymphocytes and others, that are significantly changed in patients with unstable angina or acute myocardial infarction. CRP is mostly studied. Increased concentrations of CRP are associated with a series of risk factors. CRP may predict recurrent events and mortality independently of cardiac troponin levels, and it is also an independent predictor of a cardiovascular event after adjustment for traditional risk factors. Although CRP currently appears to be the most promising biological marker, there is still controversy regarding its use in clinical practice. Both necrotic and apoptotic cell death are documented during atherogenesis, however, limited data are available about apoptotic markers in ischemic heart disease patients. Increasing evidence supports the existence of apoptotic death initiated by ligation of membrane-bound death receptors or by release of cytochrome c from mitochondria, as well as their regulators in the heart. The studies of serum markers show that the apoptotic process is disregulated in ischemic heart disease patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is present in stable atherosclerotic lesions, is increased in vulnerable plaques, but its serum levels are reduced significantly in patients with unstable angina. Serum Fas concentrations are increased and FasL are decreased in subjects at high cardiovascular risk. The results of our study show significant changes in serum Fas, FasL, and Bcl-2 concentrations, and lymphocyte caspase-3 activity in different stages of ischemic heart disease. For now, there is evidence that statins are effective in the regulation of some apoptotic markers. The better understanding of the pathways of apoptosis and their regulation is promissing in yielding novel therapeutic targets for cardiovascular disease.
The Clinical Impact of who Standardization of PSA Assays
Authors: Blanchet Jean-Sébastien , Brinkmann Thomas 
Published: May 2008

The Clinical Impact of who Standardization of PSA AssaysThe determination of serum level of the prostate specific antigen (PSA) is widely used for detection and management of prostate cancer. Analytical variability between the various PSA assays on the market has been reported. This discrepancy in the PSA results was shown to be related to non-equimolar detection of total PSA (tPSA) but also to a lack of assay standardization and could have serious clinical repercussions on the diagnostic performance of PSA testing. The recalibration of equimolar assays to common reference preparations (tPSA WHO 96/670 and fPSA 96/668) was thought to promote standardization of PSA assays and limit the clinical implication of assay variability. Comparison studies have demonstrated that PSA assay calibration to the WHO standard certainly improves the harmonisation of PSA testing, but differences between assays remain. Recent evaluations of the clinical impact of analytical variations induced by a calibration to the WHO standard reported that 15% to 30% of prostate cancer could be missed if the historical tPSA cut-off was used. In order to avoid unacceptable erosion of the clinical diagnostic performance of PSA determination for the detection of prostate cancer with WHO calibrated assays, it is critical to define new specific clinical decision points.
Tauopathies: A Distinct Class of Neurodegenerative Diseases
Authors: Ozansoy M , Başak A 
Published: May 2008

Tauopathies: A Distinct Class of Neurodegenerative DiseasesNeurodegenerative diseases are characterized by neuronal loss and intraneuronal accumulation of fibrillary materials, of which, neurofibrillary tangles (NFT) are the most common. Neurofibrillary tangles also occur in normal aging and contain the hyperphosphorylated microtubule-associated protein tau. A detailed presentation is made of the molecular bases of Alzheimer's disease (AD), postencephalitic parkinsonism, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease, frontotemporal dementia (FTD), Down's syndrome, myotonic dystrophy (DM) and Niemann-Pick Type C (NPC) disease, which are considered to be common tauopathies. The unique human tau gene extends over 100 kb of the long arm of chromosome 17 and contains 16 exons. The human brain contains six tau isoforms that contain from 352 to 441 amino acids. To date, 34 pathogenic tau mutations have been described among 101 families affected by FTD with parkinsonism linked to chromosome 17 (FTDP-17). These mutations may involve alternative splicing of exon 10 that lead to changes in the proportion of 4-repeat- and 3-repeat-tau isoforms, or may modify tau interactions with microtubules. Tau aggregates differ in degree of phosphorylation and in content of tau isoforms. Five classes of tauopathies have been defined depending on the type of tau aggregates. The key event in tauopathies is the disorganization of the cytoskeleton, which is based on mutations/polymorphisms in the tau gene and lead to nerve cell degeneration. In this review, tauopathies as a distinct class of neurodegenerative diseases are discussed with emphasis on their molecular pathology and genetics.
Molecular Pathogenesis of Hepatocellular Carcinoma
Authors: Metodieva S 
Published: May 2008

Molecular Pathogenesis of Hepatocellular CarcinomaThe most important risk factors for the development of human hepatocellular carcinoma (HCC) are chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), high dietary exposure to hepatic carcinogen aflatoxin B1 and alcohol abuse. Hepatitis B virus exerts its effects through integration of the viral DNA into the hepatocyte genome, or through acting as transcriptional regulator for several cellular proto-oncogenes and tumor-suppressor genes. Hepatitis C virus may affect hepatocytes via the transcriptional regulation activity of the HCV core protein or via the HCV non structural proteins NS5A, NS5B and NS2, interfering with the regulation of cell cycle and apoptosis. Environmental exposure to aflatoxin B1 can cause a specific missense mutation in codon 249 of the p53 tumor-suppressor gene. Habitual alcohol consumption leads to production of reactive oxygen species and peroxidation damage to DNA. The objective of this review is to make you acquainted with the most common risk factors and the most frequent genetic aberrations associated with the development of HCC.
Molecular Analysis of a Family With Congenital Adrenal Hyperplasia - Genotype/Phenotype Discrepancy
Authors: Anastasovska V , Kocova M 
Published: May 2008

Molecular Analysis of a Family With Congenital Adrenal Hyperplasia - Genotype/Phenotype DiscrepancyCongenital adrenal hyperplasia (CAH) is a common autosomal recessive disease with a variable clinical presentation caused by a spectrum of different mutations. A significant association of genotype with phenotype has been reported.The molecular analysis of a girl with a mild form of CAH presenting with precocious pubarche, confirmed that she was heterozygous for two mutations of the CYP21 gene (exon 1, codon 30/exon 8, codon 318). Her mother was homozygous for the codon 30 mutation and her father was homozygous for the codon 318 mutation. The only anomaly in the parents was a difficulty in conceiving. The molecular analysis of this family confirmed the variability of presentation in carriers of different mutations, which caused difficulties in decisions about the timing of therapy and in genetic counseling.
Cyclin D1 G870A Variant is Associated with Increased Risk of Microsatellite Instability-Positive Colorectal Cancer in Young Male Patients
Authors: Josifovski T , Matevska N , Hiljadnikova-Bajro M , Sterjev Z , Kapedanovska A , Serafimoska Z , Despotovska S , Petrusevska N , Panovski M , Suturkova L , Dimovski A 
Published: May 2008

Cyclin D1 G870A Variant is Associated with Increased Risk of Microsatellite Instability-Positive Colorectal Cancer in Young Male PatientsCyclin D1 (CCND1) is a cell cycle regulatory protein, which is often over expressed in human tumors and is associated with cell proliferation and poor prognosis. A common G870A single nucleotide polymorphism at codon 242 in exon 4 of the CCND1 gene is associated with an altered messenger RNA transcript and increased risk of colorectal cancer (CRC) and adenoma in some studies. Over expression of CCND1 modifies the effect of mutations in mismatch repair (MMR) genes, enhances microsatellite instability (MSI), and influences the age ofonset of hereditary non polyposis colorectal cancer (HNPCC). We have extended our study that indicated that the CCND1 A variant may influence the age of onset of CRC in the Macedonian population only in patients who exhibit MSI tumors by a case control study of 331 randomly selected CRC patients and 101 controls without clinical diagnosis of CRC. We did not observe a significant difference in overall allelic frequencies and genotype distribution of affected and unaffected mutation carriers, but found a statistically significant risk of CRC in carriers of the CCND1 A allele when patients were grouped according to gender, age and MSI status. A higher risk was observed in patients with MSI-positive tumors and particularly in male patients under 60 years of age. The consequences of the above observation were reversed in female patients. These results indicate that the CCND1 A variant may enhance CRC progression through a pathway influenced by estrogens in colonic epithelia.
CAG Repeat Polymorphism of the Mitochondrial DNA Polymerase Gamma Gene in Macedonian Infertile and Fertile Men
Authors: Plaseski T , Noveski P , Dimitrovski C , Efremov G , Plaseska-Karanfilska D 
Published: May 2008

CAG Repeat Polymorphism of the Mitochondrial DNA Polymerase Gamma Gene in Macedonian Infertile and Fertile MenThe catalytic subunit of human mitochondrial DNA polymerase gamma (POLG) is encoded by the POLG gene, located on chromosome 15q24 and includes a polymorphic CAG repeat. Analysis of POLG genotypes in some populations has identified an association between the absence of the 10 CAG repeat allele and male infertility and suggested that POLG gene polymorphism should be considered as a possible contributing factor in cases with idiopathic subfertility with normal spermiograms. We undertook to assess whether different POLG CAG alleles are associated with impaired spermatogenesis and infertility/subfertility in Macedonian men. We studied 225 infertile/subfertile men (74 with azoospermia, 56 with severe oligozoospermia, 27 with mild oligozoospermia, 39 with unexplained infertility and normal sperm counts, and 29 with known causes of infertility) and a control group of 123 proven fathers, by fluorescent polymerase chain reaction (PCR) andanalysis on an ABI PRISM™ 310 Genetic Analyzer. The most frequently observed POLG allele was the common one of 10 CAG repeats with a frequency of 87.6% in the infertile/subfertile group and 86.6% in the control group. The homozygous mutant POLG genotype (not10/not10) was found in both groups, 1.6% in the infertile/subfertile patients and 1.8% in the controls. In conclusion, our study showed no association between polymorphism of the POLG gene and infertility in Macedonian men.
Linkage Analysis by a Transmission/Disequilibrium Test of Russian Sibling Pairs with Coronary Artery Disease
Authors: Tupitsina T , Slominsky P , Yufereva Y , Perova N , Aronov D , Limborska S 
Published: May 2008

Linkage Analysis by a Transmission/Disequilibrium Test of Russian Sibling Pairs with Coronary Artery DiseaseWe studied the association between coronary artery disease (CAD) and polymorphisms of theABCA1, ACE, AGT, eNOSandEFNB3genes in 85 Russian patients with angiography-proven CAD and 100 of their siblings. No gene analyzed had a z-score value of more than 2.47 for CAD or for its main clinical presentations due to sibling transmission/disequilibrium test (S-TDT). However, the DD genotype ofACEis significantly more prevalent in siblings with CAD [p= 0.025, relative risk(RR)2.8], angina (p= 0.028,RR= 3.3) and myocardial infarction (MI) (p= 0.018,RR= 5.5). An increased risk of CAD, and its main manifestations, was associated with the R1587 allele of theABCA1gene: theRRfor developing CAD was 4.88, for MI 6.18, and for angina 3.69 for siblings who were carriers of the R1587R and R1587K genotypes. Index of stenosis was significantly higher in probands with the K219K and R219K genotypes (p= 0.001). The combination of genotype K219K with R219K was more frequent among siblings with CAD (p= 0.044,RR= 2.38), arterial hypertension (p= 0.023,RR= 2.87) and angina (p= 0.027,RR= 3.3). Thus, none of the genes studied can be considered as the main gene associated with CAD. However, the insertion/deletion (I/D) polymorphism of theACEgene and the R219K and R1587K variants ofABCA1are associated with a higher likelihood of developing CAD, MI and angina among Russians who have siblings affected by CAD.