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Journal of Nursing Theory and Practice

OCTOBER 30, 2019

[Biomonitoring of lead exposure among workers: the role of the occupational health nurse ]


[Biological monitoring (biomonitoring) in occupational safety and health is the detection of substances (biomarkers) in biological samples of workers, compared to reference values. This article is limited to Lead (Pb) exposures, as it is one of the most important models for biomonitoring of exposure, with the blood Pb concentration as a predominant choice in occupational health. This article examines the nature of and risk factors for lead exposure among workers, the scope of the problem, the legislative and regulatory framework relevant to biomonitoring, and the role of occupational health nurses in promoting a culture of safety to prevent exposures. ]

Lege Artis Medicinae

NOVEMBER 15, 2019

[Vascular biomarkers ]


[While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further refine the risk stratification of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for and being realized earlier than a clinical hard endpoint. In order to be suitable as a surrogate endpoint of cardiovascular events, a biomarker should meet several well-defined criteria. It has been proposed that a plenty of potential vascular biomarkers would have a role in primary and secondary cardiovascular prevention. Most of the biomarkers examined fit within the concept of early vascular aging. The only biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity. ]

Clinical Neuroscience

NOVEMBER 30, 2018

Inflammatory biomarkers in benign paroxysmal positional vertigo: A Turkey case-control study


Objective - Benign paroxysmal positional vertigo (BPPV) is the most common cause of recurrent vertigo. Inflammation is a hypothetic etiological factor in BPPV. The aim of this study was to evaluate inflammatory biomarker levels in BPPV patients and compare these with the healthy subjects. Materials and methods - This prospective case-control study was conducted with 114 newly diagnosed BPPV patients and age- and sex- matched 83 healthy subjects. The laboratory investigations included serum hemogram, full biochemistry profiles, vitamin levels, thyroid hormone profiles, high sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR). Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte to HDL-cholesterol ratio (MHR) values were calculated and compared between the patients and healthy subjects. Results - The mean age was 39.1 ± 12.4 years for patients, and 37.0 ± 11.9 for controls. Vitamin B12, hematocrit (Hct), creatinine, urea, and fT4 values, lymphocyte, total bilirubin, direct bilirubin and indirect bilirubin levels were significantly lower in BPPV patients (p ˂ 0.05), while HDL, SGOT, and ESR values were significantly higher. In the BPPV patients the mean NLR, PLR, and mean platelet volume (MPV) values were significantly higher than in the control subjects. Neutrophil, platelet, monocyte, MHR, and CRP values were similar in both groups (p ˃ 0.05). Conclusion - Our result suggests that NLR, PLR, MPV, ESR, and bilirubin levels should be taken into account as potential biomarkers of BPPV. As they are inexpensive parameters and widely available, they can be used in clinical practice for prediction of BPPV. However, further large-scale studies are required to confirm this relationship.

Clinical Oncology

FEBRUARY 10, 2018

[The role of early clinical studies in oncology]


[Although the basic theory of the early development of different drug groups is identical, due to their various pharmacological characteristics the design of the studies, the starting safe dose and the selection of the pharmacologic and therapeutic end-points show signifi cant differences. The development process of drugs is usually divided into two functionally different parts, the learning and the confi rming phases, respectively. The aim of the fi rst part is the description of the suggested targets, the mechanism of action in humans and the characterization of the drug-linked biomarkers. This section contains the microdose (phase 0), phase I and II studies. The end-point of this part is the proof of the underlying concept which was developed on the basis of the non-clinical studies. According to the internationally accepted terminology, this strategically important point is called the Proof of Concept (POC). Upon POC it has to be decided whether the drug-candidate possesses those qualities which make it worthwhile to perform human phase III studies, treating the statistically required number of patients for proving the good therapeutic effi cacy and safety of the drug. This section of the drug development is called the confi rmatory phase. The use of highly sophisticated technology opened the possibility to apply microdoses in humans for studying the pharmacokinetics and pharmacodynamics of new drugs as well as the characteristics of human biomarkers at very low, harmless drug doses. This approach made possible to draw important conclusions on the usefulness of biomarkers for the clinical practice even following the fi rst drug-application. The planning of phases I and II studies, the calculation of the applicable doses, the selection of the pharmacologic and therapeutic end-points, the use of biomarkers, are all based on the concept of translational medicine and are essentially dependent on the results obtained both in animal experiments and human microdose studies.]

Clinical Neuroscience

JANUARY 30, 2019

Additional value of tau protein measurement in the diagnosis of Creutzfeldt-Jakob disease

CSEH Katalin Edina, VERES Gábor, DANICS Krisztina, SZALÁRDY Levente, NÁNÁSI Nikolett, KLIVÉNYI Péter, VÉCSEI László, ZÁDORI Dénes

Since the definite diagnosis of Creutzfeldt-Jakob disease (CJD) can currently only be provided by autopsy, there is a special need for fine diagnostic tools in live patients to achieve accurate diagnosis as early as possible. The aim of this study was to perform a preliminary retrospective analysis on the utility of the measurement of total Tau (tTau) and some other biomarkers from the cerebrospinal fluid (CSF) of patients with rapidly progressive dementia in the diagnostic work up of CJD. Beside the assessment of relevant clinical data and the findings of electroencephalography and brain magnetic resonance imaging, the presence of 14-3-3 protein and the levels of tTau were determined by Western blot technique and enzyme-linked immunosorbent assay from the CSF of 19 patients diagnosed with rapidly progressive dementia between the period of 2004-2017 at the Department of Neurology, University of Szeged. This preliminary study provided 100% sensitivity for 14-3-3, and interestingly, only 40% specificity to support the clinical diagnosis of CJD. Regarding tTau, the sensitivity values were calculated to be 100% or 83%, whereas the specificity values were 71% or 86%, depending on the applied cut-off levels. The poor specificity of 14-3-3 is not in line with literature data and may be the result of the small number of patients in the cohort with non-prion disease, predominantly consisting of disorders with considerable tissue damage, whereas tTau presented good sensitivity and specificity values. The combined application of these and novel chemical biomarkers may increase both sensitivity and specificity to a desired level.

Clinical Neuroscience

JULY 30, 2018

Isocitrate dehydrogenase mutations in defining the biology of and supporting clinical decision making in glioblastoma


Background and purpose - Oncogenesis is related to a sequential accumulation of somatic mutations. Comprehensive characterizations of the genomic landscapes have been completed recently for several tumors, glioblastoma being among the first ones. Our own translational research studies have been focused on defining molecular subtypes of glioblastoma in the clinical setting because of an expected prognostic and therapeutic utility of the information. Somatic mutations in genes of the isocitrate dehydrogenase (IDH) enzyme family appear to be among the best-defined biomarkers that also influence tumor behavior and confer clinical utility. Methods - We have reviewed the literature including our own results to summarize basic science and clinical correlates of IDH mutations. Results - The surveyed data reveal genomic, transcriptomic, epigenomic and biochemical consequences of IDH mutations in the context of glioblastoma biology and phenotype. In addition, a few studies highlight the therapeutic potential of targeting IDH, although thus far all tests have only been conducted in the preclinical setting. Conclusions - Somatic mutations in isoforms of IDH genes represent important biomarkers that correlate with biochemical, biological and phenotypic features of glioblastoma, and may also facilitate the development of new therapeutic strategies complementing the currently available approved protocols.

Lege Artis Medicinae

NOVEMBER 30, 2020

[Some newly discovered mechanisms of action of the immune response and the conceptual transformation of immunology]

FALUS András

[Immunology is a complex science studying healthy and abnormal immune responses. This discipline of physiology and pathophysiology primarily understands the individual mechanisms through a cellular and molecular biological, genetic, epigenetic and (neuro) endocrinological approach, as well as by exploring the details of pathological processes. Im­mu­nology is one of the very rapidly evolving sciences, and its results have repercussions on other disciplines at both theoretical (eg network sciences, systems biology) and methodological (monoclonal antibodies, biomarkers, immune assays) levels. In recent decades, a number of conceptual novelty have been uncovered and immunologists have recognized essential details in their assertion in immunity. ]

Clinical Oncology

FEBRUARY 28, 2020

[Neoadjuvant and palliative drug therapy for bladder cancer]


[The survival of patients with muscle-invasive localized bladder cancer is more favorable if they receive neoadjuvant or adjuvant cisplatin-based chemotherapy before or after cystectomy. Based on the meta-analyses, in case of neoadjuvant cisplatin-based chemotherapy, the 5-year survival benefi t is 5-16%. The outcome is even more favorable in case of patients who respond well to neoadjuvant chemotherapy (pathological complete remission rate 12–50%). More than 3 months delay of cystectomy does not signifi cantly reduce the survival if chemotherapy is performed before the operation. Results of adjuvant phase III studies and meta-analyses are not so unambiguous as neoadjuvant data, but chemotherapy seems to infl uence favorably PD-L1 expression the survival, especially in case of pT3/4 and/or N+ (and high grade or margin positivity) cases. According to the recent publications, outcome data of patients have been effective in case of progression after platinum therapy, in or after second-line and in fi rst-line therapies for cisplatin ineligible, PD-L1 positive patients, respectively. Survival and tumor response data are very promising; in particular stages, they seem to be more effective than the previously administered chemotherapies. Current and ongoing trials are investigating the combinations of new remedies with other immunotherapeutic agents or chemotherapies as well as trying to identify biomarkers in order to further increase effectiveness.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[The pain-trigger role of cytokines in the nervous system – the direct analgesic effect of anti-cytokine therapy ]


[Nociceptive, neuropathic and central me­chanisms are involved in the perception, transmission and processing of chronic pain and shaping of cerebral pain image. Alar­mins – molecules alarming defence and signing the presence of pathogens and tissue damage - trigger a series of pathogenic events resulting in inflammatory pain stimuli. Proinflammatory cytokines play a determining role in the pain perception at the level of the nervous system. Continuous inflammatory stimuli while sensitizing the periferic and central neurons activate the pain-related cerebral areas and develop the complex pain image, the pain matrix. Ce­reb­ral functional connections are operating in networks and can be visualized by functional MRI. Cytokines activate the neurons directly or indirectly by other neuromediators. Cytokine receptors are expressed on no­ciceptors and even on higher-level neurons and on various non-neural cells, such as microglia and astrocytes. The most ubiquitous cytokines are the Tumour Necrosis Factor and Interleukin 6 in the nervous sys­tem. The signaling pathways are the Nuclear Factor κB and the Janus-kinase enzyme system. The proinflammatory cytokines and the Janus-kinase are therefore primary therapeutic targets. Anti-cytokine biologicals and small molecular kinase inhibitors decrease the pain and improve functional activity in rheumatoid arthritis. Decrease of pain was more pronounced than expected only from the decrease of the clinical biomarkers of inflammation. The early and ra­pid painkiller effect of targeted biological and chemical-biological response modifiers is attributed to their direct analgesic effect on the brain.]