Sepse představuje heterogenní dynamický syndrom, jehož podstatou je závažná orgánová dysfunkce způsobená dysregulovanou odpovědí hostitele na infekci. Klíčovou úlohu v reakci na infekční inzult hraje patofyziologie imunitního systému, jak vrozená, tak získaná imunitní odpověď při rozvoji sepse či septického šoku, který představuje nejtěžší formu této nozologické jednotky. Nekontrolovaná a pozdě diagnostikovaná infekce může fatálně ovlivnit i doposud zdravé jedince, zvýšeně náchylní jsou chroničtí pacienti s komorbiditami. Dramaticky nejvíce ohroženou skupinu představují kriticky nemocní pacienti všech věkových skupin se selháváním základních životních funkcí na jednotkách intenzivní péče. Rychlá a efektivní diagnostika hrozícího rozvoje septického stavu je pro zvládnutí nemoci a dobrý klinický výsledek rozhodující. Současná medicína využívá celou řadu diagnostických možností od stále důležité a neopomenutelné pečlivé anamnézy až po nejsložitější laboratorní, funkční či zobrazovací metody. Výraznou pomoc při časném rozpoznání sepse představují biomarkery, které by ideálně měly být komplexní pro časnou diagnostiku, prognózu, stratifikaci rizika onemocnění a jeho léčbu. Autoři v prezentaci předkládají výsledky studií zaměřené na dva parametry, které jsou levné, rychle dostupné a jsou součástí rutinně indikovaného vyšetření krevního obrazu s diferenciálním rozpočtem krevních buněk. Frakce nezralých trombocytů a granulocytů jsou předmětem zájmu klinických i výzkumných pracovníků při předpovědi zánětlivého procesu i v predikci tíže onemocnění a mortality. Následující text shrnuje dosavadní poznatky o nezralých formách krevních destiček a nezralých granulocytech v problematice sepse u pacientů v prostředí intenzivní péče.
Sepsis is a heterogeneous dynamic syndrome characterized by severe organ dysfunction caused by a dysregulated host response to infection. The innate and adaptive immune response plays a key role in the response to infectious insult in the development of sepsis or septic shock, the most severe form of this nosological entity. Uncontrolled and late diagnosed infection can be fatal even in previously healthy individuals, chronic patients with comorbidities have an increased risk of developing sepsis. Critically ill patients of all ages with failure of basic life functions in intensive care units are the most at risk group. Rapid and effective diagnosis of impending septicemia is crucial for disease management and good clinical outcome. Modern medicine uses a range of diagnostic options from the ever-important and unforgettable anamnesis taking to the most sophisticated laboratory, functional or imaging methods. Biomarkers play an important aid in the early recognition of sepsis and should ideally be comprehensive for early diagnosis, prognosis, disease risk stratification and treatment. This review article notes two parameters that are inexpensive, rapidly available, and part of the routinely indicated blood count with differential blood cell budget. Immature platelet and granulocyte fractions are of interest to clinicians and researchers in the diagnosis of sepsis and in the prediction of disease severity and mortality. The following text summarizes the current knowledge about immature platelet and immature granulocyte forms, mainly in the field of sepsis in intensive care patients.
- MeSH
- časná diagnóza * MeSH
- granulocyty fyziologie patologie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- sepse * diagnóza patofyziologie prevence a kontrola MeSH
- trombocytopenie diagnóza krev patologie MeSH
- trombocyty fyziologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
OBJECTIVES: Usefulness of immature granulocyte percentage (IG%) to discriminate between postoperative non-infective systemic inflammatory response syndrome (SIRS) and sepsis was tested in cardiac surgical patients. METHODS: A retrospective analysis of 124 patients who developed non-infective SIRS and sepsis after elective cardiac surgery was performed. Predictive ability of IG% to predict sepsis was compared to procalcitonin (PCT), white blood cell count, temperature and different biomarker combinations using receiver operating characteristic and logistic regression analysis. The optimal cut-off points, diagnosis sensitivity and specificity were calculated. RESULTS: There were 44 patients diagnosed with sepsis and 80 patients with non-infective SIRS. In receiver operating characteristic analysis, area under the curve was higher for IG% (0.71) and PCT (0.72) compared to white blood cell count (0.62) and temperature (0.58). The best cut-off value for IG% was 1.45% (sensitivity 70.5%, specificity 60%) and 1.43 µg/l for PCT (sensitivity 65.9%, specificity 75%). The combination of IG% and PCT provided the best sepsis prediction (area under the curve of 0.8, sensitivity 63.6% and specificity 88.8%). CONCLUSIONS: In cardiac surgical patients, IG% is a helpful marker with the moderate ability to discriminate between sepsis and non-infective SIRS, comparable to serum PCT. A combination of these parameters increased the test's overall predictive ability by improving its specificity.
- MeSH
- biologické markery krev MeSH
- granulocyty patologie MeSH
- kardiochirurgické výkony * MeSH
- lidé MeSH
- počet leukocytů MeSH
- prognóza MeSH
- prokalcitonin krev MeSH
- retrospektivní studie MeSH
- ROC křivka MeSH
- senioři MeSH
- sepse diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Granulocytic early progenitors and terminally differentiated - mature granulocytes with segmented nuclei were studied using computer-assisted diameter and heterochromatin optical image densitometry to provide more information on the nuclear size and heterochromatin condensation state. Bone marrow smears of patients suffering from chronic myeloid leukaemia untreated as well as treated with "specific" anti-leukaemic therapy with imatinib mesylate are a convenient model for such study because they possess a satisfactory number of cells for diameter and optical density measurements. In addition, the identification of developmental stages of granulocytes is very easy and the morphology is not different from that in not-leukaemic persons. As it was expected, the mean diameter of nuclear segments in fully differentiated and mature granulocytes was much smaller than that in non-segmented nuclei of early granulocytic precursors. Therefore, no wonder that the heterochromatin condensation state in nuclear segments of mature granulocytes was much larger than in non-segmented nuclei of granulocytic progenitors. On the other hand, the sum of mean diameters of all nuclear segments per cell was close to the mean nuclear diameter of early granulocytic progenitors. The heterochromatin condensation state in granulocytic progenitors or fully differentiated mature granulocytes exhibited marked stability and did not change after the anti-leukaemic therapy. In addition, Barr bodies of characteristic drumstick appearance bearing inactive X chromosome in interphase nuclei of mature granulocytes in fertile female patients exhibited a heterochromatin condensation state similar to nuclear segments. This heterochromatin condensation state was also stable and constant, and was not apparently influenced by the anti-leukaemic therapy.
- MeSH
- biologické modely MeSH
- buněčná diferenciace * MeSH
- buněčný rodokmen * MeSH
- chronická myeloidní leukemie patologie MeSH
- denzitometrie metody MeSH
- granulocyty patologie MeSH
- heterochromatin chemie MeSH
- lidé MeSH
- prekurzorové buňky granulocytů patologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Refractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory cytopenia of childhood. (The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered at clinicaltrials.gov identifiers 00499070 and 00662090, respectively).
- MeSH
- aplastická anemie diagnóza imunologie patologie MeSH
- CD antigeny imunologie MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- erytroidní buňky imunologie patologie MeSH
- granulocyty imunologie patologie MeSH
- imunofenotypizace * MeSH
- kojenec MeSH
- kostní dřeň imunologie patologie MeSH
- lidé MeSH
- lymfocyty imunologie patologie MeSH
- mladiství MeSH
- monocyty imunologie patologie MeSH
- myelodysplastické syndromy diagnóza imunologie patologie MeSH
- pancytopenie diagnóza imunologie patologie MeSH
- předškolní dítě MeSH
- průtoková cytometrie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Nuclei of hairy cells (HC) are typically oval, round or indented, but atypical shapes are occasionally described in HCL and may lead to a provisional wrong diagnosis. METHODS: The aim of this study was to quantify HC nuclei shapes classified into 11 categories on diagnostic bone marrow smears of 38 consecutive patients with HCL. RESULTS: HC in all 33 patients with evaluable smears at diagnosis exhibited a round/oval nucleus in 60.8-95.8%, an indented nucleus in 3.4-24.5% and a kidney-shaped nucleus in 0.4-7.0%. Other shapes of HC nuclei were found only in a proportion of patients: nuclei with two indentations in 0.4-6.5% HC (28 patients), overlapped nuclei in 0.5-3.5% HC (17) and lobulated nuclei in 0.4-4.5% HC (15). Two per cent or less of HC had the following nuclear shapes: that of an opposite indentation and impression (14 patients), dumb-bell (13), ring (10), horseshoe (5), two nuclei (8 patients). CONCLUSION: Different shapes of HC nuclei similar to cells typical for other diagnoses are found usually in low frequencies. However, if their numbers are increased, they may cause diagnostic problems because cytology of blood and bone marrow smears is usually the first available diagnostic method.
- MeSH
- aplastická anemie diagnóza patologie MeSH
- B-lymfocyty patologie MeSH
- buněčné jádro patologie MeSH
- cytodiagnostika MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- granulocyty patologie MeSH
- kostní dřeň patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myelodysplastické syndromy diagnóza patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tvar buněčného jádra MeSH
- vlasatobuněčná leukemie diagnóza patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Terminally-differentiated cells cease to proliferate and acquire specific sets of expressed genes and functions distinguishing them from less differentiated and cancer cells. Mature granulocytes show lobular structure of cell nuclei with highly condensed chromatin in which HP1 proteins are replaced by MNEI. These structural features of chromatin correspond to low level of gene expression and the loss of some important functions as DNA damage repair, shown in this work and, on the other hand, acquisition of a new specific function consisting in the release of chromatin extracellular traps in response to infection by pathogenic microbes. Granulocytic differentiation is incomplete in myeloid leukemia and is manifested by persistence of lower levels of HP1γ and HP1β isoforms. This immaturity is accompanied by acquisition of DDR capacity allowing to these incompletely differentiated multi-lobed neutrophils of AML patients to respond to induction of DSB by γ-irradiation. Immature granulocytes persist frequently in blood of treated AML patients in remission. These granulocytes contrary to mature ones do not release chromatin for NETs after activation with phorbol myristate-12 acetate-13 and do not exert the neutrophil function in immune defence. We suggest therefore the detection of HP1 expression in granulocytes of AML patients as a very sensitive indicator of their maturation and functionality after the treatment. Our results show that the changes in chromatin structure underlie a major transition in functioning of the genome in immature granulocytes. They show further that leukemia stem cells can differentiate ex vivo to mature granulocytes despite carrying the translocation BCR/ABL.
- MeSH
- akutní myeloidní leukemie genetika metabolismus patologie MeSH
- buněčná diferenciace * MeSH
- chromatin genetika MeSH
- chromozomální proteiny, nehistonové genetika metabolismus MeSH
- fluorescenční protilátková technika MeSH
- granulocyty metabolismus patologie MeSH
- hematopoetické kmenové buňky metabolismus patologie MeSH
- kultivované buňky MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- neutrofily patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- poškození DNA * MeSH
- proliferace buněk MeSH
- tetradekanoylforbolacetát MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
The knowledge on the heterochromatin condensation state (HChCS) in central nuclear “gene rich” regions is limited although the heterochromatin reflects the gene silencing. Therefore, the HChCS in these regions was studied in proliferating granulocytic progenitors and terminally differentiated (mature) neutrophilic granulocytes. The HChCS was measured using computer assisted image optical densitometry at the single cell level. The bone marrow smears of patients with chronic myeloid leukemia represented a convenient model because of the increased number of progenitor and mature cells for density measurements. In addition, the heterochromatin density of central nuclear regions was also measured in myeloblasts of the K 562 cell lineage originated from the patient with that disease. The HChCS in central nuclear regions of both granulocytic progenitors and mature granulocytes was heterogeneous. The maximal and minimal density values were about 9-10 per cent above and below mean values in both myeloblasts and mature granulocytes. The heavy condensed heterochromatin of central nuclear region might reflect the location of silent genes during the whole granulocytic development. In contrary, the less condensed heterochromatin structures in central nuclear regions of granulocytic progenitors and mature granulocytes might just represent foci with the potential for the gene activation regardless of the differentiation and maturation stage. The HChCS in central nuclear regions was larger in small nuclear segments of mature granulocytes than in large nuclei of their progenitors. The HChCS was also increased in apoptotic K 562 myeloblasts with the decreased nuclear diameter. Such phenomena opened an “old - new” question on mutual relationship between the reduced nuclear size and the HChCS.
- MeSH
- biomedicínský výzkum MeSH
- chronická myeloidní leukemie krev MeSH
- denzitometrie * metody přístrojové vybavení využití MeSH
- granulocyty * patologie ultrastruktura MeSH
- heterochromatin * genetika ultrastruktura MeSH
- kostní dřeň MeSH
- kultivační techniky metody využití MeSH
- lidé MeSH
- mikrofotografie využití MeSH
- neutrofily patologie ultrastruktura MeSH
- prekurzorové buňky granulocytů ultrastruktura MeSH
- statistika jako téma MeSH
- struktury buněčného jádra ultrastruktura MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- cytologické techniky metody MeSH
- granulocyty cytologie patologie MeSH
- intrakraniální krvácení MeSH
- lidé MeSH
- lymfocyty cytologie patologie MeSH
- mononukleární fagocytární systém cytologie patologie MeSH
- mozkomíšní mok cytologie chemie mikrobiologie MeSH
- nádorové cirkulující buňky klasifikace patologie MeSH
- patologické procesy etiologie klasifikace patologie MeSH
- Check Tag
- lidé MeSH
Currently, the May-Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FTNS) and Epstein (EPS) syndrome are considered to be distinct clinical manifestations of a single disease caused by mutations of the MYH9 gene encoding the heavy chain of non-muscle myosin IIA (NMMHC-IIA). Manifestations of these disorders include giant platelets, thrombocytopenia and combinations of the presence of granulocyte inclusions, deafness, cataracts and renal failure. We examined 15 patients from 10 unrelated families on whom we performed immunostaining of NMMHC-IIA in blood samples. Polymerase chain reaction (PCR) analysis of selected exons of the MYH9 gene revealed mutations in nine samples with one novel mutation. Results of fluorescence and mutational analysis were compared with clinical manifestations of the MYH9 disorder. We also determined the number of glycoprotein sites on the surface of platelets. Most patients had an increased number of glycoproteins, which could be due to platelet size.
- MeSH
- buněčná inkluze MeSH
- exony MeSH
- genetické nemoci vrozené genetika krev patologie MeSH
- glykoproteiny MeSH
- granulocyty patologie MeSH
- lidé MeSH
- molekulární motory genetika MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- polymerázová řetězová reakce MeSH
- rodina MeSH
- syndrom MeSH
- těžké řetězce myosinu genetika MeSH
- trombocytopenie MeSH
- trombocyty patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
