[Carbohydrate-deficient transferrin as a marker of alcohol abuse]
V posledním desetiletí se rozšiřuje využívání sérových hladin karbohydrát-deficientního transferinu (CDT) jako vysoce specifického a citlivého ukazatele chronického alkoholizmu. Článek se zabývá vysvětlením fyziologického principu testu a vývojem laboratorních metodik stanovení CDT. Hodnocení současných možností měření hladin CDT se opírá o publikované práce i praktické zkušenosti autorky se třemi různými komerčními soupravami. Druhá část přehledného článku upozorňuje na některé dosud nevyjasněné otázky harmonizace užívaných metodik. Diskutuje široké možnosti využití CDT v klinické praxi, specificitu a senzitivitu CDT u různých souborů a ve srovnání s dosud užívanými klasickými testy jako např. GGT.
Last decade witnessed the increasing use of serum levels of carbohydrate-deficient transferrin (CDT) as a highly specific and sensitive marker of chronic alcoholism. This paper deals with the explanation of the physiological principle of the test and the development of laboratory techniques of CDT measurement. The evaluation of the state-of-art of CDT tests is based on published data as well as on the practical experience of the author with three commercial diagnostic kits. The second part of the review article draws attention to some still open questions of how to harmonise the different methodologies used. The use of the CDT measurement in various clinical settings, the specificity and sensitivity of CDT in different population samples and/or in comparison with already established markers such as GGT is discussed.
Východisko. Karbohydrát deficientní transferin (CDT) bývá označován jako nejlepší marker chronického abúzu etanolu, literární údaje o jeho diagnostické validitě jsou však vysoce variabilní. Cílem studie bylo srovnání diagnostické přesnosti CDT s běžně užívanými markery chronického alkoholizmu se zaměřením na možné rozdíly v závislosti na pohlaví. Metody a výsledky. U 85 zdravých dobrovolníků a 50 pacientů s prokázaným chronickým abúzem etanolu bylo provedeno stanovení hladiny CDT v séru metodou aniontové chromatografie a imunoturbidimetrie (TIA) a dále vyšetření středního objemu erytrocytu (MCV) a gama-glutamyl transferázy (GMT). Pro každý ze sledovaných markerů byla stanovena senzitivita, specificita, ROC křivka a plocha pod křivkou (AUC), a to zvlášť pro muže a ženy. Hodnota cut-off pro CDT% byla stanovena na hladině 2,2 % pro muže a 2,5 % pro ženy. U mužů jsme prokázali poměrně vysokou diagnostickou validitu CDT (AUC 0,94, senzitivita 82,6 %, specificita 96,7 %) i GMT, MCV je u nich vyšetřením méně výtěžným. U žen byla diagnostická validita CDT naopak nižší oproti standardně užívaným laboratorním markerům (AUC 0,83, senzitivita 60 %, specificita 88 %). Závěry. Užití kombinace několika markerů výrazně zvyšuje senzitivitu laboratorní diagnostiky chronického alkoholismu, zařazení CDT může v takovém případě zvýšit nejen specificitu, ale i kumulativní senzitivitu tohoto souboru testů, neboť u části vyšetřených jedinců může být jedinou detekovatelnou abnormitou.
Background. Carbohydrate-deficient transferrin (CDT) has been reported to be the best laboratory marker of the chronic alcohol abuse, but there are conflicting data on its accuracy and sensitivity ranging from 19 % to 96 % in various studies. The aim of this study was to compare the diagnostic efficiency of CDT with the other markers of alcohol abuse used in clinical practice with respect to possible sex differences. Methods and Results. The serum CDT (using the method of anion-exchange chromatography and TIA), mean corpuscular volume (MCV), gamma-glutamyl-transferase (GMT) values and platelet count were evaluated in 50 alcohol-dependent patients admitted to the Center of Detoxification and in the reference group of 85 healthy teetotallers. The cut-off values for %CDT where established in the level of 2,2 % and 2,5 % for men and women respectively. In men we proved a comparatively high diagnostic efficiency of CDT (AUC 0,94, senzitivity 82,6 %, specificity 96,7 %) and GMT, MCV seem to be less accurate marker of chronic alcohol abuse. In contrast there was a lower diagnostic validity of CDT in women in comparison with common markers (AUC 0,83, senzitivity 60 %, specificity 88 %). Conclusions. The laboratory diagnosis of chronic alcohol consumption can be improved by using a combination of several markers. The specificity and also the cumulative sensitivity of such a battery of laboratory markers can be elevated by CDT evaluation. In a part of patients, CDT can be the only detectable abnormity.
- MeSH
- Alcoholism diagnosis MeSH
- Biomarkers blood MeSH
- Adult MeSH
- Research Support as Topic MeSH
- gamma-Glutamyltransferase blood MeSH
- Clinical Laboratory Techniques methods statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Erythrocyte Volume MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Transferrin analogs & derivatives chemistry blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Review MeSH
- Comparative Study MeSH
- MeSH
- Autistic Disorder etiology MeSH
- Big Data MeSH
- Data Interpretation, Statistical MeSH
- Humans MeSH
- Folic Acid Deficiency MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- rIX-FP, rVIII-SingleChain, studie AFFINITY, studie PROLONG-9FP,
- MeSH
- Factor IX therapeutic use MeSH
- Factor VIII therapeutic use MeSH
- Hemophilia A * drug therapy MeSH
- Hemophilia B * drug therapy MeSH
- Clinical Trials, Phase III as Topic MeSH
- Humans MeSH
- Recombinant Fusion Proteins * therapeutic use MeSH
- Check Tag
- Humans MeSH
Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.
- MeSH
- Common Variable Immunodeficiency pathology MeSH
- Bronchiectasis pathology MeSH
- Bronchi pathology MeSH
- Child MeSH
- Adult MeSH
- Thoracic Wall pathology MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Tomography, X-Ray Computed methods MeSH
- Child, Preschool MeSH
- Aged MeSH
- Spirometry methods MeSH
- Immunologic Deficiency Syndromes pathology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
Hereditary hemochromatosis type I is an autosomal-recessive iron overload disease associated with a mutation in HFE gene. The most common mutation, C282Y, disrupts the disulfide bond necessary for the association of HFE with beta-2-microglobulin and abrogates cell surface HFE expression. HFE-deficient mice develop iron overload indicating a central role of the protein in the pathogenesis of hereditary hemochromatosis type I. However, despite significant effort, the role of the HFE protein in iron metabolism is still unknown. To shed a light on the molecular mechanism of HFE-related hemochromatosis we studied protein expression changes elicited by HFE-deficiency in the liver which is the organ critical for the regulation of iron metabolism. We undertook a proteomic study comparing protein expression in the liver of HFE deficient mice with control animals. We compared HFE-deficient animals with control animals with identical iron levels obtained by dietary treatment to identify changes specific to HFE deficiency rather than iron loading. We found 11 proteins that were differentially expressed in the HFE-deficient liver using two-dimensional electrophoresis and mass spectrometry identification. Of particular interest were urinary proteins 1, 2 and 6, glutathione-S-transferase P1, selenium binding protein 2, sarcosine dehydrogenase and thioredoxin-like protein 2. Our data suggest possible involvement of lipocalins, TNF-alpha signaling and PPAR alpha regulatory pathway in the pathogenesis of hereditary hemochromatosis and suggest future targeted research addressing the roles of the identified candidate genes in the molecular mechanism of hereditary hemochromatosis.
- MeSH
- Electrophoresis, Gel, Two-Dimensional MeSH
- Gene Expression MeSH
- Financing, Organized MeSH
- Hemochromatosis genetics metabolism pathology MeSH
- Liver metabolism MeSH
- Membrane Proteins physiology genetics deficiency MeSH
- RNA, Messenger genetics metabolism MeSH
- Histocompatibility Antigens Class I physiology genetics MeSH
- Molecular Sequence Data MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Polymerase Chain Reaction MeSH
- Iron Overload genetics metabolism pathology MeSH
- Proteome genetics metabolism MeSH
- Proteomics methods MeSH
- Amino Acid Sequence MeSH
- Spectrophotometry, Atomic MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MeSH
- Iron metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
BACKGROUND: The Lachman test is the most reliable clinical test for diagnosing rupture of the anterior cruciate ligament (ACL). Previous X-ray studies have presented a "radiologic Lachman test". Recently anterior tibial translation was demonstrated using open access MRI. Two methods were developed to transfer a similar technique to a more widely available closed MRI. METHODS: Using closed MRI we investigated 22 knees in 21 patients with pure rupture of the ACL. Anteriorly and posteriorly directed shear forces were applied to the tibiofemoral joint at 20 degrees flexion either by positioning a 9-kg load on the distal femur (method 1) or performing a semi-manual Lachman test with a custom-made orthosis (method 2). RESULTS: Both methods produced relative anterior tibial translation in both compartments of the normal and ACL-deficient knee which could be measured on sagittal images. They were greater laterally than medially and in injured than in uninjured knees. However, instability of the medial compartment predicted clinical and symptomatic instability as translation was posterior to positions achieved in normal knees during the active and passive flexion arc. CONCLUSION: A Lachman sign can be produced in a closed magnet with different methods and findings can be used for more precise information regarding kinematics and degree of instability and could be helpful if surgical treatment is necessary.
- MeSH
- Biomechanical Phenomena MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Data Interpretation, Statistical MeSH
- Knee Joint * physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Anterior Cruciate Ligament * MeSH
- Magnetic Resonance Imaging * MeSH
- Joint Instability * diagnosis physiopathology MeSH
- Knee Injuries * diagnosis physiopathology MeSH
- Anterior Cruciate Ligament Injuries MeSH
- Rupture MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Comparative Study MeSH
To elucidate the regulator-versus-target relationship in the cyclin D1/cdk4/retinoblastoma protein (pRB) pathway, we examined fibroblasts from RB-1 gene-deficient and RB-1 wild-type littermate mouse embryos (ME) and in human tumor cell lines that differed in the status of the RB-1 gene. The RB+/+ and RB-/- ME fibroblasts expressed similar protein levels of D-type cyclins, cdk4, and cdk6, showed analogous spectra and abundance of cellular proteins complexed with cdk4 and/or cyclins D1 and D2, and exhibited comparable associated kinase activities. Of the two human cell lines established from the same sarcoma biopsy, the RB-positive SKUT1B cells contained cdk4 that was mainly associated with D-type cyclins, contrary to a predominant cdk4-p16INK4 complex in the RB-deficient SKUT1A cells. Antibody-mediated neutralization of cyclin D1 arrested the RB-positive ME and SKUT1B cells in G1, whereas this cyclin appeared dispensable in the RB-deficient ME and SKUT1A cells. Lack of requirement for cyclin D1 therefore correlated with absence of functional pRB, regardless of whether active cyclin D1/cdk4 holoenzyme was present in the cells under study. Consistent with a potential role of cyclin D/cdk4 in phosphorylation of pRB, monoclonal anti-cyclin D1 antibodies supporting the associated kinase activity failed to significantly affect proliferation of RB-positive cells, whereas the antibody DCS-6, unable to coprecipitate cdk4, efficiently inhibited G1 progression and prevented pRB phosphorylation in vivo. These data provide evidence for an upstream control function of cyclin D1/cdk4, and a downstream role for pRB, in the order of events regulating transition through late G1 phase of the mammalian cell division cycle.
- MeSH
- Cyclin D1 MeSH
- Cyclin-Dependent Kinase 4 MeSH
- Cyclin-Dependent Kinases * MeSH
- Cyclins antagonists & inhibitors immunology metabolism MeSH
- DNA Primers genetics MeSH
- Phosphorylation MeSH
- G1 Phase * physiology genetics MeSH
- Genes, Retinoblastoma * MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Neutralization Tests MeSH
- Oncogene Proteins antagonists & inhibitors immunology metabolism MeSH
- Protein Serine-Threonine Kinases * metabolism MeSH
- Proto-Oncogene Proteins * MeSH
- Retinoblastoma Protein genetics metabolism MeSH
- Base Sequence MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Covid-19 je primárně respirační onemocnění, které má často pouze mírný průběh. Naproti tomu pacienti s oslabenou imunitou, ať již v důsledku primárního imunodeficitu, nebo imunosuprese v souvislosti s chronickým onemocněním či specifickou léčbou, mají zvýšené riziko závažných projevů, hospitalizací, perzistentní infekce i úmrtí v důsledku covidu-19. Imunokompromitovaní pacienti, zejména nemocní po transplantaci solidních orgánů nebo s hematologickými malignitami, mohou mít také oslabenou odpověď na vakcinaci proti covidu-19. Přesto se u imunokompromitovaných pacientů toto očkování doporučuje, společně s dalšími běžnými preventivními opatřeními. Novým přístupem by se mohla stát preexpoziční profylaxe.
Covid-19 is primarily a respiratory disease that often has only a mild course. In contrast, immunocompromised patients, whether due to primary immunodeficiency or immuno suppression related to chronic disease or specific treatments, have an increased risk of severe symptoms, hospitalizations, persistent infection, and death due to covid-19. Immuno compromised patients, especially those with solid organ transplantation or haematological malignancies, may also have a poor response to covid-19 vaccination. Nevertheless, this vaccination is recommended in immunocompromised patients, along with other routine preventive measures. Pre-exposure prophylaxis could be a new approach.
