Determination of Imaging Biomarkers to Decipher Disease Trajectories and Differential Diagnosis of Neurodegenerative Diseases (DIsease TreND)

2018 ◽  
Vol 305 ◽  
pp. 105-116 ◽  
Author(s):  
Gurpreet Singh ◽  
Lakshminarayanan Samavedham ◽  
Erle Chuen-Hian Lim
Keyword(s):  
Differential Diagnosis ◽  
Neurodegenerative Diseases ◽  
Imaging Biomarkers

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

IMPORTANCE OF ANTIBODIES TO 21-HYDROXYLASE FOR THE DIAGNOSIS, DIFFERENTIAL DIAGNOSIS AND PROGNOSIS OF AUTOIMMUNE CHRONIC PRIMARY ADRENAL INSUFFICIENCY

2021 ◽  
Vol 100 (2) ◽  
pp. 78-86
Author(s):  
L.S. Sozaeva ◽  
◽  
N.V. Makazan ◽  
L.V. Nikankina ◽  
N.M. Malysheva ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Adrenal Insufficiency ◽  
Predictive Value ◽  
Primary Adrenal Insufficiency ◽  
Polyglandular Autoimmune Syndrome ◽  
Diagnosis And Prognosis ◽  
Specificity And Sensitivity ◽  
Enzymelinked Immunosorbent Assay

21-hydroxylase (21-OH) is the main antigen of the adrenal cortex, so the determination of antibodies (Ab) to 21-OH can help in the diagnosis and prognosis of chronic primary adrenal insufficiency (CPAI). Purpose of the study: evaluation of the relevance of Ab to 21-OH for the diagnosis and prediction of autoimmune CPAI. Materials and methods of research: the study consisted of three blocks: 1) assessment of the specificity and sensitivity, as well as the prognostic potential of Ab to 21-OH in patients with polyglandular autoimmune syndrome (APS) – individuals with APS type 1 with and without CPAI (n=106); 2) assessment of the dynamics of the level of Ab to 21-OH – patients with autoimmune CPAI were included (n=41); 3) assessment of the significance of Ab data for the differential diagnosis of various forms of CPAI, including patients with CPAI and APS type 1 exclusion (n=30). The study of Ab to 21-hydroxylase was performed using enzymelinked immunosorbent assay (BioVendor kits, Czech Republic). Results: statistically significant differences were obtained in the frequency of detection of Ab to 21-OH in patients with or without PCNI (p<0,001). The sensitivity of the method was 96%, specificity was 75%, a positive predictive value was 90%, and the negative predictive value was 89%. In 83% of patients, the level of Ab decreased with time (median size decreases – 20,4%/year). An inverse relationship was also found between the level of Ab and the duration of the course of CPAI (R=–0,460, p<0,001). In a group of 30 patients with CPAI and with exclusion of APS type 1, 21 were found to have Ab to 21-OH, only one of them had a monogenic non-autoimmune cause of CPAI (a mutation in the MC2R gene). Monogenic forms of CPAI were found in another 7 patients (mutations were found in the DAX1 and ABCD1 genes), among them an increase in Ab to 21-OH was not detected. Conclusion: determination of Ab to 21-OH is a specific and sensitive method for the diagnosis of autoimmune CPAI. An increase in Ab to 21-OH is a risk marker of autoimmune CPAI development.

Prionopathies and Prionlike Protein Aberrations in Neurodegenerative Diseases

Neurographics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 127-148
Author(s):  
K.N. Anderson ◽  
W.B. Overcast ◽  
J.R. Brosch ◽  
B.D. Graner ◽  
M.C. Veronesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Clinical Presentation ◽  
Prion Diseases ◽  
Imaging Biomarkers ◽  
Amyloid Pet ◽  
Imaging Features ◽  
Jakob Disease ◽  
The Common ◽  
Neuro Imaging

Protein misfolding has been an area of intense research and is implicated in a number of neurodegenerative diseases. Key proteins in the brain lose their native ability to fold and instead assume abnormal conformations. Misfolded proteins cluster to form pathologic aggregates, which cause cellular dysfunction, neuronal death, and neurodegeneration. The prionopathies are best known among the neurodegenerative diseases for their ability to misfold, self-propagate, and infect other organisms. There is increasing evidence of a rationale for a prionlike mechanism of spread of other neurodegenerative diseases through a similar seeding mechanism. In this review, we detail the role of a key protein aberration known to the various prion diseases, including sporadic, variant, and iatrogenic Creutzfeldt-Jakob disease; variably protease-sensitive prionopathy; Gerstmann-Straussler-Scheinker disease; fatal familial insomnia; and kuru. We also discuss the clinical presentation, the available, and emerging imaging options for these diseases. In the second part of this review, we delineate how a prionlike seeding process may be driving the progression of other neurodegenerative diseases, including Parkinson disease, Alzheimer disease, and Huntington disease. A discussion of clinical presentation and imaging features of these example diseases follows to make a case for a common approach to developing imaging biomarkers and therapies of these diseases.Learning Objective: Upon completion of this article, one should be able to describe the various types of prion diseases, recognize and identify the common the neuro-imaging findings in prion diseases, describe seeding mechanism of prion disease, list the common amyloid PET tracers used for Alzheimer’s disease, and list common imaging biomarkers in neurodegenerative diseases.

scholarly journals Measurement of Urinary d- and l-2-Hydroxyglutarate Enantiomers by Stable-Isotope-Dilution Liquid Chromatography–Tandem Mass Spectrometry after Derivatization with Diacetyl-l-Tartaric Anhydride

2004 ◽  
Vol 50 (8) ◽  
pp. 1391-1395 ◽  
Author(s):  
Eduard A Struys ◽  
Erwin E W Jansen ◽  
Nanda M Verhoeven ◽  
Cornelis Jakobs
Keyword(s):  
Mass Spectrometry ◽  
Differential Diagnosis ◽  
Liquid Chromatography ◽  
Stable Isotope ◽  
Tandem Mass Spectrometry ◽  
Tandem Mass ◽  
Internal Standards ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Abstract Background: The differential diagnosis of d-2-hydroxyglutaric aciduria (d-2-HGA), l-2-hydroxyglutaric aciduria (l-2-HGA), and the combined d/l-2-hydroxyglutaric aciduria (d/l-2-HGA) can be accomplished only by the measurement of the corresponding 2-hydroxyglutarate (2-HG). Available methods for the determination of d- and l-2-HG in urine are either time-consuming and expensive or have not been extensively validated. We aimed to develop a method for their rapid and sensitive measurement. Methods: We used liquid chromatography–tandem mass spectrometry (LC-MS/MS) for the determination of d- and l-2-HG with stable-isotope-labeled internal standards. Urine samples of 20 μL were mixed with 250 μL of methanol containing the internal standards and subsequently dried under nitrogen. The analytes were derivatized by use of diacetyl-l-tartaric anhydride (DATAN) to obtain diastereomers, which were separated on an achiral C18 HPLC column and detected by MS/MS in multiple-reaction-monitoring mode. Results: The use of DATAN as chiral derivatization reagent provided very well separated peaks of the formed diastereomers of d- and l-2-HG, with a total runtime of 5 min. The inter- and intraassay CVs for d- and l-2-HG ranged from 3.4% to 6.2%. Mean recoveries of d- and l-2-HG, evaluated on two concentrations, were 94%. Detection limit of the presented method was 20 pmol for a sample volume of 20 μL. Method comparison of the LC-MS/MS method with a gas chromatography–mass spectrometry method, in which d- and l-2-HG were derivatized with R-(−)-butanol, showed good agreement between the two methods. Conclusions: Urinary d- and l-2-HG can be analyzed by MS/MS after derivatization with DATAN. The presented method may be suitable for the differential diagnosis of 2-HGA.

scholarly journals Significance of Serial Determination of Tumor Marker with Reference to the Differential Diagnosis between Pancreatic Cancer and Tumor Forming Pancreatitis.

1992 ◽  
Vol 25 (5) ◽  
pp. 1222-1227
Author(s):  
Yoshito Yamashita ◽  
Young-Suk Chung ◽  
Hideaki Yokomatsu ◽  
Bunzo Nakata ◽  
Tetsuzi Sawada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Differential Diagnosis ◽  
Tumor Marker ◽  
Serial Determination

Procalcitonin as a diagnostic marker of infections and inflammation

2018 ◽  
Vol 54 (3) ◽  
pp. 179-184
Author(s):  
Weronika Kolasińska ◽  
Agnieszka Jankowska-Kulawy
Keyword(s):  
Differential Diagnosis ◽  
Clinical Practice ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Viral Infections ◽  
Diagnostic Marker ◽  
Systemic Inflammatory Response ◽  
Clinical Algorithms

Infections are quite common, especially in long-term hospitalized patients. Eearly differential diagnosis of severe bacterial and viral infections in patients in severe or critical condition is particularly important. Procalcitonin is a good and, above all, early marker of sepsis and generalized inflammatory states. 85% sensitivity and 91% specificity of this study were shown in the differentiation patients with systemic inflammatory response syndrome noninfectious and sepsis defined as a systemic inflammatory response syndrome induced by infection. The usage of procalcitonin assays in clinical algorithms may accelerate the diagnosis of infectious conditions, reduce the abuse of antibiotics and optimize therapy with these drugs. Therefore, the determination of procalcitonin concentration is increasingly used in clinical practice.

Quantitative gel-electrophoretic determination of serum amylase isoenzyme distributions.

1979 ◽  
Vol 25 (11) ◽  
pp. 1919-1923 ◽  
Author(s):  
B K Gillard
Keyword(s):  
Differential Diagnosis ◽  
Disease Progression ◽  
Quantitative Method ◽  
Serum Amylase ◽  
Soluble Starch ◽  
Normal Serum ◽  
Polyacrylamide Gel ◽  
Starch Solution ◽  
Amylase Isoenzymes

Abstract I report a direct, sensitive, quantitative method for determining serum amylase isoenzyme activity with commercially available reagents. Day-to-day reproducibility (CV) was 3--4% for the isoenzymes in normal serum; within-run precision was 8, 3, and 2% for low, normal and high isoenzyme activities. Amylase isoenzymes, separated into the pancreatic and salivary types by electrophoresis in polyacrylamide gel, are then quantified by directly incubating the gels in soluble-starch solution, staining with iodine, and densitometry. The proportion of pancreatic isoenzyme (47 normal sera) was 43 +/- 8% (mean +/- SD). Isoenzyme activities as low as 2% of normal can be measured accurately in 10 micro L of serum. The reproducibility, precision, and sensitivity indicate that the method is applicable to differential diagnosis of hyperamylasemia or hypoamylasemia, and is suited for monitoring the subtle changes in serum amylase isoenzyme distribution that may accompany disease progression or therapy.

Sign in / Sign up

Export Citation Format

Share Document