Normal values and within-subject variability of cardiac I-123 MIBG scintigraphy in healthy individuals: Implications for clinical studies

Background: Although several myocardial iodine 123 metaiodobenzylguanidine (MIBG) indices are increasingly used to detect alterations in myocardial sympathetic activity in various forms of cardiac pathology, published measurements of normal values and within-subject variability are lacking. Methods and Results: Twenty-five healthy volunteers underwent planar and single photon emission computed tomography (SPECT) imaging. Heart-mediastinum ratio (H/M) and myocardial washout were calculated from planar images comparing three different methods for the assessment of myocardial activity: (1) global region over the myocardium (cavity included), (2) global region over the myocardium (cavity excluded), and (3) fixed small myocardial region. Segmental (relative) uptake and washout were assessed by SPECT. For all MIBG indices, the interindividual variation was the lowest for methods 1 and 2. In SPECT this variation was low for relative segmental uptake compared with washout. In 9 subjects a second MIBG scintigraphy was performed after 3 months. The within-subject variability of H/M and washout assessed by planar methods 1 and 2 was 5%, whereas it was approximately 9% for planar method 3. For relative segmental uptake from SPECT, this variability was 5%. Conclusion: MIBG H/M (planar) and relative segmental uptake (SPECT) show a low interindividual and within-subject variability. This enables the detection of small (regional) variations in myocardial sympathetic nervous function, especially to monitor the effect of therapeutic interventions in patients with various cardiac diseases. (J Nucl Cardiol 2004;11: 126-33.

Capillary electrophoresis-mass spectrometry using noncovalently coated capillaries for the analysis of biopharmaceuticals

In this work, the usefulness of capillary electrophoresis–electrospray ionization time-of-flight–mass spectrometry for the analysis of biopharmaceuticals was studied. Noncovalently bound capillary coatings consisting of Polybrene-poly(vinyl sulfonic acid) or Polybrene-dextran sulfate-Polybrene were used to minimize protein and peptide adsorption, and achieve good separation efficiencies. The potential of the capillary electrophoresis-mass spectrometry (CE-MS) system to characterize degradation products was investigated by analyzing samples of the drugs, recombinant human growth hormone (rhGH) and oxytocin, which had been subjected to prolonged storage, heat exposure, and/or different pH values. Modifications could be assigned based on accurate masses as obtained with time-of-flight–mass spectrometry (TOF-MS) and migration times with respect to the parent compound. For heat-exposed rhGH, oxidations, sulfonate formation, and deamidations were observed. Oxytocin showed strong deamidation (up to 40%) upon heat exposure at low pH, whereas at medium and high pH, mainly dimer (>10%) and trisulfide formation (6–7%) occurred. Recombinant human interferon-β-1a (rhIFN-β) was used to evaluate the capability of the CE-MS method to assess glycan heterogeneity of pharmaceutical proteins. Analysis of this N-glycosylated protein revealed a cluster of resolved peaks which appeared to be caused by at least ten glycoforms differing merely in sialic acid and hexose N-acetylhexosamine composition. Based on the relative peak area (assuming an equimolar response per glycoform), a quantitative profile could be derived with the disialytated biantennary glycoform as most abundant (52%). Such a profile may be useful for in-process and quality control of rhIFN-β batches. It is concluded that the separation power provided by combined capillary electrophoresis and TOF-MS allows discrimination of highly related protein species

Effect of off-stoichiometric compositions on microstructures and phase transformation behavior in Ni-Cu-Pd-Ti-Zr-Hf high entropy shape memory alloys

High entropy shape memory alloys (HE-SMAs) show reversible martensitic phase transformations at elevated temperatures. HE-SMAs were derived from binary NiTi, to which the elements Cu, Pd, Zr and Hf are added. They represent ordered complex solid solutions. Their high temperature phase is of B2 type, where the added elements occupy sites in the Ni-(Cu, Pd) and Ti-sub-lattices (Zr, Hf). In the present study, advanced microstructural and thermal characterization methods were used to study the effects of the additional alloy elements on microstructures and phase transformations. The ratios of Ni-equivalent (Ni, Cu, Pd) and Ti-equivalent (Ti, Zr, Hf) elements in HE-SMAs were varied to establish systems that correspond to stoichiometric, under- and over-stoichiometric binary alloys. It is shown that basic microstructural features of cast and heat-treated HE-SMAs are inherited from the nine binary X–Y subsystems (X: Ni, Cu, Pd; Y: Ti, Zr, Hf). The phase transition temperatures that characterize the martensitic forward and reverse transformations depend on the concentrations of all alloy elements. The data obtained demonstrate how martensite start temperatures are affected by deviations from the composition of an ideal stoichiometric B2 phase. The findings are discussed in the light of previous work on the concentration dependence of SMA transformation temperatures, and directions for the development of new shape memory alloy compositions are proposed. © 2020 The Author

Comparison between tagged MRI and standard cine MRI for evaluation of left ventricular ejection fraction

Global left ventricular function is a prognostic indicator and is used to evaluate therapeutical interventions in patients with heart failure. Regional left ventricular function can be determined with tagged MRI. Assessment of global left ventricular function using the tagging data may have additional clinical value without incurring extra scanning time, which is currently a limiting factor in cardiac imaging. Direct determination of end-diastolic volume is not possible with conventional tagged MRI. However, end-systolic volume can be directly measured because myocardium-blood contrast improves through a tagged image series. We investigated the potential of tagged MRI using frequency-domain analysis software to retrospectively track end-diastolic contour from end-systolic contour and subsequently calculate the ejection fraction. Tagged MRI was compared with the standard bright-blood cine MRI in healthy volunteers (n=20) and patients with previous myocardial infarction (n=8). Left ventricular ejection fraction derived from tagged MRI is linearly correlated to left ventricular ejection fraction obtained by standard cardiac cine MRI (y=1.0x+1.31, r>0.98, p=0.014). In addition, the inter-observer and intra-observer coefficient of variation for left ventricular ejection fraction measurements was low (CVintra=0.4%, CVinter=1.3%). With tagged MRI, only end-systolic volume needs to be manually determined, and accurate estimation of left ventricular ejection fraction is obtained because end-diastolic and end-systolic volumes are determined using identical anatomical points. Our data indicate that tagged MRI can be used to quantitatively assess both regional and global left ventricular function. Therefore, tagged MRI may be a valuable clinical tool for determining the prognosis and evaluating the effect of therapeutical intervention using a single imaging session in patients with left ventricular dysfunctio

Renal Function in Relation to Cardiac 123I-MIBG Scintigraphy in Patients with Chronic Heart Failure

The aim of this study was to explore if estimates of renal function could explain variability of 123I-metaiodobenzylguanidine (123I-MIBG) assessed myocardial sympathetic activity. Furthermore estimates of renal function were compared to 123I-MIBG as predictors of cardiac death in chronic heart failure (CHF). Semi-quantitative parameters of 123I-MIBG myocardial uptake and washout were calculated using early heart/mediastinum ratio (H/M), late H/M and washout. Renal function was calculated as estimated Creatinine Clearance (e-CC) and as estimated Glomerular Filtration Rate (e-GFR). Thirty-nine patients with CHF (24 males; age: 64.4 ± 10.5 years; NYHA II/III/IV: 17/20/2; LVEF: 24.0 ± 11.5%) were studied. Variability in any of the semi-quantitative 123I-MIBG myocardial parameters could not be explained by e-CC or e-GFR. During follow-up (60 ± 37 months) there were 6 cardiac deaths. Cox proportional hazard regression analysis showed that late H/M was the only independent predictor for cardiac death (Chi-square 3.2, regression coefficient: −4.095; standard error: 2.063; hazard ratio: 0.17 [95% CI: 0.000–0.950]). Addition of estimates of renal function did not significantly change the Chi-square of the model. Semi-quantitative 123I-MIBG myocardial parameters are independent of estimates of renal function. In addition, cardiac sympathetic innervation assessed by 123I-MIBG scintigraphy seems to be superior to renal function in the prediction of cardiac death in CHF patients

The art of gathering: histories of international scientific conferences

Hundreds of thousands of conferences have taken place since their first appearance in the late eighteenth century, yet the history of science has often treated them as stages for scientific practice, not as the play itself. Drawing on recent work in the history of science and of international relations, the introduction to this special issue suggests avenues for exploring the phenomenon of the inter- national scientific conference, broadly construed, by highlighting the connected dimensions of com- munication, sociability and international relations. It lays out a typology of scientific conferences as a way of gaining an overview of their diversity in the nineteenth and twentieth centuries. It argues that the international scientific conference is a central locus for understanding science as a social, cultural and political practice

Profiling of a high mannose-type N-glycosylated lipase using hydrophilic interaction chromatography-mass spectrometry

Many industrial enzymes exhibit macro- and micro-heterogeneity due to co-occurring post-translational modifications. The resulting proteoforms may have different activity and stability and, therefore, the characterization of their distributions is of interest in the development and monitoring of enzyme products. Protein glycosylation may play a critical role as it can influence the expression, physical and biochemical properties of an enzyme. We report the use of hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) to profile intact glycoform distributions of high mannose-type N-glycosylated proteins, using an industrially produced fungal lipase for the food industry as an example. We compared these results with conventional reversed phase LC-MS (RPLC-MS) and sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE). HILIC appeared superior in resolving lipase heterogeneity, facilitating mass assignment of N-glycoforms and sequence variants. In order to understand the glycoform selectivity provided by HILIC, fractions from the four main HILIC elution bands for lipase were taken and subjected to SDS-PAGE and bottom-up proteomic analysis. These analyses enabled the identification of the most abundant glycosylation sites present in each fraction and corroborated the capacity of HILIC to separate protein glycoforms based on the number of glycosylation sites occupied. Compared to RPLC-MS, HILIC-MS reducted the sample complexity delivered to the mass spectrometer, facilitating the assignment of the masses of glycoforms and sequence variants as well as increasing the number of glycoforms detected (69 more proteoforms, 177% increase). The HILIC-MS method required relatively short analysis time (<30 min), in which over 100 glycoforms were distinguished. We suggest that HILIC(-MS) can be a valuable tool in characterizing bioengineering processes aimed at steering protein glycoform expression as well as to check the consistency of product batche