Assessment of accuracy and precision of 99mTc-HEPIDA clearances determined by means of a simplified method

BACKGROUND: The aim of the present study was the assessment of the accuracy and precision of our own simplified method for the determination of 99mTc-HEPIDA liver clearance. MATERIAL AND METHODS: It has been assumed that archived results of plasma clearance (ClPl) and hepatic (ClHp), determined by means of multisample methods, could be legitimately used as a reference standard. The accuracy and precision of the simplified method was assessed by means of a Monte Carlo method alternatively utilizing three blood sampling times (T) of 68, 75 and 83 minutes post i.v. administration of 99mTc-HEPIDA. The corresponding alternative three urine voiding times (Y) were: 75, 80, and 95 min p.i. The analysed model was created accepting values of ClPl and ClHp, of administered activity Ap and parameters of biexponential function, describing the concentration C(t) decrease of the radiopharmaceutical (RF) in plasma during time as real values. Using the function C(t) for each individual, the plasma concentrations of RF at three sampling times, urinary clearance (ClPl - ClHp), and voided activity (AUr(Y)) were calculated. Simulated random errors were added to the assumed blood sampling times T and to voiding time Y. To the activity Ap and AUr(Y), and RF plasma concentrations random errors were added, assuming normal distribution with relative SD from 0 to 5% and then clearance values were computed. For each process there were 5000 repeated simulated determinations. The accuracy of the simplified methods was assessed by comparing mean values of simulated clearance computations with the reference. Comparison of standard deviations with mean uncertainties enabled us to gain insight into the degree of agreement of the estimator of relative uncertainty with the coefficient of variation as a measure of precision. RESULTS: There were strong correlations between the reference clearance values and the mean values of determinations by means of the simplified procedure (r > 0.93). The correlations were practically insensitive to the uncertainty of pipetting. The lines of regression differed slightly from the lines of identity, giving an indication that there was a systematic error involved; it amounted to +4 ml/min at ClPl = 60 ml/min and to -7 ml/min for ClPl of 370 ml/min. For ClPl a bias of +6 ml/min was found for a clearance value of 16 ml/min and –13 ml/min at ClPl > 300 ml/min. At uncertainty of pipetting of 2%, a precision of 6-7% was found for ClPl of 300 ml/min. For ClPl of 200 and 150 ml/min the corresponding precisions were 7–8% and 10%, respectively. For ClPl of 200, 150 and 100 ml/min the corresponding precisions were 10, 12 and 17%, respectively. These precisions are 5 percent worse than those that were obtained from determinations by means of multisampling procedures

Modification of a two blood sample method used for measurement of GFR with 99mTc-DTPA

BACKGROUND Measurements of GFR may be performed with a slope/intercept method (S/I), using only two blood samples taken in strictly defined time points. The aim of the study was to modify this method in order to extend time intervals suitable for blood sampling. Modification was based on a variation of a Russel et al. model parameter, selection of time intervals suitable for blood sampling and assessment of uncertainty of calculated results. MATERIAL AND METHODS Archived values of GFR measurements of 169 patients with different renal function, from 5.5 to 179 mL/min, calculated with a multiple blood sample method were used. Concentrations of a radiopharmaceutical in consecutive minutes, from 60th to 190th after injection, were calculated theoretically, using archived parameters of biexponential functions describing a decrease in 99mTc-DTPA concentration in blood plasma with time. These values, together with injected activities, were treated as measurements and used for S/I clearance calculations. Next, values of S/I clearance were compared with the multiple blood sample method in order to calculate suitable values of exponent present in a Russel’s model, for every combination of two blood sampling time points. A model was considered accurately fitted to measured values when SEE ≤ 3.6 mL/min. Assessments of uncertainty of obtained results were based on law of error superposition, taking into account mean square prediction error and also errors introduced by pipetting, time measurement and stochastic radioactive decay. RESULTS The accepted criteria resulted in extension of time intervals suitable for blood sampling to: between 60 and 90 minutes after injection for the first sample and between 150 and 180 minutes for the second sample. Uncertainty of results was assessed as between 4 mL/min for GFR = 5–10 mL/min and 8 mL/min for GFR = 180 mL/min. CONCLUSIONS Time intervals accepted for blood sampling fully satisfy nuclear medicine staff and ensure proper determination of GFR. Uncertainty of results is entirely acceptable and for high GFR values even comparable with uncertainty of multi-sample measurements.BACKGROUND Measurements of GFR may be performed with a slope/intercept method (S/I), using only two blood samples taken in strictly defined time points. The aim of the study was to modify this method in order to extend time intervals suitable for blood sampling. Modification was based on a variation of a Russel et al. model parameter, selection of time intervals suitable for blood sampling and assessment of uncertainty of calculated results. MATERIAL AND METHODS Archived values of GFR measurements of 169 patients with different renal function, from 5.5 to 179 mL/min, calculated with a multiple blood sample method were used. Concentrations of a radiopharmaceutical in consecutive minutes, from 60th to 190th after injection, were calculated theoretically, using archived parameters of biexponential functions describing a decrease in 99mTc-DTPA concentration in blood plasma with time. These values, together with injected activities, were treated as measurements and used for S/I clearance calculations. Next, values of S/I clearance were compared with the multiple blood sample method in order to calculate suitable values of exponent present in a Russel’s model, for every combination of two blood sampling time points. A model was considered accurately fitted to measured values when SEE ≤ 3.6 mL/min. Assessments of uncertainty of obtained results were based on law of error superposition, taking into account mean square prediction error and also errors introduced by pipetting, time measurement and stochastic radioactive decay. RESULTS The accepted criteria resulted in extension of time intervals suitable for blood sampling to: between 60 and 90 minutes after injection for the first sample and between 150 and 180 minutes for the second sample. Uncertainty of results was assessed as between 4 mL/min for GFR = 5–10 mL/min and 8 mL/min for GFR = 180 mL/min. CONCLUSIONS Time intervals accepted for blood sampling fully satisfy nuclear medicine staff and ensure proper determination of GFR. Uncertainty of results is entirely acceptable and for high GFR values even comparable with uncertainty of multi-sample measurements

Final surgical interventions in primary total knee arthroplasty infections : a retrospective

Poster presented at the 2017 Health Sciences Research Day which was organized and sponsored by the University of Missouri School of Medicine Research Council and held on November 9, 2017.Conclusions: Two stage revision is largely regard as the gold standard for treatment of chronic PJI in primary TKA. Follow-up for these patients who continue to be at risk for infection related failure over an extended period of time frequently did not return to the institution where their infection management was started. Our retrospective study identified that subset (23.8%) of those undergoing two-stage intervention and who had returned for follow-up were never reimplanted. Only half of those reimplanted retain those components over a 31 month follow up from the time of their initial intervention. These results give a more guarded prognosis for the outcome of patients with prosthetic joint replacement than what has been traditionally reported in the literature. The more challenging prognosis may be impacted by host comorbidities, antibiotic susceptibility of infecting organisms, timing to surgical treatment, or other factors

30P Nowa fizyczna metoda wczesnego diagnozowania i monitorowania leczenia chorych z rozpoznaniem nowotworu

Pole magnetyczne o indukcji B > 10 tesli znajduje zastosowanie w analizie indukowanej dwójłomności kołowej surowicy krwi. Analiza oddziaływania silnego pola magnetycznego i elektromagnetycznego pola wiązki świetlnej z surowicą krwi wykazała, że w silnym polu magnetycznym ujawnia się wyraźnie ilościowa różnica magneto-optycznych efektów obserwowanych dla surowic dawców krwi chorych z nowotworami. Dokonano analizy 110 surowic krwi. Pomiary wykonano w silnym impulsowym (B ≅ 30 tesli). Próbki surowicy 23 dawców krwi zostały poddane badaniom mającym na celu określenie naturalnej aktywności optycznej. Surowice te stanowiły punkt odniesienia do analiz surowic chorych onkologicznych. Analizowano surowice chorych z rozpoznaniem raka prostaty, jelita grubego, raka jajnika, w którym w trakcie leczenia oznacza się poziom markerów nowotworowych. Druga grupa chorych to pacjenci z mierzalnymi guzami gruczołu piersiowego, mięsaka, czerniaka, szpiczaka. Dokonano pomiarów magneto-optycznych współczynników a, b, c oraz naturalnej aktywności optycznej α0 surowic.Wykazano wyraźną współzależność między stanem chorego, a wartością współczynnika b oraz jego korelacją ze wzrostem poziomu markerów nowotworowych lub wielkością ognisk przerzutowych. Prowadzone po raz pierwszy badania magnatyczno-optycznej dwójłomności kołowej surowicy są szybką metodą analityczną. Mogą w przyszłości mieć zastosowanie w diagnostyce i monitorowaniu leczenia nowotworów

Rejection in Łukasiewicz's and Słupecki's Sense

The idea of rejection originated by Aristotle. The notion of rejection was introduced into formal logic by Łukasiewicz [20]. He applied it to complete syntactic characterization of deductive systems using an axiomatic method of rejection of propositions [22, 23]. The paper gives not only genesis, but also development and generalization of the notion of rejection. It also emphasizes the methodological approach to biaspectual axiomatic method of characterization of deductive systems as acceptance (asserted) systems and rejection (refutation) systems, introduced by Łukasiewicz and developed by his student Słupecki, the pioneers of the method, which becomes relevant in modern approaches to logic

Linewidths in bound state resonances for helium scattering from Si(111)-(1x1)H

Helium-3 spin-echo measurements of resonant scattering from the Si(111)–(1 × 1)H surface, in the energy range 4–14 meV, are presented. The measurements have high energy resolution yet they reveal bound state resonance features with uniformly broad linewidths. We show that exact quantum mechanical calculations of the elastic scattering, using the existing potential for the helium/Si(111)–(1 × 1)H interaction, cannot reproduce the linewidths seen in the experiment. Further calculations rule out inelastic and other mechanisms that might give rise to losses from the elastic scattering channels. We show that corrugation in the attractive part of the atom–surface potential is the most likely origin of the experimental lineshapes

Comparison of 99mTc-HEPIDA and 99mTc-MBrIDA from the standpoint of hepatic clearance determination - preliminary communication

BACKGROUND. In order to evaluate the functional capacity of the liver by means of clearance determination, the derivative of iminodiacetic acid (99mTc-HEPIDA) has been used in recent decades. Because of recent problems with manufacturing and delivery of 99mTc-HEPIDA, an investigation was undertaken with the aim of testing whether a more widely available 99mTc-MBrIDA could be used for clearance determination and whether hepatic clearance measured with the use of this compound provides a similarly useful test of hepatic function. MATERIAL AND METHODS. Comparative investigations were performed in 73 patients of both sexes. The state of the efficiency of liver parenchyma was determined based on seven widely used biochemical tests, i.e. levels of: bilirubin, albumin, and gamma globulin; activity of AST, ALT, GGTP, and prothrombin index. The clearances of both radiopharmaceuticals, 99mTc-HEPIDA and 99mTc-MBrIDA, were determined by means of multisample technique. The results of determination were correlated among themselves and with the results of biochemical tests. The set of results of all estimations allowed a factorial analysis to be performed to find a common factor and to compute the values of factor loadings in particular tests. RESULTS. Obvious correlation between plasma and hepatic clearances of both radiopharmaceuticals was obtained and between plasma clearance of 99mTc-MBrIDA and hepatic clearance of 99mTc-HEPIDA. Correlation coefficients of 99mTc-MBrIDA clearance and the biochemical test results attained somewhat lower values than for 99mTc-HEPIDA clearance. Similarly, values of χ2 test of independence of 99mTc-MBrIDA clearances and test results were also less close than for 99mTc-HEPIDA clearances. Factorial analysis showed that common factor loading is greatest for hepatic clearance of 99mTc-HEPIDA; the values of two loadings of 99mTc-MBrIDA clearances are very close, but somewhat lower than those for 99mTc-HEPIDA. CONCLUSIONS. From the performed investigations it is possible to conclude that 99mTc-MBrIDA clearances may be used for the evaluation of liver parenchyma performance, even if the results may not be as certain as those obtained using 99mTc-HEPIDA

Comments on ``The first detections of the Extragalactic Background Light at 3000, 5500, and 8000 A'' by Bernstein, Freedman and Madore

A critical discussion is presented of the data analysis applied by Bernstein, Freedman and Madore (2002 ApJ, 571, 56; and ApJ 571, 85) in their measurement of the Extragalactic Background Light. There are questionable assumptions in the analysis of the ground-based observations of the Zodiacal Light. The modeling of the Diffuse Galactic Light is based on an underestimated value of the dust column density along the line of sight. Comparison with the previously presented results from the same observations reveals a puzzling situation: in spite of a large difference in the atmospheric scattered light corrections the derived Extragalactic Background Light values are exactly the same. The claim of the paper of a ``detection of the Extragalactic Background Light'' appears premature.Comment: 6 pages, accepted for Ap

Evinacumab — an ANGPTL3 inhibitor; a new drug in the treatment of lipid disorders. Review on the literature and clinical studies

Angiopoietin-like proteins (ANGPTL) are a family of several proteins, of which ANGPTL3, 4 and 8 are involved in lipid metabolism. These proteins, discovered relatively recently, regulate the availability of triglycerides for the heart, skeletal muscles and white and brown adipose tissue depending on the nutritional status of the body, thus contributing to the maintenance of energy homeostasis. ANGPTL3, 4 and 8 gene mutations are associated with a significant reduction in plasma lipid levels, which translates to a reduction in the risk of ischaemic heart disease and diabetes type 2. It was shown that blood levels of ANGPTL3, 4, 5 and 8 may change in various disease states, such as obesity or diabetes type 2, and thus may constitute biomarkers of the cardiovascular risk. Evinacumab, being a fully humanized anti-ANGPTL3 antibody, February, 11th, 2021, as Evkeeza® preparation, has been registered by the US Food and Drug Administration for the treatment of homozygous familial hypercholesterolaemia. In clinical trials, evinacumab was characterized by a high lipid-lowering efficacy in patients with homozygous and heterozygous familial hypercholesterolaemia, as well as treatment-resistant hypercholesterolaemia and hypertriglyceridaemia. Another drug that reduces ANGPTL3 activity are antisense oligonucleotides targeting Angptl3 mRNA (ANGPTL3 ASO) which were also characterized by lipid lowering properties in clinical trials.Angiopoietin-like proteins (ANGPTL) are a family of several proteins, of which ANGPTL3, 4 and 8 are involved in lipid metabolism. These proteins, discovered relatively recently, regulate the availability of triglycerides for the heart, skeletal muscles and white and brown adipose tissue depending on the nutritional status of the body, thus contributing to the maintenance of energy homeostasis. ANGPTL3, 4 and 8 gene mutations are associated with a significant reduction in plasma lipid levels, which translates to a reduction in the risk of ischaemic heart disease and diabetes type 2. It was shown that blood levels of ANGPTL3, 4, 5 and 8 may change in various disease states, such as obesity or diabetes type 2, and thus may constitute biomarkers of the cardiovascular risk. Evinacumab, being a fully humanized anti-ANGPTL3 antibody, February, 11th, 2021, as Evkeeza® preparation, has been registered by the US Food and Drug Administration for the treatment of homozygous familial hypercholesterolaemia. In clinical trials, evinacumab was characterized by a high lipid-lowering efficacy in patients with homozygous and heterozygous familial hypercholesterolaemia, as well as treatment-resistant hypercholesterolaemia and hypertriglyceridaemia. Another drug that reduces ANGPTL3 activity are antisense oligonucleotides targeting Angptl3 mRNA (ANGPTL3 ASO) which were also characterized by lipid lowering properties in clinical trials

Ewinakumab — inhibitor ANGPTL3 — nowy lek w terapii zaburzeń lipidowych. Przegląd literatury i badań klinicznych

Białka podobne do angiopoetyny (ANGPTL) tworzą rodzinę kilku białek, z których ANGPTL3, 4 i 8 są zaangażowane w metabolizm lipidów. Białka te, odkryte stosunkowo niedawno, regulują dostępność triglicerydów dla serca, mięśni szkieletowych oraz białej i brązowej tkanki tłuszczowej zależnie od stanu odżywienia organizmu, przyczyniając się tym samym do zachowania homeostazy energetycznej. Mutacje genów ANGPTL3, 4 i 8 objawiają się istotnym zmniejszeniem stężenia lipidów w osoczu, co przekłada się na redukcję ryzyka choroby niedokrwiennej serca i cukrzycy typu 2. Wykazano, że stężenia ANGPTL3, 4 i 8, a także ANGPTL5 we krwi mogą ulegać zmianom w różnych stanach chorobowych, takich jak otyłość czy cukrzyca typu 2, i stanowić tym samym biomarker ryzyka sercowo-naczyniowego. Ewinakumab, będący w pełni humanizowanym przeciwciałem przeciwko ANGPTL3, 11 lutego 2021 roku, jako preparat Evkeeza®, został zarejestrowany przez amerykańską Agencję ds. Żywności i Leków do terapii homozygotycznej hipercholesterolemii rodzinnej. Ewinakumab charakteryzował się dużą skutecznością hipolipemizującą u chorych z homozygotyczną i heterozygotyczną postacią hipercholesterolemii rodzinnej, a także z hipercholesterolemią oporną i hipertriglicerydemią. Innymi lekami zmniejszającymi aktywność ANGPTL3 są antysensowne oligonukleotydy (ANGPTL3 ASO), które również charakteryzowały się właściwościami hipolipemizującymi w badaniach klinicznych.Białka podobne do angiopoetyny (ANGPTL) tworzą rodzinę kilku białek, z których ANGPTL3, 4 i 8 są zaangażowane w metabolizm lipidów. Białka te, odkryte stosunkowo niedawno, regulują dostępność triglicerydów dla serca, mięśni szkieletowych oraz białej i brązowej tkanki tłuszczowej zależnie od stanu odżywienia organizmu, przyczyniając się tym samym do zachowania homeostazy energetycznej. Mutacje genów ANGPTL3, 4 i 8 objawiają się istotnym zmniejszeniem stężenia lipidów w osoczu, co przekłada się na redukcję ryzyka choroby niedokrwiennej serca i cukrzycy typu 2. Wykazano, że stężenia ANGPTL3, 4 i 8, a także ANGPTL5 we krwi mogą ulegać zmianom w różnych stanach chorobowych, takich jak otyłość czy cukrzyca typu 2, i stanowić tym samym biomarker ryzyka sercowo-naczyniowego. Ewinakumab, będący w pełni humanizowanym przeciwciałem przeciwko ANGPTL3, 11 lutego 2021 roku, jako preparat Evkeeza®, został zarejestrowany przez amerykańską Agencję ds. Żywności i Leków do terapii homozygotycznej hipercholesterolemii rodzinnej. Ewinakumab charakteryzował się dużą skutecznością hipolipemizującą u chorych z homozygotyczną i heterozygotyczną postacią hipercholesterolemii rodzinnej, a także z hipercholesterolemią oporną i hipertriglicerydemią. Innymi lekami zmniejszającymi aktywność ANGPTL3 są antysensowne oligonukleotydy (ANGPTL3 ASO), które również charakteryzowały się właściwościami hipolipemizującymi w badaniach klinicznych