Three commercial polyclonal immunoassays for cyclosporine in whole blood compared: 1. Results with patients' specimens

1990 ◽  
Vol 36 (1) ◽  
pp. 115-118 ◽  
Author(s):  
M J Strassman ◽  
G L Lensmeyer ◽  
D A Wiebe ◽  
I H Carlson

Abstract We assessed the performance of three commercially available polyclonal immunoassays for apparent cyclosporine in 120 whole-blood specimens collected from transplant recipients just before their next dose of cyclosporine (CsA). The assays were (a) Abbott's TDx fluorescent polarization immunoassay for CsA and its metabolites in whole blood; (b) the Sandoz radioimmunoassay (RIA); and (c) Incstar's Cyclo-Trac RIA. Mean respective CVs were 3.8%, 9.3%, and 24.3%. Analytical recovery was nearly 100% for concentrations up to 1000 micrograms/L for Incstar and up to 1500 micrograms/L for Abbott and Sandoz; linearity was compromised at greater concentrations. We also quantified the parent CsA concentrations by HPLC. Moreover, to follow day-to-day fluctuations in patients' "cyclosporine" concentrations with each method and to assess the impact these differences have on interpretation of the analytical results, we assayed serial specimens from six post-transplant patients. These showed significantly dissimilar, but parallel, results among the methods for any single sample. Occasionally, however, a result would not fit the established trend. Biases observed among the assays can be explained in part by the nonspecific antisera cross-reacting with CsA metabolites. Most important, we demonstrate that patients' results are not reliably interchangeable among the methods.

1990 ◽  
Vol 36 (11) ◽  
pp. 1969-1973 ◽  
Author(s):  
R W Yatscoff ◽  
K R Copeland ◽  
C J Faraci

Abstract We report here the evaluation of the Abbott TDx assay with a monoclonal antibody for selectively quantifying cyclosporine (CsA) in whole blood. Over the clinically relevant concentration ranges, results with this assay demonstrated within- and between-run CVs of less than 2.5% and 5%, respectively; sensitivity of 25 micrograms/L; good analytical recovery (100.3%); and linearity with whole-blood specimens. The percentage cross-reactivity of the major CsA metabolites varied from 15.3% for AM9 (M-1), 8.2% for AM1 (M-17), and 3.7% for AM4N (M-21), to less than 3% for the other metabolites tested. Results with the TDx assay (y) correlated well with those by the Sandimmune selective RIA (x; Sandoz) with blood specimens from 44 renal-transplant recipients (n = 44, x= 187.3, y = 198.9, y = 5.49 + 1.03x, r = 0.987). The TDx values were on average 24% higher than those by HPLC (x') with the same patients' specimens (n = 44, x' = 159.9, y = 198.9, y = 15.9 + 1.14x', r = 0.967). We conclude that the Abbott TDx monoclonal antibody assay provides a rapid, precise, and accurate means for quantifying CsA in whole blood.


2021 ◽  
Vol 2 (3) ◽  
pp. 291-293
Author(s):  
Ryan J. Winstead ◽  
Johanna Christensen ◽  
Sara Sterling ◽  
Megan Morales ◽  
Dhiren Kumar ◽  
...  

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR.


2004 ◽  
Vol 34 (6) ◽  
pp. 1065-1082 ◽  
Author(s):  
MARY AMANDA DEW ◽  
LARISSA MYASKOVSKY ◽  
ANDREA F. DIMARTINI ◽  
GALEN E. SWITZER ◽  
HERBERT C. SCHULBERG ◽  
...  

Background. Family members adopt key caregiving roles in the maintenance of transplant recipients' health. While the bulk of the caregiving literature suggests that rates of psychiatric disorder should be high in these caregivers, the potential benefits of transplantation may instead lead to less distress than in other caregiving situations. We examined prevalence and risk factors for depressive and anxiety-related disorders in caregivers throughout 3 years after their family member's heart transplant.Method. A total of 190 caregivers (97% of eligible respondents) were enrolled. They received psychiatric and psychosocial evaluations at 2, 7, 12 and 36 months post-transplant. Survival analysis determined cumulative rates of psychiatric disorders and the impact of potential risk factors.Results. Rates of depressive and anxiety-related disorders met or exceeded other caregiver populations' rates. By 3 years post-transplant, cumulative onset rates were: Major Depressive Disorder (MDD), 31·6%, Adjustment disorders, 35·4% (29·4% with anxious mood); Post-Traumatic Stress Disorder related to the transplant (PTSD-T), 22·5%, Generalized Anxiety Disorder, 7·3%, and any assessed disorder, 56·3%. PTSD-T occurred primarily during the first year post-transplant. Other disorders' rates increased over the entire study period. Risk for disorder was elevated by positive lifetime history of psychiatric disorder, greater post-transplant caregiving responsibilities, and a poorer relationship with the patient. Risk for MDD was further increased by caregiver unemployment, and risk for anxiety disorders was further increased by younger age, low sense of personal mastery, and high use of avoidance coping strategies.Conclusions. Transplantation is associated with costs and benefits for not only patients but family caregivers. Caregivers' risk for psychiatric illness should be considered when developing interventions to promote families' long-term adjustment to the transplant process.


Author(s):  
Mohammed Altaf ◽  
Katie Lineburg ◽  
Pauline Crooks ◽  
Sweera Rehan ◽  
Katherine K Matthews ◽  
...  

Abstract Cytomegalovirus (CMV) remains a significant burden in lung transplant recipients. Deficiencies in T-cell immunity post-transplant increase the risk of CMV-associated complications. However, it is not clear if underlying poor pre-transplant immunity increases risk. To assess this, we recruited 39 prospective lung transplant patients and performed QuantiFERON-CMV on their peripheral blood. More than a third of prospective CMV-seropositive transplant recipients were CMV non-immune-reactive (CMV-NIR) pre-transplant. CMV-NIR status was associated with a significantly higher incidence of CMV reactivation post-transplant, demonstrating that dysfunctional CMV immunity in prospective lung transplant recipients is associated with an increased risk of viral reactivation post-transplant.


2018 ◽  
Vol 33 (5) ◽  
pp. 897-910 ◽  
Author(s):  
Britta Höcker ◽  
Martin Aguilar ◽  
Paul Schnitzler ◽  
Lars Pape ◽  
Martin Bald ◽  
...  

1992 ◽  
Vol 38 (8) ◽  
pp. 1440-1443 ◽  
Author(s):  
J W Holman ◽  
R A Felder

Abstract Cyclosporin A (CsA) is currently the most selective immunosuppressant used clinically to prevent organ rejection after transplantation. We used a reprogrammable robot, the Benchmate (Zymark Inc., Hopkinton, MA), to automate much of the sample preparation involved in solid-phase extraction of CsA. Lysed whole-blood specimens containing previously added internal standard were placed on the Benchmate in the specimen-holding area, and a C18 Bond-Elut column was placed in the top of the sample tube. Specimen extraction from this point was handled automatically by the Benchmate, after which we manually injected the sample into the HPLC system for quantification. Analytical recovery of CsA in two concentrations of calibrator was similar for the manual and Benchmate methods. Analytical imprecision for the Benchmate was less than for manual extraction: within-run imprecision (CV) was less than 8% at either concentration. Between-run imprecision, determined by having the Benchmate extract CsA from two specimens each day for 20 days, was less than 9%. Patients' specimens were extracted manually (x) or by using the Benchmate robot (y); the results, compared by linear regression, agreed well: (y = 0.99 (SD 0.02)x + 2.6 (SD 2.8) micrograms/L (Sy[x = 7.59 micrograms/L, n = 27). We conclude that the Benchmate usefully reduces the manual steps necessary to extract specimens before HPLC analysis for CsA.


1993 ◽  
Vol 39 (11) ◽  
pp. 2235-2241 ◽  
Author(s):  
M H Beresini ◽  
D Davalian ◽  
S Alexander ◽  
R Toton-Quinn ◽  
B Barnett ◽  
...  

Abstract We evaluated the EMIT Cyclosporine Assay, designed for specific quantification of cyclosporine (CsA) in whole blood. The assay was run on the Roche Cobas Mira or Cobas Mira S analyzer. Analytical recovery from both normal donor whole blood and transplant patients' samples was within 17% of the standards. Measurement of diluted out-of-range samples also yielded excellent recovery (101-105%). Within-run, between-run, and total CVs were < or = 8.1%, 10.9%, and 12.1%, respectively. The detection limit was < 32 micrograms/L. The assay was linear from 0 to 500 micrograms/L. No significant cross-reactivity was observed for CsA metabolites AM1, AM19, and AM4N. Slight cross-reactivity occurred with metabolite AM9; 670 micrograms/L AM9 increased the measured CsA concentration by 49 micrograms/L. High concentrations of bilirubin, uric acid, triglycerides, and cholesterol, as well as 54 commonly coadministered drugs did not interfere with CsA quantification. Similarly, neither extreme values of hematocrit nor choice of anticoagulant affected CsA recovery. Sample extract stability was > 4 h, and assay calibration was stable for at least 2 weeks. Patients' samples analyzed by the EMIT assay showed strong correlation with both HPLC and 125I-RIA (r > 0.97). We conclude that the EMIT Cyclosporine Assay provides a convenient, accurate, and precise method for specific quantification of CsA in whole blood.


1989 ◽  
Vol 43 (3) ◽  
pp. 242-247
Author(s):  
Debra Jarvis

Discusses briefly the nature and characteristics of dialysis, pre-transplant patients, and post-transplant patients; and identifies pastoral care issues particularly relevant to each phase of the kidney transplant recipient's journey. Concludes that the key to offering authentic pastoral care to these patients is the wise integration of information and genuine concern.


2013 ◽  
Vol 59 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Jean-Baptiste Woillard ◽  
Nassim Kamar ◽  
Sandra Coste ◽  
Lionel Rostaing ◽  
Pierre Marquet ◽  
...  

BACKGROUND Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C>T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C>T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G>A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients. METHODS The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions. RESULTS In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, β = −0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events. CONCLUSIONS These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.


2021 ◽  
Vol 16 (2) ◽  
pp. 265-272
Author(s):  
Georgeta Daniela GEORGESCU ◽  
◽  
Felicia MIHAI ◽  
Meilin OMER ◽  
Viola POPOV ◽  
...  

Background. Stem cell transplantation is an important therapeutic approach for patients with malignant hemopathies, whether we refer to autologous or allogeneic stem cell transplantation. Aims and methods. We present the characteristics of a group of 54 patients diagnosed with malignant haemopathy in the Department of Hematology of the Colentina Clinical Hospital, between 2004 and 2018, and who have benefited from stem cell transplantation both in the country and abroad. The data analyzed were: diagnosis of the disease, type of response to induction therapy, type and timing of transplantation, transplant in first remission or relapse, if there were patients who benefited from a second transplant, post-transplant survival, as well as demographics. The statistical analysis was performed using the system MedCalc Statistical Software Version 18.11.3. Results and conclusions. Survival analysis was applied separately for autotransplant patients and those who benefited from allotransplant (Kaplan Meier survival analyses). Significant differences were observed due to transplantation type and due to relapse after transplant, in our lot of patients. Post-transplant recurrence was an unfavorable prognostic factor for both autologous and allogeneic transplanted patients. Update. A new challenge: The COVID-19 pandemic threat. The SARS-CoV-2 infection is a threat for immunocompromised patients. From a group of 9 patients hospitalized in 2020 for COVID-19 in the Department of Hematology of the Colentina Clinical Hospital, and who have benefited in the past from stem cell transplantation (2 patients) or organ transplant (1 patient – lung, 3 patients – liver, 3 patients – kidney) in Romania, 4 of them have required hospitalization in the Intensive Care Unit (ICU) (authors's observational data). New data are needed to elucidate the prognostic factors to establish the outcome of transplant patients such as for all cancer patients or immunocompromised patients in the current COVID pandemic 19 era and the impact on public health.


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