Sandra C Bryant

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (93)383.68 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent reports have suggested an association between variation in the serotonin transporter and primary pulmonary hypertension and myocardial infarction. We set out to determine whether these associations were present in a population of patients who underwent SLC6A4 genotyping and to explore whether genetic variation in the serotonin transporter might be also associated with other cardiovascular functional and structural abnormalities. Included were 3473 patients who were genotyped for the SLC6A4 5HTTLPR polymorphism and a subset for rs25531 (n=816) and STin2 (n=819). An association was observed between 5HTTLPR and primary pulmonary hypertension (p=0.0130), anomalies of the cerebrovascular system (p<0.0001), and other anomalies of great veins (p=0.0359). The combined 5HTTLPR and rs25531 genotype was associated with tachycardia (p=0.0123). There was an association of the STin2 genotype with abnormal electrocardiogram (ECG) (p=0.0366) and abnormal cardiac study (0.0311). Overall, these results represent a step toward the understanding of the impact of SLC6A4 variation on cardiovascular pathology.
    Genetic Testing and Molecular Biomarkers 02/2015; 19(3). DOI:10.1089/gtmb.2014.0250 · 1.15 Impact Factor
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    ABSTRACT: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA-TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA-TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA-TMA since transplant. Thirty-three patients diagnosed with TA-TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All-cause day-30 and day-100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P-value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30-day and 100-day all-cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P-value = 0.25 and 0.08, for 30- and 100-day all-cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA-TMA. The overall efficacy of PE is poor; however, patients who present with TA-TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Clinical Apheresis 09/2014; DOI:10.1002/jca.21352 · 1.58 Impact Factor
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    ABSTRACT: Context.- Systems-based practice (SBP) is 1 of 6 core competencies required in all resident training programs accredited by the Accreditation Council for Graduate Medical Education. Reliable methods of assessing resident competency in SBP have not been described in the medical literature. Objective.- To develop and validate an analytic grading rubric to assess pathology residents' analyses of SBP problems in clinical chemistry. Design.- Residents were assigned an SBP project based upon unmet clinical needs in the clinical chemistry laboratories. Using an iterative method, we created an analytic grading rubric based on critical thinking principles. Four faculty raters used the SBP project evaluation rubric to independently grade 11 residents' projects during their clinical chemistry rotations. Interrater reliability and Cronbach α were calculated to determine the reliability and validity of the rubric. Project mean scores and range were also assessed to determine whether the rubric differentiated resident critical thinking skills related to the SBP projects. Results.- Overall project scores ranged from 6.56 to 16.50 out of a possible 20 points. Cronbach α ranged from 0.91 to 0.96, indicating that the 4 rubric categories were internally consistent without significant overlap. Intraclass correlation coefficients ranged from 0.63 to 0.81, indicating moderate to strong interrater reliability. Conclusions.- We report development and statistical analysis of a novel SBP project evaluation rubric. The results indicate the rubric can be used to reliably assess pathology residents' critical thinking skills in SBP.
    Archives of pathology & laboratory medicine 06/2014; 138(6):809-13. DOI:10.5858/arpa.2013-0046-OA · 2.88 Impact Factor
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    ABSTRACT: Background The cold agglutinin (CAGG) titer is offered at our institution to aid in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally adjusted reference range using prospective samples and compare it to a reference range generated retrospectively.Study Design and Methods Prospective CAGG titer testing was performed on healthy blood donors. Retrospective electronic analysis was performed on patients in two groups defined by current and historical testing methods. Blood donor testing was performed in January and July to determine if seasonal variation existed. Retrospective patients with conditions associated with CAD were excluded from analysis. Additional prospective CAGG testing using reference range program volunteers was performed to verify blood donor and patient result differences.ResultsTiters from the blood donor and patient cohorts had no age association (p > 0.44). Titers from those same cohorts did not show winter/summer variation (p > 0.11). No sex association was found with titer reference ranges in the blood donor and historical patient cohort. A sex association was found with titers in the current method patient cohort (male 64 to 512 and female ≤64; p < 0.0001). Blood donor CAGG titer lower 95% reference range was not more than 4 while historical and current patient cohorts ranges were not more than 32 and not more than 64, respectively. Reference range volunteers confirmed the narrow reference range in healthy individuals when compared to patients and blood donors.Conclusion Prospective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts.
    Transfusion 05/2014; 54(5). DOI:10.1111/trf.12453 · 3.57 Impact Factor
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    ABSTRACT: The use of hematopoietic progenitor cell (HPC) transplant has risen over the past two decades. A variety of adverse events (AEs) of varying severity have been noted during HPC infusions. These AEs have been associated with several factors such as the amount of dimethyl sulfoxide and white blood cells in the HPC product. We performed a single-institution retrospective analysis to determine the effect of two different HPC infusion techniques, manual push with syringes versus infusion from bags with the aid of gravity, on the occurrence of infusion-related AEs. Infusions between December 2008 and November 2010 involving peripheral blood HPCs were reviewed. Pertinent clinical and HPC product-related information was recorded. Data were analyzed to determine the incidence of infusion-related AEs and its association with patient and product-related variables. We found 461 AEs in 645 patients during the study period. A total of 325 (50%) experienced at least one AE. Flushing was the most common type of AE followed by nausea and hypertension. The use of syringe infusion was more commonly associated with AEs (odds ratio, 1.82 [95% confidence interval, 1.32-2.50]; p = 0.002). Other independent risk factors were cryopreserved products and the amount of polymorphonuclear leukocytes in the product. To our knowledge, this is the first study examining the effect of two different infusion techniques on infusion-related AEs. Our findings suggest that the use of bags for infusion protected the patients from AEs.
    Transfusion 02/2014; 54(8). DOI:10.1111/trf.12572 · 3.57 Impact Factor
  • Mitochondrion 11/2013; 13(6):913-914. DOI:10.1016/j.mito.2013.07.042 · 3.52 Impact Factor
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    ABSTRACT: BACKGROUND: Maintaining consistency of results over time is a challenge in laboratory medicine. Lot-to-lot reagent changes are a major threat to consistency of results.METHODS: For the period October 2007 through July 2012, we reviewed lot validation data for each new lot of insulin-like growth factor 1 (IGF-1) reagents (Siemens Healthcare Diagnostics) at Mayo Clinic, Rochester, MN, and the University of Virginia, Charlottesville, VA. Analyses of discarded patient samples were used for comparison of lots. For the same period, we determined the distributions of reported patient results for each lot of reagents at the 2 institutions.RESULTS: Lot-to-lot validation studies identified no reagent lot as significantly different from the preceding lot. By contrast, significant lot-to-lot changes were seen in the means and medians of 105 668 reported patient IGF-I results during the period. The frequency of increased results increased nearly 2-fold to a high of 17%, without detectable changes in the underlying patient demographics. Retrospective statistical analysis indicated that lot-to-lot comparison protocols were underpowered and that validation studies for this assay required testing >100 samples to achieve 90% power to detect reagent lots that would significantly alter the distributions of patient results.CONCLUSIONS: The number of test samples required for adequate lot-to-lot validation protocols is high and may be prohibitively large, especially for low-volume or complex assays. Monitoring of the distributions of patient results has the potential to detect lot-to-lot inconsistencies relatively quickly. We recommend that manufacturers implement remote monitoring of patient results from analyzers in multiple institutions to allow rapid identification of between-lot result inconsistency.
    Clinical Chemistry 04/2013; 59(8). DOI:10.1373/clinchem.2013.205070 · 7.77 Impact Factor
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    ABSTRACT: BACKGROUND: Variability of response to statins has been related to polymorphisms in genes involved in cholesterol homeostasis and statin metabolism, such as CYP3A4 and CYP3A5. We investigated the effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and on CYP3A activity and their interactions with common variants. METHODS: Unrelated individuals (n=121) with hypercholesterolemia (HC) were treated with atorvastatin (10mg/day/4weeks). Ninety-two normolipidemic (NL) subjects were selected as a control group. Genotype analysis of CYP3A4*1B (rs2740574), CYP3A4*22 (rs35599367), CYP3A5*3C (rs776746), and CYP3A5*1D (rs15524) and mRNA levels in peripheral blood mononuclear cells (PBMCs) were estimated. CYP3A activity was phenotyped by the urinary cortisol to 6-beta-hydroxy-cortisol ratio. RESULTS: LDL cholesterol reduction in response to atorvastatin was positively correlated with change in CYP3A4 (R(2)=0.039, p=0.037) and CYP3A5 (R(2)=0.047, p=0.019) mRNA levels and negatively correlated with CYP3A activity (R(2)=0.071, p=0.022). CYP3A5*3C (AGT haplotype) was associated to lower basal CYP3A5 mRNA expression in HC (p<0.045), however none of the haplotype groups impacted treatment. CONCLUSION: It is likely that cholesterolemia status changes promoted by atorvastatin play a role in regulating CYP3A4 and CYP3A5 mRNA expression in PBMCs, as well as CYP3A activity. CYP3A5*3C (AGT haplotype) also contributes for the variability of CYP3A5 mRNA levels in PBMCs.
    Clinica chimica acta; international journal of clinical chemistry 03/2013; 421. DOI:10.1016/j.cca.2013.03.007 · 2.76 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2013; 19(2):S280. DOI:10.1016/j.bbmt.2012.11.397 · 3.35 Impact Factor
  • Immunohematology / American Red Cross 01/2013; 29(3):101-4.
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    ABSTRACT: Late-night salivary cortisol (LNSC) measurements have been increasingly used by physicians as an initial diagnostic test for evaluation of patients with clinical suspicion of Cushing's syndrome (CS). Published studies include various numbers of cases, controls and importantly, various assay methods (vast majority various immunoassays), as well as various methods to generate cut-points. The retrospective study evaluated the diagnostic utility of LNSC measurements in 249 patients evaluated for possibility of CS because of various clinical conditions using liquid chromatography/tandem mass spectrometry method (LC-MS/MS). CS was confirmed in 47 patients (18·9%) and excluded in 202 (81·1%) patients at the time of analysis. Late-night salivary cortisol was abnormal or >2·8 nmol/l in 35 of 47 patients with CS; sensitivity of 74·5% and elevated in 20 of 202 patients who were found not to have CS; specificity 90·1%. Using receiver-operator characteristic statistics for calculation of the most optimal sensitivity and specificity, the cut-off based on this data was LNSC > 2·1 nmol/l with sensitivity of 83·0% and specificity of 84·2%. Analysis of data at one referral institution showed somewhat limited sensitivity of LNSC for diagnosis of CS using current reference ranges.
    Clinical Endocrinology 09/2011; 76(4):467-72. DOI:10.1111/j.1365-2265.2011.04239.x · 3.35 Impact Factor
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    ABSTRACT: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25–30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders.
    Genetics in medicine: official journal of the American College of Medical Genetics 02/2011; 13(3):230-54. DOI:10.1097/GIM.0b013e31820d5e67 · 6.44 Impact Factor
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    ABSTRACT: Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer characterized by coexistence of carcinomatous and sarcomatous components. Snail is a nuclear transcription factor incriminated in the transition of epithelial to mesenchymal differentiation of breast cancer. Aberrant Snail expression results in lost expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. We aimed to identify the utility of Snail, and of traditional immunohistochemical markers, in accurate MBC classification and to evaluate clinicopathologic characteristics and outcome.We retrospectively reviewed 34 MBC cases from January 1997 to September 2007. The control group contained 26 spindle cell lesions. Immunohistochemistry used Snail, p63, epidermal growth factor receptor (EGFR), OSCAR, and wide spectrum cytokeratin (WS-KER). Negative was a score less than 1%. We found that Snail and EGFR are sensitive (100%) markers with low specificity (3.8% and 19.2%) for detecting MBC. p63 and WS-KER are specific (100%), with moderate sensitivity (67.6% and 76.5%); OSCAR is sensitive (85.3%) and specific (92.3%). A combination of any 2 of the p63, OSCAR, and WS-KER markers increased sensitivity and specificity. MBCs tended to be high-grade (77%), triple negative (negative for estrogen receptor, progesterone receptor, and HER2) [27/33; 81.8%], and carcinomas with low incidence of axillary lymph node involvement (15%), and decreased disease-free [71% (95%CI: 54%, 94%) at 3 yrs.) and overall survival. A combination of p63, OSCAR and WS-KER are useful in its work-up. On the other hand, Snail is neither a diagnostic nor a prognostic marker for MBC.
    Diagnostic Pathology 11/2010; 5:76. DOI:10.1186/1746-1596-5-76 · 2.41 Impact Factor
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    ABSTRACT: The response to beta blockers in patients with heart failure could be associated with the genotype of drug-metabolizing enzymes and/or drug targets. The purpose of the present study was to determine whether specific genetic polymorphisms in ADRB1 (encoding the beta1-adrenergic receptor), CYP2D6, and UGT1A1 correlated with dose of, or response to, metoprolol or carvedilol treatment in patients with heart failure. A cohort of patients with heart failure (n = 93), characterized as responders or nonresponders to metoprolol (n = 19) or carvedilol (n = 74) therapy, was retrospectively identified. Individual genotyping was performed for a panel of polymorphisms in the ADRB1, CYP2D6, and UGT1A1 genes. Univariate and multivariate analyses were performed to compare the genotype to the metoprolol or carvedilol response status and dose. A nonresponse was identified in 10 of 19 patients taking metoprolol and 32 of 74 patients taking carvedilol. None of the polymorphisms in ADRB1, CYP2D6, and UGT1A1 were associated with a response or nonresponse. However, a significant relation between the carvedilol (but not metoprolol) dose and the ADRB1 and CYP2D6 genotype was observed. Patients homozygous for the ADRB1 389Gly variant or who were CYP2D6 poor metabolizers achieved a significantly higher dose of carvedilol (p = 0.01 and p = 0.02, respectively). In conclusion, polymorphisms in ADRB1, CYP2D6, and UGT1A1 were not associated with a response to metoprolol or carvedilol therapy in our cohort of patients with heart failure. The ADRB1 and CYP2D6 genotype, alone and in haplotype, were significantly associated with the dose of carvedilol.
    The American journal of cardiology 08/2010; 106(3):402-8. DOI:10.1016/j.amjcard.2010.03.041 · 3.43 Impact Factor
  • Gastroenterology 05/2010; 138(5). DOI:10.1016/S0016-5085(10)62058-6 · 13.93 Impact Factor
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    ABSTRACT: Our institution has reported on delayed hemolytic transfusion reaction (DHTR) and delayed serologic transfusion reaction (DSTR) incidence changes. From January 1993 to June 2003, a polyethylene glycol (PEG) tube-based technique was used for red blood cell (RBC) antibody screen. In June 2003, a gel microcolumn technique was implemented. Impact of this on antibody detection and DHTR and DSTR incidence was investigated. Positive antibody screen frequency and antibody specificity from January 2002 to March 2003 and July 2003 to September 2004 were compared. Overall incidence of DHTR and DSTR as well as the number and identity of the RBC antibodies implicated from August 1999 through June 2003 (PEG) and July 2003 through July 2007 (gel) were compared. The mean length of hospital stay (LOS) and number of RBC units transfused per patient were compared. Equivalent numbers of antibody screens were performed with equivalent numbers of positive screens. Significant differences were not seen in the detection of clinically significant antibodies but significantly fewer clinically insignificant antibodies were detected with gel. Ninety-six DHTRs and DSTRs were diagnosed. The LOS and number of transfused RBC units were not statistically different. A significantly higher incidence of DHTRs and DSTRs was seen with PEG compared to the gel. The gel microcolumn method is similar to the PEG in detecting clinically significant antibodies but detects fewer clinically insignificant antibodies. The implementation of gel resulted in a lower incidence of DHTRs and DSTRs compared to PEG.
    Transfusion 03/2010; 50(7):1444-52. DOI:10.1111/j.1537-2995.2010.02609.x · 3.57 Impact Factor
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    ABSTRACT: This descriptive population study of 307 public high school students, ages 15 to 17 years, was performed to establish reference ranges for orthostatic changes in heart rate and blood pressure in adolescents, and to identify influential variables. Noninvasive measurements of blood pressure and heart rate were obtained. Reference ranges for orthostatic heart rate change in this population at 2 minutes were -2 to +41 beats per minute and at 5 minutes were -1 to +48 beats per minute. Orthostatic blood pressure changes were within the adult range for 98% of adolescents tested. One-third of participants experienced orthostatic symptoms during testing. In conclusion, this study shows that orthostatic symptoms and large orthostatic heart rate changes occur in adolescents. This suggests that the current orthostatic heart rate criterion aiding the diagnosis of adult orthostatic intolerance syndromes is likely not appropriate for adolescents and should be reevaluated.
    Journal of child neurology 03/2010; 25(10):1210-5. DOI:10.1177/0883073809359539 · 1.67 Impact Factor
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    ABSTRACT: Patients with ulcerative colitis (UC) are at increased risk for developing colorectal cancer (CRC). Surveillance in this at-risk population remains challenging. We assessed the methylation status of genes in the non-neoplastic mucosa of UC-CRC patients and controls to identify potential biomarkers of CRC. We evaluated the methylation status of 10 genes (p16, p14, runt-related transcript factor-3 (RUNX3), cyclooxygenase-2 (COX-2), E-cadherin, methylated-in-tumor-1 (MINT1), MINT31, HPP1, estrogen receptor, SLC5A8) in UC-CRC tumors and non-neoplastic sections from both UC-CRC cases and UC controls (n=114 for each) using methylation-specific PCR. Amplification was successful for 96 UC controls, 83 tumors, and 66 non-adjacent, non-neoplastic samples. The prevalence of methylation was significantly greater in UC-CRC tumors for p16, RUNX3, MINT1, MINT31, and HPP1. Methylation of COX-2 and E-cadherin was greater in UC controls than in tumors. Univariate testing of these genes using non-adjacent, non-neoplastic sections from UC-CRC cases indicated that associations between p16, RUNX3, MINT1, MINT31, E-cadherin, and COX-2 and UC-CRC remained significant. In multivariable analysis of the six genes, only RUNX3, MINT1, and COX-2 remained significantly associated with the UC-CRC cases (odds ratio=12.6, 9.0, and 0.2, respectively). The results remained unaffected by the presence of PSC or severity of inflammation. Logistic regression modeling with the three genes showed interactions that increased the odds ratio for each gene. RUNX3, MINT1, and COX-2 are potential biomarkers for detecting the presence of CRC in patients with UC. These genes should be evaluated as biomarkers for colorectal dysplasia.
    The American Journal of Gastroenterology 02/2010; 105(7):1610-9. DOI:10.1038/ajg.2010.22 · 9.21 Impact Factor

Publication Stats

3k Citations
383.68 Total Impact Points

Institutions

  • 1992–2014
    • Mayo Clinic - Rochester
      • • Department of Laboratory Medicine & Pathology
      • • Department of Gastroenterology and Hepatology
      • • Department of Health Science Research
      • • Department of Endocrinology, Diabetes, Metabolism and Nutrition
      • • Department of Urology
      • • Department of Anesthesiology
      Rochester, Minnesota, United States
  • 2010
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
  • 2008
    • Mayo Foundation for Medical Education and Research
      • Division of Endocrinology, Diabetes, Metabolism, and Nutrition
      Scottsdale, AZ, United States
  • 2007
    • McMaster University
      Hamilton, Ontario, Canada