Browsing by Author "Zimmerman, Michelle K."

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    Can We Detect Chronic Pancreatitis With Low Serum Pancreatic Enzyme Levels?
    (Lippincott, Williams, and Wilkins, 2016-09) Kwon, Chang-Il; Kim, Hong Joo; Korc, Paul; Choi, Eun Kwang; McNulty, Gail M.; Easler, Jeffrey J.; El Hajj, Ihab I.; Watkins, James; Fogel, Evan L.; McHenry, Lee; Zimmerman, Michelle K.; Sherman, Stuart; Lehman, Glen A.; Department of Medicine, IU School of Medicine
    Objectives: The aims of this study were to evaluate whether serum pancreatic enzyme levels could be used to aid screening for chronic pancreatitis (CP). Methods: 170 healthy volunteers were screened and prospectively enrolled in the control group. 150 patients who were diagnosed with calcific CP were enrolled in the patient group by retrospective review. Serum amylase and lipase levels were compared between the 2 groups. Results: The mean values ± SD of the control group were compared with those of the patient group for serum amylase level (48.1 ± 13.2 vs 34.8 ± 17.2 U/L, P < 0.001) and serum lipase level (26.4 ± 11.3 vs 16.3 ± 11.2 U/L, P < 0.001). On the receiver operating characteristic curve analysis for amylase level, area under the curve was 0.740 (95% confidence interval), and sensitivity and specificity were 38.7% and 94.1%, respectively, with a cutoff value of 27.5 U/L. On the receiver operating characteristic curve analysis for lipase level, area under the curve was 0.748 (95% confidence interval), and sensitivity and specificity were 33.3% and 95.9%, respectively, with a cutoff value of 10.5 U/L. Conclusions: Our results suggest that low serum pancreatic enzyme levels can be used to aid in detection of CP.
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    Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma, a diagnostic challenge
    (e-Century Publishing Corporation, 2017-04-15) Mansour, Ahmad T.; Esmaeili Shandiz, Alaleh; Zimmerman, Michelle K.; Roth, Trenton D.; Zhou, Jiehao; Pathology and Laboratory Medicine, School of Medicine
    BACKGROUND: Lymphoplasmacytic lymphoma and plasma cell myeloma are two B cell lymphoproliferative neoplasms derived from mature B-lymphocytes in different differentiation stages. The coexistence of these two tumors in the same patient is exceedingly rare and can be difficult to diagnose. CASE PRESENTATION: A 76-year-old male presented with a pathologic fracture after a fall. Radiography showed a lytic lesion in the pelvis. Serum immunofixation showed distinct IgM kappa and IgA kappa monoclonal protein bands. Bone marrow examination revealed aggregates of small, mature lymphoid cells with admixed plasma cells. Immunohistochemical studies and flow cytometric analysis showed the lymphoid cells were CD10-/CD5- kappa restricted monoclonal B cells. The plasma cells were monoclonal with kappa light chain restriction. The majority of plasma cells were positive for IgA and cyclin D1 with a few plasma cells positive for IgM. Additional studies showed the presence of both a positive MYD88 L265P mutation and a CCND1/IGH fusion. A diagnosis of concomitant lymphoplasmacytic lymphoma and plasma cell myeloma was rendered. CONCLUSION: Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma can be rarely encountered and is diagnostic challenging. It is commonly associated with biclonal monoclonal proteins. This case demonstrates the importance of a comprehensive work-up in the diagnosis of this disease combination and highlights the diagnostic role of MYD88 mutation study.
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    Excessive matrix metalloproteinase-1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID-19
    (Cold Spring Harbor Laboratory Press, 2021-01) Syed, Fahim; Li, Wei; Relich, Ryan F.; Russell, Patrick M.; Zhang, Shanxiang; Zimmerman, Michelle K.; Yu, Qigui; Microbiology and Immunology, School of Medicine
    COVID-19 starts as a respiratory disease that can progress to pneumonia, severe acute respiratory syndrome (SARS), and multi-organ failure. Growing evidence suggests that COVID-19 is a systemic illness that primarily injures the vascular endothelium, yet the underlying mechanisms remain unknown. SARS-CoV-2 infection is believed to trigger a cytokine storm that plays a critical role in the pathogenesis of endothelialitis and vascular injury, eventually leading to respiratory and multi-organ failure in COVID-19 patients. We used a multiplex immunoassay to systematically profile and compare 65 inflammatory cytokines/chemokines/growth factors in plasma samples from 24 hospitalized (severe/critical) COVID-19 patients, 14 mild/moderate cases, and 13 healthy controls (HCs). Patients with severe/critical and mild/moderate COVID-19 had significantly higher plasma levels of 20 analytes than HCs. Surprisingly, only one cytokine (MIF) was among these altered analytes, while the rest were chemokines and growth factors. In addition, only MMP-1 and VEGF-A were significantly elevated in hospitalized COVID-19 patients when compared to mild/moderate cases. Given that excessive MMP-1 plays a central role in tissue destruction in a wide variety of vascular diseases and that elevated VEGF-A, an EC activation marker, increases vascular permeability, we further studied MMP-1 enzymatic activity and other EC activation markers such as soluble forms of CD146, ICAM-1, and VCAM-1. We found that plasma MMP-1 enzymatic activity and plasma levels of MMP-1 and EC activation markers were highly dysregulated in COVID-19 patients. Some dysregulations were associated with patients’ age or gender, but not with race. Our results demonstrate that COVID-19 patients have distinct inflammatory profiles that are distinguished from the cytokine storms in other human diseases. Excessive MMP-1 and hyperactivation of ECs occur in COVID-19 patients and are associated with the severity of COVID-19.
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    Low Serum Pancreatic Amylase and Lipase Values Are Simple and Useful Predictors to Diagnose Chronic Pancreatitis
    (Editorial Office of Gut and Live, 2017-11) Oh, Hyoung-Chul; Kwon, Chang-Il; El Hajj, Ihab I.; Easler, Jeffrey J.; Watkins, James; Fogel, Evan L.; McHenry, Lee; Sherman, Stuart; Zimmerman, Michelle K.; Lehman, Glen A.; Medicine, School of Medicine
    Background/Aims This study aimed to evaluate the diagnostic role of low serum amylase and lipase values in the detection of chronic pancreatitis. Methods Patients underwent endoscopic retrograde cholangiopancreatography and were diagnosed with non-calcific chronic pancreatitis (NCCP; n=99) and calcific chronic pancreatitis (CCP; n=112). Patient serum amylase and lipase values were compared with those of healthy controls (H; n=170). Results The median serum amylase (normal range, 19 to 86 U/L) and lipase values (7 to 59 U/L) (P25–P75) were 47.0 (39.8 to 55.3) and 25.0 (18.0 to 35.0) for H, 34.0 (24.5 to 49.0) and 19.0 (9.0 to 30.0) for NCCP, and 30.0 (20.0 to 40.8) and 10.0 (3.0 to 19.0) for CCP, respectively. The cutoff values with the highest diagnostic accuracy for discriminating NCCP from H were 40 U/L for amylase and 20 U/L for lipase, respectively, and for CCP from H were 38 U/L for amylase and 15 U/L for lipase, respectively. For the diagnosis of NCCP with a criterion of serum amylase <40 and lipase <20 U/L, the sensitivity, specificity, positive predictive value, and negative predictive values were 37.4%, 88.8%, 66.1%, and 70.9%, respectively. Conclusions Serum amylase and/or lipase levels below the normal serum range are highly specific for chronic pancreatitis patients. Clinicians should not ignore low serum pancreatic enzyme values.
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    Multi-center evaluation of analytical performance of the Beckman Coulter AU5822 chemistry analyzer
    (Elsevier, 2015-09) Zimmerman, Michelle K.; Friesen, L. R.; Nice, A.; Vollmer, P. A.; Dockery, E. A.; Rankin, J. D.; Zmuda, K.; Wong, S. H.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Objectives Our three academic institutions, Indiana University, Northwestern Memorial Hospital, and Wake Forest, were among the first in the United States to implement the Beckman Coulter AU5822 series chemistry analyzers. We undertook this post-hoc multi-center study by merging our data to determine performance characteristics and the impact of methodology changes on analyte measurement. Design and methods We independently completed performance validation studies including precision, linearity/analytical measurement range, method comparison, and reference range verification. Complete data sets were available from at least one institution for 66 analytes with the following groups: 51 from all three institutions, and 15 from 1 or 2 institutions for a total sample size of 12,064. Results Precision was similar among institutions. Coefficients of variation (CV) were < 10% for 97%. Analytes with CVs > 10% included direct bilirubin and digoxin. All analytes exhibited linearity over the analytical measurement range. Method comparison data showed slopes between 0.900-1.100 for 87.9% of the analytes. Slopes for amylase, tobramycin and urine amylase were < 0.8; the slope for lipase was > 1.5, due to known methodology or standardization differences. Consequently, reference ranges of amylase, urine amylase and lipase required only minor or no modification. Conclusion The four AU5822 analyzers independently evaluated at three sites showed consistent precision, linearity, and correlation results. Since installations, the test results had been well received by clinicians from all three institutions.
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    Serum from COVID-19 patients early in the pandemic shows limited evidence of cross-neutralization against variants of concern
    (Nature, 2022-03) Griffin, Amanda J.; O'Donnell, Kyle L.; Shifflet, Kyle; Lavik, John-Paul; Russell, Patrick M.; Zimmerman, Michelle K.; Relich, Ryan F.; Marzi, Andrea; Pathology and Laboratory Medicine, School of Medicine
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 SARS-CoV-2 isolate had detectable but limited neutralizing antibodies against the emerging SARS-CoV-2 Alpha, Beta and Delta variants. This study highlights the potential of re-infection for recovered COVID-19 patients.
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    Serum from COVID-19 patients early in the pandemic shows limited evidence of cross-neutralization against variants of concern
    (Springer Nature, 2022-03-10) Griffin, Amanda J.; O’Donnell, Kyle L.; Shifflett, Kyle; Lavik, John-Paul; Russell, Patrick M.; Zimmerman, Michelle K.; Relich, Ryan F.; Marzi, Andrea; Pathology and Laboratory Medicine, School of Medicine
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 SARS-CoV-2 isolate had detectable but limited neutralizing antibodies against the emerging SARS-CoV-2 Alpha, Beta and Delta variants. This study highlights the potential of re-infection for recovered COVID-19 patients.
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    Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia
    (American Society for Microbiology, 2016-03) Lei, Guang-Sheng; Zhang, Chen; Zimmerman, Michelle K.; Lee, Chao-Hung; Department of Pathology and Laboratory Medicine, IU School of Medicine
    The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4+ cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11blow CD11chigh alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP.