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Biomedical subjects

Mitchell G Scott

Publications and source records attributed to Mitchell G Scott.

13 recordsLinked to original sources

Point-of-care urine trypsinogen testing for the diagnosis of pancreatitis.

OBJECTIVES: To assess a point-of-care (POC) urine trypsinogen (UT) test for the diagnosis of pancreatitis in the emergency department (ED). METHODS: This was a prospective cohort study of a convenience sample of patients presenting to the ED with abdominal pain or symptoms suggestive of pancreatitis. A 3-minute POC UT test (Actim Pancreatitis; Medix Biochemica, Kauniainen, Finland) was compared with plasma lipase and amylase measurements, imaging results when performed, and final discharge diagnoses. The criterion standard was a final discharge diagnosis of acute pancreatitis. RESULTS: Of 191 patients included in this study, 17 patients were diagnosed with either acute or acute-on-chronic pancreatitis. The sensitivity and specificity of UT for acute pancreatitis were, respectively, 100% (95% confidence interval [CI] = 77% to 100%) and 96% (95% CI = 92% to 98%). Seven of the 17 patients with pancreatitis (41%) had diagnostic findings on CT and positive UT tests but had nondiagnostic plasma lipase and amylase levels. CONCLUSIONS: A POC UT screening test for pancreatitis in the ED compared favorably with plasma lipase and amylase levels. Future studies should be performed to explore whether this test in the ED setting has better clinical utility than plasma lipase or amylase.

Abdominal Pain↗

Ischemia-modified albumin increases after skeletal muscle ischemia during arthroscopic knee surgery.

BACKGROUND: Ischemia can alter the ability of albumin to bind free metal atoms. Based on these biochemical changes, methods to quantify ischemia modified albumin (IMA) were developed to assist in the evaluation of patients with symptoms of cardiac ischemia. Since ischemia can occur in any vascular bed, the specificity of IMA for cardiac muscle ischemia is unclear and requires further investigation. METHODS: We evaluated the specificity of an IMA test in patients with skeletal muscle ischemia during arthroscopic knee surgery. A pressurized thigh cuff was continuously inflated to 300 mm Hg on the operative leg, in order to arrest blood flow during the procedure. Samples were collected before surgery, 15 min after surgery, and prior to discharge. RESULTS: Twenty-three patients were enrolled in the study. Median tourniquet time was 29 min (range 19-108). Median pre-operative IMA was 90.2 KU/l (range 77-101.6). Statistically significant (p<0.05) increases in IMA and myoglobin concentrations, and decreases in albumin concentrations were observed following tourniquet release and before discharge. CONCLUSIONS: Post-operative myoglobin elevations indicated that skeletal muscle ischemia was sufficient to produce detectable myocyte necrosis. Post-operative IMA increases are consistent with ischemic modification of albumin during exposure to ischemic conditions in skeletal muscle during and /or immediately after tourniquet application. However, the negative correlations between IMA and albumin results suggest that increases in IMA were in part due to lower post-operative albumin concentrations resulting in decreased cobalt binding.

Adult↗

Laboratory assessment of oxygenation in methemoglobinemia.

BACKGROUND: This case conference reviews laboratory methods for assessing oxygenation status: arterial blood gases, pulse oximetry, and CO-oximetry. Caveats of these measurements are discussed in the context of two methemoglobinemia cases. CASES: Case 1 is a woman who presented with increased shortness of breath, productive cough, chest pain, nausea, fever, and cyanosis. CO-oximetry indicated a carboxyhemoglobin (COHb) fraction of 24.9%. She was unresponsive to O(2) therapy, and no source of carbon monoxide could be noted. Case 2 is a man who presented with syncope, chest tightness, and signs of cyanosis. His arterial blood was dark brown, and CO-oximetry showed a methemoglobin (MetHb) fraction of 23%. ISSUES: Oxygen saturation (So(2)) can be measured by three approaches that are often used interchangeably, although the measured systems are quite different. Pulse oximetry is a noninvasive, spectrophotometric method to determine arterial oxygen saturation (S(a)O(2)). CO-oximetry is a more complex and reliable method that measures the concentration of hemoglobin derivatives in the blood from which various quantities such as hemoglobin derivative fractions, total hemoglobin, and saturation are calculated. Blood gas instruments calculate the estimated O(2) saturation from empirical equations using pH and Po(2) values. In most patients, the results from these methods will be virtually identical, but in cases of increased dyshemoglobin fractions, including methemoglobinemia, it is crucial that the distinctions and limitations of these methods be understood. CONCLUSIONS: So(2) calculated from pH and Po(2) should be interpreted with caution as the algorithms used assume normal O(2) affinity, normal 2,3-diphosphoglycerate concentrations, and no dyshemoglobins or hemoglobinopathies. CO-oximeter reports should include the dyshemoglobin fractions in addition to the oxyhemoglobin fraction. In cases of increased MetHb fraction, pulse oximeter values trend toward 85%, underestimating the actual oxygen saturation. Hemoglobin M variants may yield normal MetHb and increased COHb or sulfhemoglobin fractions measured by CO-oximetry.

Adult↗

Model for predicting the impact of gadolinium on plasma calcium measured by the o-cresolphthalein method.

BACKGROUND: Gadolinium formulations, which are administered as contrast agents in magnetic resonance imaging examinations, interfere with colorimetric serum calcium determinations. METHODS: We performed an in vitro study to determine the extent to which three gadolinium formulations-gadodiamide (Omniscan), gadopentetate dimeglumine (Magnevist), and gadoversetamide (OptiMARK)-affect measurements by two methods that use o-cresolphthalein (Dade Behring, Inc. and Roche Diagnostics) and one that uses arsenazo dye (Equal Diagnostics). We also compared values from the o-cresolphthalein methods for 116 samples from patients administered gadodiamide. RESULTS: Magnevist did not affect any of the methods evaluated, whereas Omniscan and OptiMARK were identical in their effects. For the Dade method, the differences from the control sample were < or =4.0 and 7.0 mg/L at 0.25 and 0.5 mmol/L gadolinium, respectively. For the Roche method, the differences were 19, 9.0, and 5.0 mg/L at 0.5, 0.25, and 0.125 mmol/L gadolinium, respectively. Falsely increased calcium values were seen when samples were measured by the arsenazo-based method: differences were 6.0 and 3.0 mg/L at 1.0 and 0.5 mmol/L gadolinium. Using patient data collected at our institution, we were able to generate a model for predicting, from a patient's glomerular filtration rate and the time elapsed since administration, the impact of Omniscan on calcium measurements by the o-cresolphthalein method from Roche Diagnostics. CONCLUSIONS: The predictive model can be used to calculate, in patients who have received gadodiamide, the minimum length of time to wait before blood collection to avoid pseudohypocalcemia when the Roche o-cresolphthalein method is used.

Calcium↗

Analytical performance of the i-STAT cardiac troponin I assay.

BACKGROUND: This study determines the analytical characteristics of the i-STAT cardiac troponin I assay (cTnI; i-STAT, Princeton, NJ), a 10-min POC assay, designed to be performed at the bedside. METHODS: Three different hospitals participated in a patient specimen and analytical validation study (n=186) for the i-STAT cTnI assay carried out in real time. A total of 186 whole blood specimens (lithium heparin) were collected from patients presenting with symptoms suggestive of acute coronary syndromes (ACS) for correlation studies as well as from 162 healthy subjects for reference interval determination. Factors studied included antibody specificity, detection limit, imprecision, linearity, assay specificity, sample type stability, interferences, reference limit determination and comparison vs. the Dade Stratus CS cTnI assay. RESULTS: Total imprecision (CV) of 10% and 20% were seen at 0.09 and 0.07 microg/l, respectively. The detection limit was 0.02 microg/l. The 99th percentile reference limit was 0.08 microg/l. The assay was not affected by common interferents. An equimolar response within 5% was found for reduced and phosphorylated forms of TIC and IC complexes. Regression analysis for the i-STAT cTnI between whole blood and plasma specimens and for whole blood between the i-STAT and Stratus CS cTnI assays demonstrated slopes of 1.06 and 0.89, respectively. CONCLUSIONS: The i-STAT cTnI assay is a sensitive and precise monitor of cTnI, poised for point-of-care/near bedside clinical utilization for triage, diagnostics and risk management of acute coronary syndrome patients.

Adult↗

Osmole gap in neurologic-neurosurgical intensive care unit: Its normal value, calculation, and relationship with mannitol serum concentrations.

OBJECTIVE: To determine a) if the admission osmole gap, the difference between osmolality and osmolarity, is the same in the neurologic-neurosurgical intensive care unit (NNICU) population as in healthy controls; b) which of 11 osmole gap formulas, or osmolality, correlates best with mannitol serum concentrations; c) whether osmole gap correction for plasma water content improves this correlation; and d) whether the osmole gap can predict mannitol serum concentrations. DESIGN: Prospectively collected data. SETTINGS: NNICU of a tertiary teaching hospital. SUBJECTS: Ten NNICU patients on mannitol and eight not on mannitol, and 95 healthy controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the admission osmole gap between all 18 NNICU patients and healthy controls and the correlation between osmole gap or osmolality and mannitol serum concentrations in ten NNICU patients while receiving mannitol. The osmole gap was calculated using 11 osmolarity formulas (six corrected for plasma water content). Student's t-test was used to compare the mean osmole gap between control and patient groups.We found that the mean osmole gap in healthy subjects and NNICU patients was not different. There were no statistically significant differences between any of the 11 osmole gap formulas and the correlation of osmole gap with serum mannitol concentrations; the highest R =.80, with formula 4, 1.86 (sodium + potassium) + (blood urea nitrogen/2.8) + (glucose/18) + 10, requires the least laboratory measurements. Osmolality had the lowest correlation with mannitol concentration (R =.60), significantly lower than any of the osmole gap calculations. Plasma water content correction did not improve this correlation. The osmole gap-mannitol serum concentrations relationship is 1 to 0.81, not accurate enough to predict specific mannitol serum concentrations. CONCLUSIONS: The osmole gap correlates better with mannitol serum concentrations than osmolality, and although it cannot predict a specific mannitol serum concentration, a normal osmole gap concentration, as we find at trough times, indicates sufficient clearance for a new mannitol dose.

Adolescent↗

Use of a major medical center clinical laboratory as a reference laboratory for a developing country: ordering patterns help set laboratory priorities.

BACKGROUND: The test menus for developed and developing countries may differ, depending on many factors, including the expected volume of testing, disease frequency and therapies available, clinical impact of the test, technical skill and equipment needed, cost, the patient population served, and whether alternative testing sites are available, and some of them may not be exactly known. We assessed test priorities in a developing country by making a broad range of tests available and then assessing which tests were actually used by the physicians in the country for the care of their patients. METHODS: The Barnes-Jewish Hospital laboratory and Washington University Medical Center provided patients in the developing country of Eritrea access to the same tests as patients in St. Louis for all analytes that are stable at 4 degrees C, the lowest temperature that could be used for shipping. RESULTS: The use of the St. Louis laboratories increased steadily from 1998 to 2001. More than one-half of the physicians in Eritrea used the reference laboratories, with requests for thyroid function and female fertility representing 48-71% of the test requests over the 4 years evaluated. The high degree of utilization for these test batteries was not predicted. Testing for thyroid function, female fertility, and lipid panels are now performed, or soon will be performed, in Eritrea based on the experience of the reference laboratory system. The reference laboratory system is continuing so that the test priorities of the country can be evaluated on an ongoing basis and specialized tests can be made available at a low cost. CONCLUSION: The experiences of a reference laboratory for a developing country can help to identify unanticipated priorities for medical testing within the country.

Clinical Laboratory Techniques↗

Cystatin C: an improved estimator of glomerular filtration rate?

BACKGROUND: Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR. APPROACH: In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations. CONTENT: This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients. SUMMARY: Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.

Biomarkers↗

Performance of a revised cardiac troponin method that minimizes interferences from heterophilic antibodies.

BACKGROUND: Recent guidelines for use of cardiac troponin to detect cardiac damage and for cardiovascular risk stratification have made increasingly sensitive troponin assays important. Troponin assays continue to be plagued by interferences caused by heterophilic antibodies (HAs). We evaluated the performance of a revised cardiac troponin I (cTnI) assay designed to have increased analytical sensitivity and to minimize the effect of HAs. METHODS: The revised Dade Behring Dimension cTnI assay was evaluated according to NCCLS EP5-A at five institutions. Plasma samples from 14 309 patients were assayed by the original Dimension cTnI assay. To identify samples that may have interfering HAs, samples with values >1.4 microg/L were reanalyzed on the Dade Behring Stratus CS cTnI assay. Samples with possible interfering antibodies were also analyzed before and after selective absorbance studies on the revised Dade Behring Dimension cTnI assay. RESULTS: The limit of quantification in the revised method was 0.1 microg/L with imprecision (CV) of 11-17% at 0.1 microg/L. Values correlated well with the Stratus CS cTnI method: revised = 1.06(original) + 0.01; r = 0.98, S(y/x) = 0.25 microg/L). Falsely increased results consistent with myocardial infarction by the original Dimension cTnI assay and presumably attributable to HAs were identified in 0.17% of all patients with samples submitted for cTnI analysis. The revised Dimension cTnI assay eliminated the interference in 17 of 25 samples identified and greatly decreased the interference in the other 8. CONCLUSIONS: The revised Dimension cTnI method greatly minimizes the effect of interfering HAs. It also exhibits analytical performance characteristics consistent with recent guidelines for use of this assay to detect cardiac damage.

Adolescent↗

Evaluation of a no-pretreatment cyclosporin A assay on the Dade Behring dimension RxL clinical chemistry analyzer.

BACKGROUND: Monitoring whole-blood concentrations of cyclosporin A (CsA) is common practice in the management of solid organ and bone marrow transplant recipients. In a multicenter study we evaluated a new, direct (no pretreatment) CsA assay on the Dade Behring Dimension RxL system and compared results with those from the Abbott TDx CsA immunoassay and a HPLC method. METHODS: Whole-blood samples from heart (n = 111; 35 patients), liver (n = 201; 44 patients), kidney (n = 279; 65 patients), and miscellaneous organ (n = 77; 12 lung, 12 bone marrow, 5 kidney/pancreas, and 1 pancreas patient) recipients were obtained from patient populations of the participating institutions. Routine clinical monitoring of CsA was performed using either the TDx method or HPLC. RESULTS: The minimum detectable concentration of CsA averaged 9.4 microg/L, and the lower limit of quantification was 30 microg/L. The method was linear from 30 to 500 microg/L. Cross-reactivity with seven different CsA metabolites ranged from 0.0% to 5.7% for the Dimension RxL assay compared with 0.4-15.9% for the TDx assay. Total imprecision (CV) averaged 6.2%, and within-run imprecision averaged 4.9%. Passing-Bablok linear regression analyses of all samples from two sites yielded the following: RxL = 0.81 x TDx - 16.8; and RxL = 1.12 x HPLC - 1.7. CONCLUSIONS: The Dade Behring CsA assay for the random-access Dimension platform offers adequate performance characteristics for routine clinical use, does not require a manual pretreatment step, and demonstrates less cross-reactivity with CsA metabolites than another commonly used immunoassay.

Antibodies, Monoclonal↗