Search PubMed⌕ Search

Biomedical subjects

R H Christenson

Publications and source records attributed to R H Christenson.

At least 55 records · Page 3Linked to original sources

Multicenter study of Abbott AxSYM Digoxin II assay and comparison with 6 methods for susceptibility to digoxin-like immunoreactive factors.

Performance characteristics of the Abbott nonpretreatment AxSYM Digoxin II assay were evaluated for quantification of digoxin at four independent sites. Correlation of digoxin measurements with the Abbott pretreatment AxSYM, Baxter Stratus II, Abbott TDx/ TDxFLx II, Abbott IMx, Emit 2000, and Beckman Synchron CX digoxin assays showed acceptable agreement, as indicated by: slope values > 0.84, r > 0.90, y-intercepts for all comparisons at or below the assay detection limit, and Sy/x ranging between 7.5% and 15.4% of the average digoxin value. Susceptibility to interference from digoxin-like immunoreactive factors (DLIFs) was examined in 233 samples from renal patients, liver disease patients, cord blood, and third-trimester pregnancies; the AxSYM Digoxin II assay demonstrated the least DLIFs interference. DLIF susceptibility for four of the methods was significantly greater (P < 0.05) than in the AxSYM Digoxin II assay; susceptibilities of the Stratus II and Emit 2000 methods were similar to the AxSYM Digoxin II assay.

Autoanalysis↗

Cardiac markers in the assessment of acute coronary syndromes.

Biochemical markers provide clinicians with an important tool for the assessment of acute coronary syndromes. Biochemical markers, including total creatine kinase (total CK), creatine kinase-MB (CK-MB), the MB isoforms, and myoglobin, as well as the troponins--cardiac troponin T (cTnT) and cardiac troponin I (cTnI)--are all used for assessment of the suspected acute myocardial infarction (AMI) patient. In the context of myocardial infarction (MI) diagnosis, total CK is a relatively sensitive marker, but it lacks myocardial specificity because skeletal muscle contains high concentrations of CK. CK-MB is the benchmark for biochemical markers and has both high sensitivity and specificity; however, CK-MB is also present in skeletal muscle and is not diagnostic until eight to twelve hours after onset of symptoms. The MB isoforms are diagnostic earlier but have the same cardiac specificity issues as CK-MB. Myoglobin becomes abnormal about one hour after onset of symptoms and is a sensitive marker for MI; however, myoglobin is cleared quickly and is not cardiac specific. Both cTnT and cTnI are cardiac specific and show high sensitivity and specificity for MI. Risk stratification of acute coronary syndrome patients is another role for biochemical markers; CK-MB, cTnT and cTnI have all been proposed for this function. Compared with CK-MB, both cTnT and cTnI are better able to predict short-term mortality following the index event. Analysis using a logistic regression model that included the electrocardiogram, cTnT, and cTnI showed that cTnT was the most useful marker for risk stratification. Finally, cTnT was reported to be able to predict which patients will benefit from treatment with regimens of low molecular weight heparin.

Angina Pectoris↗

Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators.

BACKGROUND: The prognosis of patients hospitalized with acute myocardial ischemia is quite variable. We examined the value of serum levels of cardiac troponin T, serum creatine kinase MB (CK-MB) levels, and electrocardiographic abnormalities for risk stratification in patients with acute myocardial ischemia. METHODS: We studied 855 patients within 12 hours of the onset of symptoms. Cardiac troponin T levels, CK-MB levels, and electrocardiograms were analyzed in a blinded fashion at the core laboratory. We used logistic regression to assess the usefulness of baseline levels of cardiac troponin T and CK-MB and the electrocardiographic category assigned at admission-ST-segment elevation, ST-segment depression, T-wave inversion, or the presence of confounding factors that impair the detection of ischemia (bundle-branch block and paced rhythms)-in predicting outcome. RESULTS: On admission, 289 of 801 patients with base-line serum samples had elevated troponin T levels (> 0.1 ng per milliliter). Mortality within 30 days was significantly higher in these patients than in patients with lower levels of troponin T (11.8 percent vs. 3.9 percent, P < 0.001). The troponin T level was the variable most strongly related to 30-day mortality (chi-square = 21, P < 0.001), followed by the electrocardiographic category (chi-square = 14, P = 0.003) and the CK-MB level (chi-square = 11, P = 0.004). Troponin T levels remained significantly predictive of 30-day mortality in a model that contained the electrocardiographic categories and CK-MB levels (chi-square = 9.2, P = 0.027). CONCLUSIONS: The cardiac troponin T level is a powerful, independent risk marker in patients who present with acute myocardial ischemia. It allows further stratification of risk when combined with standard measures such as electrocardiography and the CK-MB level.

Acute Disease↗

Lesion-directed administration of alteplase with intracoronary heparin in patients with unstable angina and coronary thrombus undergoing angioplasty.

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and alter lesion-directed therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for > or = 4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiographic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus.

Adult↗

The case for cardiac troponin T: marker for effective risk stratification of patients with acute cardiac ischemia.

Availability of markers such as cardiac troponin T (cTnT) has brought new insights into ischemic heart disease (IHD). cTnT is a distinct protein that differs from other markers in biological function, molecular mass, and cytosolic pool. cTnT has been utilized for diagnosis of acute myocardial infarction (AMI) and risk stratification of patients with IHD. For AMI diagnosis, cTnT showed high sensitivity (94-100%) but generally lower specificity (46-99%), possibly because of increases in non-AMI patients with minor myocardial damage. Outcome studies have demonstrated that IHD patients with increased cTnT are at significantly greater risk for cardiac events; revascularization in patients with increased cTnT may improve outcome. Estimated costs for batched ES 300 cTnT results and for a cTnT rapid assay run "on demand" were $17.48 and $21.65, respectively. cTnT currently has no specific common procedure test code; expected reimbursement is $18.32 for the ES 300 and is not established for the rapid assay.

Biomarkers↗

Thyroid function testing evaluated on three immunoassay systems.

Total thyroxine (TT4), tracer uptake, thyroid-stimulating hormone (TSH), and free T4 (FT4) testing was examined in the ACS 180, Abbott IMx, and Stratus II systems. TSH sensitivity studies demonstrated that the ACS and IMx are second-generation assays; the Stratus showed between first- and second-generation performance. Except for one control below the detection limit, TSH imprecision was 3-10%. TSH accuracy was adequate for all systems. TT4 imprecision was 4-7%, except for the lowest control with the Stratus (18%). TT4 method agreement showed bias of about 20% between the systems. TT4 accuracy was compromised at the low end for the Stratus II, but was satisfactory otherwise. FT4 imprecision was 20% for the Stratus, < 5% for the IMx and 6% for the ACS. Uptake assays showed imprecision of 5-10%. The laboratory diagnosis indicated by each system's FT4 and calculated FT4 Index results were compared to determine diagnostic accuracy. In routine specimens, different clinical classifications were observed for 25% of specimens with the ACS, 19% with the Stratus, and 7% with the IMx; in the altered protein group, the Stratus showed 9% discordant results, the ACS showed 3%, and the IMx 0%. Of the three systems examined here, the Abbott IMx system showed the best overall performance.

Humans↗

Oxygen transport and cardiovascular effects of resuscitation from severe hemorrhagic shock using hemoglobin solutions.

OBJECTIVE: To test the short-term efficacy of three hemoglobin solutions in restoring cardiac output, intravascular pressures, oxygen transport (DO2), and oxygen consumption (VO2) after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Beagle dogs. INTERVENTIONS: After anesthesia and instrumentation, hemorrhagic shock was induced for 2 hrs by blood withdrawal to maintain systolic blood pressure at 50 mm Hg. Resuscitation then occurred with one of four different resuscitation fluids. One group of dogs was not resuscitated. Survival rate was monitored for 8 days. MEASUREMENTS AND MAIN RESULTS: In 33 beagle dogs, cardiovascular variables (DO2 and VO2) were compared after resuscitation with 8% stroma-free hemoglobin, 4% or 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP44 and PHP88, respectively), or autologous whole blood. The dogs were anesthetized, paralyzed, mechanically ventilated (FIO2 of 0.21), and instrumented with arterial and pulmonary artery catheters. An average of 63% of estimated blood volume was removed to maintain systolic blood pressure at 50 mm Hg for 2 hrs. The dogs then were either not resuscitated (n = 4) or resuscitated with 8% stroma-free hemoglobin (n = 7), PHP44 (n = 6), PHP88 (n = 8), or whole blood (n = 8), with a volume equivalent to the withdrawn blood. Cardiovascular variables, DO2, VO2, oxygen extraction ratios, and blood concentrations of lactic acid and catecholamines were determined before, and for < or = 6 hrs after, resuscitation from hemorrhagic shock. Blood smears were microscopically examined. In addition, the survival rate was monitored for 8 days after resuscitation. By 2 hrs of hemorrhagic shock, there was a large decrease in DO2 (p < .05) and an increase in oxygen extraction ratio from 0.27 to 0.70 (p < .05). There was a 3.5-fold increase in lactate concentrations and a 25-fold increase in catecholamine concentrations as compared with preshock values. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. After resuscitation with whole blood, all cardiovascular and oxygen transport variables returned to approximately prehemorrhage values and remained so throughout the measurement period. After resuscitation with any hemoglobin solution, DO2 returned transiently to control values. However, recovery of DO2 was short-lived in all hemoglobin solution groups, and, by 4 hrs postresuscitation in all groups, DO2 was less than the DO2 of the dogs receiving whole blood (p < .05). These changes were associated with decreases in total hemoglobin concentrations compared with the values immediately before resuscitation (p < .05). In addition, with resuscitation using the PHP solutions, blood smears demonstrated aggregation of red blood cells and platelets. On day 8 after hemorrhagic shock, the survival rate was 100% for whole blood and PHP44, 86% for 8% stroma-free hemoglobin, and 33% for PHP88. CONCLUSIONS: Resuscitation from severe hemorrhagic shock with 8% stroma-free hemoglobin, PHP44, or PHP88 is equally effective in restoring cardiac index and vascular pressures as using whole blood. However, resuscitation with the three hemoglobin solutions only transiently restored DO2 after hemorrhagic shock. The subsequent reduction of DO2 compared with the DO2 value using whole blood was due mostly to hemodilution. With the two PHP solutions, formation of red blood cell aggregates probably resulted in sequestration of red cell mass and additional loss of oxygen carrying capacity.

Animals↗

Creatine kinase MM and MB isoforms in patients receiving thrombolytic therapy and acute angiography. TAMI Study Group.

Creatine kinase isoforms markers, including MB2 concentration, MB2/MB1 and MM3/MM1 ratios, and MT index (based on the "tissue" M subunits), were measured in serial specimens from 207 patients receiving thrombolytic therapy followed by acute angiography. The slope of release showed a significant relation (P < 0.05) between MB2 concentrations and patency, graded as TIMI 0 through TIMI 3; with regard to the precatheterization/baseline ratio, the MB2 concentrations, the MM3/MM1 ratio, and the MT index were all significantly related to graded patency (P < 0.004). Patients having patency graded as either TIMI 2/3 (Open) or TIMI 0/1 (Closed) showed highly significant differences (P < 0.03) in the slope of release and precatheterization/baseline ratio for all markers except the MB2/MB1 ratio. Defining Open as TIMI 3 and Closed as TIMI 0/1/2 showed very similar results. Despite these significant differences between the Open and Closed groups after thrombolytic therapy, none of the C index calculations (areas under ROC curves) for any of the isoform markers--either alone or combined--exceeded 0.70, suggesting that these markers have limited diagnostic utility for assessing patency.

Aged↗

Eight compact analysis systems evaluated for measuring total cholesterol.

We examined the analytical performance of eight compact systems for measuring total cholesterol: AccuMeter, Cobas Ready, Discovery f2, DT60, L-D-X, Reflotron, QCA, and Vision. We determined average bias at two decision levels, the mean absolute bias, and the percentage of results differing from the comparison method results by > 8.9% allowable total error limit for multiple reagent lots. Average bias was < 3% for all lots tested for AccuMeter, Discovery f2, and DT60, but > 3% for one or more lots or sample types tested with the other systems. Of results from each reagent lot, > 95% were within the 8.9% total error specifications with Discovery f2, DT60, and QCA, whereas the performance of L-D-X, Vision, and Reflotron depended on reagent lot and (or) sample type. Of all results from each lot tested with AccuMeter and Cobas Ready, > 5% exceeded the total allowable error limit. We determined imprecision for five systems: Cobas Ready, Discovery f2, and QCA had CVs < 3%, whereas CVs for AccuMeter and L-D-X were > 3% but < 5%.

Bias↗

Specificity of an immunochemical reagent for quantifying the isoforms of creatine kinase-MB.

Fractionation of the creatine kinase-MB isoforms is promising for use in diagnosing acute myocardial infarction and for monitoring myocardial perfusion status after thrombolytic therapy. An immunochemical reagent intended for use in fractionating the MB1 and MB2 isoforms of creatine kinase-MB was examined before and after immunoextraction, qualitatively by visually examining electrophoresis separation of various MB1 and MB2 mixtures, and quantitatively by comparing the observed and predicted enzymatic activity of various MB1 and MB2 mixtures. Qualitatively the reagent showed greater reactivity for MB1 than for MB2, as demonstrated by a marked decrease in the MB1 electrophoretic region following immunoextraction. Quantitatively, the reagent consistently eliminated about 75% of MB1 activity; however, the assay also eliminated about 40% of MB2 activity from isoform mixtures. Although the performance of the immunochemical reagent was not ideal, the greater reactivity for MB1 may have clinical use.

Creatine Kinase↗

Noninvasive detection of reperfusion after thrombolysis based on serum creatine kinase MB changes and clinical variables. TAMI 7 Study Group. Thrombolysis and Angioplasty in Myocardial Infarction.

Coronary artery patency after thrombolytic therapy has important prognostic implications for survival after acute myocardial infarction. The ability to noninvasively identify patients early after thrombolysis may therefore allow other strategies, such as adjunctive therapy or rescue angioplasty, to be used to restore patency of the infarct-related artery. This study examined the use of a rapid creatine kinase (CK)-MB assay in conjunction with selected clinical variables for noninvasive detection of reperfusion after thrombolysis. Patients were enrolled in a study evaluating accelerated plasminogen activator dose regimens with patency assessments by first angiographic injection during acute angiography at a median and interquartile range (25th and 75th percentiles) 142 (96,195) minutes after starting thrombolytic therapy. Serum CK-MB samples measured by a rapid dual monoclonal antibody assay were obtained in 207 patients before (baseline) and 30 minutes, 90 minutes, and 3 hours after starting thrombolytic therapy. In 109 patients a CK-MB sample was obtained within 10 minutes of acute angiography (angio sample). At acute angiography the infarct-related artery was patent (Thrombolysis in Myocardial Infarction trial grade 2 to 3 flow) in 71%. Baseline CK-MB values were similar in patients with and without later reperfusion at acute angiography: 3 (0,8) ng/ml and 0 (0,4) ng/ml, respectively. At acute angiography, patients with successful reperfusion had higher CK-MB values [46 (20,138) ng/ml] compared with patients with persistent occlusion of the infarct-related artery [8 (3,63) ng/ml; p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

Temporal creatine kinase curves in acute myocardial infarction. Implications of a good empiric fit with the log-normal function.

To maximize the information one can obtain from the temporal curves of creatine kinase (CK) after acute myocardial infarct (AMI), the authors tested how well the curves were fit by three functions: the log-normal function, the gamma function, and the function of Schwerdt and associates (Cardiovasc Res 1990;24:328-334). The log-normal function fit best. Using time course curves of the isoenzyme CK-MB in 16 patients with AMI, the authors found that the integrated area under the fitted log-normal function correlated closely with the postinfarct ejection fraction. Together, the success of the log-normal function and mathematical analysis of the kinetics of CK-time curves impose a form on the release of CK from the heart, and they imply that k, the first-order rate constant of loss of CK from the serum, may be indeterminate from the CK-time curve alone. Although this indeterminancy of k helps explain the prior successes and failures in sizing AMIs from CK-time curves, it should not discourage one from obtaining important quantitative and prognostic information from these CK-time curves. It does suggest that such associations will be largely empiric.

Animals↗

Lecithin cholesterol acyltransferase in human cerebrospinal fluid: reduced level in patients with multiple sclerosis and evidence of direct synthesis in the brain.

Several studies suggest that apolipoproteins and the low-density lipoprotein receptor are implicated in lipid transport in the brain. Given that cerebrospinal fluid has been reported to contain cholesteryl esterifying enzyme, and that lipid metabolism in the brain is abnormal in subjects with multiple sclerosis, we examined the cerebrospinal fluid from eight control subjects with a normal cerebrospinal fluid IgG index, and without active demyelinating disease, and from eight subjects (6 were diagnosed as having multiple sclerosis) with an increased IgG index and the presence of oligoclonal banding in the cerebrospinal fluid, for the presence of the enzyme lecithin cholesterol acyltransferase and apolipoprotein(a). None of the subjects demonstrated impairment of their blood-cerebrospinal fluid barrier, as estimated by the cerebrospinal fluid/serum quotient of albumin. Lecithin cholesterol acyltransferase was detected in the cerebrospinal fluid of all control subjects, being 0.12 +/- 0.06 microgram/ml (mean +/- SD) or about 2.2% of that in serum (5.4 +/- 1.4 micrograms/ml). The cerebrospinal fluid lecithin cholesterol acyltransferase index was 5.2 +/- 2.5, very similar to the cerebrospinal fluid index of apolipoprotein E, a protein known to be synthesized in the brain. Since lecithin cholesterol acyltransferase mRNA is also expressed in the brain, we can conclude that the protein is synthesized and secreted in the brain. The cerebrospinal fluid concentration of lecithin cholesterol acyltransferase in the subjects with active demyelinating disease or multiple sclerosis was only about one-half of that found in control subjects (0.06 +/- 0.02 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serum release of the creatine kinase tissue-specific isoforms MM3 and MB2 is simultaneous during myocardial reperfusion.

The release sequence of the creatine kinase MM and MB tissue-specific subforms after myocardial reperfusion was elucidated by computer-fitting serial enzyme data from 6 humans in whom coronary flow in the infarct-related artery was angiographically documented as initially zero, opening to normal after angioplasty. The model equation used demonstrated acceptable performance according to standard criteria including visual examination and statistical parameters. The model successfully described the sequential conversion of the MM3 and MB2 tissue isoforms to their respective MM2 and MM1, and MB1 isoforms. Release of MM3 and MB2 was simultaneous, differing in calculated release times by 0.2 to 10%, median 3%. Since MB2 release is not retarded after myocardial reperfusion compared to the more clinically established CK-MM3 isoform, assays for sensitive and rapid measurement of MB2 should be the focus for the non-invasive assessment of myocardial reperfusion due to its higher cardiospecificity.

Aged↗

Issues in cerebrospinal fluid management. CSF Venereal Disease Research Laboratory testing.

Three policies for decreasing unnecessary cerebrospinal fluid (CSF) management Venereal Disease Research Laboratory (VDRL) tests were compared. The first policy attempted to educate physicians about the use of serologic tests for diagnosing neurosyphilis but allowed the CSF VDRL to be performed either as a screening test or as a retrospective test. The second policy required that the CSF VDRL be performed as a retrospective test without regard to the patient's serologic status. The third policy required that a patient be seropositive by either rapid plasma reagin (RPR) or fluorescent treponemal antibody absorbance (FTA-ABS) before a CSF VDRL could be performed. Before these policies were instituted, VDRL testing was performed on 18.2% of all CSF samples. The optional and required retrospective policies decreased the CSF VDRL rate to 13.0% and 8.5%, respectively, but the percentages of seropositive patients for whom these procedures were performed were only 7.3% and 12.9%. The third policy decreased the CSF VDRL test rate to 1.8% (P less than 0.001) with seropositivity improving to 90%. To assure serologic tests are obtained in the evaluation of neurosyphilis, requirement for seropositivity must be implemented with the use of retrospective CSF VDRL testing.

Antibodies, Bacterial↗