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Biomedical subjects

R H Christenson

Publications and source records attributed to R H Christenson.

At least 19 recordsLinked to original sources

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

Issues in cerebrospinal fluid management. Acid-fast bacillus smear and culture.

Meningeal tuberculosis is an uncommon disease in the United States with an annual incidence of fewer than 200 cases. This study evaluates three approaches to improving the use of the cerebrospinal (CSF) acid-fast bacillus (AFB) smear and culture procedure: (1) education alone; (2) optional screening by which physicians can select to have the AFB analysis stopped if the initial CSF findings are unremarkable; and (3) mandatory screening before the performance of all CSF AFB analyses. With education alone, the CSF AFB culture rate decreased from 20.6% of all CSF acquisitions to 15.7% (P less than 0.001); however, the effect may have been related to a decrease in all types of AFB testing. Optional screening had no impact on the AFB testing rate. Mandatory screening significantly decreased the CSF AFB rate to 6.7% (P less than 0.001), unrelated to changes in other types of AFB testing. Laboratories that employ mandatory screening should report the screening results immediately and have a mechanism whereby physicians can bypass the screen, providing CSF AFB analysis on unremarkable fluid from high-risk patients.

Adolescent

Anti-inflammatory effects of pentoxifylline in claudication.

We measured neutrophil elastase/alpha 1 proteinase inhibitor complex (E/alpha) levels by ELISA in plasma samples drawn from 19 patients with claudication, before and at 1 and 2 months after initiation of pentoxifylline (PTF), 400 mg. p.o. tid. Plasma E/alpha levels declined in all eight patients whose initial values were more than 300 ng elastase per ml. Whole blood viscosity (wbv) was reduced by two months' treatment in 12 of 14 patients tested. The relative change in wbv was significantly related to the relative change in E/alpha (R2 = 0.8), for patients with elevated initial E/alpha levels, suggesting a common or related mechanism for the two effects. Plasma crosslinked fibrin D-dimer fragments (XDP) measured by ELISA as indicators of coagulation activity were lower compared to pretreatment levels in 9 of 10 samples drawn when symptoms were improved on PTF, whereas they were increased in 6 of 9 samples drawn when symptoms were worse or unchanged. Plasma viscosity, C-reactive protein and alpha 1-acid-glycoprotein did not change significantly with PTF treatment. Together these findings are consistent with the possibility that reduced microvascular neutrophil activation and coagulation play a role in the clinical efficacy of PTF in intermittent claudication.

Anti-Inflammatory Agents, Non-Steroidal

Improving the reliability of total and high-density lipoprotein cholesterol measurements. Four testing strategies compared in a high-risk population.

Four testing strategies for assessing total and high-density lipoprotein cholesterol are compared in a homogeneous group of male outpatients at increased risk for cardiovascular disease: (1) a single measurement at one occasion; (2) the mean of duplicate measurements at one occasion; (3) the mean of single measurements in specimens collected 1 week apart; and (4) the overall mean of duplicate measurements at two occasions 1 week apart. Results of strategy 1 were comparatively less reliable as demonstrated by lower intraclass correlation coefficients and higher within-subject variance components. Use of strategy 3 decreased within-subject variance by 50% and improved the 95% confidence interval by 30% for both total and high-density lipoprotein cholesterol, compared with strategy 1. Duplicate testing on either one or two occasions resulted in a nominal improvement in reliability and confidence. Calculating the mean of single measurements in specimens collected 1 week apart is clinically useful because: (1) it reduces the risk of misclassification, (2) it improves intervention monitoring, (3) it supports the National Cholesterol Education Program guidelines for total cholesterol, and (4) it improves the use of high-density lipoprotein as an independent risk factor.

Adult

Management of cerebrospinal fluid.

In traditional practice, doctors order tests and the laboratory performs them. A series of tests are requested before the results of any of the tests are known. The authors of this paper examine the interface between the clinicians and the laboratory. They produce a cost effective and clinically useful routine for handling spinal fluid. They bring to their practice an excellent example of quality assurance which is genuine, improves practice and is not "busy work." The editor heard Dr. Albright present this material and urged him to make it available to North Carolina doctors.

Adolescent

Relative increase in creatine kinase MB isoenzyme during reperfusion after myocardial infarction is method dependent.

We compared relative increases in creatine kinase (EC 2.7.3.2) MB isoenzyme (CK-MB) after reperfusion in myocardial infarction for four popular methods: electrophoresis, immunoinhibition, the "Magic Lite" (Ciba-Corning) system, and the Stratus (Dade). In a method comparison study, we confirmed that all four methods correlated (r greater than 0.95). Electrophoresis demonstrated the greatest scatter about the regression line, immunoinhibition the least. For CK-MB quantities near each method's "positive cutoff" indicating myocardial infarction, results by all methods agreed in 95% of samples. To characterize relative increases in CK-MB, we computer-fitted data obtained from each method for serial specimens collected from six acute myocardial infarction patients during myocardial reperfusion. Although for each individual patient the four methods appeared to exhibit parallelism, the methods differed significantly in terms describing their appearance rate, peak-time & fall-off, and time-to-peak activity. Consistent with these data, we found that the relative CK-MB increases at various times after reperfusion, compared with baseline concentrations, are method-dependent. Therefore, when using CK-MB for indicating coronary patency, one must develop specific limits for each method utilized.

Adult

Immunochemical assays for IgG, IgA, IgM and transferrin compared.

We compared immunochemical methods for determining IgG, IgA, IgM, and transferrin in serum by studying calibrator crossover, patient comparison, and, for a newly developed technology, normal reference intervals. For the immunoglobulins, we compared radial immunodiffusion (RID), rate nephelometry using the Beckman ICS, and a new nephelometric method adapted to the Abbott TDx; for transferrin we compared the ICS, TDx, and immunoturbiditry. The methods examined for quantifying IgA and transferrin showed good agreement in calibrator crossover and patient comparison studies. In studies comparing IgG methods, the ICS and TDx demonstrated acceptable agreement, although neither showed accordance with RID. For IgM determination, crossover studies and patients having less than 4300 mg/L in this protein showed good agreement, even though more elevated samples, run on the TDx, showed a discrepancy in proportionally compared to the other two methods. Normal reference intervals (95% confidence limits) determined on the TDx agreed well with those established for the other immunochemical methods.

Adolescent

Cerebrospinal fluid: electrophoresis and methods for determining immunoglobulin G compared.

We describe the use of a microconcentrator membrane with a 10,000 dalton cutoff for treating cerebrospinal fluid (CSF) specimens before electrophoresis. We also examine immunochemical methods based on radial immunodiffusion, rate nephelometry, and nephelometry at quasi-equilibrium for quantifying IgG in CSF by studying calibrator crossover, imprecision at low IgG levels, and patient correlation. Calibrator crossover studies showed that values for all standard materials agreed well with assigned. At IgG quantities lower than 30.0 mg/L, we found the radial immunodiffusion (RID) method difficult to use; the rate and quasi-equilibrium methods were reliable to 11.2 and 3.0 mg/L, respectively. Above their respective cutoffs, correlation studies revealed that all three methods compared well. We performed IgG quantification and protein electrophoresis on 40 CSF specimens from patients having non-neurologic disease, finding normal reference intervals which generally agreed with those established previously; however, the albumin, beta, and gamma electrophoretic fractions we observed differed from those reported previously.

Adult