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Biomedical subjects

R H Christenson

Publications and source records attributed to R H Christenson.

At least 73 records · Page 4Linked to original sources

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↗

Characteristics of creatine kinase-MB and MB isoforms in serum after reperfusion in acute myocardial infarction.

Characteristics of CK-MB, the MB1 and MB2 isoforms, and the MB2/MB1 ratio are described in six acute myocardial infarction (AMI) patients in whom the infarct-related artery was identified and, after intervention, normal coronary flow was re-established. After myocardial reperfusion, washout of CK-MB and the MB2 isoform occurred in parallel, with CK-MB peaking between 5.75 and 10.0 h, and MB2 peaking between 4.50 and 8.00 h. In five of the six patients, MB1 peaked between 8.75 and 15.5 h; the MB2/MB1 ratio demonstrated the earliest peak from 0.75 to 2.25 h. When we compared this study group to an additional 10 AMI patients who had achieved myocardial reperfusion earlier, we found a significant difference (P less than 0.005) for all tests, except MB1 isoform activity, as early as 50 min after reperfusion. This same comparison, by logistic-regression analysis, showed that the MB2/MB1 ratio discriminated between the groups 50 min after reperfusion (P less than 0.05); MB2 showed near-significance at 100 min (P less than 0.057); and CK-MB achieved significance after 200 min (P less than 0.05). CK-MB, the MB2 isoform, and especially the MB2/MB1 ratio show potential for the early, noninvasive detection of myocardial reperfusion.

Aged↗

CSF TRAP: a procedure to improve laboratory testing with myelography.

CSF TRAP (Transport and Rapid Accessioning for Additional Procedures) is a procedure that provides storage of and rapid access to cerebrospinal fluid (CSF) specimens and allows clinicians to review initial findings before ordering low-yield CSF studies. The cost-effectiveness of routinely using the CSF TRAP procedure with myelography is examined in a study group of 819 patients, 74% with disc diseases, spinal stenosis, spondylolisthesis, or pain syndromes, 10% with cancer, and 16% with neuropathies and miscellaneous conditions. Routine studies on CSF obtained during myelography provided little additional clinical information, except for patients with cancer (of 80 patients with cancer, the results of cytological examination of the CSF were positive in 12) and patients with multiple sclerosis, for whom oligoclonal band and IgG analysis provided supportive diagnostic data. The utilization of the CSF TRAP procedure with elimination of unnecessary culture and cytological studies on patients with disc diseases, spinal stenosis, spondylolisthesis, and pain syndromes, reduces myelographic CSF procedures by 20%, for a savings exceeding $14,000. The CSF TRAP procedure allows for a more cost-efficient analysis of CSF obtained using myelography, while providing fluid for analysis in patients with unexpected findings.

Adult↗

Cerebrospinal fluid (CSF) TRAP. A method to improve CSF laboratory efficiency.

Establishment of a procedure termed cerebrospinal fluid (CSF) TRAP ("Transport and Rapid Accessioning for Additional Procedures") allows clinicians to appropriately store, at -75 degrees C, and rapidly access CSF specimens. The CSF TRAP enhances patient care by decreasing the need for repeat lumbar punctures and providing reserve fluid for the following: (1) further CSF testing; (2) repeating questionable test results; and (3) laboratory accidents. The CSF TRAP has been approved for third-party payment because it promotes efficient laboratory utilization by encouraging clinicians to review initial CSF findings before ordering low-yield CSF assays such as the venereal disease research laboratory (VDRL) and cryptococcal antigen latex agglutination tests. Currently, CSF TRAP samples are being obtained with 40% of all CSF acquisitions at the Duke University Medical Center. The availability of the CSF TRAP was associated with a significant decrease in the ordering of CSF VDRL and cryptococcal antigen assays (P less than 0.05); however, there was no significant change in the proportion of those studies being performed on normal CSF. The CSF TRAP procedure provides the framework for an overall restructuring of CSF testing that is being investigated.

Antigens, Bacterial↗

Establishment of a CSF bank.

A bank of well-characterized CSF has been established by collecting and storing (-70 degrees C) CSF samples remaining after completion of routine clinical studies. Over 1,700 individual patient samples were collected during a 12-month period. A database derived largely from information down-loaded from existing hospital-based systems includes the results of individual CSF laboratory studies, in addition to the patient age, primary diagnoses, and details of any malignancy. CSF control material is used to verify storage conditions. The CSF bank supplies investigators with CSF handled in a standardized manner for more precise investigation of CNS disease.

Adolescent↗

Digoxin-like immunoreactivity eliminated from serum by centrifugal ultrafiltration before fluorescence polarization immunoassay of digoxin.

Digoxin determined in the Abbott "TDx" by fluorescence polarization immunoassay by the manufacturer's recommended method involving precipitation of protein with 5-sulfosalicylic acid (SSA) is subject to interference from endogenous compounds having digoxin-like immunoreactivity. Guided by the work of Graves et al. (Clin Chem 1986;32:1506-9), we eliminated interference caused by digoxin-like immunoreactivity by substituting ultrafiltration for precipitation with SSA to remove protein. Using the manufacturer's method, we quantified digoxin in serum from 53 patients in three clinically defined groups who were receiving no digoxin, finding apparent digoxin in excess of the 200 ng/L detection limit in 24% of the 17 pregnant women, 59% of the 17 renal-dialysis patients, and all of 19 neonatal cord-blood samples examined. No measurable digoxin immunoreactivity was observed by fluorescence polarization immunoassay for any of the 53 clinically defined patients after removal of protein by ultrafiltration. For 22 men for whom digoxin was prescribed, digoxin measurement after protein removal by SSA and by ultrafiltration correlated well (r = 0.98), with good proportionality (slope = 1.04). Analytical recovery of added digoxin from adulterated serum was 115% after SSA, but 100% after ultrafiltration. Thus, before this assay procedure, we recommend ultrafiltration, to remove digoxin-like interference.

Digoxin↗

Changes in cerebrospinal fluid IgG and apolipoprotein E indices in patients with multiple sclerosis during demyelination and remyelination.

Approximately 85% of patients with multiple sclerosis (MS) can be diagnosed by using magnetic resonance imaging and laboratory tests such as determination of the cerebrospinal fluid (CSF) IgG Index and electrophoresis to detect oligoclonal banding. However, these tests results are abnormal in MS patients whether they are in clinical remission or acute exacerbation. Because apolipoprotein E (apo E) is synthesized in the central and peripheral nervous system, particularly during remyelination, we propose that apo E might be a reliable marker of the remyelination that accompanies clinical remission in MS patients. We studied 33 patients with MS, 22 in remission and 11 in exacerbation, and 26 controls of comparable ages. The apo E Index, calculated from the concentrations of apo E and albumin in CSF and serum, allowed us to discriminate between MS patients in remission and MS patients in exacerbation (P less than 0.001); the IgG Index failed to show similar differences. However, combining the apo E and IgG indices gave maximum discrimination between controls, MS patients in remission, and those in exacerbation. This study suggests that apo E measurements should be included in the laboratory evaluation of MS patients.

Adult↗

Increased lactate dehydrogenase isoenzyme 1 in serum and tumor tissue of a patient with small-cell carcinoma.

Histological examination of supraclavicular lymph node tissue obtained at biopsy from a 63-year-old man disclosed metastatic small-cell carcinoma. On admission and for four days subsequently, total lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum was 6.5 times normal; studies of LD isoenzyme showed persistently increased LD-1, with LD-1 greater than LD-2. Isoenzyme electrophoresis of tissue homogenates prepared from the patient's tumor also showed the LD-1 greater than LD-2 pattern. Isoenzyme studies for supraclavicular lymph node tissue from five control subjects showed contrasting isoenzyme patterns as compared with the patients in whom LD-2, LD-3, and LD-4 predominated. Because these abnormalities were persistent, they differ from the temporal sequence for LD usually seen in myocardial infarction. This emphasizes the importance of repetitive sampling for clinical interpretation of data on this enzyme.

Carcinoma, Small Cell↗

Relationship between serum lactate and ionized calcium in open-heart surgery.

We studied 16 patients undergoing open-heart surgery and heart-lung bypass, to examine the relationship between ionized calcium and lactate. Blood was sampled at successive stages of the operation for measurement of ionized and total calcium, lactate, blood gases, pH, hematocrit, and other constituents. We found that correlations between ionized calcium and lactate were positive and statistically significant (p less than 0.05), both among and within patients. The linear regression of ionized calcium on lactate remained highly significant (p less than 0.0001) after adjustment for variability among patients and across operative stages as well as after correction for pH and hemodilution. The significant regressions between calcium and lactate, both before and after administration of calcium, indicate a relationship for calcium and lactate in patients undergoing open-heart surgery.

Blood↗

Oligoclonal banding in cerebrospinal fluid assessed by electrophoresis on agarose after centrifugal sample concentration through a microconcentrator membrane.

We describe use of a microconcentrator membrane with a 30 000-Da cutoff for treatment of cerebrospinal fluid (CSF) specimens before detection of oligoclonal bands by electrophoresis on agarose. After centrifugation at 2000 X g for 25 min, 0.5-, 1.0-, and 2.0-mL aliquots of CSF were concentrated 15-, 25-, and 40-fold. Analytical recovery of immunoglobulins G and A from the microconcentrators was about 90% (CV 5-8%). We found good correlation between results by this method and by a silver-stain procedure in a study comparing oligoclonal banding in CSF from multiple sclerosis and control patients. After 40-fold concentration of 2 mL of CSF, 2 mg of immunoglobulin G per liter can be detected, because the analytical sensitivity of the electrophoresis is 80 mg/L.

Centrifugation↗