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Sources of error in measuring cerebrospinal fluid formation by ventriculocisternal perfusion.

Ventriculocisternal perfusion is regarded as a precise method of measuring the rate of formation of cerebrospinal fluid (CSF) but it possesses inherent potential sources of error. Using the technique to measure CSF formation rate in the rhesus monkey, we have observed rate changes when none were expected. Most puzzling has been the steady decline of CSF formation rate at 4 percent each hour during the final five hours of a seven hour perfusion although variables known to affect CSF formation remained stable. In addition, alterations in rate caused by artefacts were observed in experiments in which craniospinal blood volume was changed by sudden changes of either PCO2 or central venous pressure. Mobilisation or sequestration of incompletely equilibrated CSF is believed responsible. In other experiments, a small increase of intracranial pressure produced by increasing outflow resistance was quickly followed by an apparent reduction of CSF formation. We have concluded that to assess accurately the effect a variable has on the rate of CSF formation, one must control perfusion time and craniospinal blood volume as well as intracranial pressure.

Animals

Accuracy of end-tidal carbon dioxide tension analyzers.

Substantial mean differences between arterial carbon dioxide tension (PaCO2) and end-tidal carbon dioxide tension (PETCO2) in anesthesia and intensive care settings have been demonstrated by a number of investigators. We have explored the technical causes of error in the measurement of PETCO2 that could contribute to the observed differences. In a clinical setting, the measurement of PETCO2 is accomplished with one of three types of instruments, infrared analyzers, mass spectrometers, and Raman spectrometers, whose specified accuracies are typically +/- 2, +/- 1.5, and +/- 0.5 mm Hg, respectively. We examined potential errors in PETCO2 measurement with respect to the analyzer, sampling system, environment, and instrument. Various analyzer error sources were measured, including stability, warm-up time, interference from nitrous oxide and oxygen, pressure, noise, and response time. Other error sources, including calibration, resistance in the sample catheter, pressure changes, water vapor, liquid water, and end-tidal detection algorithms, were considered and are discussed. On the basis of our measurements and analysis, we estimate the magnitude of the major potential errors for an uncompensated infrared analyzer as: inaccuracy, 2 mm Hg; resolution, 0.5 mm Hg; noise, 2 mm Hg; instability (12 hours), 3 mm Hg; miscalibration, 1 mm Hg; selectivity (70% nitrous oxide), 6.5 mm Hg; selectivity (100% oxygen), -2.5 mm Hg; atmospheric pressure change, less than 1 mm Hg; airway pressure at 30 cm H2O, 2 mm Hg; positive end-expiratory pressure or continuous positive airway pressure at 20 cm H2O, 1.5 mm Hg; sampling system resistance, less than 1 mm Hg; and water vapor, 2.5 mm Hg. In addition to these errors, other systematic mistakes such as an inaccurate end-tidal detection algorithm, poor calibration technique, or liquid water contamination can lead to gross inaccuracies. In a clinical setting, unless the user is confident that all of the technical error sources have been eliminated and the physiologic factors are known, depending on PETCO2 to determine PaCO2 is not advised.

Algorithms

Sources of error in the spike-triggered averaging method of motor unit number estimation (MUNE).

Motor unit number estimation (MUNE) is an electrophysical technique to estimate the number of motor units innervating a muscle or muscle group. MUNE may be useful as a measure of progression of lower motor neuron loss in amyotrophic lateral sclerosis (ALS). Several methods of MUNE have been developed. The spike-triggered averaging method can be readily performed on EMG machines with signal averaging capabilities and is suitable for estimating the number of motor neurons innervating proximal muscles. We have used MUNE as a measure of disease state in a drug efficacy trial for ALS. From our experience with this method we have identified sources of error which can affect MUNE accuracy. We have investigated these sources and report their effect on MUNE.

Action Potentials

[The risk of gastrostomy in childhood. Sources of error and prevention (author's transl)].

The indication for gastrostomy in childhood arises from the possibilities of decompression and enteral feeding. The demand for an operative procedure to children involves simple technique, safety, efficacy and uncomplicated nursing. The most important sources of error in the creation of a gastrostoma arise from the position and size of the catheter, atraumatic suture technique; on the other hand there is the threat of postoperative extension of the gastrostoma, local infection and sepsis. The results of our own procedure are described and the results given of 172 of our own cases.

Aftercare

Factors influencing the accuracy of the cardiac output monitoring and diagnostic unit for pneumatic artificial hearts.

The Cardiac Output Monitor and Diagnostic Unit (COMDU) has been the most widely used method to noninvasively determine cardiac output in pneumatic ventricles for the past 10 years. Clinical observation has suggested a discrepancy between the COMDU and expected cardiac outputs. In vivo tests verified and quantified this error. The error sources were examined using in vitro test conditions, with both the inflow and outflow, as well as COMDU flow readings, being analyzed. Transducer and calibration error sources were also identified, and the accuracy of the method for determining cardiac output for the in vitro test conditions was quantified. With a more accurate calibration scheme, the in vitro average error was reduced from -16.2% (range of 0.1% to -41.1%) to 0.1% (range 4.8% to -3.65). The major error sources were identified as missed inflow, transducer calibration and drift, and system variance.

Animals

Interactions with hemoglobin: a source of error in measurements of transketolase activity in hemolysates.

Measurements of the activity of transketolase in human erythrocyte lysates by an assay coupled to NADH oxidation indicate that interactions of assay substrates with hemoglobin can give rise to overestimations of transketolase activity. Three potential sources of error are identified. Thus, in lysates containing methemoglobin, NADH oxidation can be due firstly to methemoglobin reductase activity or secondly to the monooxygenase activity of methemoglobin, for which the substrate can be ribose 5-phosphate, a substrate also of transketolase. Thirdly, the addition of high concentrations of the transketolase cofactor, TDP, to an insufficiently buffered reaction mixture can cause the aggregation and precipitation of hemoglobin: a phenomenon that may be misconstrued as an enhanced increase in absorbance at 340 nm and hence as additional transketolase activity. Although the present study concentrates on these potential artefacts in assays of transketolase activity, the findings may well be relevant to the measurement of other enzyme activities in hemolysates by procedures based ultimately on the rate of consumption or production of NAD(P)H.

Chromatography, Gel

Measurement of blood flow by ultrasound: accuracy and sources of error.

Doppler ultrasound has now developed to the point where the rate of flow of blood in a given vessel can be measured with appropriate instrumentation. The theoretical basis of Doppler flow measurement is reviewed in this paper, with particular emphasis on the potential and actual sources of error. Three distinct approaches are identified, and the strengths and weaknesses of each discussed. The separate errors involved in estimating the vessel cross-sectional area, the angle of approach, and the Doppler shift are analyzed, together with the question of the uniformity of scattering from the blood. In vivo and in vitro tests of the accuracy obtained using a number of Doppler flow measuring instruments are then reviewed. It is concluded that the Doppler methods are capable of good absolute accuracy when suitably designed equipment is used in appropriate situations, with systematic errors of 6% of less. There are, however, considerable random errors, attributable primarily to errors in measuring the cross-sectional area and the angle of approach. Repeating the measurement of flow several times and averaging the results can reduce these random errors to an acceptable level.

Blood Flow Velocity

Tissue sampling as a potential source of error in experimental studies of cartilage.

Although it might seem trite to point out that tissue sampling is a potential source of experimental error, this survey disclosed that even experienced investigators in fact often work with cartilage that is contaminated by non-cartilaginous tissue of which they were unaware. Twenty-two specimens ranging from chick embryo sternum to bovine nasal septum were studied by serial sectioning. Eighteen of the 22 contained extraneous tissue comprising from 3 to 50% of the cross-sectional area. The impact of the contamination depends on the use being made of the material and probably is greatest in cell culture studies because chondrocytes and fibroblasts have large differences in population doubling time. Several approaches for minimizing the error are suggested by the findings. Histological examination of specimen material is thus a desirable quality control procedure in the design and interpretation of experiments on cartilage as well as other tissues.

Animals

Sources of error in heparin therapy of thromboembolic disease.

We observed a series of patients with thromboembolic disease treated intravenously with heparin sodium and monitored by the activated coagulation time (ACT) of whole blood. When patients responded slowly, had dangerous hemorrhage, or had ACTs well outside our target range, we analyzed infusion records to determine actual infusion rates. We found the following sources of error: (1) lack of pump precision, (2) interruption of infusion, (3) errors in making up solutions, and (4) failure of infusion or charting techniques.

Adult

Sources of error and their correction in the measurement of carbon dioxide elimination using the Siemens-Elema CO2 Analyzer.

The Siemens-Elema CO2 Analyzer 930 allows calculation of carbon dioxide elimination from the instantaneous measurement of expired gas flow (VE) and carbon dioxide fraction (FECO2). VE is measured in the ventilator and FECO2 at the Y-piece. The most important source of error in the measurement of carbon dioxide elimination is rebreathing, which corresponds to about 24 ml of end-expiratory gas per breath with the standard Y-piece and tubing. This problem may be decreased by the use of non-return valves in the Y-piece. Allowance must be made for the effects of intermolecular interaction between carbon dioxide and the carrier gas, as the reading is about 20% greater with nitrous oxide than with oxygen. This problem can be largely circumvented by calibration with appropriate gas mixtures. Errors resulting from analyser delay are small, and are eliminated completely by the inclusion of fast electronic components. Carbon dioxide analysis is linear with air as carrier gas, but slightly alinear with nitrous oxide in oxygen mixtures. This error can be minimized by using calibration gases with a carbon dioxide content close to that of expired gas. The expiratory flow meter is linear if kept in good condition. Variations in temperature and water content of expired gas cause overestimation of mean expired carbon dioxide fraction (FECO2) by a factor of 1.01-1.02. Compressed gas in the tubing causes a small error which may be neglected at normal airway pressures with tubing of low compliance. Carbon dioxide measurement is slightly affected by barometric pressure. During mechanical ventilation of the lungs in 10 patients with air, FECO2 obtained after corrections for known errors agreed well with Scholander analysis of mixed expired gas.

Carbon Dioxide

[Sources of error in the radioimmunochemical determination of digoxin in serum].

In a study with numerous samples of serum we compared 5 Digoxin RIA and evaluated the reliability of tests by simultaneous determinations. There were found considerable differences in the determinations with the various RIA for the same serum; evident differences also were recorded in the recovery and in the reproducibility of the assays. Among some other sources of error the dependence of temperature and of the duration of the dextran-charcoal separation were observed; therefore, the charcoal incubation is recommendable at 4 degrees C. Each laboratory which is able to perform the determinations of digoxin concentrations in the serum should declare its own range for the therapeutic and toxic levels for the used RIA in collaboration with the clinicians.

Absorption

[Sonographic diagnosis of hip dysplasia. Principles, sources of error and consequences].

Sonography of the hip in infants is being increasingly employed. This method of examination involves several specialist disciplines. The more widespread its use, the greater the likelihood of faulty diagnoses if one is not aware of its weak points. Faulty diagnoses are the order of the day if the method is employed by persons whose knowledge has not been updated to latest advances in the field; other sources of error are faulty scanning, unsuitable sonographic equipment and insufficient documentation. Hence, it is mandatory to describe the demands to be made on the equipment according to update standards and to draw up guidelines that will help to avoid quality loss. The criteria for assessing a hip sonogram are defined and the problem of age limit is considered. A review is given of disturbances of normal development of the hip. The possibility of effecting dynamic examination should not mislead one to neglect assessment of the hip joints as precisely as possible by means of an exacting measurement technique. The weak points of the technique of measurement and the valuation of the angles must be known. A review of the literature reveals many problems in hip sonography. A multitude of these problems is unnecessary and can be considered as solved if one would try to match modern quality demands and not be satisfied with a quality standard that is many years old. To achieve best possible hip examination via sonography it will often be necessary to considerably modify principles of general sonography of the soft parts.

Diagnostic Errors

[The reaction time as a source of error in threshold audiometry (author's transl)].

An investigation of reaction times at the threshold of hearing is described. 96 subjects were classified into two groups of sensorineural hearing loss utilizing Types I and II Bekesy audiometry, and compared with one normal group as control. The results show that reaction times are largely unaffected by the type of hearing loss and test frequency. Increasing age, however, may result in increasing reaction times. These results and possible sources of error are discussed as effecting an exact threshold audiometry.

Adult

On sources of error in the biochemical study of perilymph (guinea-pig).

Contamination of perilymph with other fluids (cerebrospinal fluid, tissue fluid, blood, endolymph) together with sampling, anaesthesia, surgical intervention or food intake of the animals may considerably affect the analytical result. The numerous possible artefacts seem to be the main reason why varying values are given in the literature for the same chemical component of perilymph. This is also partly true of cerebrospinal fluid and blood. The effect of some sources of error on selected chemical components of perilymph, cerebrospinal fluid and blood is briefly summarized.

Anesthesia

[The reliability and sources of error in basic clinical documentation--a critical report of experiences].

Since 1. 1. 1985, computer-aided basic medical documentation has been routine at the University Orthopedic Clinic in Friedrichsheim, near Frankfurt. In addition to data on patient's histories, all data needed to satisfy the criteria of the Federal Directive on Operating Cost Rates are gathered. The diagnoses are stored in clear text, in a modified Eichler code, and according to ICD 9. Conversion from the Eichler code to ICD 9 is almost fully automated. In a study covering 100 hospitalized cases the following findings were obtained relating to sources of error and reliability: Without any additional in-house plausibility checks, the rate of error in the ID code, created by coding family name, date of birth, and sex, was 7%. In clear text all diagnoses except one and all forms of therapy were correctly reproduced as contained in the medical report. On the other hand, 7% of the conversions into the Eichler code contained errors. The reason for the difference in the quality of data is pointed out. In some of the other surveys, e.g., of infection rates, the rates of error were very high; most errors had been caused by the ward physicians. Data quality is enhanced by exploitation of routine process data when these control administrative procedures or are used for communication between physicians, since they then become relevant to actions and decisions and hence have to be reliable, regardless of documentation purposes.

Bone Diseases

[Radioimmunoassay and its problems: quality, sources of error and quality control of in vitro procedures for thyroid diagnosis].

A review is made of methodical aspects of the performance of radioimmunoassays with special regard to the determination of T3, T4, TSH and free thyroxine. The quality of the analytical systems is determined by specificity, sensitivity, correctness and accuracy. To ensure quality, guidelines are given for the procedure of obtaining test samples as well as for the transport and storage; furthermore, the dependence of the results on the employed method is documented. For determination of the normal range particular emphasis has to be given to the methodical details, regional differences and the age of the patients. To ensure quality, the most frequent sources of error have to be known. These are listed for the determination of thyroid hormones, TSH, thyroxine-binding globulin, thyroglobulin and for the T3U-test; a critical review of the methods is added. Suggestions are given for the systematic internal control of quality; a method for continuous control by a computer program is presented.

Female

Heterophilic antibody as a source of error in immunoassay.

We describe our experience with a young woman believed to be hypothyroid and menopausal because of erroneously elevated TSH, LH, and FSH estimates. These errors were found to be due to the presence of antibodies to rabbit IgG in the patient's blood. We found that antibody-limited assays for TSH, LH, and FSH using antisera raised in rabbits were affected by this problem unless rabbit IgG was included, whereas antibody-excess assays were not. These problems were most simply detected by observing inappropriate results when measurements were made in dilutions of the patient's serum. The presence of endogenous antibody directed against antibodies used in immunoassays is a significant potential source of error requiring awareness on the part of both the clinician caring for such patients and the clinical laboratory making the measurements.

Adult

Sources of error in the isotopic cholesterol balance method in African green monkeys consuming a cholesterol-free diet.

Six African green monkeys were labeled intravenously with [1,2-(3)H]cholesterol while consuming a cholesterol-free liquid formula diet. The plasma cholesterol specific activity was compared with the specific activity of the biliary cholesterol and bile acids and with the fecal neutral steroids in order to determine whether the traditional isotopic balance method was valid for the calculation of endogenous cholesterol excretion. The specific activity of biliary cholesterol and bile acids averaged 10-15% lower than plasma cholesterol specific activity. Fecal cholesterol and coprostanone specific activities were similar to that of the biliary cholesterol, but the specific activity of fecal coprostanol was approximately 25% lower. This suggests that biliary cholesterol and bile acids were derived from a pool of hepatic cholesterol that did not completely equilibrate with the whole body exchangeable cholesterol pool. In addition, there was further reduction in the specific activity of coprostanol, the major fecal neutral steroid, presumably by cholesterol synthesized in the lower intestine and preferentially converted to coprostanol. As a result, the traditional isotopic balance procedure underestimated endogenous neutral steroid excretion by 46% and bile acid excretion by 31% in African green monkeys fed the cholesterol-free diet. Within 7 days after the addition of 1 mg cholesterol/kcal to the diet, the specific activities of plasma and biliary cholesterol and biliary bile acids were identical and there was no difference in the specific activities of the individual fecal neutral steroids. Thus, the traditional isotopic balance procedure (DPM fecal neutral steroids + bile acids/specific activity [DPM/mg] plasma cholesterol) can be used for calculation of endogenous cholesterol excretion in cholesterol-fed animals during the nonsteady state when plasma cholesterol concentrations are rapidly increasing, as well as after a new steady state has been achieved.-Henderson, G. R., and R. W. St. Clair. Sources of error in the isotopic cholesterol balance method in African green monkeys consuming a cholesterol-free diet.

Animals