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[Cervical cancer in Frederiksborg County 1990-1991].

One hundred and eight patients from Frederiksborg County, Denmark with cervical cancer diagnosed from 1990 to 1993 were analysed concerning type of carcinoma, tumour stage and screening history. The following types of carcinoma were found: 87 (81%) squamous, 5 (5%) adenosquamous, 15 (14%) adenocarcinoma and one (1%) small cell carcinoma. All women aged 23-60 receive a written invitation to participate in the screening programme. Of the 57 patients who had never or only sporadically been screened 23 were outside the target population. Tumour stage was generally higher for the non-screened, i.e. only 57.9% stage I compared to 82.4% for the screened population. In 51 cases the following errors had occurred: seven sampling errors, 21 screening errors, 15 lack of follow-up of abnormal or inadequate smears, six inadequate cryotherapy and two interval cancers.

Adenocarcinoma

A propagation of error analysis of the enzyme activity expression. A model for determining the total system random error of a kinetic enzyme analyzer.

We present a total system error evaluation of random error, based on a propagation of error analysis of the expression for the calculation of enzyme activity. A simple expression is derived that contains terms for photometric error, timing uncertainty, temperature-control error, sample and reagent volume errors, and pathlength error. This error expression was developed in general to provide a simple means of evaluating the magnitude of random error in an analytical system and in particular to provide an error evaluation protocol for the assessment of the error components in a prototype Miniature Centrifugal Analyzer system. Individual system components of error are measured. These measured error components are combined in the error expressiion to predict performance. Enzyme activity measurements are made to correlate with the projected error data. In conclusion, it is demonstrated that this is one method for permitting the clinical chemist and the instrument manufacturer to establish reasonable error limits.

Aspartate Aminotransferases

[Quality control of intraoperative diagnosis. Annual review of 1490 frozen sections].

A retrospective evaluation of the accuracy of frozen section diagnoses over 1-year period has been carried out. Of 20998 surgical pathology specimens accessioned during 1991, 1265 (6.0%) had intraoperative pathologic consultation; 1490 were the frozen section examinations effectively carried out, with an average of 1.2 frozen section diagnoses per case. Of all frozen sections performed, 4.6% were deferred; in the remaining cases, the concordance between frozen sections and the final histologic diagnoses was 97%. The reasons for diagnostic discordances were gross sampling error (51.2%), misinterpretation (44.2%), microscopic sampling (9.3%), technical problems in sectioning (2.3%). We believe that a similar continuous monitoring should be performed in every pathology department, to recognize the reasons of errors and, if possible, to reduce them.

Academies and Institutes

Parameters that bias the measurement of airborne concentration within a respirator.

This paper describes the theoretical basis upon which a test system has been set up to evaluate the sampling error associated with in-facepiece sampling on half-mask respirators. The in-facepiece sampling technique evaluated in this study is the one currently used in the U.S. to conduct quantitative facepiece fit testing. An experimental design was developed to study the sampling bias associated with in-facepiece sampling when selected parameters of the man/respirator system were varied. The results indicated that significant errors can be made in estimating concentration within a respirator when the current in-facepiece sampling technique is employed. Sampling bias was determined when in-facepiece samples were collected only during the inhalation phase of the respiratory cycles. They were found to range from greater than -99% to greater than +98%. The mean sampling bias was -17 +/- 38%. When measured in-facepiece concentrations were used to calculate a fit factor the resulting range was 44 to 4728 even though the actual fit factor was only 87. Based upon the data presented, it was hypothesized that faceseal leakage was streamlining within the respirator cavity. As a result, quantitative facepiece fit data on half-mask respirators may be biased by the large measurement error.

Acetone

Protonation of interacting residues in a protein by a Monte Carlo method: application to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides.

We used Monte Carlo methods to treat statistical problem of electrostatic interactions among many titrating amino acids and applied these methods to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides, including all titrating sites. We computed the average protonation of residues as a function of pH from an equilibrium distribution of states generated by random sampling. Electrostatic energies were calculated from a finite difference solution to the linearized Poisson-Boltzmann equation using the coordinates from solved protein structures. For most calculations we used the Metropolis algorithm to sample protonation states; for strongly coupled sites, we substantially reduced sampling errors by using a modified algorithm that allows multiple site transitions. The Monte Carlo method agreed with calculations for a small test system, lysozyme, for which the complete partition function was calculated. We also calculated the pH dependence of the free energy change associated with electron transfer from the primary to the secondary quinone in the photosynthetic reaction center. The shape of the resulting curve agreed fairly well with experiment, but the proton uptake from which the free energy was calculated agreed only to within a factor of two with the observed values. We believe that this discrepancy resulted from errors in the individual electrostatic energy calculations rather than from errors in the Monte Carlo sampling.

Electron Transport

Time sampling and measurement error: the effect of interval length and sampling pattern.

The accuracy of momentary time-sampling was evaluated for behaviors occurring for different proportions of time, for different momentary time-samples and for sessions of different lengths. For 1-hr sessions, momentary time-samples of 10, 20 or 30 see intervals between observations yielded 90% of estimates within 10% of the comparison standard, for behaviours of 25%, 50% and 70%. Behaviours occurring for 2% of the session were not accurately recorded even at 10-sec momentary time-samples. For a 5-min momentary time-sample, this criterion was only approached when 8 hr data was averaged to give a single score for each individual, for behaviours of 25% or more. The 5-min momentary time-sample was also compared with a 1 in 5-min cluster sample; although less accurate, cluster-sampling might be a useful strategy in some settings.

Behavior

Adaptive control of theophylline therapy: importance of blood sampling times.

A two-observation protocol for estimating theophylline clearance during a constant-rate intravenous infusion is used to examine the importance of blood sampling schedules with regard to the information content of resulting concentration data. Guided by a theory for calculating maximally informative sample times, population simulations are used to assess the effect of specific sampling times on the precision of resulting clearance estimates and subsequent predictions of theophylline plasma concentrations. The simulations incorporated noise terms for intersubject variability, dosing errors, sample collection errors, and assay error. Clearance was estimated using Chiou's method, least squares, and a Bayesian estimation procedure. The results of these simulations suggest that clinically significant estimation and prediction errors may result when using the above two-point protocol for estimating theophylline clearance if the time separating the two blood samples is less than one population mean elimination half-life.

Blood Specimen Collection

Comparison of two techniques for obtaining samples for coagulation studies: venipuncture and intraarterial line.

The purpose of this study was to compare blood coagulation values drawn by venipuncture and from an intraarterial catheter. A 10 ml discard was obtained from 50 consecutive patients before obtaining the coagulation sample from the intraarterial catheter, and a 0.5 ml discard was obtained from the venipuncture specimen. A two-tailed t test for related samples was performed. The results revealed no significant difference between the two methods (p less than 0.05). The small differences seen were attributed to sampling error. These results suggest that blood samples obtained from heparinized intraarterial catheters after a 10 ml discard provide an accurate assessment of patients' mean clotting time.

Adult

Analysis of polymorphic variation in different types of habitat.

A correlation between the distribution of an organism and features of its environment can be taken as indirect evidence of natural selection. Biologists may therefore collect samples from polymorphic populations at a number of locations, classify the locations into habitat types, and consider whether the distribution of morphs varies with the habitat. Statistical aspects of this type of study are discussed in this paper. A randomization test for habitat effects is proposed and a negative binomial model is suggested for the distribution of morphs from random locations within one type of habitat. Data on the distribution of Cepaea hortensis and C. nemoralis snails in southern England provide an example. For both species there is clear evidence of differences between habitats, although the morph distributions are rather variable within habitats. The negative binomial model suggests that, for the snail data, variation in morph proportions is mainly due to location differences. The binomial sampling error is relatively unimportant unless the sample size at a location is very small. Therefore it is reasonable to analyse morph proportions by standard methods without giving different weights to data from different locations. The snail data are analysed in this way. Discriminant function analyses are used to test for habitat effects. The relationships between C. hortensis and C. nemoralis morph frequencies within one habitat are examined by a canonical correlation analysis.

Animals

Tissue diagnosis for carcinoma of the pancreas and periampullary structures.

In a county hospital, 217 patients were operated on for suspected cancer of the pancreas (186 patients) and periampullary structures (31 patients). The surgeons' philosophy was to avoid biopsy of the pancreas whenever possible, they often performed radical resection based on clinical judgment alone (8% of the resections were chronic pancreatitis). Follow-up of the 65 patients who were presumed to have carcinoma without histologic proof showed the surgeon's clinical diagnosis to be incorrect in over 7% of the cases (maximum error - 18%). Among patients with carcinoma of the pancreas, one third of the pancreatic biopsies missed the lesion (surgeon's sampling error). Frozen section examination of pancreatic biopsies in 63 patients showed false positive and negative rates of 3% and 4%, respectively (pathologist's sampling or interpretation errors). Two of 31 incisional biopsy of the pancreas resulted in pancreatic fistula; none of 24 needle biopsies did. Otherwise, biopsy of the pancreas did not influence mortality or morbidity after either resection or bypass procedures.

Acute Disease

Stability of arterial concentrations during continuous inhalation of C15O2 and 15O2 and the effects on computed values of CBF and CMRO2.

Stability of arterial whole blood and plasma concentrations is a basic requirement in the application of the oxygen-15 (15O2) steady-state inhalation technique for measuring regional cerebral blood flow and oxygen use. The level of stability obtainable in practice is reported in the form of retrospectively analysed blood data from 626 consecutive studies in patients with a range of clinical conditions. Serial arterial whole blood and plasma concentrations were measured during both C15O2 and 15O2 inhalations, and coefficients of variation were calculated. In addition, these concentrations were compared with the corresponding values recorded at the start of each study and maximum variations were calculated. For all four concentrations, mean and median coefficients of variation were around 5 and 4%, respectively. Mean and median maximum variations were around 9 and 7%, respectively. The effects of these variations on the calculations of regional cerebral blood flow, oxygen extraction, and oxygen use were estimated. Mean expected errors were found to be between 4 and 9%, and median expected errors between 3 and 6%. Inherent blood sampling errors were assessed from blood volume studies using 11CO-labeled red cells. These errors were found to be less than 3%.

Arteries

Accuracy of breast frozen section diagnosis in the community hospital setting: a detailed analysis of 628 cases.

The author presents a detailed analysis of 628 breast frozen sections performed at Columbia Hospital over a 35-month period. These 628 frozen sections came from a total of 574 females and 13 males (mean age 55.3 years and range 20.1 to 95.0 years). Frozen section diagnosis was deferred in 18 cases (2.8%) and diagnostic accuracy for presence or absence of malignant neoplasia was 99.2%; one false positive case (pathologist judgement error) and four false negative cases (two sampling errors and two pathologist judgement errors) were detected. Strict diagnostic accuracy for this series was 98.7%. Fifty-three of 223 positive frozen sections (23.8%) were immediately followed by completion mastectomy. The author discusses the philosophy of frozen section technique and concludes that breast frozen section analysis in a busy community hospital setting can meet and even exceed the accuracy level attained at large academic medical centers.

Adult

Paired cervical smears: a method of reducing the false-negative rate in population screening.

Cervical smears taken by the wooden Ayre spatula (widely used in the United Kingdom) and by a plastic spatula (Armovical) were compared for their ability to detect dysplastic cervical epithelium and endocervical cells. At the same time, the value of taking duplicate smears was assessed. Paired cervical smears were obtained at a single attendance from 21,352 women, using the 2 types of spatulas in 4 different sequences. Although individually the Armovical proved superior to the Ayre spatula for the collection of endocervical epithelial material, this advantage was not complemented by any marked improvement in its detection of cervical dysplasia. Paired smear sampling, however, was clearly more rewarding in this respect and also allowed the introduction of laboratory quality control, as each preparation of any given pair was examined by a different screener. The false-negative rate was 18.5%: it comprised 11.1% sampling error and 7.4% screening error. It is concluded that paired smear sampling in population screening would significantly reduce the false-negative rate.

Carcinoma in Situ

Problems with measurements caused by high concentrations of serum solids.

There have been numerous reports of spectrophotometric and volume problems caused by elevated levels of lipids in blood. The offending lipids, primarily triglycerides, not only cause turbidity leading to optical aberrations when added to analytical reagents, but also result in short-sampling errors leading to the measurement of inaccurate volumes of sample. Numerous methods have been developed to clear the lipemia, including ultracentrifugation organic solvent extraction, chemical precipitation and, most recently, enzymic hydrolysis. Although the latter procedures eliminate the optical problems, they do not deal with the volume dilution error created by the triglycerides. In turn, corrective mathematics have been developed to compensate for the inaccurate pipetting caused by the elevated lipids in a sample; however, these empirical calculations are not truly accurate at high concentrations of total lipids. This monograph will describe the problems caused by the presence of elevated lipids and the means available for treating them.

Blood Chemical Analysis