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Quality control and automation in cervical cytology.

Pap smear is a clinical screening test and does not have 100% sensitivity and specificity. Sensitivity of pap smear can be improved with proper collection techniques and education of all concerned. Implementation and maintenance of quality control measures help to detect, reduce and correct deficiencies in pap smear analysis. Advent of automated devices has provided an opportunity to further improve the sensitivity of pap smear. Automation in cytology, seemed wildly speculative a decade ago, is becoming a reality now. Areas of automation include: Data storage and retrieval by computers, automatic staining and coverslipping machines, sample preparation methods, screening process control-devices and imaging systems for searching and interpretation of abnormal cells.

Automation↗

Evaluation of an automated hematologyanalyzer (CELL-DYN 4000) for counting CD4+ T helper cells at low concentrations.

In human immunodeficiency virus (HIV) infection, CD4 cell counts are useful in defining the disease state, monitoring antiviral treatment, and identifying patients at risk for opportunistic infections. Counting CD4 cells typically relies on traditional immuno-flow cytometric analyzers that require opening the tube for manipulation of the blood sample. In addition to automated blood cell counting, the CELL-DYN 4000 hematology analyzer performs a completely enclosed and automated analysis of the T lymphocyte subsets. We studied the performance characteristics of this method in blood samples containing low levels of CD4+ T cells. In one set of experiments, we emulated low level CD4 counts by use of a CD4 Positive Isolation Kit to deplete the CD4+ cells from blood samples. We used the FACScan analyzer for reference counts. Measurements were made exactly 12 hr after venepuncture in samples that were stored at room temperature. In normal samples and those with low CD4+ cell counts, there was excellent correlation between the results of the CELL-DYN and FACScan methods. Using the CELL-DYN 4000 analyzer, the precision of CD4+ and CD8+ T-cell counts was high (CV = 2 to 8%). The CD4+ T-cell count was linear over a wide range (35 to 1640 cells/microl). This study shows that CD4 and CD8 T cell counts using the CELL-DYN 4000 analyzer is suitable for normal samples and also for those with low CD4+ T cell counts. The method is rapid and automated, and blood specimens remain enclosed, minimizing the biohazard of exposure to blood of HIV patients.

Automation↗

Automated measurement of intima-media thickness of carotid arteries in ultrasonography by computer software.

PURPOSE: Intima-media thickness (IMT) has been proposed to be a morphological criterion of atherosclerosis. The purpose of this study was to investigate the interobserver variability of manual and also of computer software measurements of IMT. MATERIALS AND METHODS: High-resolution common carotid artery (CCA) images of 88 patients that have been obtained by a linear broadband L5-12 MHz transducer and archived in PACS were retrospectively evaluated. Two separate investigators, who were unaware of the former results, evaluated the same images by using computer software that had a dedicated tool for automatic measurement of IMT. The results of the investigators were compared. RESULTS: According to the two investigators who have performed manual measurements, mean values of IMT of right CCA were 0.6396 mm and 0.6356 mm; of the left CCA were 0.6662 mm and 0.6575 mm, respectively. The interobserver variability of measurements revealed the mean IMT as 0.6071 mm and 0.6048 mm for the right, 0.6216 mm and 0.6227 mm for the left CCA. Manual measurements of both investigators were found to be higher than the automatic measurements and the differences were statistically significant. Interobserver correlation of manual measurements was between 0.80-0.88 and of the automated measurements was between 0.93-0.98. CONCLUSION: Manual measurements reveal higher values than the automated measurements of IMT. The interobserver correlation of automated measurements is higher than manual measurements. The use of dedicated software may be proposed to reduce the measurement errors.

Adult↗

Use of an automated medication storage and distribution system.

The effects of an automated medication storage and distribution system in a hospital setting were evaluated. The Pyxis Medstation system was implemented on two nursing units at a 1000-bed tertiary-care referral hospital. The system, which is designed like an automated bank teller, dispenses items to authorized users and records all transactions. Floor-stock controlled substances and noncontrolled medications, large-volume i.v. solutions, and i.v. administration sets were stocked in the system. The system was evaluated (1) by comparing the mean patient charge capture rates for six months before and for three months after implementation, (2) by measuring nurse and pharmacy technician time required for various tasks before and after implementation, and (3) through questionnaires filled out by nurses and technicians. After the system was installed, nursing personnel spent less time on medication-related activities, charting, and documentation and more time interacting with patients. Pharmacy technicians spent more time on floor-stock activities and less time on billing activities. Nurses indicated positive attitudes toward the system features. Both nurses and pharmacy technicians indicated that the system should remain in use. After implementation, the charge capture rate for noncontrolled medications, i.v. solutions, and i.v. sets increased from 63% to 97%. This increase, extrapolated to the entire hospital, reflects $35,000 in additional revenue over the total costs of implementation of the system. Implementation of an automated medication storage and dispensing system is expected to increase hospital revenue and enable nurses to spend more time interacting with patients at this institution.

Attitude of Health Personnel↗

Usefulness of sequential automated analysis of fragmented red blood cells for the differential diagnosis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic hematopoietic cell transplantation.

Differentiating thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) from other complications following allogeneic hematopoietic cell transplantation (HPCT) requires objective, reliable markers. To this purpose, we assessed the clinical usefulness of sequential quantified analysis of fragmented red blood cells (FRC) with the Sysmex XE-2100 automated hematology analyzer. The correlation between manual and automated counting was significant (r = 0.917; P < .0001). Of 25 cases, the peak FRC percentage (FRC%) exceeded 1.3% after allogeneic HPCT in 11 cases, and lactate dehydrogenase levels were elevated in 5 of these 11 cases. Two patients received diagnoses of TTP-HUS following allogeneic HPCT, and both had initial diagnoses of acute graft-versus-host disease. In both cases, the sharp increase in the FRC% to >3% simultaneously with clinical exacerbation was helpful for differentiating TTP-HUS following allogeneic HPCT from other complications. We conclude that FRC% data sequentially obtained by an automated count seem to be useful as an objective marker of TTP-HUS following allogeneic HPCT.

Acute Disease↗

Utility of white blood cell suspect flags and histogram pattern in the detection of acute leukemia by Advia-60 automated hematology analyzer.

Blood samples from patients with acute leukemia, when analyzed with automated hematology counters, tend to introduce inaccuracies in the automated differential count and can cause diagnostic confusion without providing definite clues to the presence of abnormal cells. We designed this study to assess the utility of white blood cell (WBC) flags and histogram pattern generated by Advia-60 automated hematology analyzer in the recognition and categorization of acute leukemia. Data printouts of 31 newly diagnosed cases of acute leukemia, 22 with acute myeloid leukemia (AML) and 9 with acute lymphoblastic leukemia (ALL) were reviewed. All cases of AML and ALL generated the WBC suspect blastflag M2 associated with two of the non blast suspectflags G1 and G2. Among the cases of AML, 95.5% of the WBC histogram patterns were definitive of the presence of abnormal cells and were indicative of the myeloid nature of cells. Only 44.4% of the histograms in the cases of ALL could be definitive of the presence of abnormal cells and 33.3% were indicative of their lymphoid nature. Significantly, 55.5% of the histograms in ALL were normal. The false positives for both AML and ALL were 10.5% when only WBC flagging was considered and were reduced to 0.05% when the flags were combined with histogram patterns for interpretation. Combined flagging and histogram recognition can be of aid in identifying cases of acute leukemia and the morphologist can then assess these samples further. This ensures that cases of acute leukemia, especially in high output laboratories, are not inadvertently missed.

Automation↗

Spurious automated red cell parameters due to cold agglutinins--a report of two cases.

Although automation in hematology has resulted in improved accuracy of results, there are certain clinical conditions in which even the technologically advanced cell counters give out spurious results. It is therefore important that operators of these instruments are aware of these factitious results and the clues in the automated data that can be of help in identifying them. Two cases with spurious automated red cell parameters due to cold agglutinins are reported here.

Adult↗

Automation of semen analysis using flow cytometer in comparison with manual methods.

In order to standardize techniques and limit the effect of human factors on the results of analyses of biological fluids, automation seems to be mandatory. In an attempt to automate semen analysis, computer assisted sperm analysis (CASA) system has been developed, however its use is still limited and its practical applications have many criticisms. In a trial to automate semen analysis, this study aimed to evaluate the usefulness of flow cytometer in the detection of some seminal parameters in comparison with the traditional manual methods. Isolated spermatogenic cells and isolated sperms from semen and EDTA blood of volunteers were analyzed by flow cytometer in order to define their respective regions. Ejaculates of 28 male patients were subjected to routine semen analyses, leucocytes detection by peroxidase test and monoclonal antibody CD53 using flow cytometer after preparation of the patients' semen samples for flow cytometeric analysis. A highly significant correlation (r=0.96, p= 0.001) of absolute neutrophils (pus cells) detected by peroxidase versus flow cytometer using CD53 monoclonal antibody. A poor correlation (r=0.39, p=0.035) of sperm counts assessed by manual technique and flow cytometer and a spurious sperm counts of 1.08 million/ml detected by flow cytometery in azoospermic patients. Flow cytometer could be used for the assessment of pus cells in semen but seems to be non reliable for the assessment of sperm count if gating depend on sperm size and granularity alone.

Adult↗

Automation in cervical cytology: an overview.

Cancer of the uterine cervix is one of the more common female cancers and a major source of premature female mortality. UK deaths in 1987 exceeded 2000. To reduce these rates, national screening programmes have been introduced using the Papanicolaou method. In screening for cancer, the examination of specimens is an intensive and expensive task. Its high cost has led to a number of attempts to automate the process, either fully or partially. Over the last 30 years, various experimental prescreening systems have been developed for the diagnosis of cytological samples including the use of image processing techniques. This paper presents a historical overview of automation in cervical cytology and the status of current developments for automated cytological diagnosis.

Automation↗

Automation and computerization of chromogenic LAL assay method for bacterial endotoxin using 96-well microtiter plate.

A high degree of automation was achieved for a chromogenic substrate Limulus amebocyte lysate (LAL) assay method for bacterial endotoxin using a Cetus Pro/Group Liquid Handler and 96-well microtiter plates. A Titertek Multiskan Reader was interfaced with an IBM PC using a LOTUS MEASURE software to capture optical density values of samples in a LOTUS 1-2-3 spreadsheet. A password protected, menu-driven macro programmed in LOTUS 1-2-3 automates the calculation, evaluation of assay parameters, documentation, and generation of a formatted three-page report suitable as a primary record. All assay operations, including testing 19 samples against a four-point standard curve in replicates of four each, the calculation of results, and generation of a report, are completed in less than 40 minutes. The relative standard deviation (RSD) of the assay is approximately 7%, which compares favorably with the robot automated system.

Automation↗

A comparison of two computer-automated semen analysis instruments for the evaluation of sperm motion characteristics in the stallion.

Two commercially available computer-automate semen analysis instruments (CellSoft Automated Semen Analyzer and HTM-2000 Motion Analyzer) were compared for their ability to report similar results based on the analysis of pre-recorded video tapes of extended, motile stallion semen. The determinations of the percentage of motile cells by these instruments were more similar than the comparisons between subjective estimates and either instrument. However, mean values obtained from the same sample may still differ by as much as 30 percentage units between instruments. Instruments varied with regard to the determinations of mean sperm curvilinear velocity and sperm concentration, but mean sperm linearity determinations were similar between the instruments. We concluded that the determinations of sperm motion characteristics by subjective estimation, CellSoft Automated Semen Analyzer, and HTM-2000 Motility Analyzer are often dissimilar, making direct comparisons of results difficult.

Animals↗

Standardization of dyes and stains for automated cell pattern recognition.

An extensive review is presented of the various factors involved in the standardization of dyes and stains for cytologic material, which is a crucial point in achieving objective and reproducible measurements of cells for recognition by automated microscopy (high-resolution cell image analysis; automated cell pattern recognition [ACPR]). Two principal methods of standardization are considered at length: (1) standardization based on the physical and chemical characterization of the dyes (physicochemical standardization), as adopted by the German Bureau of Standards, and (2) standardization based on direct visual assessment of stain performance (performance standardization), as adopted by the United States Biological Stain Commission. The procedures, achievements and problems of both methodologies are discussed, as are such related matters as staining time, solution pH, etc., especially with regard to the two most important stains in diagnostic cytology: the Papanicolaou stain and the Romanowsky-Giemsa stain. The standardization of these two stains is considered in detail, with an eye towards their suitability for ACPR. The mechanisms of the staining results produced by these stains are examined, as are the extant problems with each. The Papanicolaou stain, while neither standardized nor stoichiometric, has proven to be of use in cytophotometry. Similarly, the Romanowsky-Giemsa stain, while standardized, is also not a stoichiometric stain. Yet both have been successfully used in some aspects of ACPR; no "ideal" stain has yet been found that would make cell samples ideally suited for machine evaluation. It is concluded that the standardization of biologic dyes and stains, which can contribute to the success of ACPR, should be undertaken by multidisciplinary expert panels, in which the current concerned organizations could play a role. It is also concluded that ACPR may, in fact, contribute to the standardization of dyes and stains: that computer-directed morphometry and automated image analysis with sophisticated statistical analysis may become major tools in the validation of data on staining. For example, computer analysis could be used to pinpoint the particular variant of the Papanicolaou stain that leads to the best overall reproducibility of cell descriptors, in effect achieving "preliminary standardization by computer judgment of stain performance."

Adjuvants, Pharmaceutic↗

Aztreonam for injection (lyophilized): development of an automated solution batching process utilizing volumetric powder feeders.

As part of a commitment to fully automate the manufacture of a lyophilized dosage form of Azactam (Aztreonam for Injection), an automated solution batching procedure was developed. The lyophilization process requires solution batching of Aztreonam and L-arginine, the two constituents of the product. To avoid preblending of aztreonam and L-arginine prior to dissolution, a batching process was developed which makes use of two separate volumetric powder feeders. In conjunction with a feedback pH control system, these powder feeders provided for (a) a faster batching process, (b) a tight control of solution pH during batching, (c) a failsafe system to prevent operator error and equipment malfunction. Data are presented correlating bulk densities of various powders with feeder output along with solution pH profiles determined using the manual mode and the automated feedback pH control system.

Automation↗

Automated office hematology instruments.

Evaluation of an automated hematology instrument begins with analysis of one's practice needs, followed by analysis of initial start-up costs, cost of maintenance, and staffing. In one situation, the decision to purchase an automated instrument may allow personnel working with low-efficiency pipetting and slide chamber counting time to assist in other functions of the clinic. In another practice, an automated counter may permit in-office complete blood counts to be added to the workload of current staff. These instruments are more than time-saving conveniences. They can facilitate clinical decision making and monitoring for complications of disease and therapy by making it easier for the physician to obtain reliable hematologic results. They can generate additional practice income and reduce patient cost by improving the quality and efficiency of medical care.

Automation↗

Ellipse test for the reduction of false positive signals in automated cytology.

One of the major problems in automated cytology is the elimination of false positive 'abnormal cell' alarms caused by objects such as overlapping cell pairs, leukocyte clusters, etc. The paper describes an algorithm for the separation of images of abnormal cell nuclei and non=nuclear objects in computer image analysis systems for automated cytology. The algorithm involves the measurement of the agreement between the object outline and a computer ellipse of equal area, aspect ratio and orientation. Results obtained with the CERVISCAN experimental computer image analysis system show that the algorithm gives good discrimination between abnormal cell nuclei and typical non-nuclear objects found in cervical scrape specimens prepared specially for automated analysis.

Cell Nucleus↗

An evaluation of the CODABAR symbol in blood-banking automation.

The CODABAR system has been used in blood banking automation since 1976 when it was introduced by 16 blood centers and transfusion services throughout the United States in a test program coordinated by the American Blood Commission Committee for Commonality in Blood Banking Automation. Since then CODABAR has been used in sample identification on Groupamatic and Technicon automated blood-typing equipment, in the labeling of blood products and in their distribution. It is widely used by a number of blood centers in the United States and has been adopted by the 14 regional blood centers in the United Kingdom, as well as blood centers in Switzerland, the Netherlands and Japan. Some properties of the CODABAR symbol that are relevant to the high accuracy requirements of blood banking are described and preliminary test data are presented.

Autoanalysis↗

[Automated analyzer of enzyme immunoassay].

Automated analyzers for enzyme immunoassay can be classified by several points of view: the kind of labeled antibodies or enzymes, detection methods, the number of tests per unit time, analytical time and speed per run. In practice, it is important for us consider the several points such as detection limits, the number of tests per unit time, analytical range, and precision. Most of the automated analyzers on the market can randomly access and measure samples. I will describe the recent advance of automated analyzers reviewing their labeling antibodies and enzymes, the detection methods, the number of test per unit time and analytical time and speed per test.

Alkaline Phosphatase↗

Semiautomated inspection versus fully automated inspection of lyophilized products.

The development of fully automated inspection systems for parenteral products has created a situation of high expectations regarding productivity and quality improvements. However, not all products and production situations are suited for automation. A guideline for inspection and automation strategies will be discussed, structuring the field of lyophilized products according to the critical decision parameters.

Automation↗