The fall of the serum anion gap.

Using modern electrode technology (Beckman ASTRA analyzer), we evaluated the reference range for the anion gap (calculated as sodium minus chloride minus bicarbonate concentrations) in serum to determine whether the 8 to 16 mmol/L reference range in common use is still valid. After measurement of electrolytes in (1) serum from 29 healthy volunteers, (2) aqueous standards verified against National Bureau of Standards reference material, and (3) serum from 120 blood donors, we drew the following conclusions. (1) The reference range for the anion gap has shifted downward (to 3 to 11 mmol/L in one of our laboratories), primarily because of an upward shift in chloride values. (2) Using the ASTRA analyzer, a majority of normal individuals can be expected to have serum anion gaps of 6 mmol/L or less unless chloride calibration is deliberately altered. (3) If the anion gap is to remain an effective tool in diagnosing acid-base disorders, clinicians need to be aware that the traditional reference range may not be appropriate with new instrumentation.

An indirect method of measuring widths suitable for automated bone histomorphometry.

Orthogonal intercepts from random test lines (OIr), uniformly distributed intercepts (OIu), and areas and lengths (Ar/Le) were measured manually and by computer to determine individual profile and sample widths of artificial profiles and human osteoid seams. Individual widths were equal by Ar/Le and OIu methods. The means of individual profile widths (all methods), of all orthogonal intercepts (OIu and OIr), or of profile widths weighted in proportion to their lengths (Ar/Le) were also equal. Ar/Le and OIu had smaller variance than OIr. Discrepant individual OIu and Ar/Le widths in digitized images were corrected by thresholding and did not significantly affect sample means. Unweighted Ar/Le sample means were 15-44% lower than weighted means. Distributions of osteoid seam widths were not normal, and all but one had more than one mode. We conclude that the Ar/Le method is comparable to direct orthogonal intercept methods and suitable for automated histomorphometry.

Diagnosis of Pneumocystis carinii pneumonia by induced sputum in a city with moderate incidence of AIDS.

Examination of induced sputum from AIDS patients has been reported to provide the noninvasive diagnosis of PCP in 10 to 76 percent of cases. Since previous studies were done in centers with a high incidence of AIDS, we asked whether this test could be implemented successfully in a center with a lower incidence of AIDS. Over a 13-month period 25 of 38 (66 percent) AIDS patients with PCP had positive Giemsa (Diff-Quik) stains of induced sputum. We were unable to predict before sputum induction which patients would be positive based on clinical severity (increased A-a gradient or serum LDH levels). We confirmed prior observations that a normal serum LDH level was found in only 5 percent of documented PCP cases. This noninvasive technique significantly decreased the number of bronchoscopies performed and led to a considerable cost savings.

Academic medical centers and managed care.

Academic medical centers are threatened by the expansion of managed care. Hampered by their higher cost, lack of primary care capability and specialist orientation, organizational sluggishness and inflexibility, and relative lack of managerial expertise, these organizations, long a national resource in education, research, and clinical care, face an uncertain future. Academic pathology departments must aggressively manage their resources and maximize their market advantages to compete effectively.

Six-year trends in productivity and utilization of 73 clinical laboratories: a College of American Pathologists Laboratory Management Index Program study.

OBJECTIVES: To describe longitudinal trends in the efficiency, labor productivity, and utilization of clinical laboratories in the United States. METHODS: Financial and activity data were prospectively collected from 73 clinical laboratories continuously enrolled in the College of American Pathologists Laboratory Management Index Program from 1994 through 1999. Each laboratory reported quarterly on its costs, labor inputs, and test activity using uniform data definitions. RESULTS: During the 6-year study period, there was a significant increase in laboratory labor productivity (2.1% more tests/full-time equivalent/y; P <.001). Productivity increases were offset by increasing labor expense (1.5%/full-time equivalent/y; P <.001), consumable expense (1.7%/on-site test/y; P =.005), and blood expense, which comprised more than 10% of laboratory expenses by 1999 (4.4% increase/y; P <.001). As a result, overall expense per test showed no significant change in non-inflation-adjusted dollars. Reference laboratory expense per test did not change significantly during the study period; the proportion of tests sent to reference laboratories grew slightly (0.06% increase/y; P <.001). Test volume of the median laboratory grew by 5442 tests per year (2.3% annual increase; P <.001), while the proportion of testing from inpatients declined by 1.7% per year (P <.001). Inpatient test utilization declined on a discharge basis (annual decline of 1.2 tests/inpatient discharge; P <.001) and on a per diem basis (annual decline of 0.08 tests/inpatient day; P =.002). Inpatient laboratory expense declined on a discharge basis (annual decline of $2.40 or 1.3% per discharge; P <.001), but did not change significantly per inpatient day. Most of the reduction in the expense per discharge occurred during 1994-1996. CONCLUSIONS: Between 1994 and 1999, clinical laboratories in the United States experienced significant changes in the cost of operations, utilization, and labor productivity. Laboratory administrators who compare local institutional performance with that of peers are advised to use current or forward-trended peer data. Quarter-to-quarter improvement in many measures of laboratory financial activity may not signal a superior operation, as performance of the whole industry appears to be improving.

Semiautomated methods for cancellous bone histomorphometry using a general-purpose video image analysis system.

Semiautomated methods are used to measure elongated, curved and complex branching profiles and isolated perimeter segments in monochrome video images with a general-purpose analysis system. These methods are used to make the major primary measurements of bone histomorphometry. Accuracy and reproducibility of the image acquisition, processing and measurement system is documented by measuring a semicircular standard of known dimensions. Semiautomated applications of the Ar/Le method for measuring areas and perimeters, and calculating lengths and widths of osteoid seams, lengths of mineralization labels and mineral apposition rate, wall width, indirect measurements of eroded, osteoclastic and osteoblastic perimeters without tracing, and measurement of mineralized or total cancellous bone area and perimeter gave values comparable to measurements of the same parameters by tracing or grid counting techniques with equal or better reproducibility and much greater efficiency. Intraindividual variation in measuring multiple bone biopsies methods. Major sources of variability for semi-automated methods were image magnification and selection of profile edges by thresholding, and sources of variability for manual methods are image magnification, numbers of orthogonal intercepts, tracing speed and accuracy of the algorithm used to measure traced pixels. Semiautomated methods are accurate, reproducible and rapid methods suitable for bone histomorphometry.

Establishment of the Colorado Physician Health Program with a legislative initiative.

The Colorado Physician Health Program, a statewide peer health assistance program for physicians, has been developed as a not-for-profit, freestanding corporation through the cooperative efforts of organized medicine. A recently enacted Colorado statute provides for funding through a surcharge on physician licensure fees. The use of an employee assistance model has minimized potential conflicts of interest and allowed the program to assist both physicians and the Colorado Board of Medical Examiners.

Characterization of uterine epithelium apoptotic cell death kinetics and regulation by progesterone and RU 486.

The authors show here that progesterone suppresses apoptosis, and its antagonist RU 486 induces it in rabbit uterine epithelium, as assessed by morphologic and biochemical studies. The authors' studies demonstrate that internucleosomal DNA fragments are identifiable as early as 24 hours after ovariectomy of pseudopregnant rabbits, and become undetectable 6 days after ovariectomy. Maximal levels of DNA fragmentation (about 74% of total isolated DNA) were observed 36 hours after ovariectomy. The number of apoptotic cells appeared to increase parallel to the increased DNA breakdown, and accounted for approximately 26% of the uterine epithelial cells at 48 hours after ovariectomy. Levels of progesterone in serum dropped precipitously 6 hours after ovariectomy and remained very low for several days. Administration of progesterone, more than any other steroid hormone, to pseudopregnant ovariectomized rabbits, prevented the increase in apoptotic cell death. By contrast, administration of the anti-progestin RU 486 to pseudopregnant rabbits triggered apoptosis, which attained levels similar to those observed in ovariectomized animals. The authors' findings establish that uterine epithelium apoptosis occurs in a time-dependent fashion and provides strong evidence that the actions of progesterone in that tissue are not only to stimulate cell proliferation and differentiation, but also to suppress apoptosis.

Will quality management paradigms of the 1990s survive into the next century?

This article offers four views of the future importance of quality management. First, a pathologist author describes current controversies surrounding the viability of established schools of practice. A vice president at the Joint Commission on Accreditation of Healthcare Organizations outlines the continued need for some form of total quality management and continuous quality improvement from the accreditation stance. A laboratory director from a university medical center discusses the economic changes that are fueling the continued emphasis on quality management. And, a laboratory manager from a community hospital focuses on the impact of quality management, pointing out what is required for quality management to be successful at the operational level in a laboratory. These four independent view-points reveal a clear consensus that the practice of quality management will continue to be important in our laboratories into the 21st century.

"Carryback": effect of viscous liquid controls on the preceding sample analyzed with the SMA II continuous-flow analyzer.

We systematically studied the "carryback" effect of ethylene glycol-based controls on the preceding sample on an SMA II continuous-flow analyzer. Including Beckman Level 1 unassayed liquid control material as a sample lowered the 12 analyte values of the preceding sample by an average of 2.7%, Level 2 (the most viscous) by an average of 4.4%, and Level 3 by 3.2%. Water-reconstituted lyophilized control material caused no carryback effect, but lyophilized control reconstituted with 330 mL/L ethylene glycol decreased the preceding sample's results by 4.1% (average carryback). We believe that carryback is caused by the drag placed on the sample line by a viscous sample, which decreases the volume of the preceding sample that is delivered to the reagent or pre-dilution mixing coils. Our findings were confirmed on another SMA II. Limited study of a SMAC analyzer gave inconclusive results, but further evaluation of continuous-flow systems for carryback is warranted. Carryback substantially increases total analytical variability.