1560 CLINICAL CHEMISTRY, Vol. 29, No. 8, 1983 universal phenylketonuria/hypothyroidism screen. The project was based on an hypothesis first outlined by Crossley et al. (1), viz., that an abnormally high blood IRT value for a newborn is suggestive of cystic fibrosis (CF). Details of the methods were previously described (2). We tested 25 000 newborns and identified seven infants confirmed to have CF. One of the seven was not detected in the initial assay, but a repeat card, taken one week later because the infant was premature (birth weight, 1086 g), revealed an increased value for IRT. Values for all affected infants were within the top 1% of each assay run of 200 specimens. During the project period, eight infants were diagnosed with CF. The one not detected by the IRT program did not have a filter paper card taken at birth. From our experience, we conclude that the IRT test is a reliable indicator of infants with CF if the reagents used are of good quality and the specimens are fresh. We would use only reagents comparable to those outlined by Crossley et al. (3) and would assay the specimens within a few days of their arrival at the screening laboratory.

We assayed more than 5000 blood spots dried on filter paper and approximately 1000 serum samples for immunoreactive trypsin, with commercial reagents (Behring and Sorin). The assay procedures were modified so that newborn screening is technically feasible. Both kits are satisfactory for serum assay, but the Sorin materials are better adapted for blood spot analysis. lmmunoreactive trypsin in blood spots rapidly decreases with specimen age, but is stable in frozen serum. Values for premature infants do not differ significantly from those for full-term babies. Children with cystic fibrosis were readily distinguished from those without, up to at least one year of age.

Pathologists are under siege by corporate medicine, managed care systems, or varieties of government-initiated health care restructuring. The pressure is on us to attend at least equally to fiscal pressures, as well as to our patients' medical needs. These pressures must be accommodated within the limits of our professional duties and responsibilities. We must have more than an intuitive sense of what it is to be a professional and to work in a system that is overseen typically by a directorate and that includes managers and innovators. The example of the failure of the corporate managers and directors of a national blood transfusion service highlights the need to balance the inter-relationships of managers, professionals, and innovators by a directorate knowledgeable in these complex systems.

Although most individuals who head clinical laboratories are still named Director of Laboratories, their training for this has focused principally on management training in addition to their postgraduate medical education. The implicit assumption seems to be either that direction and management are synonymous or that management is the most important aspect of laboratory administration. Common usage, albeit imprecise, fosters both of these paradigms. The proposition of this article is that directing and managing are two discrete activities of sufficiently different orientation as to require different training, attitudes, and values. Management as a generic phenomenon was codified early in this century through the works of F.W. Taylor (1), whose concepts of scientific management were embraced with zeal during World War I and were also an important conceptual basis for the managed economy of the Soviet Union as proposed by Lenin. Gradually, management with concern for efficiency and hierarchic control structures has diffused throughout social as well as business systems. Many will remember the introduction of the corporate governance system into hospitals beginning in the 1930s and its spread throughout the medical system until at present administrators of hospitals, for example, are called CEOs or presidents. Management, as narrowly defined and as traditionally practiced, is based on control of a system by adherence to prescribed standards for uniform production, to particularized timelines for delivery of product or service precisely when needed, and to predetermined budgets for efficiency and predictability. All of these are laudable and essential to the internal administration of any system. They also require a specific set of values and a set of behaviors that center on adaptability and compliance.

Expenditures on laboratory tests have increased by 468% in real dollars in two decades although the cost per test has remained constant. Cost of labor has doubled over that period, with an approximately similar increase in personnel productivity as the offset. Part of the increased labor cost relates to increased pay for technologist work of apparent increased complexity. We found that technologists perceived less than 20% of all work and less than 4% of all tests performed to be highly complex or of moderately high complexity. Implications of these findings for test complexity analysis and for technologist training are discussed.

In this review we have tried to identify some of the management issues affecting laboratories in the past, present, and future. In particular, we have focused on the increases in utilization and cost and have attempted to demonstrate some of the factors affecting the supply and demand sides of these issues. In the absence of a price mechanism to allocate resources, alternative strategies to evaluate and regulate laboratory use were discussed. Although promise is held out by some of these approaches, they are not, in our view, fully workable at this stage. We suggest that, in the interim, sound medical direction and management of the laboratory as a production function can be of benefit in inhibiting, if not actually controlling, cost increases. In particular, we recommend concentration on the management of technology because of its crucial role in laboratory costs and utilization. Emerging trends in clinical laboratory and monitoring technologies suggest that issues relating to decentralization, quality control, and funding will have to be addressed in the near future. The prime motivation for clinical laboratory use, i.e., the generation of answers to clinical questions, seems destined to continue and expand. The challenge for practitioners, researchers, and policy-makers is to harness, evaluate, and manage the technologies that can best contribute to both medical practice and health.

A computerized decision-support system has been developed and implemented to assist in the economic evaluation of alternative clinical chemistry equipment configurations. The capabilities, structure, and relative merits of the system are discussed. This decision-support system is now being used extensively by hospitals in British Columbia. An alternative equipment configuration, identified with the aid of the system, resulted in one hospital alone saving an annual $200,000 in consumables and reagents costs. Further development of computerized economic evaluation systems is encouraged.

A new method for analyzing factors that contribute to the rising costs of hospital laboratories was used to analyze data from a Canadian teaching hospital for the period of 1971 to 1981. Results indicated that real cost per acute care admission has doubled, primarily because more tests are performed and the factors of production in laboratories are costlier. Increasingly sophisticated technology in the laboratory has increased productivity, and thus reduced cost per test; however, increased intensity of testing apparently has not been accompanied by reduced length of stay.

A conceptual framework is outlined as the basis for analysis and evaluation of laboratory test-ordering patterns. This framework highlights the input, process, and output phases of the laboratory inquiry system. Data are presented from a contemporary Canadian study to show that the cost of laboratory testing is escalating and represents a sizable proportion of hospital costs. Practical policy interventions intent on reducing the costs in this complex system will require thorough analysis within a conceptual framework such as is outlined here and will require ultimately sophisticated control programs at various levels in the laboratory inquiry system.

1. Between 1971 to 1977, 74,521 urines, collected on filter paper and mailed in, were screened by the Metabolic Screening Program of the Children's Hospital. These represented 45.9% of live births in B.C. hospitals were the program has been available. The mean age of the infants was 4.4 weeks. Urines were examined by chromatography with ethyl acetate-pyridine-water for sugars. 1423 (2.13%) had an abnormal pattern necessitating a repeat urine card. A persistent abnormality was noted in 167 (0.22%) and from these a liquid urine sample was obtained for two dimensional amino acid chromatography and/or a repeat sugar chromatography. 2. In 47 (0.06%) of these a definite metabolic abnormality was confirmed. These included cases of Iminoglycinuria (8), Hartnup trait (4), Nonketotic hyperglycinemia (2), Histidinemia (1), Cystathioninuria (5), Argininosuccinic aciduria (1), Maple Syrup Urine Disease (1), Diabetes Mellitus (1), Renal glycosuria (1) and Persistent galactosuria (3). 201 infants had a slight increase of cystine and/or lysine, and 19 of these were documented to be heterozygous for cystinuria.

Rats were exposed to gaseous carbon tetrachloride, twice weekly over a period of 10 weeks, to induce hepatic cirrhosis. Simultaneously some animals were fed chlordane twice weekly to give a dose rate of 0.1 mg/kg/day. Half the animals in each group were sacrificed at 10 weeks, the remaining animals received a further 10 weeks exposure to chlordane. Progress of the disease was monitored by weekly measurements of serum-glutamate pyruvate transaminase and alkaline phosphatase concentrations. At 10 weeks and 20 weeks livers were removed from sacrificed animals and micropathological examinations were made. Liver lipid, microsomal protein, cytochrome P 450 content, and, where applicable, tissue content of oxychlordane, the stable metabolite of chlordane, were determined. After 10 weeks of treatment animals which had received the dual treatment, CCl 4 and chlordane, showed a significant loss of microsomal protein and liver lipid compared to the controls. After 20 weeks these animals showed significant differences (p < 0.05) from control animals in the liver content of oxychlordane and hepatic cytochrome P 450 content. Their histopathological appearance was also different to that of the controls. A high negative correlation (r = −0.8) was found between the degree of necrosis and oxychlordane content of livers treated animals. Continued exposure to chlordane after cessation of exposure to CCl 4 apparently promotes a more rapid return to the normal functional state of the liver.

Rats were exposed to gaseous carbon tetrachloride, twice weekly over a period of 10 weeks, to induce hepatic cirrhosis. Simultaneously some animals were fed chlordane twice weekly to give a dose rate of 0.1 mg/kg/day. Half the animals in each group were sacrificed at 10 weeks, the remaining animals received a further 10 weeks exposure to chlordane. Progress of the disease was monitored by weekly measurements of serum-glutamate pyruvate transaminase and alkaline phosphatase concentrations. At 10 weeks and 20 weeks livers were removed from sacrificed animals and micropathological examinations were made. Liver lipid, microsomal protein, cytochrome P450 content, and, where applicable, tissue content of oxychlordane, the stable metabolite of chlordane, were determined.After 10 weeks of treatment animals which had received the dual treatment, CCl4 and chlordane, showed a significant loss of microsomal protein and liver lipid compared to the controls. After 20 weeks these animals showed significant differences (p < 0.05) from control animals in the liver content of oxychlordane and hepatic cytochrome P450 content. Their histopathological appearance was also different to that of the controls. A high negative correlation (r = −0.8) was found between the degree of necrosis and oxychlordane content of livers treated animals. Continued exposure to chlordane after cessation of exposure to CCl4 apparently promotes a more rapid return to the normal functional state of the liver.