Development of standards for laboratory automation.

In clinical laboratories, the installation of total laboratory automation systems and/or modular systems has grown dramatically in the 1990s, particularly in the US, Japan, and Europe. As the number of installations and level of interest grew, several individuals and corporations active in the automation field recognized that the development of prospective standards might enable customers of such systems or equipment to purchase analyzers, automation systems or devices, and software from different vendors and retain interconnectivity of such equipment. These individuals also believed that the total market for automation systems and equipment would be significantly greater with standards than without standards, especially if customers were not forced to purchase everything from one vendor, and that there might be competitive pricing and new technology fostered via the standards. This early interest in standards development led to the initiation of a program by NCCLS in 1996 to develop prospective standards for laboratory automation. Part of the NCCLS effort has involved interaction and cooperation with other standards organizations in the US and other countries. This report describes the current status of the development of prospective standards for laboratory automation by NCCLS and the relationship of those standards to those of other standards organizations.

Transition in quality: from quality assurance to strategic quality management.

The 1990s and beyond present formidable challenges to health-care providers, including clinical laboratories and pathology departments. However, numerous opportunities lie within these challenges. Discovering these opportunities and exploiting them will be critical success factors for future survival. Quality assurance, continuous quality improvement, and strategic and financial planning are all activities used to a varying extent by clinical laboratories. The cumulative potential benefits to an organization in which these activities are integrated can far exceed their sum as individual components. Coordinating these interdependent processes is the basis for managing strategically. The experience of one organization's efforts to plan and develop such a strategy is presented and discussed.

Alterations in calcium, phosphorus and C-terminal parathyroid hormone levels in equine acute renal disease.

The changes in serum and urinary levels of calcium and phosphorus and serum parathyroid hormone (PTH) were studied during controlled, chemically induced, acute renal disease in 4 ponies. There was an initial rise in daily urinary calcium and hydroxyproline excretion in 2 ponies which may have indicated increased bone resorption. Mild hypercalcemia, hypophosphatemia and elevated C-terminal PTH levels were associated with oliguria. Total daily urinary excretion of calcium and phosphorus decreased as oliguria developed. The levels of C-terminal PTH were increased in all four animals. This appears to have been related to their diminished renal function in that C-terminal fragments of intact PTH (which require functioning kidneys in order to be cleared) were probably being accumulated. Although there was no evidence with regard to an actual increase in PTH secretion, prolongation of intact PTH half-life due to renal tubular damage may have contributed to the development of hypercalcemia.

Absence of effect of 24,25-dihydroxycholecalciferol on serum immunoreactive PTH in patients with persistent hyperparathyroidism after renal transplantation.

Three hypercalcemic renal transplant recipients with stable, excellent renal function (creatinine clearance 74 +/- 11.8 ml/min) were treated with 60 micrograms 24,25(OH)2D3 by mouth daily for three months. Immunoreactive c-terminal PTH, intact PTH, 1,25(OH)2D3, 25(OH)D3, 24,25(OH)2D3, and serum and 24 h urine calcium, phosphate, magnesium and creatinine were obtained before, at one week, one month and three months of treatment, and at six weeks post-treatment. Significant elevations in serum levels of 24,25(OH)2D3 were induced by therapy (1.32 +/- .16 ng/ml to 30.06 +/- 5.18 ng/ml at one month). Moderate elevations of c-terminal PTH and normal levels of intact PTH remained unchanged throughout the study. Serum calcium remained elevated, serum phosphate and magnesium remained depressed and creatinine clearance and urinary excretion of calcium, phosphate, and magnesium remained unchanged. Furthermore, 1,25(OH)2D3 and 25(OH)D3 remained in the normal range throughout the study. We conclude that 24,25(OH)2D3 did not have a suppressant effect on levels of iPTH in the clinical setting of persistent hyperparathyroidism after successful renal transplantation.

Pathogenic mechanisms of the hypocalcemia of the staphylococcal toxic-shock syndrome.

Hypocalcemia is a common finding in TSS. This has been causally related to the hypoalbuminemia of TSS. To more clearly define the mechanism responsible for this hypocalcemia, we examined the serum concentrations of CaT, Ca+ +, iCT, albumin, and DBP in 28 women meeting the case-study definition of TSS. Mean CaT was 2.18 +/- 0.36 mM/L (S.D.), Ca+ + was 0.93 +/- 0.19 mM/L, and iCT was 1941 +/- 978 pg/ml; all were significantly different (p less than 0.01) from the normal values of CaT (2.38 +/- 0.09), Ca+ + (1.09 +/- 0.04) and iCT (less than 30 to 135). A significant inverse correlation was found between iCT and both CaT and Ca+ +, p less than 0.001. Serial values were measured in two women in whom the iCT values declined each day. Gel filtration of the iCT from two patients with the highest values suggested that some polymeric molecular species, rather than authentic CT, accounted for 90% of the circulating iCT value. No abnormalities of DBP levels were found, and no correlation with CaT, Ca+ +, or iCT was evident. The hypocalcemia of the TSS represents a reduction in both CaT and Ca+ + concentrations, which may be at least partially accounted for by the elevated iCT concentrations.

Hormonal responses to high-dose fentanyl anaesthesia. A study in patients undergoing cardiac surgery.

The hormonal responses to anaesthesia and cardiac surgery were studied in 20 patients. Ten patients were anaesthetized with fentanyl 60 microgram kg-1 and nitrous oxide in oxygen and 10 with etomidate 0.3 mgkg-1 and nitrous oxide in oxygen plus halothane. There were no significant changes in cortisol, growth hormone or insulin concentrations in response to surgery in either group, although cortisol concentrations decreased during cardiopulmonary bypass. Both groups showed increases in prolactin concentrations. Patients anaesthetized with etomidate and halothane showed a significant increase in adrenaline and glucose concentrations not seen in the fentanyl group. Cardiopulmonary bypass was associated with marked increases in catecholamines in both groups.

Prompt resolution of osteomalacia by switching from phenytoin to phenobarbital.

It has been reported that patients taking the anticonvulsant drugs phenytoin and/or phenobarbital may experience osteomalacia. In a phenytoin-treated patient with osteomalacia, switching the drug regimen to phenobarbital led to prompt resolution of her symptoms and restoration of normal serum calcium and serum 25-hydroxyvitamin D values. It seems prudent, when feasible, to switch patients from phenytoin to phenobarbital when their anticonvulsive management is complicated by the onset of osteomalacia. Such simple manipulation of anticonvulsive drug therapy may obviate the need for vitamin D and calcium administration.

Parathyroid hormone in chronic renal failure: studies with two different parathyroid hormone radioimmunoassays.

Two assays for immunoreactive parathyroid hormone (iPTH) with different specificities were used to evaluate the role of iPTH measurement in patients with chronic renal failure (CRF). One measured largely C-terminal iPTH fragments, the other largely intact iPTH. In untreated CRF, the log iPRH for each assay was significantly correlated with the reciprocal of the creatinine clearance (CCr). C-terminal iPTH was elevated at relatively high CCr values, but intact iPTH was not elevated until later in the progression of CRF. In hemodialysis patients treated with 25-hydroxyvitamin D3, intct iPTH correlated better than C-terminal iPTH with clinical improvement. These two assays used together were more helpful in evaluation of CRF patients than either assay alone.

Radioimmunoassay for intact and carboxyl-terminal parathyroid hormone: clinical interpretation and diagnostic significance.

The phenomenal growth in our knowledge of parathyroid hormone (PTH) physiology, chemistry and radioimmunoassay in the past 15 years has produced a significant increase in the use of the assay in the clinical laboratory evaluation of patients with disorders of calcium homeostasis. Recent experience with assays that have specificities for different regions of the amino acid sequence of the hormone and that can thus measure different portions of the total immunoreactivity in blood suggests that there may be different clinical applications for such assays. This report describes two different radioimmunoassay procedures and the clinical experience with each and suggests how each assay may be utilized in clinical evaluation of possible parathyroid dysfunction. The assay for carboxyl-terminal PTH is more useful in the differential diagnosis of the possible causes of hypercalcemia, the intact PTH assay is preferred in selective venous catheterization for preoperative localization of hyperfunctioning tissues, and both assays have usefulness in the evaluation of patients with hypocalcemia. In chronic renal failure, the considerations are more complex. In many patients, the intact PTH assay is preferred for monitoring the clinical course; however, in other patients the carboxyl-terminal PTH assay has been more useful. The best assay for each patient must be determined by initial evaluation with both assays.

Hypocalcemia, hypomagnesemia, and transient hypoparathyroidism during therapy with potassium phosphate in diabetic ketoacidosis.

The effects of intravenous administration of potassium phosphate in the treatment of diabetic ketoacidosis were studied in nine children, ages 9 9/12 to 17 10/12 yr. During phosphate infusion (20--40 meq/L of fluid), all children maintained normal serum concentrations of phosphorus. Transient hypocalcemia occurred in six and transient hypomagnesemia in five patients. One child developed carpopedal spasms refractory to intravenous infusion of calcium gluconate but responsive to intramuscular injection of magnesium sulfate. In three patients, serum levels of intact parathyroid hormone were low at the time of hypocalcemia, an observation that suggests transient hypoparathyroidism. This study indicates that the use of potassium phosphate as the sole source of potassium replacement might potentiate ketoacidosis-induced hypocalcemia through multiple mechanisms.

Measurement of digoxin by radioimmunoassay.

A sensitive, specific and precise procedure for the measurement of digoxin by radioimmunoassay is presented. The method is rapid, convenient and highly reliable for this very important measurement. Studies designed to evaluate the validity and reproducibility of the assay are presented and discussed.

Acute myeloblastic leukemia and hypercalcemia. A case of probable ectopic parathyroid hormone production.

We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukmia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freeze-thawing experiments, 39 pg of parathyroid hormone was released form 1 x 108 of the patient's myeloblasts; no hormone was released from the normocalcemia cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells.

Parathyroid hormone: radioimmunoassay and clinical interpretation.

A radioimmunoassay for serum immunoreactive parathyroid hormone (iPTH), which has had widespread clinical use for five years, is described in detail. The iPTH results in large groups of patients are reported, and are discussed in relation to the specificity of the assay and in relation to other assays. The assay has excellent precision and is highly proficient in discrimination of groups of patients. Ninety-three percent of 412 patients with surgically proven primary hyperparathyroidism were confidently separated from normal subjects or patients with hypercalcemia owing to other causes, while 86 percent of 160 patients with chronic renal failure and secondary hyperparathyroidism had iPTH values more than 2 S.D. above the normal mean. Results in patients with ectopic hyperparathyroidism were lower than in primary hyperparathyroidism although these groups showed considerable overlap. The antiserum used in this assay for iPTH appears to be specific for the carboxy-terminal region of the secreted or intact form of PTH but recognizes predominantly the secreted form rather than carboxy-terminal fragments believed to be in the circulation. It does not recognize amino terminal fragments. The assay is useful in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue.