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Objectives: Harris Health System (HHS) is a safety net system providing health care to the underserved of Harris County, Texas. There was a 6-month waiting period for a rheumatologist consult for patients with suspected systemic lupus erythematosus (SLE). The objective of the intervention was to improve access to specialty care., Methods: An algorithmic approach to testing for SLE was implemented initially through the HHS referral center. The algorithm was further offered as a "one-click" order for physicians, with automated reflex testing, interpretation, and case triaging by clinical pathology., Results: Data review revealed that prior to the intervention, 80% of patients did not have complete laboratory workups available at the first rheumatology visit. Implementation of algorithmic testing and triaging of referrals by pathologists resulted in decreasing the waiting time for a rheumatologist by 50%., Conclusions: Clinical pathology intervention and case triaging can improve access to care in a county health care system., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Numerous investigators have demonstrated that derangements in serum transferrin and iron can contribute to susceptibility to infection, but the complexity and imprecision of assays have impeded both research and development of clinical testing in this area. This article describes an automated assay for measuring the microbial inhibitory activity of transferrin in serum and its use in patients with acute myelogenous leukemia (AML) and in normal controls. The assay measured the ability of heat-inactivated serum to inhibit the growth of an antibiotic-resistant strain of Pseudomonas aeruginosa. The serum dilutions were prepared in a special low iron chemically defined broth. An inhibition index, the reciprocal of the serum dilution producing 50% inhibition of bacterial growth when compared with the growth in broth alone, was determined. The results showed the serum from the patients with leukemia had a significantly lower inhibition index than that of controls (16 +/- 11 vs. 35 +/- 13, P less than 0.01). In addition, they had higher serum iron levels (162 +/- 65 vs. 75 +/- 27, P less than 0.01), lower serum transferrin levels (231 +/- 65 vs. 309 +/- 71, P less than 0.01), and higher percentage saturation of transferrin with iron (59 +/- 21 vs. 20 +/- 8, P less than 0.01) than did controls. Because the assay uses equipment available in many clinical laboratories, it could be developed for routine use as an index of susceptibility to infection in selected patients.

The cerebrospinal fluid (CSF) IgG index, the CSF to serum albumin ratio, and electrophoresis on agarose gel of CSF and serum were evaluated retrospectively for their usefulness in the differential diagnosis of multiple sclerosis (MS). Standardized procedures were adopted for grading the intensity of oligoclonal banding and for the certainty of diagnosis of MS. One hundred and forty-nine patients were studied, including 23 with definite multiple sclerosis (MS), 12 with probable MS, 20 with possible MS, 20 with inflammatory neurologic disease, 65 with noninflammatory neurologic disease, and nine with no neurologic disease. The CSF IgG index and the CSF to serum albumin ratio were calculated from nephelometric measurements of serum and CSF IgG and albumin. The intensity of oligoclonal banding was graded relative to the density of the prealbumin band. Eighty-eight per cent of cases of definite MS had distinct oligoclonal bands, and an equal number had an elevated IgG index. These tests were not specific for MS, however, since 50% of cases of inflammatory neurologic disease and 5% of those with noninflammatory neurologic disease had an elevated IgG index. Similarly, 48% of cases with inflammatory disease and 25% with noninflammatory disease had oligoclonal bands. However, only patients with definite MS (21%) or possible MS (4%) had prominent oligoclonal bands whose density was greater than or equal to that of prealbumin, together with a CSF IgG index greater than 1.50. This combination of findings therefore may enhance the level of suspicion of MS. By contrast, an isolated increase in the CSF to serum albumin ratio may suggest a diagnosis other than MS.

The authors developed a cost-effective procedure for high-resolution protein electrophoresis in agarose gel which results in electrophoretic patterns that can be both visually interpreted and densitometrically quantitated. Unique features include the development of special molds for the preparation of several gels simultaneously and the combination of chemical with densitometric procedures to accurately quantitate the protein fractions in both normal and pathologic sera. Since the albumin concentrations obtained by densitometric scan of either cellulose acetate or agarose gel were erratic with respect to colorimetric (ACA) or immunochemical (ICS) measurements, the authors incorporated colorimetric measurements of albumin and total protein with densitometric quantitation of the electrophoretic bands into an algorithm for calculating protein concentrations. The densitometric quantitation of the gamma globulin fractions compared well with the sum of the immunochemically determined IgG and IgM concentrations (r = 0.98). Alpha and beta globulins were calculated using mathematically adjusted densitometric scan percentages and the total alpha and beta globulin protein concentration. The agarose gel procedure was more sensitive than cellulose acetate in the detection of paraprotein bands in a comparison of 93 sera containing paraproteins.

Transferrin levels were measured immunochemically and the levels of several other plasma proteins were estimated by high resolution agarose gel electrophoresis in serial serum samples from nine patients undergoing bone marrow transplantation for aplastic anemia or leukemia. Three of five patients with low pretreatment transferrin levels died during initial hospitalization, and the other two suffered severe complications prior to recovery. All four patients with pretreatment transferrin levels within the normal range were discharged, three of them with minimal complications. Serial studies demonstrated that transferrin levels fell with the onset of infections or graft-versus-host disease and rose with recovery. Similar changes were not seen with any of the other plasma proteins measured. These results suggest that measurement of serum transferrin may reveal important prognostic information about patients undergoing bone marrow transplantation.

Pulmonary hyalinizing granuloma (PHG) is a disease of slowly enlarging pulmonary nodules made up of dense bundles of collagen accompanied by an infiltrate of chronic inflammatory cells. The etiology is unknown. Although it has been suggested that the lesions represent an exaggerated immune response to unidentified agents, results of a detailed immunologic work-up of these patients have not been published. This report presents the laboratory findings of two patients with biopsy-proven PHG who have been followed four and eighteen years. Autoantibodies were detected (antinuclear antibody, rheumatoid factor, and positive antiglobulin tests), although clinically there was no evidence of a specific collagen-vascular disorder. Both patients had elevated levels of circulating immune complexes. These data suggest that immune complex mechanisms may be important in the pathogenesis of PHG.

Patients with leukemia were found to have a high percentage of saturation of their serum transferrin with iron to an extent only rarely observed with other malignancies. This was associated with a reduced ability of their serum to inhibit the growth of a test strain of Pseudomonas aeruginosa. Serum iron, transferrin, and related parameters were measured serially in patients undergoing bone marrow transplantation for leukemia or aplastic anemia. It was found that a high proportion of these patients also have a high saturation of their transferrin with iron. This was related to three distinct physiologic deficits: a low level of serum transferrin; a high level of iron; and an inability to reduce the level of serum iron during infection. Three of six patients who were unable to reduce their serum during fever and infection subsequently died of sepsis. These data support the hypothesis that derangements in nonspecific serologic defense mechanisms involving iron contribute to susceptibility to infection in patients with leukemia undergoing bone marrow transplantation.