Identification and Characterization of EDTA Test Strip Interfering Substances Using a Digital Color Detector.

BACKGROUND: Rapid test strips for ethylenediaminetetraacetic acid (EDTA) can be used to verify correct specimen types for clinical assays which require, or cannot be performed on, plasma collection tubes containing EDTA anticoagulant. As the test strip reaction chemistry is based on a color change induced by chelation of bismuth from a xylenol orange complex, we hypothesized that any agent capable of chelating bismuth might induce false positive test strip reactivity. The present study was therefore designed to evaluate the potential for test strip interference by chelating agents commonly used in the treatment of trace and heavy metal toxicity. METHODS: A digital color detector mounted on a 3D-printed test strip holder was used to quantitatively assess test strip reactivity and evaluate concentration-response relationships of eight commercially available chelating agents. RESULTS: This approach revealed the following rank-order potency: K2EDTA = Na2EDTA > ethylene glycol tetra-acetic acid (EGTA) > dimercaptosuccinic acid (DMSA) > 2,3-dimercapto-1-propanesulfonic acid (DMPS) > penicillamine (PEN). Both deferoxamine (DEF) and alpha lipoic acid (ALA) were non-reactive at 10 mM concentrations. CONCLUSIONS: These experiments demonstrate that multiple substances can induce EDTA rapid test strip reactivity, but only at concentrations higher than might be expected during therapeutic chelation therapy. These agents are therefore unlikely to cause false positive results in routine clinical laboratory specimens.

Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease.

Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion. Kcnn4 is required for osteoclast and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca(2+) signaling, increases bone mass, and improves clinical outcome in arthritis. Pharmacological blockade of Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in macrophage multinucleation, identifying it as a potential therapeutic target for inhibition of bone resorption and chronic inflammation.

Analysis of vitamin D status at two academic medical centers and a national reference laboratory: result patterns vary by age, gender, season, and patient location.

BACKGROUND: Testing for 25-hydroxyvitamin D [25(OH)D] has increased dramatically in recent years. The present report compares overall utilization and results for 25(OH)D orders at two academic medical centers - one in New York and one in Iowa - in order to characterize the vitamin D status of our inpatient and outpatient populations. Results are also compared to those from a national reference laboratory to determine whether patterns at these two institutions reflect those observed nationally. METHODS: Retrospective data queries of 25(OH)D orders and results were conducted using the laboratory information systems at Weill Cornell Medical College / New York Presbyterian Hospital (WCMC), University of Iowa Hospitals and Clinics (UIHC), and ARUP Laboratories (ARUP). Chart review was conducted for cases with very high or low serum 25(OH)D levels in the WCMC and UIHC datasets. RESULTS: The majority of tests were ordered on females and outpatients. Average serum 25(OH)D levels were higher in female versus male patients across most ages in the WCMC, UIHC, and ARUP datasets. As expected, average serum 25(OH)D levels were higher in outpatients than inpatients. Serum 25(OH)D levels showed seasonal periodicity, with average levels higher in summer than winter and correlating to regional UV index. Area plots demonstrated a peak of increased 25(OH)D insufficiency / deficiency in adolescent females, although overall worse 25(OH)D status was found in male versus female patients in the WCMC, UIHC, and ARUP datasets. Surprisingly, improved 25(OH)D status was observed in patients starting near age 50. Finally, chart review of WCMC and UIHC datasets revealed over-supplementation (especially of ≥ 50,000 IU weekly doses) in the rare cases of very high 25(OH)D levels. General nutritional deficiency and/or severe illness was found in most cases of severe 25(OH)D deficiency. CONCLUSIONS: 25(OH)D status of patients seen by healthcare providers varies according to age, gender, season, and patient location. Improved 25(OH)D status was observed later in life, a finding that may reflect the previously described increased use of vitamin D-containing supplements in such populations. Severe vitamin D deficiency is much more common than vitamin D toxicity.