Tacrolimus metabolite cross-reactivity in different tacrolimus assays

Objectives: Tacrolimus (FK506) is an immunosuppressive drug with great clinical promise. There is a controversy regarding the role of tacrolimus metabolites in immunosuppression and toxicity, and immunoassays and immunophilin binding assays have not been adequately tested for metabolite cross-reactivity. Methods are limited to HPLC and HPLC-MS for quantifying the parent drug. Mixed lymphocyte culture assay (MLC) is the preferred functional bioassay for the measurement of parent drug and active metabolites but it is not practical for routine laboratory use. Due to differences in assay methods and reagent specificity, the concentration of tacrolimus in a given specimen may vary among different assay kit manufacturers. The objective of this study was to evaluate the degree of cross-reactivity or interference of the three first-generation tacrolimus metabolites [13-O-demethyl (M-I), 31-O-demethyl (M-II) and 15-O-demethyl (M-III)] among two different tacrolimus immunoassays (Immunoassay: PRO-Trac II FK506, Abbott IMx tacrolimus-II); and the radioreceptor assays (RRA) using minor immunophilins (14, 37, and 52 kDa immunophilins) and tacrolimus binding protein (FKBP12).

Methods: First-generation tacrolimus metabolites (M-I, M-II, and M-III) spiked in drug-free whole blood were assayed with RRA using three minor immunophilins (14, 37, and 52 kDa) and two commercial immunoassay procedures (Incstar PRO-Trac II tacrolimus, Abbott IMx tacrolimus II). The results were compared to previously published FKBP-12 RRA data and their immunosuppressive potency.

Results and conclusion: The first generation tacrolimus metabolites (M-I, M-II, and M-III) were tested using concentrations of 10 and 20 ng/mL. The significance of the metabolite interference (% of the total interference) was calculated based on the relative concentration of each metabolite present at steady-state trough concentrations in renal transplant recipients [22]. Metabolite I, which has no functional immunosuppressive activity showed minimal interference compared to M-II and M-III in all assays except the 14 kDa RRA. The Incstar PRO-Trac II tacrolimus assay showed the least M-I interference. Metabolite-II, which has a pharmacologic potency similar to the parent drug, showed a significant interference in the immunoassays and significant interference in radioreceptor assays. Metabolite III, which is pharmacologically inactive, produces 3–10% interference in the different assays if its presence in the blood is 6% of the parent drug. The total interference from these three metabolites was greater in the immunoassays than in the receptor assays. Receptor assays for tacrolimus provide results closer to the target value than do immunoassays.     

Reliability of a Store Observation Tool in Measuring Availability of Alcohol and Selected Foods

Alcohol and food items can compromise or contribute to health, depending on the quantity and frequency with which they are consumed. How much people consume may be influenced by product availability and promotion in local retail stores. We developed and tested an observational tool to objectively measure in-store availability and promotion of alcoholic beverages and selected food items that have an impact on health. Trained observers visited 51 alcohol outlets in Los Angeles and southeastern Louisiana. Using a standardized instrument, two independent observations were conducted documenting the type of outlet, the availability and shelf space for alcoholic beverages and selected food items, the purchase price of standard brands, the placement of beer and malt liquor, and the amount of in-store alcohol advertising. Reliability of the instrument was excellent for measures of item availability, shelf space, and placement of malt liquor. Reliability was lower for alcohol advertising, beer placement, and items that measured the “least price” of apples and oranges. The average kappa was 0.87 for categorical items and the average intraclass correlation coefficient was 0.83 for continuous items. Overall, systematic observation of the availability and promotion of alcoholic beverages and food items was feasible, acceptable, and reliable. Measurement tools such as the one we evaluated should be useful in studies of the impact of availability of food and beverages on consumption and on health outcomes.     

Structure and culture of schools of public health to support academic public health practice.

Schools of public health have been cautioned about producing graduates and research that were disconnected from public interest. Although institutions may implement a variety of strategies to rectify the situation, institutional structural and cultural barriers impede progress. Public health practice coordinators in accredited schools of public health were surveyed to describe the presence of structural and cultural barriers to academic public health practice using the Stevens model. Administrative leadership and faculty reward systems are described as critical to advance academic public health practice.     

Intraocular pressure effects on optic nerve-head oxidative metabolism measured in vivo

The effects of acute intraocular pressure (IOP) on the reduction/oxidation ratio of cytochromea,a ₃ were measured from intact cat optic nerve by microfiber reflection spectrophotometry. This enabled the real-time analysis of optic nerve-head oxidative metabolism following IOP or mean arterial pressure (MAP) changes. Findings included: (1) cytochromea,a ₃ became more reduced and relative blood volume decreased at lower perfusion pressures, even at IOP of <20 mm Hg; (2) metabolic inhibition began at variable perfusion pressures but invariably progressed as perfusion pressure declined; and (3) increased IOP or decreased MAP caused metabolic inhibition. These findings demonstrate that: (1) optic nerve metabolic dysfunction is possible at low IOPs; (2) lowering IOP can reverse metabolic dysfunction; (3) the metabolic response is dependent on IOP and/or MAP changes; and (4) the metabolic inhibition is related to optic nerve ischemia. Presented at the 8th International Congress of Eye Research-Symposium on Retinal Oxygenation, San Francisco, September 1988     

Safety Concerns Affecting Delivery of Home Health Care

Abstract Factors influencing the remarkable growth of home health care include increased elderly population, decreased average length of hospital stay, and technological advancements that reduce the need for hospitalization. Societal changes have prompted increasing concern about personal risk to home care providers. The purpose of this pilot study was to: 1) ascertain factors related to perception of risk by home health care administrators and staff and to identify strategies used by home health care administrators to reduce risk to staff; and 2) determine whether quality of care is affected when home-visit situations present risk. A convenience sample of 36 home health care administrators and 62 staff was surveyed about risks and measures provided by the home health care agency to minimize risk. Factors associated with risk are geographic location, high incidence of crime, inappropriate patient or caregiver behavior, infectious diseases, and evening assignments. Strategies used to minimize risk include safety programs, preplanning of visits, personal protective equipment, escorts, and buddy systems. Perceived ability to refuse high-risk assignments, however, is questionable, as 66% of the staff stated that they leave a situation "as soon as possible." These findings will be used to strengthen inservice programs and to provide a basis for future studies.     

Case studies in acute aortic dissection: Strategies to avoid a catastrophic outcome

Aortic dissection is a catastrophic illness that is a significant source of liability for hospitals if diagnosis and treatment are not done promptly. The diagnosis is often difficult to make because not all dissections have the typical presentation of sudden severe chest pain radiating to the back. Symptoms often include abdominal pain, flu‐like complaints, vomiting and diarrhea, low back pain, stroke syndromes and syncope. Patients at risk include those with Marfan syndrome and other connective tissue diseases, familial aortic disease, age and hypertension. Aortic dissection is a different clinical entity than abdominal aortic aneurysm. Strategies to reduce risk and improve outcome include staff education on various presentations and risk factors, rapid availability of diagnostic testing modalities such as chest CT scan or transesophageal echocardiogram, and protocols to ensure prompt transfer for cardiothoracic surgery.