Quantitative measurement of JWH-018 and JWH-073 metabolites excreted in human urine.

"K2/SPICE" products are commonly laced with aminoalkylindole synthetic cannabinoids (i.e., JWH-018 and JWH-073) and are touted as "legal" marijuana substitutes. Here we validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring urinary concentrations of JWH-018, JWH-073, and several potential metabolites of each. The analytical procedure has high capacity for sample throughput and does not require solid phase or liquid extraction. Evaluation of human urine specimens collected after the subjects reportedly administered JWH-018 or a mixture of JWH-018 and JWH-073 provides preliminary evidence of clinical utility. Two subjects that consumed JWH-018 primarily excreted glucuronidated conjugates of 5-(3-(1-naphthoyl)-1H-indol-1-yl)-pentanoic acid (>30 ng/mL) and (1-(5-hydroxypentyl)-1H-indol-3-yl)(naphthalene-1-yl)-methanone (>50 ng/mL). Interestingly, oxidized metabolites of both JWH-018 and JWH-073 were detected in these specimens, suggesting either metabolic demethylation of JWH-018 to JWH-073 or a nonreported, previous JWH-073 exposure. Metabolic profiles generated from a subject who consumed a mixture of JWH-018 and JWH-073 were similar to profiles generated from subjects who presumably consumed JWH-018 exclusively. Oxidized metabolites of JWH-018 and JWH-073 were of the same pattern, but JWH-018 metabolites were excreted at lower concentrations. These results begin clinically validating the LC-MS/MS assay for detecting and quantifying aminoalkylindole metabolites. Full validation awaits further testing.

Biochemical characterization of alpha-ketooxadiazole inhibitors of elastases.

A series of alpha-ketooxadiazole compounds was prepared and evaluated in vitro as potential inhibitors of human neutrophil elastase (HNE), proteinase-3 (PR-3), and porcine pancreatic elastase (PPE). Several compounds have been found to be very potent, fast, reversible, and selective inhibitors of HNE with Ki values below 100 pM. The highest kon value exceeded 10(7) M(-1) s(-1). Some alpha-ketooxadiazoles were also very effective against PR-3 and PPE with Ki values in the range of 5(-10) nM and 0.1(-2) nM, respectively. The two rings, 1,2,4- and 1,3,4-oxadiazole, are amenable to substitutions, extending the P' side of the inhibitor and allowing additional binding interactions at S' subsites of the enzyme. Nonpeptidic HNE inhibitors containing the oxadiazole heterocycle displayed promising oral bioavailability.

Fewer black kidney donors: what's the problem?

This article describes a qualitative study which explored the factors that influence relatives' decisions about donating kidneys for transplantation within a specific minority culture, i.e., African-American, in the United States. The researchers interviewed caregiving relatives of End Stage Renal Disease patients to learn their ideas and feelings about donation and transplantation. Data analysis revealed six themes; each theme is presented with relevant social work activities.

A kidney donor's dilemma: the sibling who can donate--but doesn't.

The decision making process undertaken by a sibling who chooses not to donate a kidney to a brother or sister who needs a transplant is the subject of this article. Presented from the perspective of the potential donor client, the paper focuses on the moral and ethical concerns indicated when there are two equal but competing rights involved in the decision. It also addresses pertinent attitudinal dimensions and social and health issues that affect all parties--the client, the marital partner, the family of origin, and the patient's immediate family. The article concludes by addressing "what" and "how" social workers assist clients after the difficult decision not to donate has been made.

Middle ear disease and the practice of pediatrics. Burden during the first five years of life.

To determine the burden on pediatricians imposed by disease of the middle ear, we analyzed data from 2,570 children followed up prospectively since birth. Disease of the middle ear accounted for a large proportion of all visits made during the first five years of life, rising from 22.7% during the first year to about 40% in years 4 and 5. About one visit in three made for illness of any kind resulted in the diagnosis of disease of the middle ear. Approximately three fourths of all visits to follow up any illness were made to follow up disease of the middle ear. Disease of the middle ear was diagnosed at between 5% and 10% of all well-baby visits. Children from private practice averaged fewer visits for all reasons than did children using a large neighborhood health center, but the proportions of visits accounted for by disease of the middle ear were similar in both settings.

Use of pneumococcal vaccine for prevention of recurrent acute otitis media in infants in Boston. The Greater Boston Collaborative Otitis Media Study Group.

The efficacy of pneumococcal polysaccharide vaccine for children suffering from recurrent acute otitis media (AOM) was determined by administration, in a randomized double-blind fashion, of one of two polyvalent vaccines to 124 children aged five to 21 months. The octavalent vaccine contained serotypes commonly associated with AOM: 1, 3, 6A, 7F, 14, 18C, 19F, and 23F. The heptavalent control contained serotypes not commonly associated with AOM: 2, 4, 5, 8, 9N, 12F, and 24F. Recipients of the octavalent vaccine experienced significantly (P less than 0.05) less AOM due to serotyes contained in the octavalent vaccine than did children who received the control vaccine. Although the recipients of octavalent vaccine suffered less from AOM due to types in that vaccine than did controls, their clinical experience with AOM was not different. Both groups of children were equally likely to experience at least one episode of AOM after vaccination (70% for octavalent vaccine and 78% for heptavalent vaccine). The mean numbers of episodes of AOM after vaccination also were similar (2.1 for octavalent vaccine and 2.3 for heptavalent vaccine). Similarly, the period of effusion in the middle ear after pneumococcal AOM was identical for both groups. Although immunization with pneumococcal vaccine appeared to reduce the number of episodes of AOM due to serotypes contained in octavalent vaccine, the clinical experience of the children was not favorably affected by this vaccine.

Outcome of unsuspected pneumococcemia in children not initially admitted to the hospital.

The records were reviewed of 97 episodes of unsuspected pneumococcemia in children not initially admitted to the hospital. Antimicrobial agents were prescribed at the first visit for 46 children; at the second visit 37 of them were improved and nine were not. No antimicrobial agents were prescribed at the first visit for 51; at the second visit 16 of these patients were improved and 35 were not. Pneumococcemia persisted in two treated children and in 13 untreated children. Meningitis was identified later in four children (two treated and two untreated). Although pneumococcemia in children may be a transient event, it may also persist or result in meningitis or other localized infections.