Crystal engineering of the composition of pharmaceutical phases.

The carboxylic acid-pyridine supramolecular heterosynthon can be exploited to predictably generate binary crystalline phases involving rac-ibuprofen, rac-flurbiprofen or aspirin.

Rhodococcus equi: fatal pneumonia in a patient without AIDS.

Rhodococcus equi infections are being recognized with greater frequency in immunocompromised patients and the population infected with the human immunodeficiency virus (HIV). R. equi usually causes a progressive pneumonia that may or may not cavitate and is relatively refractory to antibiotic therapy. We report a case of fatal R. equi pneumonia in a normal host.

Development and validation of an alternative dermal sensitization test: the mouse ear swelling test (MEST).

Traditional predictive tests for dermal sensitization in humans use the albino guinea pig as a model. A number of factors make the prospect of an alternative attractive. Guinea pig designs are labor intensive, require significant animal, caging, and husbandry resources, and are expensive. Extensive development and validation was conducted of an alternative using swelling of mouse ears as a quantitative end point. Ten strains of mice, ten age groups, both sexes, induction forms (number, route, timing), the use of an adjuvant, different vehicles and intervals to challenge, two induction sites, and three measurement intervals were evaluated. A methodology was developed for preparing induction sites to increase test sensitivity. A small battery of standard compounds was used to evaluate these design variables and a final test design was developed. The basic process was also demonstrated to occur in rats and guinea pigs and to be dose responsive. The final mouse ear swelling test (MEST) design was used to evaluate 72 materials representing a broad spectrum of chemicals and testing problems. These included 49 known positives and 23 known negatives. Guinea pig maximization test data on 37 of these resulting by studies conducted in our laboratories, along with closed patch guinea pig and human test data on many of these compounds, are also reported here for the first time. The MEST correctly identified 71 of 72 materials as potential human sensitizers or nonsensitizers. Additionally, both the efficacy of an occluded patch induction method and the duration of responsiveness of mice were evaluated. In the studies, the MEST was found to be an accurate, sensitive, and efficient alternative test design for evaluating delayed-contact sensitization.