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Baclofen is a racemic GABA(B) receptor agonist that has a number of significant pharmacokinetic limitations, including a narrow window of absorption in the upper small intestine and rapid clearance from the blood. Arbaclofen placarbil is a novel transported prodrug of the pharmacologically active R-isomer of baclofen designed to be absorbed throughout the intestine by both passive and active mechanisms via the monocarboxylate type 1 transporter. Arbaclofen placarbil is rapidly converted to R-baclofen in human and animal tissues in vitro. This conversion seems to be primarily catalyzed in human tissues by human carboxylesterase-2, a major carboxylesterase expressed at high levels in various tissues including human intestinal cells. Arbaclofen placarbil was efficiently absorbed and rapidly converted to R-baclofen after oral dosing in rats, dogs, and monkeys. Exposure to R-baclofen was proportional to arbaclofen placarbil dose, whereas exposure to intact prodrug was low. Arbaclofen placarbil demonstrated enhanced colonic absorption, i.e., 5-fold higher R-baclofen exposure in rats and 12-fold higher in monkeys compared with intracolonic administration of R-baclofen. Sustained release formulations of arbaclofen placarbil demonstrated sustained R-baclofen exposure in dogs with bioavailability up to 68%. In clinical use, arbaclofen placarbil may improve the treatment of patients with gastroesophageal reflux disease, spasticity, and numerous other conditions by prolonging exposure and decreasing the fluctuations in plasma levels of R-baclofen.

Two patients were suspected of having extrinsic allergic alveolitis due to exposure to an agent in their home environment. On inspection of their houses, fungal decay was evident in the floorboards, and fungal spores were found deposited on many surfaces. The decay fungus was later identified as Leucogyrophana pinastri. Using an extract of the fruiting bodies and mycelium of this fungus, precipitating antibodies were identified in the sera of both patients. Based on the known exposure by the two patients to these small spores, the absence of a likely alternative allergen, the similarity between these two cases, and the positive precipitin test results, L. pinastri was considered to be the most likely cause of extrinsic allergic alveolitis in our cases.

We report 50 immunocompromised patients with pulmonary infiltrates who underwent fibreoptic bronchoscopy, including bronchoalveolar lavage, on 56 occasions. The underlying diseases were mostly lymphoma, leukemia, other malignancies and renal failure. The commonest immunodeficiency factors were chemotherapy, steroids and neutropenia. A positive diagnosis could be made from analysis of the bronchoalveolar lavage on 59% (33/56) occasions. This was a comparable yield to transbronchial lung biopsy 57% (16/27), and superior to proximal airways wash 24% (13/55), or bronchial brushings 29% (10/34). Open lung biopsy added additional diagnostic information in three of the four cases in which it was performed. The most common final diagnoses were bacterial, viral or Pneumocystis carinii pneumonia and recurrent malignancy. We conclude that bronchoalveolar lavage is a safe procedure with a high diagnostic yield in the immunocompromised host with suspected opportunistic pneumonia.