Citations

The immunosuppressive properties of morbilliviruses including measles and canine distemper virus (CDV) are well known, but the host cells supporting infection are poorly characterized. To identify these cells, a recombinant CDV expressing green fluorescent protein was produced by reverse genetics based on a wild-type strain lethal for ferrets. This recombinant virus fully retained virulence and blazed three lymphocyte-based pathways through the immune system of its host: first, it infected rapidly and massively circulating B and T cells; second, it took over and damaged secondary lymphatic organs including spleen, lymph nodes, and gut-associated and mucosal lymphoid tissues; third, it infected most thymocytes. In contrast, replication in epithelial cells was initially not detectable, but substantial before host death. Thus, CDV initially infects lymphocytes and massively replicates therein, thereby causing immunosuppression and preparing systemic invasion and host escape.

Two patients with cerebrospinal fluid (CSF) leak, one at the level of fourth thoracic spine and another with undetermined level of leak, presented with paradoxical postural headaches in that the headaches were present when in a horizontal position and resolved if the patients were upright. One patient improved spontaneously and the other responded to a targeted epidural blood patch. Paradoxical postural headache is yet another headache type that can be associated with CSF leak and CSF volume depletion. Its mechanism is uncertain, but it could be related to congestion and dilatation of cerebral venous sinuses and large veins.

Abstract Inhaled glucocorticosteroids (ICS) are commonly prescribed for chronic obstructive pulmonary disease. No adverse effect on bone mineral density (BMD) has been proven. In a randomized double-blind, placebo-controlled trial at seven centers in North America, we recruited 412 current smokers or recent quitters with mild to moderate chronic obstructive pulmonary disease. They used inhaled triamcinolone acetonide, 600 mcg, or placebo, twice daily. We measured femoral neck and lumbar spine BMD at baseline and after 1 and 3 years, and serum osteocalcin at baseline, 3 months, 1 year, and 3 years. After 3 years, BMD at the femoral neck decreased 1.78% more with ICS than with placebo (p < 0.001). More participants in the ICS group experienced 6% or more loss of femoral neck BMD (p = 0.002). Lumbar spine BMD increased in the placebo group by 0.98% but decreased by 0.35% in the ICS group (a difference of 1.33%, p = 0.007). Changes in osteocalcin did not correlate with changes in BMD. Fractures, lost height, or osteoporosis diagnoses were not increased among ICS users compared with placebo users. In summary, the use of inhaled triamcinolone acetonide was associated with loss of BMD at the femoral neck and lumbar spine after 3 years of treatment.

Eosinophils are often dominant inflammatory cells present in the lungs of asthma patients. Nonetheless, the role of these leukocytes remains poorly understood. We have created a transgenic line of mice (PHIL) that are specifically devoid of eosinophils, but otherwise have a full complement of hematopoietically derived cells. Allergen challenge of PHIL mice demonstrated that eosinophils were required for pulmonary mucus accumulation and the airway hyperresponsiveness associated with asthma. The development of an eosinophil-less mouse now permits an unambiguous assessment of a number of human diseases that have been linked to this granulocyte, including allergic diseases, parasite infections, and tumorigenesis.