Selected clinical abstracts from a variety of journals

1 Effectiveness of isoniazid treatment for latent tuberculosis infection among human immunodeficiency virus (HIV)-infected and HIV-uninfected injection drug users in methadone programs

from Clinical Infectious Diseases. 2003;37:000.

Jerod N. Scholten,¹ Cynthia R. Driver,¹ Sonal S. Munsiff,¹ Katherine Kaye,¹ Mary Ann Rubino,¹ Marc N. Gourevitch,⁶ Caroline Trim,² James Amofa,⁵ Randy Seewald,³ Esther Highley,⁴ and Paula I. Fujiwara^1,7

Injection drug users (IDUs) were heavily affected by the tuberculosis (TB) resurgence in New York City in the 1990s. We assessed the effectiveness of screening for latent TB infection in methadone users and of selective treatment with isoniazid. Risk for future TB was classified as low or high on the basis of tuberculin, anergy, and HIV test results. The cohort of 2,212 IDUs was followed up for a median of 4.2 years; 25 IDUs, of whom 20 (80%) were infected with human immunodeficiency virus (HIV), developed TB. In an adjusted Cox proportional hazards model of high-risk IDUs, the risk of TB was associated with HIV infection (HR 10.3; 95% CI, 3.4-31.3); receipt of < 6 months of isoniazid therapy (HR 7.6; 95% CI, 1.02-57.1); a CD4+ T lymphocyte count of < 200 cells/mm³ (HR 6.6; 95% CI, 1.7-25.9); and tuberculin positivity (HR 4.0; 95% CI, 1.6-10.2). Treatment with isoniazid was beneficial in HIV-infected, tuberculin-positive IDUs.

Affiliations
¹New York City Department of Health and Mental Hygiene, ²Greenwich House West, ³Greenwich House East, and ⁴Lower Eastside Services Center, New York, and ⁵Bronx Lebanon Hospital and ⁶Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and ⁷Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta

2 Eosinophil-induced release of acetylcholine from differentiated cholinergic nerve cells

Deborah A. Sawatzky,¹ Paul J. Kingham,¹ Niamh Durcan,² W. Graham McLean,¹ and Richard W. Costello²

from American Journal of Physiology Lung Cellular and Molecular Physiology. 2003;285:L1296-L1304.

One immunological component of asthma is believed to be the interaction of eosinophils with parasympathetic cholinergic nerves and a consequent inhibition of acetylcholine muscarinic M₂ receptor activity, leading to enhanced acetylcholine release and bronchoconstriction. Here we have used an in vitro model of cholinergic nerve function, the human IMR32 cell line, to study this interaction. IMR32 cells, differentiated in culture for 7 days, expressed M₂ receptors. Cells were radiolabeled with [³H]choline and electrically stimulated. The stimulation-induced release of acetylcholine was prevented by the removal of Ca²⁺. The muscarinic M₁/M₂ receptor agonist arecaidine reduced the release of acetylcholine after stimulation (to 82 ± 2% of control at 10^-7 M), and the M₂ receptor antagonist AF-DX 116 increased it (to 175 ± 23% of control at 10-5 M), indicating the presence of a functional M₂ receptor that modulated acetylcholine release. When human eosinophils were added to IMR32 cells, they enhanced acetylcholine release by 36 ± 10%. This effect was prevented by inhibitors of adhesion of the eosinophils to the IMR32 cells. Pretreatment of IMR32 cells with 10 mM carbachol, to desensitize acetylcholine receptors, prevented the potentiation of acetylcholine release by eosinophils or AF-DX 116. Acetylcholine release was similarly potentiated (by up to 45 ± 7%) by degranulation products from eosinophils that had been treated with N-formyl-methionyl-leucyl-phenylalanine or that had been in contact with IMR32 cells. Contact between eosinophils and IMR32 cells led to an initial increase in expression of M₂ receptors, whereas prolonged exposure reduced M₂ receptor expression.

Affiliations ¹Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom; and ²Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland

3 Human mast cell subtypes in conjunctiva of patients with atopic keratoconjunctivitis, ocular cicatricial pemphigoid, and Stevens-Johnson syndrome

from Ocular Immunology and Inflammation. 2003;11:211-222.

Lijing Yao,¹ Stefanos Baltatzis,² Panayotis Zafirakis,² Charalampos Livir-Rallatos,² Adamantia Voudouri,² Nikos N. Markomichelakis,² Tongzhen Zhao,¹ and C. Stephen Foster¹

Purpose: Investigate mast cell (MC_S) subtypes in atopic keratoconjunctivitis (AKC), ocular cicatrical pemphigoid (OCP), and Stevens-Johnson syndrome (SJS). Methods: MC_S subtypes were determined by immunohistochemistry of conjunctiva (obtained from 34 patients—9 AKC, 9 OCP, 9 SJS, and 7 normal) using monoclonal antibodies directed against chymase (MC_C) and tryptase (MC_T). Double staining was used to distinguish MC_S as positive for both chymase and tryptase (MC_TC). Results: The number of MC_S was significantly increased in AKC, OCP, and SJS patients, compared to normal subjects. MC_C were especially high in AKC, and moderately high in OCP. MC_T and MC_TC were similar in each disease group. Conclusions: While the AKC findings were not surprising, the result in OCP and SJS suggests that MC_S play an underappreciated role in the inflammatory process of these disorders. Disparate proportions of MC_S subtypes in these diseases may imply differential functions of MC_S in these disorders.

Affiliations ¹Immunology and Uveitis Service and Hilles Immunology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston

²Immunology and Uveitis Service and Hilles Immunology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, and Department of Ophthalmology, General Hospital of Athens Medical School, Athens, Greece