Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, including inflammatory epithelial cells. NO has been detected in the exhaled air of normal human subjects, and its concentration is raised in asthmatic patients. To study whether exhaled NO arises from the respiratory tract, we administered a NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA), by inhalation (490 mg) in a double-blind randomized manner in nine normal and six asthmatic subjects. Because exhaled NO may arise from an inducible isoform of NO synthase that may be inhibited by glucocorticosteroids, we also studied the effects of oral prednisolone (30 mg orally for 3 d) in seven normal and six asthmatic subjects in a separate double-blind crossover study with matched placebo. After nebulized L-NMMA, there was a significant fall in peak exhaled NO compared with saline control values, with a mean fall of 43.6 +/- 5.6% in normal subjects (p < 0.01) and of 39.7 +/- 6.5% (p < 0.01) in asthmatic subjects, which persisted for 4 h. There were no effects of L-NMMA inhalation on heart rate, blood pressure, or FEV1 in either normal or asthmatic patients. Administration of oral prednisolone (30 mg) resulted in a fall in exhaled NO concentrations in asthmatic subjects by 21.6 +/- 5.0% at 48 h (p < 0.01) but no significant change in normal subjects. These data suggest that NOS inhibitors may be safely given in normal and asthmatic patients and that the increased exhaled NO seen in asthmatic patients is likely to be caused by induction of inducible NOS.     

The mammalian Y chromosome: a new perspective

If pityriasis lichenoides et varioliformis acuta (PLAVA) exists in the vagina or cervical os of the uterus, it may cause premature labor and premature rupture of the membranes.     

Management of otitis media in a high risk population

BACKGROUND: Rural and remote Aboriginal and Torres Strait Islander children have extremely high rates of otitis media and hearing loss. Despite considerable evidence, clinical practice continues to vary. This may be partly related to the failure of recent guidelines to be explicit about which factors should influence decision making. OBJECTIVE: To provide rural and remote GPs caring for young Aboriginal and Torres Strait Islander children with an evidence based guide to the principles that determine the clinical management of otitis media and hearing loss. DISCUSSION: While population health strategies are extremely important, the GP also needs to be able to advise families of affected children of the benefits and risks of the medical, surgical and audiological interventions available. The key to this process is the ability to distinguish between suppurative and non-suppurative disease, and a familiarity with the natural history and the likely hearing loss associated with different disease states in high risk populations.     

A new model for risk stratification and delivery of cardiovascular rehabilitation services in the long-term clinical management of patients with coronary artery disease

A case of multiple dorsal dislocations of the metacarpophalangeal joints is presented with a review of literature. Prompt recognition of the dislocation type is essential, followed by trial of closed reduction under proper anesthesia; open reduction is sometimes required. A short period of immobilization is needed, followed by intensive rehabilitation.     

Mature T cell reactivity altered by peptide agonist that induces positive selection

Recent studies have investigated how defined peptides influence T cell development. Using a T cell receptor-transgenic beta2-microglobulin-deficient model, we have examined T cell maturation in fetal thymic organ cultures in the presence of various peptides containing single-alanine substitutions of the strong peptide agonist, p33. Cocultivation with the peptide A4Y, which contains an altered T cell contact residue, resulted in efficient positive selection. Several in vitro assays demonstrated that A4Y was a moderate agonist relative to p33. Although A4Y promoted positive selection over a wide concentration range, high doses of this peptide could not induce clonal deletion. Thymocytes maturing in the presence of A4Y were no longer able to respond to A4Y, but could proliferate against p33. These studies demonstrate that (a) peptides that induce efficient positive selection at high concentrations are not exclusively antagonists; (b) some agonists do not promote clonal deletion; (c) positive selection requires a unique T cell receptor-peptide-major histocompatibility complex interaction; and (d) interactions with selecting peptides during T cell ontogeny may define the functional reactivity of mature T cells.