In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)

The tracheoarterial fistula is an unusual but devastating complication of tracheostomy. It occurs with a frequency of approximately 0.7%, and it is uniformly fatal if not recognized and surgically corrected. Mucosal damage from the tracheal cannula, pressure necrosis from high cuff pressure, or mucosal trauma from an improperly positioned cannula tip results in erosion through the tracheal wall into the vascular structures that lie in the pretracheal space. Bleeding from this complication almost always occurs late (> 48 hours postprocedure). It is often preceded by sentinel hemoptysis. A paucity of signs and symptoms that precede or are associated with this complication require a high index of clinical suspicion to make the diagnosis. In addition to bleeding, other potential clues include a low-lying tracheostomy tube, pulsation of the tracheostomy tube, and the presence of infection, hypotension, malnutrition, and corticosteroid use. Unfortunately, there are no consistently useful diagnostic tools for tracheoarterial fistula. Fiberoptic bronchoscopy and angiography have been performed with mixed results. Should no other cause be found to explain the hemorrhage from or around the tracheostomy, or from disease distal to the primary carina, the patient must be taken to the operating room for a more definitive examination and possible vascular repair. Management is divided into acute stabilization and support, with protection of the airway and restoration of circulating blood volume, followed by definitive repair should the patient survive. Measures to prevent tracheal damage by the tracheostomy tube, such as proper surgical technique and proper inflation of the tracheostomy tube cuff, may go a long way to avoid this potentially lethal complication. Early consideration of this entity may be what saves the life of its victim.

Linezolid was initially discovered as an antidepressant because of its effect on blocking intracellular metabolism of serotonin, norepinephrine, and other biogenic amines. As time passed, it was realized that linezolid possessed antibacterial activity, and linezolid has been developed and marketed as such. In medicine we are quick to categorize drugs into specific classes as a mechanism to recall indication and use. By classifying linezolid as an antibacterial, it is common to forget about its antidepressant roots. A case report involving linezolid with citalopram and mirtazepine in the precipitation of serotonin syndrome in a critically ill bone marrow transplant patient is described in this article.

Pulmonary disease due to Mycobacterium avium complex (MAC) typically occurs in patients with impaired cellular immunity or chronic lung disease. Recently, there has been an increase in the number of reports of pulmonary disease caused by MAC occurring in otherwise healthy individuals, including those reporting recent hot tub use. It is not clear if this respiratory illness represents a true infectious process or a hypersensitivity pneumonitis. We report a case of diffuse pulmonary disease caused by MAC in an immunocompetent individual after hot tub use. The patient's clinical course, transbronchial lung biopsy results, and microbiologic examination findings all pointed to a hypersensitivity reaction due to MAC. With avoidance of the hot tub, and no pharmacological treatment, the patient had complete resolution within 2 months. In light of the number of new cases of "hot tub lung" in otherwise healthy individuals, clinicians should advise their patients of the potential risk associated with hot tub use.

Aspirin is one of the world’s most commonly used medications and its use benefits many diverse conditions. Adverse reactions, however, are relatively common as well. Hypersensitivity to aspirin can be manifested as acute asthma, urticaria and/or angioedema, or a systemic anaphylactoid reaction. We report 3 cases in whom aspirin was indicated for secondary prophylaxis of myocardial infarction but in whom a remote history of an untoward reaction to it prevented its initial use. These patients all underwent further evaluation of their pulmonary and allergic history and all 3 were challenged with aspirin. Two patients were found not to be sensitive and started on aspirin, the other had a classic asthmatic reaction to the drug and was successfully desensitized to aspirin allowing for its use.

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In airway smooth muscle, muscarinic agonists inhibit synthesis of adenosine 3',5'-cyclic monophosphate (cAMP). The goal was to characterize the relationship between agonist occupancy of muscarinic receptors and regulation of cAMP for bovine trachealis cells. For intact cells dispersed by enzyme, carbachol maximally inhibited 58 +/- 4% (mean +/- SE, n = 5) of isoproterenol-stimulated cAMP accumulation at low concentrations [log half-maximal effective concentration (EC50) = -8.34 +/- 0.16]. In radioligand binding experiments, carbachol competed for [3H]quinuclidinyl benzilate (n = 7) and [N-methyl-3H]scopolamine (n = 3) binding sites on intact cells with both low (log KL = -4.26 +/- 0.06 and -4.50 +/- 0.20, respectively) and high affinities (log KH = -5.91 +/- 0.24 and -6.39 +/- 0.19, respectively). In separate experiments, a fraction of the muscarinic receptors on intact cells were inactivated with either phenoxybenzamine (POB) or propylbenzylcholine mustard (PBCM). We compared equally effective concentrations of carbachol before and after partial inactivation of receptors, and the calculated equilibrium dissociation constants for agonist (log KA = -4.36 +/- 0.42 to -3.20 +/- 0.40 for POB; log KA = -4.27 +/- 0.45 for PBCM) were much greater than the half-maximally effective concentration of carbachol in control cells (log EC50 = -8.34 +/- 0.16). Based on these equilibrium dissociation constants, we calculated that maximum responses (EC95) to carbachol were obtained by occupancy of 0.8% of the receptors coupled to cAMP regulation. We concluded that muscarinic inhibition of cAMP accumulation is characterized by a muscarinic receptor reserve.