Intranasal salmeterol inhibits allergen-induced vascular permeability but not mast cell activation or cellular infiltration

BACKGROUND: Salmeterol is a long-acting beta2-adrenergic agonist that is widely used in the treatment of asthma. It has been suggested that non-bronchodilator actions of salmeterol may contribute to its efficacy. OBJECTIVE: To further evaluate the potential non-bronchodilator actions of salmeterol in vivo, using a model of nasal challenge with allergen. METHODS: Twelve asymptomatic subjects with seasonal allergic rhinitis participated in a randomized, double-blind, placebo-controlled crossover trial of the effects of a single dose of 100 microg of salmeterol on the response to allergen challenge. Sneezing and symptom scores, and levels of histamine and albumin in nasal lavages, were measured throughout the protocol. Concentrations of tryptase, prostaglandin D2 and lysozyme were measured during the acute allergic response, while levels of IL-3, IL-5 and IL-8 were measured at later time points. Numbers of eosinophils and of total white blood cells were also recorded. RESULTS: Salmeterol did not affect sneezing or symptom scores at any point. During the immediate response to allergen challenge, mast cell activation, reflected by concentrations of histamine, tryptase and prostaglandin D2, and serous glandular secretion, assessed by measurements of lysozyme, were unaffected by salmeterol treatment but vascular permeability, reflected by concentrations of albumin in nasal lavages, was significantly reduced. At later time points, salmeterol had no effect on levels of histamine or albumin and did not affect cellular infiltration. Concentrations of IL-3, IL-5 and IL-8 were not increased by allergen challenge in these subjects, so the effects of salmeterol could not be evaluated. CONCLUSIONS: Treatment with a single dose of salmeterol had no effect on activation of mast cells or cellular infiltration but inhibited vascular permeability. The ability of salmeterol to inhibit antigen-induced vascular permeability may contribute to its therapeutic efficacy in asthma.     

Tumor growth modulates macrophage nitric oxide production following paclitaxel administration

The antineoplastic agent paclitaxel (Taxol) mimics bacterial lipopolysaccharide (LPS) in normal host macrophages (Mphis), enhancing antitumor cytotoxicity in vitro. Because paclitaxel is used as an antitumor chemotherapeutic agent and tumor growth alters Mphi phenotype and function, we assessed effector molecule production and cytotoxic activity by normal host and tumor-bearing host (TBH) Mphis following paclitaxel administration. Paclitaxel treatment, duplicating human chemotherapeutic regimens, primed normal host splenic Mphis for enhanced production of the cytotoxic mediator nitric oxide (NO); in contrast, paclitaxel's NO-inducing activity was significantly suppressed in TBHs. In contrast to NO regulation, Mphi capacity for tumor necrosis factor-alpha (TNF-alpha) production in both normal hosts and TBHs was enhanced by paclitaxel administration. Although tumor growth modulated paclitaxel-induced Mphi NO production, paclitaxel administration enhanced both normal host and TBH Mphi cytotoxic antitumor activity. Blocking NO with a competitive inhibitor abrogated Mphi cytotoxicity, suggesting paclitaxel-induced TBH Mphi NO production, although suboptimal, remains sufficient to mediate antitumor activity. These data demonstrate that paclitaxel's in vivo immune activities are differentially regulated during tumor burden and suggest that paclitaxel's immunotherapeutic functions may contribute to its success as an anticancer agent.     

Pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively

OBJECTIVE: To determine changes in clinical signs of disease and response to pulmonary function testing in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. ANIMALS: 6 horses with inducible and reversible heaves. PROCEDURE: Episodes of heaves were induced by exposure (challenge) to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone dipropionate, parenterally administered dexamethasone, aerosolized propellant [control]), and respiratory frequency and subjective assessment of respiratory effect were determined twice daily. Maximal change in pleural pressure (delta-Pplmax), pulmonary resistance (RL), and dynamic compliance (Cdyn) was determined on days 0, 7, 10, 14, and 21. RESULTS: The RL and delta Pplmax were increased, and Cdyn was decreased in all horses in response to natural challenge. Beclomethasone reduced RL on day 10, reduced delta Pplmax on days 14 and 21 and increased Cdyn on day 14. Dexamethasone reduced RL and delta Pplmax on days 10, 14, and 21 and increased Cdyn on days 10 and 14. Respiratory effort (subjective assessment) improved after 2 and 3 days of beclomethasone and dexamethasone administration but rebounded to pretreatment values 1 and 3 days after discontinuation of drugs. CONCLUSIONS: Pulmonary function testing responses and clinical signs of airway obstruction were improved by administration of beclomethasone. The magnitude of response to aerosolized beclomethasone generally was less marked than the response to parenterally administered dexamethasone. Higher or more frequent dosing of aerosolized beclomethasone may be necessary to achieve the anti-inflammatory response to parenterally administered dexamethasone.     

Uncharged S4 residues and cooperativity in voltage-dependent potassium channel activation

The purpose of this study was to investigate psychological testing features of children and adolescents with dissociative disorder diagnoses to provide diagnostic information that might facilitate early intervention. The psychological testing protocols of 30 children diagnosed with dissociative disorders were compared with the testing protocols of 30 consecutive admissions to the Sheppard Pratt Hospital who did not receive a dissociative identity disorder (DID; formerly termed multiple personality disorder) or dissociative disorder not otherwise specified (DDNOS) diagnosis. A rater, blind to the diagnosis, scored these protocols for the presence or absence of behavioral and testing response variables hypothesized to discriminate between the dissociative patients and the mixed group of other diagnoses. Behavioral features significantly more common in the dissociative group included forgetting, staring, unusual motor behaviors, dramatic fluctuations, fearful and angry reactions to stimuli, physical complaints during testing, and expressions of internal conflict. Significant indications of dissociation in the test responses included images of multiplicity, malevolent religiosity, dissociative coping, depersonalized imagery, emotional confusion, extreme dichotomization, images of mutilation and torture, and magical transformation. A combination of these behavioral and response variables was able to select 93% of the dissociative sample. These results add support to the discriminant validity of DID and DDNOS as diagnostic categories in childhood and provide clinical information that may be useful for early diagnosis of traumatized children with dissociative pathology.     

Keratinizing desquamative squamous metaplasia of the kidney mimicking transitional cell carcinoma

A 54-year-old patient, who had a remote history of radial nephrotomy for nephrolithiasis, presented with a symptomatic renal mass. The lesion was suspicious for malignancy on excretory urography, retrograde pyelogram, and computed tomography. A nephroureterectomy was performed. The histologic sections showed keratinizing squamous metaplasia.