Adenosine receptors and asthma in humans.

According to an executive summary of the GINA dissemination committee report, it is now estimated that approximately 300 million people (5% of the global population or 1 in 20 persons) have asthma. Despite the scientific progress made over the past several decades toward improving our understanding of the pathophysiology of asthma, there is still a great need for improved therapies, particularly oral therapies that enhance patient compliance and that target new mechanisms of action. Adenosine is an important signalling molecule in human asthma. By acting on extracellular G-protein-coupled ARs on a number of different cell types important in the pathophysiology of human asthma, adenosine affects bronchial reactivity, inflammation and airway remodelling. Four AR subtypes (A(1), A(2a), A(2b) and A(3)) have been cloned in humans, are expressed in the lung, and are all targets for drug development for human asthma. This review summarizes what is known about these AR subtypes and their function in human asthma as well as the pros and cons of therapeutic approaches to these AR targets. A number of molecules with high affinity and high selectivity for the human AR subtypes have entered clinical trials or are poised to enter clinical trials as anti-asthma treatments. With the availability of these molecules for testing in humans, the function of ARs in human asthma, as well as the safety and efficacy of approaches to the different AR targets, can now be determined.

A novel A1 adenosine receptor antagonist, L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], reduces allergic responses to house dust mite in an allergic rabbit model of asthma.

Adenosine, an important signaling molecule in asthma, produces bronchoconstriction in asthmatics. Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans by activating A1 adenosine receptors (ARs). Effects of L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxyethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione] a water-soluble, small molecule A1 AR antagonist were investigated on early and late phase allergic responses (EAR and LAR) in a hyper-responsive rabbit model of asthma. Rabbits were made allergic by intraperitoneal injections of house dust mite [HDM; 312 allergen units (AU)] extract within 24 h of their birth. Booster HDM injections were given weekly for 1 month, biweekly for 4 months, and continued monthly thereafter. Hyperresponsiveness was monitored by measuring lung dynamic compliance (Cdyn), after histamine or adenosine aerosol challenge in allergic rabbits. Hyper-responsive rabbits were subjected to aerosol of HDM (2500 AU), 1 h after intragastric administration of L-97-1 (10 mg/kg) solution or an equivalent volume of saline. Cdyn was significantly higher after treatment with L-97-1 compared with untreated controls (p < 0.05 n = 5). Histamine PC30 was significantly higher (p < 0.05; n = 5) after L-97-1 at 24 h compared with histamine PC30 at 24 h after HDM. Adenosine PC30 was significantly higher at 15 min and 6 h after L-97-1 compared with control (p < 0.05; n = 5). L-97-1 showed strong affinity for human A1 ARs in radioligand binding studies and no inhibition toward human phosphodiesterase II, III, IV, and V enzymes. These data suggest that L-97-1 produces a significant reduction of histamine or adenosine-induced hyper-responsiveness and HDM-induced EAR and LAR in allergic rabbits by blocking A1 ARs and may be beneficial as an oral therapy for human asthma.

Organizational characteristics associated with hospital CEO turnover.

Using a Probit regression model, this study examines organizational factors contributing to hospital chief executive officer (CEO) turnover. The study concludes that some organizational environments are more conducive to turnover. Hospitals that are smaller, are on the West Coast, are investor owned, are church related, offer many services, have high service usage, and larger hospitals with female CEOs are more likely to experience turnover.

Multimedia training in nursing education.

The new developments in computer technology are changing the way training professionals look at computer-assisted instruction (CAI). Nursing educators and practitioners can plan on CAI capabilities that will be both possible and economical as well as within the reach of most organizations. Health care delivery may not be in a position to forego multimedia training as part of its repertoire. In this article, we review interactive video instruction as a multimedia tool in nursing education with an emphasis on the new developments in hardware and software technology. In particular, we examine the changing role of CD-ROM technology and how it has become a tool to change the face of CAI. We define the current status and future trends in CAI and interactive video instruction for nursing education. Several key definitions are introduced to reflect the new direction of multimedia in nursing education.

NLRB rule making. The impact of regulatory reform on hospital unionization.

Many hospital executives feared that the National Labor Relations Board's 1991 decision to recognize eight hospital employee bargaining units would lead to increased union activity. However, this study shows that union activity actually decreased after that decision.

Education needs of hospital governing boards.

Hospital governing board members serve voluntarily, however they are integral to their hospitals' operations. This article investigates if there is a discrepancy between board members' knowledge of healthcare issues and how important they perceive these issues to be in their hospitals' operations and direction. In addition, it offers preliminary steps on how to ensure that board members are kept well-informed and up-to-date on issues for strategy planning in the healthcare marketplace.