Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+- ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel- Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.     

Virus-induced airway inflammation and hyperresponsiveness in the guinea-pig is inhibited by levodropropizine

Summary Intratracheal Parainfluenza type 3 (PI-3) virus inoculation of guinea pigs leads to a non-specific airway hyperresponsiveness in vivo and in vitro which coincides with a significant increase in the number of inflammatory cells in the broncho-alveolar lavage fluid (90% increase, 4 days after inoculation). The activity of the bronchoalveolar cells, as measured by the chemiluminescence production of infected animals is significantly diminished (34.2%, 4 days after inoculation) after renewed stimulation with PI-3 virus in vitro as compared to the chemiluminescence production by bronchoalveolar cells obtained from control guinea pigs.Pretreatment of the guinea-pigs with the antitussive agent levodropropizine, administered intra-peritoneally twice a day for five successive days at a dose of 10 mg/kg, prevents the virus-induced airway hyperresponsiveness in vivo and in vitro, and inhibits the influx of broncho-alveolar cells. Levodropropizine at a dose of 1 mg/kg did not modulate these responses. Further, the decrease in chemiluminescence production of broncho-alveolar cells obtained from virus-infected animals after PI-3 virus stimulation in vitro was inhibited by levodropropizine (10 mg/kg).These data demonstrate the ability of levodropropizine to counteract the hyperresponsiveness phenomenon and the associated inflammatory event induced by PI-3 virus, an effect which may be due to its capacity to act on the peptidergic system or may be due to the anti-allergic/bronchoconstrictor property of this compound. Correspondence to G. Folkerts at the above address     

Functional characterization of muscarinic receptors in murine airways.

1. The effects of muscarinic receptor antagonists considered to be selective for M1 receptors (pirenzepine; PZ), M2 receptors (AFDX-116), and for M3 receptors (4-diphenyl acetoxy N-methyl-piperidine (4-DAMP)) were used to investigate the existence of muscarinic receptors subtypes in murine airways. Atropine was used as a nonselective antagonist. The effects of these antagonists were studied upon tracheal contractions induced either by EFS (electric field stimulation) or by application of an exogenous cholinoceptor agonist (arecoline). 2. The muscarinic receptor antagonists tested inhibited arecoline-induced tracheal contractions with the following rank order of potency: 4-DAMP = atropine > pirenzepine = AFDX-116. The rank order of potency of the muscarinic antagonists used in inhibiting EFS-induced tracheal contractions was: 4-DAMP = atropine > PZ > AFDX-116. The pA2 values for these antagonists were similar when compared to the pA2 values determined in guinea-pig and bovine airway smooth muscle. 3. In addition to in vitro studies, the effects of inhalation of the different muscarinic antagonists on lung function parameters in vivo were investigated. Inhalation of 4-DAMP induced a decrease in airway resistance and an increase in lung compliance. In contrast, inhalation of AFDX-116 induced an increase in airway resistance and almost no change in lung compliance. Apart from some minor effects of atropine on airway resistance, atropine, PZ, and pilocarpine failed to induce changes in lung mechanics as determined by in vivo lung function measurements. 4. The results provide evidence for the existence of M3 receptors on murine tracheae that are involved in the contraction of tracheal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is caring the ethical ideal?

This paper will examine the claim that caring is an appropriate ethical ideal for nursing. Initially it will examine nursing's philosophy of care and caring, highlighting some areas of difficulty and dissatisfaction articulated by many of its contemporary theorists Evaluation of the notion of caring as an appropriate ethical ideal for nursing will be balanced against those in opposition, and in this process their critique will be discussed This discussion will focus on areas such as virtue, virtue ethics, moral responsibility, feminine values, mothering and the debate between male and female caring Different forms of caring will be evaluated and balanced against different forms of nursing The paper will then suggest that current views which hold aloft nursing as a bedmate of caring may be detrimental to both the cared-for and the carer, advocating in the process a move toward change     

Bovine polymorphonuclear leukocytes increase sensitivity to noradrenaline in isolated mesenteric arteries.

1. The effects of polymorphonuclear leukocytes (PMN) on vascular function to (-)-noradrenaline were examined in vitro. Purified bovine PMN were incubated in siliconized organ baths containing rings of bovine mesenteric arteries, after which a concentration-effect curve in response to (-)-noradrenaline was obtained. 2. PMN-derived products induced a long lasting concentration-dependent contraction of the blood vessels generating 24.4 +/- 6.8% of the maximal tension to (-)-noradrenaline at a cell concentration of 2.5 x 10(6) ml-1. The contractile response was also found in endothelium-denuded vascular rings. 3. PMN present in the organ bath caused an increase in the sensitivity of vascular rings to (-)-noradrenaline. At a cell number of 2.5 x 10(6) PMN ml-1 the pD2-value for (-)-noradrenaline was augmented 0.40 +/- 0.05 (P less than 0.001), while total contraction at the highest concentration (-)-noradrenaline was not affected. This increase in sensitivity was dependent on an intact endothelium. 4. The increase in sensitivity to (-)-noradrenaline by PMN was inhibited by superoxide dismutase, but not by catalase, dimethylthiourea, indomethacin or nordihydroguaiaretic acid. The non-stimulated bovine PMN produced oxygen radicals as measured by chemiluminescence. 5. Simultaneous incubation of PMN and (-)-noradrenaline with arterial rings induced an increase in the release of prostacyclin, measured by an elevated concentration of 6-keto-prostaglandin F1 alpha in the supernatant. 6. It is concluded that PMN can increase vascular tone directly or indirectly probably via the interaction of PMN-derived superoxide anions with endothelium-derived relaxing factor.     

Centrally induced hypotension and bradycardia after administration of alpha-methylnoradrenaline into the area of the nucleus tractus solitarii of the rat.

1 In anaesthetized rats, bilateral injections of alpha-methylnoradrenaline, noradrenaline or adrenaline into the area of the nucleus tractus solitarii (NTS) of the brain stem caused dose-dependent decreases of systemic arterial blood pressure and heart rate. The effects of alpha-methylnoradrenaline were most pronounced and lasted longest. 2 The cardiovascular effects of alpha-methylnoradrenaline appeared to be restricted to the medio-caudal part of the NTS. 3 Prior administration of the alpha-adrenoceptor blocking agent, phentolamine, reversed the fall in blood pressure and heart rate induced by alpha-methylnoradrenaline into an increase. 4 Systemic administration of atropine combined with vagotomy potentiated the inhibitory effects of alpha-methylnoradrenaline on the cardiovascular system.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Neuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: future therapeutic targets

The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory bowel disease and irritable bowel syndrome. Since both disorders are associated with increased immune cell numbers, nerve growth and activation of both immune cells and nerves, we focus in this review on the involvement of immune cell–nerve interactions in inflammatory bowel disease and irritable bowel syndrome. Firstly, the possible effects of enteric nerves, especially of the nonadrenergic and noncholinergic nerves, on the intestinal immune system and their possible role in the pathogenesis of chronic intestinal inflammatory diseases are described. Secondly, the possible effects of immunological factors, from the innate (chemokines and Toll-like receptors) as well as the adaptive (cytokines and immunoglobulins) immune system, on gastro-intestinal nerves and its potential role in the development of inflammatory bowel disease and irritable bowel syndrome are reviewed. Investigations of receptor-mediated and intracellular signal pathways in neuro-immune interactions might help to develop more effective therapeutic approaches for chronic inflammatory intestinal diseases.