Autonomic modification of intestinal smooth muscle contractility

Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe this spontaneous activity and its modification by agents associated with parasympathetic and sympathetic nerve activity. A section of the rabbit small intestine is suspended in an organ bath, and the use of a pressure transducer and data-acquisition software allows the measurement of tension generated by the smooth muscle of intestinal walls. The application of the parasympathetic neurotransmitter ACh at varying concentrations allows students to observe an increase in intestinal smooth muscle tone with increasing concentrations of this muscarinic receptor agonist. Construction of a concentration-effect curve allows students to calculate an EC50 value for ACh and consider some basic concepts surrounding receptor occupancy and activation. Application of the hormone epinephrine to the precontracted intestine allows students to observe the inhibitory effects associated with sympathetic nerve activation. Introduction of the drug atropine to the preparation before a maximal concentration of ACh is applied allows students to observe the inhibitory effect of a competitive antagonist on the physiological response to a receptor agonist. The final experiment involves the observation of the depolarizing effect of K+ on smooth muscle. Students are also invited to consider why the drugs atropine, codeine, loperamide, and botulinum toxin have medicinal uses in the management of gastrointestinal problems.

Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs.

PURPOSE:

To explore the potential association between adverse corneal events and the use of topical nonsteroidal antiinflammatory drugs (NSAIDs).

SETTING:

Practice-based reports.

METHODS:

A detailed case-reporting form and request for medical records were sent to all practices reporting cases of corneal or conjunctival pathology in association with the use of topical NSAIDs to the American Society of Cataract and Refractive Surgery. Cases were classified as "mild," "moderate," or "severe" according to predetermined clinical criteria.

RESULTS:

Records of 140 eyes (129 patients) were reviewed; 51 cases (36.4%) were mild, 55 (39.3%) moderate, and 34 (24.3%) severe. An association with a specific topical NSAID was confirmed in 117 cases (81.8%). Most confirmed cases (53.8%) involved generic diclofenac (Falcon). Cases associated with brand diclofenac (Voltaren, CIBA Vision) and ketorolac (Acular, Allergan) were more likely to have ocular comorbidity and to have received significantly higher total doses of NSAIDs. Neither "off-label" use nor use of any specific agent was associated with severe compared to mild or moderate disease. However, patients with more severe adverse events were more likely to have a history of diabetes, previous surgery in the affected eye, and surgery other than cataract. Cases not occurring in the perioperative period had significantly worse outcomes, had significantly more ocular comorbidities, and received nearly 3 times the dose of NSAIDs.

CONCLUSIONS:

While topical NSAIDs as a class may be associated with severe adverse events, such events appeared to require potentiation in the form of high total doses, ocular comorbidities, or both with Acular and Voltaren. Severe adverse events might have been more likely to occur at lower doses and in routine postoperative settings with generic diclofenac.

The basic principles of uncertain information fusion. An organised review of merging rules in different representation frameworks.

We propose and advocate basic principles for the fusion of incomplete or uncertain information items, that should apply regardless of the formalism adopted for representing pieces of information coming from several sources. This formalism can be based on sets, logic, partial orders, possibility theory, belief functions or imprecise probabilities. We propose a general notion of information item representing incomplete or uncertain information about the values of an entity of interest. It is supposed to rank such values in terms of relative plausibility, and explicitly point out impossible values. Basic issues affecting the results of the fusion process, such as relative information content and consistency of information items, as well as their mutual consistency, are discussed. For each representation setting, we present fusion rules that obey our principles, and compare them to postulates specific to the representation proposed in the past. In the crudest (Boolean) representation setting (using a set of possible values), we show that the understanding of the set in terms of most plausible values, or in terms of non-impossible ones matters for choosing a relevant fusion rule. Especially, in the latter case our principles justify the method of maximal consistent subsets, while the former is related to the fusion of logical bases. Then we consider several formal settings for incomplete or uncertain information items, where our postulates are instantiated: plausibility orderings, qualitative and quantitative possibility distributions, belief functions and convex sets of probabilities. The aim of this paper is to provide a unified picture of fusion rules across various uncertainty representation settings.