Susan L. Elliott

INDOMETHACIN DAMAGE TO RAT GASTRIC MUCOSA IS MARKEDLY DEPENDENT ON LUMINAL pH

1. There is good evidence that acid is a prerequisite for aspirin induced gastric mucosal damage; however, there is inconsistent information available for non‐salicylate NSAID. The present study examines the effect of gastric luminal pH on indomethacin‐induced gastric mucosal damage.

Efficacy of 12 months' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial.

We performed a 12-month, double-blind, randomised, placebo-controlled study to determine the long term effect of misoprostol (600-800 micrograms/d) in the prevention of gastric ulcers and gastroduodenal erosions in 83 arthritis patients on chronic NSAID therapy. Patients underwent endoscopy at 0, 3, 6 and 12 months. At the initial endoscopy, 12 patients had an ulcer (11 gastric), which was healed prior to randomization. Seventy eligible patients reached the 3 month endoscopy. Four (12.5%) of the 32 patients given misoprostol developed a gastric ulcer compared with 11 (28.9%) of the 38 on placebo (p < 0.05, life-table analysis). Six of the 11 patients with an initial gastric ulcer developed a further gastric ulcer, compared to 9 of 58 patients without an initial ulcer (p < 0.05). We conclude that misoprostol decreases the cumulative development of NSAID-induced gastric ulcers. Patients with a previous NSAID-ulcer have a higher risk of further ulceration.

Comparing the academic performance of graduate- and undergraduate-entry medical students

Medical Education 2010 44: 197–204

Gastric mucosal adaptation to diclofenac injury

Adaptation occurs to the gastric injury produced by nonsteroidal antiinflammatory drugs during continued dosing. The aim of this study was to identify characteristics of this phenomenon that might help in the search for underlying mechanisms. The time frame for onset and offset of adaptation of diclofenac (damage assessed planimetrically) was examined in rats. Adaptation to oral diclofenac took three to five days to develop, and persisted for up to five days after the last dose. It was also demonstrable after subcutaneous dosing or when injury was measured by a change in mucosal potential difference. Diclofenac-adapted rats were protected against injury induced by subsequent exposure to ethanol, indomethacin, aspirin, or piroxicam, indicating that adaptation is not specific to injury by the adapting agent. This cross-adaptation was dose-dependent and characterized histologically by a reduction in deep damage. In conclusion, gastric adaptation to diclofenac is mediated by mechanisms that take several days to develop and be lost. The route of administration appears to be unimportant, but the development of both adaptation and cross-adaptation is influenced by dosage size.

In-training assessment – its potential in enhancing clinical teaching

In‐training assessment (ITA) has established its place alongside formative and summative assessment at both the undergraduate and postgraduate level. In this paper the authors aimed to identify those characteristics of ITA that could enhance clinical teaching.

First-year medical students' willingness to participate in peer physical examination.

Background: There is little research on student attitudes toward participating in peer physical examination (PPE). Purpose: This study explored first-year medical students’ attitudes toward PPE and their willingness to participate in PPE before they had experience with PPE as part of their course. Methods: First-year medical students (n = 119) rated their willingness to participate in PPE for 15 body regions, with male or female peers, and when examining or being examined by others. Attitudes toward participating in PPE were also assessed. Results: Low-sensitivity examinations (e.g., hands, head) in PPE were generally accepted by male and female students. Significant variation in willingness across different body regions was, however, evident for male and female students depending on the type of examination and their examination partners gender. Students generally held positive attitudes toward participating in PPE as part of the course. Moreover, students with more positive attitudes provided higher ratings of willingness to participate in PPE for all examination types. Conclusions: Findings suggest high levels of willingness to participate in PPE for low-sensitivity examinations of the kind employed in university teaching contexts. Nonetheless, gender effects appear more complex than previously described, and for some regions of the body, there are subtle preferences for particular examination types, in particular performing examinations, rather than being examined.

An Educational Approach to Improving Healthcare Safety and Quality

Keywords: Competency; education; health professional education; medical school curricula; patient safety

The effect of hypoxia and acidosis on propranolol clearance in the isolated perfused rat liver preparation.

The effect of hypoxia and acidosis on the elimination of an oxidatively metabolized drug, S-propranolol, was examined in the single-pass isolated perfused rat liver (IPRL). The experiments (N = 6) consisted of four consecutive 30 min phases: normal pH (pH 7.4)/normal oxygen delivery, normal pH/hypoxia, hypercapnic acidosis (pH 7.1)/normal oxygenation and hypercapnic acidosis/hypoxia. Hypoxia and acidosis were produced by equilibrating the perfusate with appropriate mixtures of O2, N2 and CO2. With normal oxygen delivery there was no difference in hepatic clearance of propranolol between normal pH and acidosis (9.65 +/- 0.34 and 9.78 +/- 0.11 mL/min, respectively. P < 0.05). During hypoxia, propranolol clearance was impaired to a similar extent under both pH conditions (7.41 +/- 0.97 and 8.06 +/- 0.81 mL/min, respectively, P > 0.05). Therefore, respiratory acidosis does not affect the clearance of propranolol by the IPRL, nor does it influence the sensitivity of propranolol clearance to hypoxia. Neither acidosis nor hypoxia resulted in a significant reduction in bile flow compared with the normal pH/normal oxygen phase and there was no correlation between bile flow and perfusate bicarbonate concentration (P > 0.05).

Repair of Rat Gastric Mucosa (Effect of 16,16-Dimethyl Prostaglandin E2)

Prostaglandins protect the gastric mucosaagainst a variety of injurious agents and may acceleratethe recovery of the gastric mucosa following damage. Inprevious studies prostaglandins were given prior to the injurious agent, so it was not possibleto distinguish their potential effects on acceleratingrepair or reducing initial damage. We have investigatedthe effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) on the repair of thegastric muscosa after injury induced by severalinjurious agents. dmPGE2 was given orally 15min prior to aspirin or sodium salicylate, or 30 minafter aspirin, sodium salicylate, or ethanol. dmPGE2 delivered priorto injury reduced the aspirin-induced fall in mucosalpotential difference (PD), but had no effect on thatinduced by sodium salicylate. dmPGE2administered after ASA injury significantly increased recovery of PD (P <0.05), but did not alter the rate of recovery of PD withother damaging agents. Histological damage was decreasedin rats treated with dmPGE2 after aspirincompared to aspirin-only-treated rats (P < 0.02).Exogenous dmPGE2 protects and restoresgastric mucosal integrity after aspirin damage but hasno effect on the repair of sodium salicylate and ethanolinjured mucosa, suggesting that repair of the gastric mucosaafter aspirin damage is enhanced by dmPGE2due to its ability to prevent ongoing damage, ratherthan directly enhancing repair processes.

SENSITIVITY OF PROPRANOLOL ELIMINATION TO HYPOXIA IN THE ISOLATED PERFUSED RAT LIVER PREPARATION

1. The relationship between the hepatic elimination of propranolol and hepatic oxygen delivery was examined in the single‐pass isolated perfused rat liver preparation. Varying rates of oxygen delivery were produced (1.35–8.10 μmol/min per g liver) by equilibrating the perfusate with O2/N2 mixtures.