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Biomedical subjects

J Seaton

Publications and source records attributed to J Seaton.

14 recordsLinked to original sources

Impact of introducing guidelines on anticoagulant reversal.

The production of clinical guidelines has become an accepted and lauded part of modern medicine. It is also widely perceived that these guidelines provide some sort of panacea for the problems that medicine faces. Our experience suggests otherwise. Triggered by on going anecdotal evidence of poor practice, we reviewed the effect on practice of a recently introduced local guideline on the management of major bleeding in patients on warfarin. Comparing 34 patients treated before and 48 patients after the introduction of the guideline, we found no significant improvement in prothrombin complex concentrate dosing or administration of vitamin K. The only improvement witnessed was in early assessment of the effect of the intervention on coagulation which improved from 10 to 35% of cases. Of major concern, in 10% of cases, there was no documentation to confirm or refute that prothrombin complex concentrate (PCC), which had been issued, had actually been administered to the patient. The production and widespread dissemination of this local guideline did not achieve significant improvement in clinical practice. Possible reasons for failure to adhere to the guideline are discussed.

Anticoagulants↗

The treatment of selected fractures of the humeral shaft with the True-Flex nail.

The True-Flex nail was used in 23 selected non-pathological and eight pathological fractures/lesions of the humeral shaft. The overall fracture union rate was 69.5 per cent and the patients achieved a good range of movement of the shoulder and elbow. Nailing did not lead to union of established non-unions or fractures which were previously treated unsuccessfully by surgery despite bone grafting. All patients with pathological fractures/lesions regained good function of the arm and a good range of movement of the shoulder and the elbow. In one case the nail migrated proximally and impinged on the rotator cuff. This was revised. No other technical difficulties or complications were seen. The True-Flex nail is useful in the treatment of difficult and relatively recent humeral shaft fractures. Established non-unions or cases where previous surgery has failed should be treated by alternative methods.

Adult↗

The association between PGE2 activity and mucosal permeability in proximal small bowel.

Little is known about the ontogeny of cyclooxygenase activity and synthesis of prostaglandins in the developing gastrointestinal tract. We tested the hypothesis that an age-related increase in cyclooxygenase as reflected in production of PGE2 in the proximal small bowel (PSB) is associated with the maturation of the mucosal barrier as determined by 51Cr-EDTA permeability. Cyclooxygenase activity in PSB of rats at 10, 22, 36, and 63 (adult) days of age was determined by the generation of PGE2 using specific radioimmunoassay. Systemic 51Cr-EDTA clearance into the lumen was used to assess mucosal barrier function in PSB in 10- to 12-day-old and adult rats. Prostaglandin E2 generation rose significantly from 24.8 +/- 0.4 pg/mg/min in 10-day-old rats to 125.0 +/- 7.8 in adult rats. The 51Cr-EDTA clearance decreased significantly from 5.08 +/- 0.90 ml/min/100 g in 10- to 12-day-old rats to 0.43 +/- 0.18 ml/min/100 g in adult rats. To assess the possible role of endogenous PGE2 in directly mediating these observed changes in the mucosal permeability, a group of adult rats chronically received indomethacin (2.5 mg/kg/day) over a 3-day period, while another group of vehicle-treated rats served as controls. The 51Cr-EDTA clearance of the indomethacin-treated rats was significantly higher than the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Localization of central prostaglandin E2 antisecretory effects.

Intracerebroventricular prostaglandin E2 (PGE2) inhibits stimulated gastric acid secretion; however, the central site of action is unknown. Specific PGE2 binding sites have been localized to the ventromedial hypothalamic nucleus and central amygdala (A). The nuclear accumbens has been shown to play a role in central neurotensin-induced antisecretory effects. These studies tested the hypothesis that microinjections of PGE2 into the ventromedial hypothalamic nucleus, central amygdala, and nuclear accumbens inhibit stimulated gastric acid secretion. The hippocampus served as a cerebral control region. Two days before the experiments, metal cannulas were stereotaxically positioned bilaterally into specific areas of the brain, and metal gastric cannulas were operatively implanted, under nembutal anesthesia, in male 250-g Sprague-Dawley rats. On the experimental day, the rats, fasted for 14 hours, were given saline or PGE2 (0.1-1.0 micrograms in 0.2 microL/side) through the central cannulas 10 minutes before administering pentagastrin (40 micrograms/kg SC). Gastric secretion was measured at 30-minute intervals and expressed as acid output, micromoles per hour. Acid output (mean +/- SE) in control animals was 161 +/- 14 mumol/h. Prostaglandin E2 administration at doses of 0.10, 0.50, and 1.0 micrograms/side (a) into ventromedial hypothalamic nucleus reduced acid output to 53 +/- 11,* 36 +/- 10,* and 27 +/- 11* mumol/h regularly; (b) into NACB reduced acid output to 157 +/- 36, 60 +/- 12,* and 38 +/- 12* mumol/h; and (c) into A reduced acid output to 144 +/- 31, 141 +/- 26, and 90 +/- 19* mumol/h, respectively (*P less than 0.05 by Neuman-Keuls test). Prostaglandin E2 (0.50 micrograms/side) administration into hippocampus had no significant effect on acid output (134 +/- 28 mumol/h). Although central PGE2 administration was associated with hyperthermia, this occurred at lower doses than those required to inhibit acid secretion. Prostaglandin E2 administration into specific brain areas known to have PGE2 receptors, the central amygdala and ventromedial hypothalamic nucleus, and into nuclear accumbens inhibits stimulated gastric acid secretion. These observations suggest that PGE2 may have a physiological role in the central control of gastric acid secretion.

Amygdala↗

Mesolimbic dopamine mediates gastric mucosal protection by central neurotensin.

Bilateral microinjection (1.0 microliter/side) of neurotensin (NT; 0.3, 1.5, and 3.0 micrograms/side) into the nucleus accumbens (NACB) and ventral tegmental area (VTA) but not in substantia nigra and striatum reduced gastric mucosal injury produced by 2 h of cold-water restraint (CWR). The minimal effective dose for NT-induced protection was 10-100 times lower when administered directly into NACB than into the lateral ventricle. These effects were blocked by pretreatment with the dopamine (DA) receptor antagonist, haloperidol (Hal; 0.5 microgram/side) given directly into NACB. Injection of 6-hydroxydopamine into VTA depleted endogenous DA and inhibited gastric mucosal protection against CWR-induced injury afforded by NT pretreatment. NT, given into either VTA and NACB, inhibited pentagastrin-stimulated gastric acid secretion. These results suggest that VTA and NACB, which represent the mesolimbic DA system, are important locations for interaction between NT and DA receptors to produce gastric mucosal protection against CWR-induced injury.

Animals↗

Monoamine oxidase B inhibition reduces gastric mucosal blood flow, basal acid secretion, and cold water restraint-induced gastric mucosal injury in rats.

Inhibition of monoamine oxidase B (MAO B) by selective inhibitors pargyline and L-deprenyl increases dopamine (DA) and norepinephrine (NE) concentrations in nucleus accumbens (NACB) and is associated with reduction in cold water restraint-induced gastric mucosal injury, inhibition of basal gastric acid output, and regional gastric mucosal blood flow. Similar effects were not observed with administration of MAO A inhibitors. These observations suggest that activation of central dopamine and norepinephrine receptors, particularly in NACB, are involved in the control of gastric mucosal function.

Animals↗