Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Pharmacokinetic Drug Interactions with Gastrointestinal Motility Modifying Agents

Abstract: Drugs may affect gastrointestinal motility and, therefore, absorption of other concomitantly administered drugs. Gastrointestinal prokinetic agents increase the rate of gastric emptying and also upper intestinal motility. These effects would be expected to increase the initial rate of absorption of orally administered drugs, but reduce total bioavailability of the agents. Metoclopramide has been shown to increase the rate of absorption of several classes of drug, reflected by reduced time taken to achieve maximal plasma concentration (tmax) and increased maximal plasma concentration (Cmax). However, the effect of these agents on the area under the plasma concentration-time curve from zero to infinity (AUC0-∞), when measured, is not consistent. Cisapride and domperidone appear to have similar effects, but there are relatively less data available regarding these products. Opioids may delay gastric emptying considerably, an effect which will often have significant clinical and therapeutic implications. Most of the data confirming this observation concern oral analgesics, but the effect should be considered when prescribing any oral medication. Drugs with anticholinergic or sympathomimetic activity are likely to have a similar effect and this is confirmed, in the main, by the limited data available. Although many effects reported in the literature are of limited clinical importance, they may be significant when prescribing a drug with a narrow therapeutic index, especially if it is absorbed poorly.

Carbon dioxide reactivity of the cerebral circulation in extremely premature infants: effects of postnatal age and indomethacin.

Abstract: Little is known about the vasoactivity of cerebral arterioles in extremely premature infants. We have assessed the effects of a small rise in PaCO2 of 1 kPa (7.5 mm Hg) on cerebral blood flow velocity measured by duplex Doppler ultrasound. Nineteen mechanically ventilated infants of 33 wk gestational age or less in whom direct arterial blood pressure monitoring was available, were studied on 45 occasions. There was a close relationship between increasing PaCO2 and increasing cerebral blood flow velocity (p < 0.005) but on seven of 45 occasions the cerebral blood flow velocity fell with rising PaCO2. There was a 44% (median value) rise in cerebral blood flow velocity per 1 kPa rise in PaCO2 (5.9%/l mm Hg) in 21 infants tested within 24 h of birth and this increased to a 53% (median value) rise (7%/l mm Hg) in 20 infants tested after 24 h (p < 0.001). Eleven infants had paired studies, the first within 24 h and a second at a median age of 48 h. There was a statistically significant increase in percentage reactivity when the later group was compared to those tested within 24 h (p < 0.001). Carbon dioxide reactivity was also assessed before and after indomethacin infusion (0.2 mg/kg) on four occasions and there was a reduction in reactivity from a median value of 144 to 49.5%, 10 min after indomethacin. The extremely immature, ill infant is less sensitive to a small change in PaCO2 within 24 h of birth and after indomethacin infusion. We speculate that this may be related to a state of relative arteriolar vasoconstriction compared with infants 24 h or more after birth and those not influenced by the vasoconstrictor properties of indomethacin.

Total Knee Arthroplasty for Osteoarthritis in Patients Less Than Fifty-Five Years of Age: A Systematic Review

Abstract: Background The proportion of younger patients undergoing total knee arthroplasty (TKA) is increasing and predictions state that the Methods The search identified 980 studies for title and abstract review. Forty-three full texts were then assessed. Thirteen studies underwent quality assessment and data extraction. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed throughout. Outcomes extracted included pre-operative and post-operative functional scores, range of motion, and patient satisfaction. Clinical complications and survival were also recorded. Results Across 13 studies we were able to demonstrate 54-point improvement in clinical Knee Society Score and a 46-point improvement on functional Knee Society Score. A 2.9° improvement in range of motion was found at final follow-up. Satisfaction rate was 85.5%. Cumulative percentage all-cause revision rate was 5.4% across 1283 TKAs at a mean 10.8 years of follow-up. Ten-year survival, for aseptic loosening alone, was 98.2%. Conclusion TKA is an excellent treatment option for the young osteoarthritic knee with a >50% improvement in functional knee scores. Satisfaction is high and the revision rate remains 0.5% per year.