SummarySodium hyaluronate solutions have been advocated in the management of a variety of dry-eye states. By virtue of their non-Newtonian rheological properties, for mulations exhibiting high zero-shear viscosities may be used as an artificial tear with the expectation of prolonged precorneal residence times and improved tolerance.Quantitative gamma scintigraphy was used to evaluate the residence times of 0.2% and 0.3% sodium hyaluronate solutions and a polymer-free solution of buffered saline in 12 patients with keratoconjunctivitis sicca and a group of six normal volun teers. Using several indices of residence time, mean values for the sodium hyalur. onate solutions were significantly longer than those for buffered saline. Parallel changes in tear film thickness were also demonstrated using a technique based on laser interferometry.Although a variety of therapeutic strategies can be utilised in the management of dry-eye disorders,1.2 the basis of therapy remains the artificial tear. The principal limitation of currently available tear substitutes is the short duration of symptom control experienced by some patients. A number of approaches have, therefore, been adopted to prolong the time they remain in contact with the ocular surface including the use of high viscosity formula tions,"· slow-release artificial tears' and occlusion of the lacrimal puncta.1> However, none of these methods have met with uniform success.Polymer solutions formulated at high vis cosity have longer residence times, 7 .H but are poorly tolerated because of transmitted 'University of Oxford, Department of Ophthalmology.shearing forces associated with blinking and rapid eye movements. It is in this respect that formulations of polymers that display non Newtonian or pseudoplastic properties offer a potential therapeutic advantage over conven tional artificial tears. At concentrations of 0. 2% and 0.3% , sodium hyaluronate solu tions exhibit high static. or zero-shear, vis cosities but undergo dramatic reduction in viscosity with increasing shear rate� (Fig. 1), thereby offering significantly less resistance to the movement of the lid over the globe than viscous Newtonian formulations. It is the expectation of prolonged residence time asso ciated with high zero-shear viscosities, and of patient acceptance owing to its shear-thinning behaviour, that has lead to the investigation of

Test meals are invariably used in the B3C-urea breath test (UBT) but their effect on the intragastric distribution and gastric residence time of urea given in the test is unknown. The site of Helicobacter pyloni urease measured in the test is unknown and whether the test measures total or regional gastric urease is uncertain. This study reports the results of paired UBTs with simultaneous gastric distribution studies, one with and one without a fatty test meal, two weeks apart on seven H pyloni infected subjects. The test meal did not affect UBT results at 10 minutes, but increased values at 30 minutes and thereafter. The amount of scintigraphic label in the antrum at 10 minutes was also unaffected by the meal but increased at 30 minutes and thereafter, whereas the amount in the body/fundus was greatly increased both at 10 minutes and throughout the test. There was considerable variation in intragastric distribution of urea between subjects, both with and without the test meal. This study shows that a test meal profoundly affects intragastric distribution of urea solution in the UBT, and increases UBT values at 30 minutes and later. Variability between subjects, however, means that accurate measurement of total or regional gastric urease is probably unrealistic.

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The choice of local anaesthetic is influenced by several factors; it must provide effective anaesthesia and analgesia for the duration of the procedure and meet the expectations for post-operative pain management. Of primary concern is patient safety. Bupivacaine, currently the most widely used long acting local anaesthetic agent in both surgery and obstetrics, generally has a good safety record but its use has resulted in fatal cardiotoxicity, usually after accidental intravascular injection. Hence, for several years there has been a need for a long acting local anaesthetic, similar to bupivacaine, but with an improved cardiovascular safety profile. Levobupivacaine, the single enantiomer version of bupivacaine, offers a new long acting local anaesthetic, clinically equivalent in anaesthetic potency to bupivacaine, but with a reduced toxicity profile. Preclinical studies, from in vitro in single ion channels to whole large animal models, have unquestionably demonstrated that levobupivacaine is significantly less CNS toxic and cardiotoxic than bupivacaine. Cardiotoxicity is less easy to study in man, as the clinical signs are not usually seen until the CNS toxicity is marked, and well beyond that which is tolerable to volunteers or patients. Nevertheless, levobupivacaine has been shown to have less effect on myocardial contractility and QTc prolongation, early signs of cardiotoxicity, than bupivacaine in healthy subjects. In clinical use levobupivacaine has been shown to be equally efficacious as bupivacaine at comparable doses and concentrations, and has been found to produce similar anaesthetic characteristics (onset, duration and density of block). As levobupivacaine now becomes commercially available, the database available with which to make efficacy and safety comparisons with other local anaesthetics will increase, and the true value of this new long acting local anaesthetic should become even more apparent.

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