Roundness of grains in cellular microstructures.

Many physical systems are composed of polyhedral cells of varying sizes and shapes. These structures are simple in the sense that no more than three faces meet at an edge and no more than four edges meet at a vertex. This means that individual cells can usually be considered as simple, three-dimensional polyhedra. This paper is concerned with determining the distribution of combinatorial types of such polyhedral cells. We introduce the terms fundamental and vertex-truncated types and apply these concepts to the grain growth microstructure as a testing ground. For these microstructures, we demonstrate that most grains are of particular fundamental types, whereas the frequency of vertex-truncated types decreases exponentially with the number of truncations. This can be explained by the evolutionary process through which grain growth structures are formed and in which energetically unfavorable surfaces are quickly eliminated. Furthermore, we observe that these grain types are "round" in a combinatorial sense: there are no "short" separating cycles that partition the polyhedra into two parts of similar sizes. A particular microstructure derived from the Poisson-Voronoi initial condition is identified as containing an unusually large proportion of round grains. This microstructure has an average of 14.036 faces per grain and is conjectured to be more resistant to topological change than the steady-state grain growth microstructure.

Topological similarity of random cell complexes and applications.

Although random cell complexes occur throughout the physical sciences, there does not appear to be a standard way to quantify their statistical similarities and differences. The various proposals in the literature are usually motivated by the analysis of particular physical systems and do not necessarily apply to general situations. The central concepts in this paper-the swatch and the cloth-provide a description of the local topology of a cell complex that is general (any physical system that can be represented as a cell complex is admissible) and complete (any statistical question about the local topology can be answered from the cloth). Furthermore, this approach allows a distance to be defined that measures the similarity of the local topology of two cell complexes. The distance is used to identify a steady state of a model grain boundary network, quantify the approach to this steady state, and show that the steady state is independent of the initial conditions. The same distance is then employed to show that the long-term properties in simulations of a specific model of a dislocation network do not depend on the implementation of dislocation intersections.

Statistical topology of cellular networks in two and three dimensions.

Cellular networks may be found in a variety of natural contexts, from soap foams to biological tissues to grain boundaries in a polycrystal, and the characterization of these structures is therefore a subject of interest to a range of disciplines. An approach to describe the topology of a cellular network in two and three dimensions is presented. This allows for the quantification of a variety of features of the cellular network, including a quantification of topological disorder and a robust measure of the statistical similarity or difference of a set of structures. The results of this analysis are presented for numerous simulated systems including the Poisson-Voronoi and the steady-state grain growth structures in two and three dimensions.

Anaesthetist's responses to patients' self-reported drug allergies.

BACKGROUND: Patients with drug allergies are commonplace in anaesthetic practice. We investigated the incidence and nature of drug 'allergies' reported by surgical patients attending a hospital pre-admission clinic, and went on to ascertain to what degree drug allergies recorded in the records influenced drug prescribing during the patients' hospital stay and determine whether any adverse events occurred in relation to drug prescribing in this population. METHODS: Patients attending for anaesthetic assessment at a Pre-Admission Clinic over a 30 week period were questioned concerning drug allergies. Medical records of these patients were then examined after their hospitalization to assess medications prescribed during that period. RESULTS: Of 1260 patients attending the Pre-admission clinic during the study period 420 (33.4%) claimed to have a total of 644 individual drug 'allergies'. The most common agents implicated were antibiotics (n=272), opioid analgesics (n=118) and NSAIDs (n=62); the most common form of these reactions were dermatological (n=254) and nausea and vomiting (n=124). There were 41 self-reports specifically of anaphylaxis and a further 61 where there was significant respiratory system involvement. CONCLUSIONS: The majority of the self-reported allergies were in fact simply accepted adverse effects of the drugs concerned. The patients' reported drug 'allergy' history was generally well respected by anaesthetists and other medical staff. There were 13 incidents, mainly involving morphine, where patients were given a drug to which they had claimed a specific allergy. There were 101 incidents in 89 patients where drugs of the same pharmacological group as that of their allergic drug were used. There were no untoward reactions in 84 patients who had claimed a prior adverse reaction to penicillin who were given cephalosporins. There were no sequelae from any other events. While anaesthetists generally respected patients self-reported 'allergies', more attention needs to be paid to the accurate recording of patients' events and a clear distinction should be made both in medical records and to the patient between true drug allergy and simple adverse drug reactions.

Electroconvulsive therapy in patients with cardiac pacemakers.

There are few contraindications to electroconvulsive therapy and it is generally well tolerated. However, electroconvulsive therapy in elderly patients with cardiac pacemakers in situ theoretically presents an increased risk of complications. We undertook a retrospective audit of all patients who received anaesthesia for electroconvulsive therapy between January 1999 and September 2005. There were ten patients who had cardiac pacemakers in situ. They underwent a total of 147 electroconvulsive therapy treatments. In 146 out of the 147 treatments, the anaesthesia proceeded uneventfully. The findings suggest that provision of anaesthesia and electroconvulsive therapy in patients with cardiac pacemakers, including rate-responsive pacemakers, is a safe undertaking, with no extra precautions being needed except for routine ECG monitoring.

Pharmaceutics for the anaesthetist.

Pharmaceutics is that branch of science concerned with the manufacture and formulation of pharmaceutical products, and is a subject almost exclusively in the domain of pharmacists and those concerned with pharmaceutical manufacture. However, there are some aspects of pharmaceutics that are of particular importance to the anaesthetist, such as the pharmacology of the various preservatives, antimicrobials and other additives found in anaesthetic products, and an understanding of basic processes such as emulsification and lyophylisation. This review aims to survey those areas.

The pharmacological basis of contemporary pain management.

Pain management has become an increasingly well researched area in medicine over recent years, and there have been advances in a number of areas. While opioids remain an integral part of pain-management strategies, there is now an emphasis on the use of adjuvant drugs, such as paracetamol and anti-inflammatory agents, which through physiological or pharmacological synergism, both enhance pain control and reduce opioid use. The management of neuropathic pain continues to be a challenge. Anti-epileptics and antidepressants, together with clonidine and ketamine, provide the foundations for treatment. Another area of interest has been the widespread use of patient-controlled analgesia and the administration of some drugs, especially opioids, by means other than traditional oral and parenteral routes. The number of new drugs that have reached the stage of clinical trials has been small, yet they offer exciting possibilities. The epibatidine analogue ABT-594 and zinconitide both offer novel approaches to the management of neuropathic pain states, while selective cyclo-oxygenase-2 inhibitors and nitroaspirins may see advances in the management of nociceptive pain states.

Halothane attenuates myogenicity in the rabbit ear artery.

UNLABELLED: The aim of this study was to test the hypothesis that halothane interferes with the myogenic response to an increase in intraluminal pressure. Myogenic responsiveness refers to the intrinsic property of vascular smooth muscle to dilate and then constrict in response to an increase in intraluminal pressure, in an attempt to maintain vessel diameter. Vessel segments taken from the rabbit central ear artery were cannulated, pressurized to 60 mm Hg, and perfused with and suspended in Krebs solution. After exposure to extraluminal l-norepinephrine, vessels contracted to an initial diameter (Di) and were subjected to intraluminal pressure increases to 100 mm Hg. Myogenic reactivity was assessed by measurement of the extent of dilatation after the pressure increase from Di to a maximal diameter (Dm) and then the constriction and recovery (against the pressure increase) to a final (Df) diameter. Myogenicity was further assessed by determining the rate of return of the vessel diameter (angle of recovery) and vessel recovery (defined as Dm - Df/Dm - Di) and expressed as a percentage. Myogenicity was determined before and after exposure to halothane in concentrations of between 1-5%. Halothane significantly attenuated the myogenic response at all concentrations studied. The effect of halothane was maximal at a concentration of 5% where there was virtual abolition of the myogenic response with recovery assessed at 6+/-2.7% (SEM), compared with control (98+/-2.5%, P < 0.05). The angle of recovery was likewise attenuated. These data suggest that halothane, in a dose-dependent manner, attenuates myogenicity in the isolated rabbit ear artery preparation. IMPLICATIONS: Blood pressure is controlled partially by the myogenic response. This refers to the capacity of arteries to dilate and then constrict in response to pressure increase. Using arteries from rabbits, we have shown that administration of halothane reduces or abolishes this response. This observation may be a contributing factor to hypotension caused by halothane.

Propofol attenuates the myogenic response of vascular smooth muscle.

The myogenic response is the tendency of certain vessels, most notably small arteries and arterioles, to constrict in response to an increase in intravascular pressure. The effects of propofol on the myogenic response of the isolated pressurized rabbit ear artery were studied in segments preconstricted either with norepinephrine or 5-hydroxytryptamine and subjected to pressure increases from 60 to 100 mm Hg applied either rapidly (jumps over 500 ms) or slowly (ramps over 120 s). In the control experiments the preconstricted vessels initially dilated, then rapidly returned toward their initial diameter. In response to pressure ramps, vessels slowly dilated, but closely retained their resting diameter. Administration of propofol (1.6 x 10(-4) to 1.6 x 10(-3) M) resulted in dilation of the constricted vessels. With pressure jumps vessels had a reduced capacity to recover their initial diameters, and with pressure ramps vessels dilated to greater diameters. When the concentration of vasoconstrictor was increased to antagonize the propofol-induced dilation the myogenicity was not restored. This attenuation of myogenicity, distinct from the drug's vasodilator effect may represent a further mechanism by which anesthetic agents can affect cardiovascular function.

Intraarterial propofol is not directly toxic to vascular endothelium.

To determine if accidental intraarterial injection of propofol results in vascular damage, the effect of bolus administration of propofol on vascular smooth muscle and the endothelium was investigated using the isolated rabbit ear artery. Ear artery segments, removed from urethane anesthetized rabbits, were perfused with Krebs solution (1 ml.min-1) and pressurized to 60 mmHg before being constricted with extraluminal norepinephrine (1.8-4.2 x 10(-6) M). The external diameter of the vessel was measured by an array of light-dependent diodes. Functional responsiveness was determined by the degree of constriction to norepinephrine and the subsequent dilatation of the artery to intraluminal acetylcholine (2 x 10(-6) M) and glyceryl trinitrate (2 x 10(-6) M), and by the myogenic reactivity to a pressure increase from 60 to 100 mmHg. These responses were measured before and after perfusion with 1% propofol for 120 s. Administration of propofol did not result in any vasoactivity nor did it increase the sensitivity to norepinephrine. Vessels maintained their capacity to dilate to both agents, while the myogenic activity was unaffected. Histologic examination of the propofol exposed vessels showed no changes to smooth muscle structure, and the endothelial layer remained intact.

Measurement of gastric secretion as a student teaching exercise.

Teaching gastrointestinal physiology to preclinical medical students presents problems in finding suitable practical exercises to demonstrate the physiology of gastric acid secretion. In our course, students measure their own gastric secretory activity by the use of nasogastric tubes. Gastric secretion can be stimulated by insulin-induced hypoglycemia or by pentagastrin, a synthetic gastrin analogue. The time course of the secretory responses, i.e., volume, acid output, and pH, are followed by collecting control and poststimulatory secretions into 15-min samples. The effect of antiulcer drugs, such as cimetidine, can be easily studied in such experiments. The results of these experiments are very reproducible, allowing year-to-year comparisons of treatments. Examples of results of various experimental protocols are shown. We believe this to be a useful class exercise not only because of the excellent results it yields but because of the experience and insights it produces.

Intra-arterial thiopentone is directly toxic to vascular endothelium.

Ear artery segments removed from urethane-anaesthetized rabbits were mounted, perfused with Krebs solution, and pressurized before constriction with extraluminal noradrenaline. Vessel diameter was measured using a diode array mounted above the artery. After the degree of dilatation in response to intraluminal acetylcholine and glyceryl trinitrate was measured, vessels were perfused for 120 s with solutions of either 2.5-10% thiopentone or isotonic sodium carbonate in saline of matched pH. Administration of thiopentone solutions in all concentrations resulted in destruction of endothelial cells. The dilatation of vessels to glyceryl trinitrate and their myogenic reactivity was unaltered. Isotonic solutions of sodium carbonate (pH 10.6) had no effect on either endothelial cell function or direct vasodilatation. These data show that administration of thiopentone removes arterial endothelial cells, while vascular smooth muscle function is essentially unaltered.

Myogenic response of isolated pressurized rabbit ear artery is independent of endothelium.

Central ear artery segments, removed from urethan-anesthetized rabbits, were used to assess whether distention activation was dependent on intact and functional endothelium (ENDO). Changes in external arterial diameter were measured with light-dependent diode array mounted above the vessel. After constriction with norepinephrine, slow increases in pressure from 60 to 80 or 100 mmHg performed over 120 s (pressure ramps) failed to initiate distention, but initial diameter was maintained. Rapidly applied (500 ms) pressure increases (pressure jumps) across same pressure ranges gave rise to initial distention and a myogenic response resulting in a return to almost initial diameter while new pressure was maintained for 120 s. Myogenic activity was measured from extent of recovery of vessel to its initial diameter during maintenance of pressure jumps or ramps. Rapid jumps and slow ramps were performed in presence of an intact ENDO and again after ENDO was removed by passage of intraluminal gas. With pressure jumps 60 to 80 mmHg, degree of recovery in ENDO-denuded vessels was 91.9% compared with 89.5% in ENDO intact vessels. For pressure jumps 60 to 100 mmHg, extent of recovery was 87.4 and 89.6%. During application of pressure ramps of 20 or 40 mmHg, vessel diameter did not increase by greater than 5%. There are no significant differences in these data, and we conclude that myogenic response in rabbit ear artery is mediated independently of endothelial-derived factors, irrespective of whether myogenic activation is induced by pressure jumps or ramps.