Collectively Encoded Rydberg Qubit.

We demonstrate a collectively encoded qubit based on a single Rydberg excitation stored in an ensemble of N entangled atoms. Qubit rotations are performed by applying microwave fields that drive excitations between Rydberg states. Coherent readout is performed by mapping the excitation into a single photon. Ramsey interferometry is used to probe the coherence of the qubit, as well as to test the robustness to external perturbations. We show that qubit coherence is preserved even as we lose atoms from the polariton mode, preserving Ramsey fringe visibility. We show that dephasing due to electric field noise scales as the fourth power of field amplitude. These results show that robust quantum information processing can be achieved via collective encoding using Rydberg polaritons, and hence this system could provide an attractive alternative coding strategy for quantum computation and networking.

Single-photon stored-light Ramsey interferometry using Rydberg polaritons.

We demonstrate a single-photon stored-light interferometer, where a photon is stored in a laser-cooled atomic ensemble in the form of a Rydberg polariton with a spatial extent of 10×1×1µm3. The photon is subject to a Ramsey sequence, i.e., "split" into a superposition of two paths. After a delay of up to 450 ns, the two paths are recombined to give an output dependent on their relative phase. The superposition time of 450 ns is equivalent to a free-space propagation distance of 135 m. We show that the interferometer fringes are sensitive to external fields and suggest that stored-light interferometry could be useful for localized sensing applications.

Multi-targeted directed ligands for Alzheimer's disease: design of novel lead coumarin conjugates.

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by central nervous system insults with progressive cognitive (memory, attention) and non-cognitive (anxiety, depression) impairments. Pathophysiological events affect predominantly cholinergic neuronal loss and dysfunctions of the dopaminergic system. The aim of the current study was to design multi-targeted directed lead structures based on the coumarin scaffold with inhibitory properties at two key enzymes in disease relevant systems, i.e. acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Conventional and microwave synthetic methods were utilized to synthesize coumarin scaffold-based novel morpholino, piperidino, thiophene and erucic acid conjugates. Biological assays indicated that the coumarin-morpholine ether conjugate BPR 10 was the most potent hMAO-B inhibitor. The coumarin-piperidine conjugates BPR 13 and BPR 12 were the most potent inhibitors of eeAChE at 100 µM and 1 µM, respectively. Molecular modelling studies were conducted with Accelrys® Discovery Studio® V3.1.1 utilising the published hMAO-B (2V61) and hAChE (4EY7) crystal structures. Compound BPR 10 occupies both the entrance and substrate cavities of the active site of MAO-B. BPR 13 resides in both the peripheral anionic site (PAS) and the catalytic anionic site (CAS) of hAChE. This study demonstrated that the coumarin scaffold serves as a promising pharmacophore for MTDLs design.

Surgical smoke - a health hazard in the operating theatre: a study to quantify exposure and a survey of the use of smoke extractor systems in UK plastic surgery units.

Surgeons and operating theatre personnel are routinely exposed to the surgical smoke plume generated through thermal tissue destruction. This represents a significant chemical and biological hazard and has been shown to be as mutagenic as cigarette smoke. It has previously been reported that ablation of 1 g of tissue produces a smoke plume with an equivalent mutagenicity to six unfiltered cigarettes. We studied six human and 78 porcine tissue samples to find the mass of tissue ablated during 5 min of monopolar diathermy. The total daily duration of diathermy use in a plastic surgery theatre was electronically recorded over a two-month period. On average the smoke produced daily was equivalent to 27-30 cigarettes. Our survey of smoke extractor use in UK plastic surgery units revealed that only 66% of units had these devices available. The Health and Safety Executive recommend specialist smoke extractor use, however they are not universally utilised. Surgical smoke inhalation is an occupational hazard in the operating department. Our study provides data to quantify this exposure. We hope this evidence can be used together with current legislation to make the use of surgical smoke extractors mandatory to protect all personnel in the operating theatre.

Randomized controlled trial of fibrin sealant to reduce postoperative drainage following elective lymph node dissection.

BACKGROUND: Excessive postoperative drainage following groin and axillary lymphadenectomy may be associated with a prolonged hospital stay and an increased complication rate. The use of fibrin sealant before wound closure may reduce postoperative wound drainage. METHODS: Consecutive patients undergoing elective groin or axillary lymphadenectomy were randomized to standard wound closure or to having fibrin sealant sprayed on to the wound bed before closure. Postoperative wound drainage, duration of drainage and complications were recorded, as were locoregional recurrence, distant metastasis and mortality. RESULTS: A total of 74 patients requiring 38 groin and 36 axillary dissections were randomized. The median postoperative wound drainage volume for the groin dissection cohort was 762 (range 25-3255) ml in the control group and 892 (265-2895) ml in the treatment group (P = 0·704). Drainage volumes in the axillary cohort were 590 (230-9605) and 565 (30-1835) ml in the control and treatment groups respectively (P = 0·217). There was no difference in the duration of drainage or postoperative complication rate between the treatment groups in both the axillary and groin cohorts. Local recurrence, distant metastasis and mortality rates did not differ between the treatment groups. CONCLUSION: There was no advantage in using fibrin sealant during elective lymphadenectomy in terms of reducing drainage output or postoperative complication rate.

The pharmacological effects of ozone on isolated guinea pig tracheal preparations.

Ozone is a potent oxidizing agent with a variety of potential uses, including its antimicrobial and deodorising properties. The recent increased use of ozone led to questions regarding its safety in humans. This study specifically focussed on the in vitro effect of ozone on isolated guinea pig tracheal tissue as well as its effect on the isolated trachea in the presence of various drugs with well-known effects, including methacholine and isoproterenol. The results found in this study identified two direct effects on the isolated trachea due to ozone exposure: (1) a definite contraction of the isolated trachea immediately after exposure to ozone, and (2) a clearly visible and significant hyper responsiveness of the isolated trachea to irritants, e.g. methacholine. Although ozone has a negative effect on the trachea, it was concluded that ozone has no adverse effect on muscarinic receptors. We found that ozone has a significant desensitizing effect on the pharmacological response of beta sympathomimetics (isoproterenol), while isoproterenol itself has a relaxing effect on the ozone-induced contraction of the isolated trachea. Observations in this in vitro study further emphasised that ozone does have a negative effect on respiratory health. It is underlined that the inhalation of ozone should be avoided by workers who are often in contact with the gas, and especially by those with existing airway diseases. An apparent EC(50) value of ozone on the trachea was established by two different methods as 5.71 and 9.78 x 10(-3 )M, respectively.

In vivo measurements of the cerebral perfusion and cardiovascular effects of the novel guanidine ME10092 in the non-human primate, Papio ursinus.

The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the first time pharmacological effects of ME10092 in the primate, viz. the Cape baboon Papio ursinus. The effects of ME10092 (1 and 2 mg/kg doses) on the cerebral blood flow, heart rates and the systolic and diastolic blood pressure were investigated after intravenous injection to the baboon under anaesthesia. The cerebral perfusion effects of ME10092 were assessed using Single Photon Emission Computed Tomography according to the split-dose approach and 99mTc-hexamethyl-propylene amine oxime as brain perfusion tracer. The observation that the recovery times from the anaesthesia were unacceptably prolonged excluded doses beyond 2 mg/kg. The data indicate that no cerebral perfusion changes were induced at both the 1 and 2 mg/kg doses of ME10092. Both these doses of ME10092 showed blood pressure and heart rate effects, with the latter being more significant. Decreases in heart rate were seen directly after ME10092 administration reaching levels of about 20% for the 2 mg/kg dose and about 15% for the 1 mg/kg dose at around 6 min post drug administration. A transient decrease in both systolic and diastolic blood pressure was observed for the higher dose. The blood pressure data further suggest an attenuation of the anaesthesia induced increase in pressure usually present in non-intervention studies. ME10092 clearly exhibits mycocardial effects in the non-human primate, similar to the effects previously observed in the ischaemia-reperfusion rat model, where ME10092 showed strong protection.

Hirudo Medicinalis and the plastic surgeon.

Medicinal leech therapy is an ancient craft that dates back to ancient Egypt and the beginnings of civilisation. The popularity of Hirudo Medicinalis has varied throughout history, reaching such a peak in Europe in the early 19th century that supplies were exhausted. During the latter half of the 19th century, their use fell out of favour, as they did not fit in with the emerging concepts of modern medicine. Leeches have enjoyed a renaissance in the world of reconstructive microsurgery during recent years, and their first reported use in alleviating venous engorgement following flap surgery was reported in this journal [M Derganc, F Zdravic, Venous congestion of flaps treated by application of leeches, Br J Plast Surg 13 (1960) 187]. Contemporary plastic and reconstructive surgeons in units throughout the United Kingdom and Ireland continue to use leeches to aid salvage of failing flaps. We carried out a survey of all 62 plastic surgery units in the United Kingdom and the Republic of Ireland to assess the current extent of use, and to investigate current practice. We have shown that the majority of plastic surgery units in the UK and Ireland use leeches post-operatively and that the average number of patients requiring leech therapy was 10 cases per unit per year. Almost all units use antibiotic prophylaxis, but the type of antibiotic and combination used is variable. We outline current practice and suggest a protocol for the use of leeches. Whilst the use of leeches is widespread, the plastic surgery community has progressed little in defining indications for their use or in achieving an accepted protocol for their application in units throughout the UK and Ireland.

Recent advances in drug action and therapeutics: relevance of novel concepts in G-protein-coupled receptor and signal transduction pharmacology.

PROBLEM STATEMENT: During especially the past two decades many discoveries in biological sciences, and in particular at the molecular and genetic level, have greatly impacted on our knowledge and understanding of drug action and have helped to develop new drugs and therapeutic strategies. Furthermore, many exciting new drugs acting via novel pharmacological mechanisms are expected to be in clinical use in the not too distant future. SCOPE AND CONTENTS OF REVIEW: In this educational review, these concepts are explained and their relevance illustrated by examples of drugs used commonly in the clinical setting, with special reference to the pharmacology of G-protein-coupled receptors. The review also addresses the basic theoretical concepts of full and partial agonism, neutral antagonism, inverse agonism and protean and ligand-selective agonism, and the relevance of these concepts in current rational drug therapy. Moreover, the mechanisms whereby receptor signalling (and eventually response to drugs) is fine-tuned, such as receptor promiscuity, agonist-directed trafficking of receptor signalling, receptor trafficking, receptor 'cross-talk' and regulators of G-protein signalling (RGSs) are discussed, from theory to proposed therapeutic implications. CONCLUSIONS: It is concluded that the understanding of molecular receptor and signal transduction pharmacology enables clinicians to improve their effective implementation of current and future pharmacotherapy, ultimately enhancing the quality of life of their patients.

Effective management of the airway in the Pierre Robin syndrome using a modified nasopharyngeal tube and pulse oximetry.

Pierre Robin syndrome is a rare condition, first described by the French stomatologist, Pierre Robin in 1923. The severity of the syndrome varies widely, and associated upper airway obstruction is the most difficult problem to overcome. We present a case in which the airway was successfully managed with a modified naso-pharyngeal tube in addition to pulse oximetry. We also present a literature review discussing management of the airway in the Pierre Robin syndrome. The simple technique presented allows earlier patient discharge with home monitoring equipment.

Publication rates for abstracts presented at the British Association of Plastic Surgeons meetings: how do we compare with other specialties?

We present a retrospective study of the publication rates of articles presented to five meetings of the British Association of Plastic Surgeons between 1995 and 1999. The PubMed database (http://www.ncbi.nlm.nih.gov/PubMed/) was searched using the presenter's name and key words from the abstract. Publication rates varied from 23% for the Winter Meeting of 1999 to 54% for the Winter Meeting of 1997. The mean time lag from presentation to publication varied between 13 and 25 months (range: 1-46 months). These results are comparable to those found in some other medical specialties.

A prospective, randomized, double-blind trial of the use of fibrin sealant for face lifts.

Fibrin sealant imitates the final phase of the blood coagulation process. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin, which is then cross-linked by factor XIIIa, creating a mechanically stable fibrin network. This fibrin network is thought to reduce the amount of postoperative bleeding by sealing capillary vessels and allowing raw operative surfaces to adhere. The authors conducted a prospective, double-blind, randomized, controlled trial on the use of fibrin sealant in 20 consecutive patients undergoing bilateral face lifts by the same surgeon. Each patient was randomized for the use of fibrin sealant on either the right or the left side with the contralateral side acting as the control. Total drainage was recorded on each side for 24 hours before drains were removed. The age range of the patients in the trial (all of whom were women) was 44 to 70 years (mean, 55). The side treated with fibrin glue had a median drainage of 10 ml and the control side 30 ml. The Wilcoxon signed rank test shows a significant difference in drainage between sides (p = 0.002). The reduction in postoperative drainage could also reduce pain and bruising, increasing patient satisfaction with this procedure. The need for drains may also be obviated.

Tutorial on risk-adjusted P-charts.

Several books are available that describe how to construct control charts. Unfortunately none of these books show how to adjust control charts for the severity of the patients' illness. Without such adjustments control charts not only loose face validity but could lead to wrong conclusions. In this article we provide a step-by-step guide regarding how to control for changes in patients' severity of illness across time periods. We illustrate the use of the approach in examining falls in nursing homes. A control chart was constructed to compare observed falls to the residents' risk of fall measured on admission. Analysis led to conclusions radically different from an unadjusted chart.

Measurement of cerebral perfusion after zolpidem administration in the baboon model.

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.

Discrimination between the functional and biochemical effects of two herbal oxytocics on the rat myometrium.

This study on the rat myometrium is the first report where the effects of herbal extracts used as oxytocics in traditional medicine have been systematically analysed in the same preparation at the level of functional (contractile) and biochemical (second messenger generation) responses. Extracts of Agapanthus africanus and Clivia miniata (used in South African traditional medicine) were compared with other uterotonic agents with regard to their ability to stimulate phosphoinositide metabolism in the rat myometrium and cause accumulation of [3H]inositol phosphates. The maximal contractile response of the isolated rat myometrium in response to stimulation by the herbal extracts and agonists was compared with the maximal contractile response to cumulative addition of acetylcholine. The rank order of intensity of stimulation of [3H]inositol phosphate generation was: oxytocin > Agapanthus > prostaglandin F2alpha(PGF2alpha) > serotonin > acetylcholine > Clivia > ergometrine. This differed from the rank order of maximum contractile response: oxytocin > acetylcholine > PGF2alpha > serotonin approximately Clivia > Agapanthus > ergometrine. Activity was also identified in chemical fractions of the plants and components common to both plants have been identified in the isolated active fractions. These results have identified that the uterotonic activity of Agapanthus is linked to increased turnover of phosphoinositides as a signal transduction mechanism, whereas this appears to play a less significant role in the uterotonic activity of Clivia. This study illustrates the benefits of using the measurement of stimulation of phosphoinositide metabolism as a bioassay in phytomedical research.