Efficacy of a new dual channel laryngeal mask airway, the LMA®Gastro™ Airway, for upper gastrointestinal endoscopy: a prospective observational study.

BACKGROUND: Significant cardiorespiratory events are frequent in patients undergoing gastrointestinal endoscopy. Central to the occurrence of respiratory events is an unsecured airway. This study sought to determine the efficacy of a new laryngeal mask airway, the LMA®GastroTM Airway (Teleflex Medical, Athlone, Ireland), in patients undergoing upper gastrointestinal endoscopy. New design features include a dedicated channel for oesophageal intubation and separate channel with terminal cuff for lung ventilation. METHODS: In a prospective, open label, observational study, 292 ASA physical status classification 1 and 2 patients at low risk of pulmonary aspiration undergoing upper gastrointestinal endoscopy received i.v. propofol anaesthesia and standardized insertion of the LMA®GastroTM Airway. Endoscopy outcomes included insertion success, first attempt success, and ease of endoscope insertion. LMA®GastroTM Airway outcomes included insertion success, first attempt success, ease of insertion, lowest oxygen saturation, airway compromise, laryngospasm, bloodstained device, and sore throat. RESULTS: Per protocol analysis (n=290), the endoscopy success rate amongst the cohort with successful LMA®GastroTM Airway insertion was 99% [95% confidence interval (CI): 98, 100]. LMA®GastroTM Airway insertion success rate (n=292) was 99% (95% CI: 98, 100). For endoscopy and LMA®GastroTM Airway insertion success, the lower limit of the 95% CIs was at least 98%, indicating LMA®GastroTM Airway efficacy. Median (inter-quartile range) lowest intraoperative oxygen saturation was 98% (98, 99). Only one serious adverse event occurred (re-admission for sore throat and inability to tolerate fluids) and was reported to the Tasmanian Health and Medical Human Research Ethics Committee. CONCLUSIONS: The LMA®GastroTM Airway appears effective for clinical use in upper gastrointestinal endoscopy. CLINICAL TRIAL REGISTRATION: ACTRN12616001464459.

Surface behavior of amphiphiles in aqueous solution: a comparison between different pentanol isomers.

Position isomerism is ubiquitous in atmospheric oxidation reactions. Therefore, we have compared surface-active oxygenated amphiphilic isomers (1- and 3-pentanol) at the aqueous surface with surface- and chemically sensitive X-ray photoelectron spectroscopy (XPS), which reveals information about the surface structure on a molecular level. The experimental data are complemented with molecular dynamics (MD) simulations. A concentration-dependent orientation and solvation of the amphiphiles at the aqueous surface is observed. At bulk concentrations as low as around 100 mM, a monolayer starts to form for both isomers, with the hydroxyl groups pointing towards the bulk water and the alkyl chains pointing towards the vacuum. The monolayer (ML) packing density of 3-pentanol is approx. 70% of the one observed for 1-pentanol, with a molar surface concentration that is approx. 90 times higher than the bulk concentration for both molecules. The molecular area at ML coverage (≈100 mM) was calculated to be around 32 ± 2 Å(2) per molecule for 1-pentanol and around 46 ± 2 Å(2) per molecule for 3-pentanol, which results in a higher surface concentration (molecules per cm(2)) for the linear isomer. In general we conclude therefore that isomers - with comparable surface activities - that have smaller molecular areas will be more abundant at the interface in comparison to isomers with larger molecular areas, which might be of crucial importance for the understanding of key properties of aerosols, such as evaporation and uptake capabilities as well as their reactivity.

Molecularly Designed Additives for Chemically Deconstructable Thermosets without Compromised Thermomechanical Properties.

"Drop-in" additives that introduce chemically cleavable bonds into thermosets without compromising thermomechanical properties could enable triggered material deconstruction and enhanced sustainability. While the installation of cleavable bonds into the strands of the commercial thermoset polydicyclopentadiene (pDCPD) using comonomers facilitates chemical deconstruction, these additives can lower the material's glass transition temperature (Tg). By contrast, the installation of cleavable crosslinkers into pDCPD can maintain or potentially increase Tg but does not facilitate chemical deconstruction. Here, we introduce "strand-cleaving crosslinker" (SCC) additives that provide cleavable pDCPD network junctions. Notably, pDCPD samples featuring 10% v/v of SCCs can be deconstructed under mild conditions to yield soluble products and display a 48 °C higher Tg than analogous decontructable pDCPD made using cleavable comonomers and an equivalent Tg to virgin pDCPD. The SCC concept could offer a general strategy for the design of chemically deconstructable thermoset materials without compromise on thermomechanical performance.

Effects of central administration of insulin or l-NMMA on rat skeletal muscle microvascular perfusion.

AIM: Intracerebroventricular (ICV) administration of a nitric oxide synthase (NOS) inhibitor to rats has been reported to raise blood pressure (BP) and cause insulin resistance, suggestive of a central effect of insulin that is NO dependent. Herein we test whether ICV insulin has peripheral haemodynamic and metabolic effects and whether peripheral effects of systemic insulin are affected by the ICV administration of the NOS inhibitor N(G) -methyl-l-arginine (l-NMMA). METHODS: Anaesthetized rats were fitted with an ICV cannula for insulin, artificial cerebrospinal fluid (aCSF) or l-NMMA infusion. Rats receiving ICV l-NMMA (500 µg) underwent systemic insulin clamp (10 mU/min/kg) or saline treatment for 70 min and were compared with animals receiving an equal amount of l-NMMA infused systemically. RESULTS: ICV aCSF or insulin (135 mU/min/kg brain) for 70 min or systemic l-NMMA (500 µg) had no effect on BP, heart rate (HR), femoral blood flow (FBF), glucose infusion rate, muscle 2-deoxyglucose uptake, microvascular perfusion or plasma insulin. However, ICV l-NMMA reduced systemic insulin-mediated increases in FBF (2.05 ± 0.08 to 1.55 ± 0.15 ml/min), 2-deoxyglucose uptake (17.7 ± 0.15 to 10.0 ± 0.03 µg/g/min) and microvascular perfusion (10.5 ± 0.5 to 6.6 ± 1.1 mol/min) (each mean ± SE, p < 0.05); plasma insulin, HR and BP were unaffected. CONCLUSIONS: Central insulin administration had no effect on skeletal muscle haemodynamics or glucose metabolism. However, systemic insulin-mediated increases in limb blood flow, muscle microvascular perfusion and glucose uptake may be regulated by a central pathway that is NO dependent.

Reducing delirium in elderly patients with hip fracture: a multi-factorial intervention study.

BACKGROUND: There is an evident need for improved management of elderly patients with trauma in order to avoid common and troublesome complications such as delirium. The aim of this study was to investigate whether an implementation of a multi-factorial program including intensified pre-hospital and perioperative treatment and care could reduce the incidence of delirium in elderly patients with hip fracture, cognitively intact at admission to the hospital. In addition, we explored the factors that characterize patients who developed delirium. METHODS: A prospective, quasi-experimental design was used. A total of 263 patients with hip fracture (> or = 65 years), cognitively intact at admission, were consecutively included between April 2003 and April 2004. On 1 October 2003, a new program was introduced. All patients were screened for cognitive impairment within 30 min after admission to the emergency department using The Short Portable Mental Status Questionnaire (SPMSQ). To screen for delirium, patients were tested within 4 h of admission and thereafter daily, using the Organic Brain Syndrome scale. RESULTS: The number of patients who developed delirium during hospitalization was 74 (28.1%), with a decrease from 34% (45 of 132) in the control group to 22% (29 of 131) in the intervention group (P=0.031). Patients who developed delirium were statistically older, more often had > 4 prescribed drugs at admission and scored less well in the SPMSQ test. CONCLUSION: The use of a multi-factorial intervention program in elderly hip fracture patients, lucid at admission, reduced the incidence of delirium during hospitalization by 35%.

Dopaminergic neurons protected from degeneration by GDNF gene therapy.

Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneration induced by the neurotoxin 6-hydroxydopamine (6-OHDA) injected into the striatum. Ad GDNF gene therapy reduced loss of DA neurons approximately threefold 6 weeks after 6-OHDA lesion, as compared with no treatment or injection of Ad lacZ or Ad mGDNF (encoding a biologically inactive deletion mutant GDNF). These results suggest that Ad vector-mediated GDNF gene therapy may slow the DA neuronal cell loss in humans with Parkinson's disease.

National survey of potential heart beating solid organ donors in Sweden.

Sweden has about 135 heart beating solid organ donors per year among 9.2 million inhabitants. Earlier estimations have suggested that 250-300 of potential heart beating donors might be available in the country annually. The present study is the first nationwide survey to establish the number of potential heart-beating donors, based on all patient deaths in Swedish intensive care units (ICUs). In the present study, a potential heart-beating solid organ donor was strictly defined as "a patient in an ICU on mechanical ventilation with the diagnosis of brain death." All 85 eligible ICUs reported all patient deaths over a 3 month period of October through December 2007. The instrument consisted of 10 questions. The majority of data were entered electronically by the ICU staff into the "Swedish Intensive Care Registry." The total number of reported patient deaths was 875 with 7.4% of patients who died meeting the criteria for a potential heart-beating solid organ donor. Actually 51% of them became donors. Reasons for not becoming a donor were refusals in 31%, medical reasons in 14%, impossibility to obtain consent in 1.5%, and no suitable recipient in 3%. Furthermore, 1.5% of patients did not become donors because of preferential forensic examinations. The main conclusion of the study was that the actual number of potential heart-beating solid organ donors in Sweden seems to be less than earlier estimates. Another interesting observation is the existence of a group of artificially ventilated, brain injury patients in whom the death was diagnosed by cardiac arrest. We think that this group of patient deaths deserves further investigation in future projects.

Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.

alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn-/- mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn-/- mice display a standard pattern of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn-/- mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.

Light vs. heavy sedation during mechanical ventilation after oesophagectomy--a pilot experimental study focusing on memory.

BACKGROUND: To assess and compare the feasibility and stressful memories of light vs. heavy sedation during post-operative mechanical ventilation. METHODS: Randomized clinical trial in one general intensive care unit (ICU) in a Swedish university hospital. Thirty-six adults were randomly assigned to receive either light [Motor Activity Assessment Scale (MAAS) 3-4] or heavy (MAAS 1-2) sedation with continuous i.v. infusion of propofol during post-operative invasive mechanical ventilation after oesophagectomy. The patients were interviewed at the general ward 5 days post-ICU using the ICU Memory Tool and the ICU Stressful Experience Questionnaire, and 2 months post-ICU using the Impact of Event Scale Revised. Patient data and hourly recorded MAAS values were collected after the interviews. RESULTS: Seventy-four per cent of the 139 MAAS values in the light sedation group (n=18) and 79% of the 142 in the heavy sedation group (n=18) were within the targeted levels, and the median MAAS scores were 3.0 vs. 1.25, respectively. Intention-to-treat analyses showed no significant difference in the prevalence of stressful memories between groups, including endotracheal tube discomfort, presenting wide 95% confidence intervals for the difference in outcome estimates. Excluding the patients with a prolonged ICU stay (n=3), a higher prevalence of delusional memories was found in the heavy sedation group (31% vs. 0%, P=0.04). CONCLUSIONS: This small randomized-controlled pilot study suggests that a light sedation regimen during short-term post-operative mechanical ventilation after major surgery is feasible without increasing patient discomfort.

Tailoring the internal structure of liquid crystalline nanoparticles responsive to fungal lipases: A potential platform for sustained drug release.

Lipases are key components in the mechanisms underlying the persistence and virulence of infections by fungi, and thus also promising triggers for bioresponsive lipid-based liquid crystalline nanoparticles. We here propose a platform in which only a minor component of the formulation is susceptible to cleavage by lipase and where hydrolysis triggers a controlled phase transition within the nanoparticles that can potentially allow for an extended drug release. The responsive formulations were composed of phytantriol, which was included as a non-cleavable major component and polysorbate 80, which serves both as nanoparticle stabilizer and potential lipase target. To monitor the structural changes resulting from lipase activity with sufficient time resolution, we used synchrotron small angle x-ray scattering. Comparing the effect of the two different lipases used in this work, lipase B from Candida Antarctica, (CALB) and lipase from Rhizomucor miehei (RMML), only CALB induced phase transition from bicontinuous reverse cubic to reverse hexagonal phase within the particles. This phase transition can be attributed to an increasing amount of oleic acid formed on cleavage of the polysorbate 80. However, when also a small amount of a cationic surfactant was included in the formulation, RMML could trigger the corresponding phase transition as well. The difference in activity between the two lipases can tentatively be explained by a difference in their interaction with the nanoparticle surface. Thus, a bioresponsive system for treating fungal infections, with a tunable selectivity for different types of lipases, could be obtained by tuning the composition of the nanoparticle formulation.

Adenovirus-mediated transgene expression in nonhuman primate brain.

Transgene expression in the brain of St. Kitts green monkey, Cercopithecus aethiops sabeus, was studied following injection of a serotype 5 adenoviral vector deleted in E1 and E3. The vector harbored the transgene for Escherichia coli beta-galactosidase (beta-Gal) with the simian virus 40 (SV40) nuclear localization signal under control of the Rous sarcoma viral (RSV) long terminal repeat. Several titers ranging from 5 x 10(7) to 2 x 10(9) plaque-forming units (PFU) in volumes ranging from 5 to 250 microl were injected into the caudate nuclei of 18 monkeys. Monkeys were treated with dexamethasone for 9 days, beginning the day prior to surgery, and were sacrificed at 1 week or at 1, 2, or 3 months. At 1 week, beta-Gal was expressed in thousands of cells, including both neurons and astrocytes. In addition, some dopaminergic neurons in the substantia nigra expressed transgene, suggesting retrograde transport of the vector. At 1 month 162,000+/-68,000 (SEM) or 65,000+/-29,000 beta-Gal-expressing cells persisted in striatum injected with 6 x 10(8) PFU in 30 microl or 5 x 10(7) PFU in 5 microl, respectively. Transgene expression was also observed in one of two monkeys sacrificed at 2 months and in a single monkey sacrificed at 3 months. No transgene expression was observed at 1 month in striatum injected with a higher titer (2 x 10(9) PFU in 100 microl) or more dilute vector (5 x 10(7) PFU in 30 microl). Staining for the major histocompatibility complex II (MHC II) subtype DR showed intense staining in sites injected with a higher vector titer, in which no transgene persisted at 1 month, whereas low to moderate staining was present in sites with high transgene expression. These observations suggest that there is an optimal range of vector titers for obtaining persistent transgene expression from E1E3-deleted adenovirus in primate brain, above which host responses limit transgene stability.

Protein metabolism in the black bear before and during hibernation.

During 3 to 5 months of hibernation, the American black bear does not defecate, urinate, or require food or water. Although the bear loses 15 to 25% of its body weight during this period, there is no significant change in its lean body mass. No net accumulation of the usual nitrogenous products of protein catabolism can be demonstrated in the dormant bear, and there is a decrease in urea production during hibernation. Because of these findings, it has been hypothesized that the black bear can alter its protein metabolism during hibernation by some unknown mechanism. During this study, the metabolis rate of protein turnover in four adult male black bears was measured before, during, and after hibernation, using 125I-labeled serum albumin from black bears as an indicator protein and 14C-labeled leucine as an indicator amino acid. For albumin during both phases, the disappearance rate of labeled albumin from serum was measured over 2 weeks and its turnover rate was calculated from these data. For [14C]leucine, the amino acid was injected during and after hibernation and its appearance in total proteins of plasma was measured. The results using labeled albumin revealed a threefold increase in turnover of protein during hibernation compared with protein turnover before hibernation. Leucine data supported these findings; more labeled leucine was incorporated in plasma proteins during hibernation than in the active state in spring. There were no significant changes in hematocrit, serum albumin concentration, thyroxin, or thyroxine-binding globulin between active and dormant periods, although triiodothyronine tended to decrease during hibernation. We speculate that increased protein turnover suggests a strongly acting protein-anabolic mechanism that would tend to compete with other catabolic pathways for amino acids. Another consequence of this increased protein turnover would be thermogenesis. This may have helped prevent any undue decrease in body temperature. It is notable that the body temperature of the dormant bear is appreciably higher than that of other hibernating animals.

Evidence for a dopamine interaction with the central respiratory control system in the rat.

Respiratory activity was studied in adult rats during light halothane anesthesia. Dopamine agonists and antagonists were injected intracerebroventricularly (i.c.v.) or systemically. The respiratory parameters were recorded after exposure to O2 or to CO2 in O2. Apomorphine (i.c.v. 300 microgram) induced a biphasic response with an initial decrease in respiratory frequency (f) followed by pronounced tachypnoea after 5 min. The changes in tidal volume (VT) showed an inverse pattern. When apomorphine was administered into the fourth ventricle, only the later phase of the biphasic response was observed. Haloperidol (2 mg/kg i.p.) antagonized the apomorphine-induced response in contrast to domperidone (2 mg/kg i.v.), a dopamine receptor blocking agent which does not pass the blood brain barrier. Administered i.c.v., haloperidol as well as domperidone induced a decrease in f while VT was increased. The same response was observed after the presynaptic dopamine receptor agonist 3-PPP, 3-(3-hydroxyphenyl)-N-n-propylpiperidine. Hypercapnea was found to decrease the tachypnea in apomorphine-treated animals. Apomorphine also induced a decrease in blood pressure and heart rate, which was not reversed by haloperidol. It is concluded that there is a centrally located, tonically activated dopamine system involved in respiratory regulation. The predominant effect seems to be of a respiratory stimulating nature. The possible role of presynaptic and different postsynaptic dopamine receptor mechanisms is discussed.

Dopaminergic interaction with the respiratory control system in the rat.

Apomorphine given to rats lightly anesthetized with halothane produces a dose dependent increase in respiratory frequency and minute ventilation. Although basal arterial CO2 tensions were not significantly altered by apomorphine, the mechanical response to exogenous CO2 exposure was greatly increased in rats given apomorphine. Haloperidol returned the apomorphine-stimulated respiratory pattern to control values. It is concluded that dopamine neurons may have important interactions with respiratory control.

Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta family isolated from the rat glial tumor cell line, B49. In embryonic dopaminergic (DA) neurons in vitro, GDNF promotes survival, high-affinity dopamine uptake, and neurite outgrowth. We have used a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific to GDNF to study the developmental expression of GDNF mRNA in central nervous system (CNS) and peripheral organs of embryonic rat on gestational days E11.5, E13.5 and E18, neonatal rat on postnatal days P0 and P10, and adult rat. GDNF mRNA is expressed throughout the CNS, with highest levels in P0 spinal cord and in P0 and P10 striatum. Lower levels are present in the brainstem (including the ventral mesencephalon, which contains the DA neurons of the substantia nigra), cerebellum, diencephalon, and telencephalon, as well as in primary cultures of cerebellar granule cells prepared from P7 cerebellum and astrocytes prepared from P1 cortex. The cerebellum has an unusual temporal pattern of expression, high at birth and in the adult, but undetectable at P10. GDNF mRNA is also expressed in many peripheral tissues at higher levels than in brain. These include embryonic limb bud, kidney and gut; neonatal kidney, gut, lung and testis; and adult lung, liver and ovary. In addition to the predicted RT-PCR product, we also observed a minor band which was shown to be identical to GDNF in the mature peptide sequence, but which has a 78 base pair deletion in the preproprotein sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Central respiratory stimulant effect by thyrotropin in releasing hormone in the rat.

Anaesthetized male rats were injected intracerebroventricularly with the tripeptide, thyrotropin releasing hormone (TRH). Respiratory frequency (f), tidal volume (VT) and minute volume (VE) were measured in a closed whole body plethysmograph by a low pressure transducer connected to a Grass polygraph. TRH induced an approximately 50% increase in f, while VT was not altered. VE increased in the same proportion as f. Our results indicate that TRH neurons or TRH-sensitive receptors may be involved in the regulation of central respiratory activity.

Cerebellar cGMP varies with motor function and respiratory gas exchange.

Paralysis of rats with d-tubocurarine decreased cerebellar guanosine 3': 5'-cyclic monophosphate (cGMP) content to about one third of normal values when arterial oxygen and carbon dioxide were maintained at normal values. In addition, altering arterial carbon dioxide tensions in these paralyzed rats revealed that cerebellar cGMP was inversely related to arterial carbon dioxide tension, and that this relationship could be blunted by increasing arterial oxygen tension. It is possible that part of the decrease in cerebellar cGMP content by CNS depressants observed in several species in many laboratories may be simply secondary to the decreased motor function and/or respiratory depression produced.

Effect of ethanol on cyclic nucleotides in vivo: consequences of controlling motor and respiratory changes.

Many psychotropic drugs alter cerebellar cyclic guanosine-3',5'-monophosphate (cGMP) content. Whereas apomorphine increased levels, central depressants such as ethanol, chlordiazepoxide or barbiturates, reduce the content of cerebellar cGMP without altering levels of cyclic adenosine-3',5'-monophosphate (cAMP). Additional data indicate that tolerance develops to this reduction of cerebellar cGMP by ethanol. In paralyzed animals, the increase in cerebellar cGMP content induced by apomorphine and the decrease caused by ethanol were dramatically attenuated. Since relatively high doses of ethanol were needed to decrease blood CO2 tension in spontaneously moving rats, changes in respiratory function appear to be of only minor importance in the ethanol-induced decrease in cerebellar cGMP. It is concluded that ethanol-induced changes in content of cerebellar cGMP in vivo may be secondary to alterations in motor and, to a lesser extent, in respiratory function.

GABA-ergic mechanisms in central respiratory control in the anesthetized rat.

Rats lightly anesthetized with halothane were injected intracerebroventricularly (i.c.v.) with gamma aminobutyric acid (GABA) and the GABA-like drugs muscimol, baclofen, and gamma-hydroxybutyric acid (GHBA). Respiratory frequency (f) was reduced after GABA (1 mg) but increased after baclofen (0.5 microgram), while muscimol (0.5 microgram) or GHBA (1 mg) did no affect f. However, GHBA administered repeatedly caused a dose-dependent increase in f. Tidal volume (VT) decreased in a dose-dependent fashion after i.c.v. administration of all the drugs used. Taken together, these changes in f and VT resulted mainly in a dose dependent decrease in minute volume (VE) after GABA and muscimol while after baclofen and GHBA VE was increased due to the marked stimulation of f after repeated administration. Mean arterial pressure (MAP) decreased after GABA and muscimol while no effect or a slight increase was seen after baclofen and GHBA. Heart rate (HR) was unaltered after muscimol, decreased after gaba but slightly increased after GHBA and baclofen. No alterations were seen in blood gases except after administration of GABA which induced a slight hypoxia, hypercapnia and acidosis. The data indicate that an activation of GABA-ergic mechanisms results in a respiratory depression. Moreover, the effects of GABA and muscimol are probably due to a direct GABA-ergic receptor activation while the effects elicited by baclofen and GHBA are due to other mechanisms than direct GABA receptor activation or indirect effects via other system on respiratory regulating centers.

Disposable CO2-detector, a reliable tool for determination of correct tracheal tube position during resuscitation of a neonate.

Undetected displacement of the endotracheal tube may lead to death of the patient. The present report illustrates the benefits of using a disposable carbon dioxide detector, designed for adults, also in a new-nate during resuscitation. The infant had asystole after delivery by caesarean section. The trachea was intubated, but the tube was displaced soon after return of spontaneous circulation. The oesophageal position of the tube was, however, discovered before bradycardia had occurred, thanks to the use of the CO2 detector.