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Outlet glaciers drain the majority of ice flow in the Antarctic ice sheet. Theory and numerical models indicate that local bed topography can play a key role in modulating outlet glacier response to climate warming, potentially resulting in delayed, asynchronous, or enhanced retreat. However, the period of modern observations is too short to assess whether local or regional controls dominate ice sheet response on time scales that are critical for understanding ice sheet mass loss over this century and beyond. The recent geological past allows for insight into such centennial-scale ice sheet behavior. We present a cosmogenic surface-exposure chronology from Mawson Glacier, adjacent to a region of the Ross Sea that underwent dynamic marine-based ice sheet retreat following the Last Glacial Maximum. Our data record at least 220 m of abrupt ice thinning between 7.5 and 4.5 ka, followed by more gradual thinning until the last millennium. The timing, rates, and magnitudes of thinning at Mawson Glacier are remarkably similar to that documented 100 km to the south at Mackay Glacier. Together, both outlet glaciers demonstrate that abrupt deglaciation occurred across a broad region in the Mid-Holocene. This happened despite the complex bed topography of the western Ross Sea and implies an overarching external driver of retreat. When compared to regional sea-level and ocean-temperature changes, our data indicate that ocean warming most likely drove grounding-line retreat and ice drawdown, which then accelerated as a result of marine ice sheet instability.

Editor—As veterinary anaesthetists we are raising three concerns with the paper recently published in the British Journal of Anaesthesia by Chandra and colleagues.1

Objective Attention is drawn to the potential of global warming to influence the health and wellbeing of the human race. There is increasing public and governmental pressure on healthcare organisations to mitigate and adapt to the climate changes that are occurring. The science of anaesthetic agents such as nitrous oxide and the halogenated anaesthetic agents such as greenhouse gases and ozone-depleting agents is discussed and quantified. Additional environmental impacts of healthcare systems are explored. The role of noninhalational anaesthetic pharmaceuticals is discussed, including the environmental life-cycle analyses of their manufacture, transport, disposal and use. The significant role of anaesthetists in recycling and waste management, resource use (particularly plastics, water and energy) and engagement in sustainability are discussed. Finally, future directions for sustainability in veterinary anaesthesia are proposed. Conclusions Veterinary anaesthetists have a considerable opportunity to drive sustainability within their organisations through modification of their practice, research and education. The principles of sustainability may help veterinary anaesthetists to mitigate and adapt to our environmental crisis. Due to their particular impact as greenhouse gases, anaesthetic agents should be used conservatively with the lowest safe fresh gas flow possible. Technologies for reprocessing anaesthetic agents are described.

Recent ice sheet mass loss in Antarctica has been attributed to an influx of warm ocean waters, which drove grounding‐line retreat and ice thinning. Episodic retreat and rapid thinning also occurred in the southwestern Ross Sea during the Holocene, which today accommodates cold ocean waters. We applied finite‐element ice‐flow modeling to investigate the roles of ocean temperature and bed topography in the deglaciation of this region. First, our experiments demonstrate that bed topography controlled the spatial pattern of grounding‐line retreat. Topographic pinning points limited the rate of ice loss until retreat progressed beyond a bathymetric threshold. Second, ocean thermal forcing determined the timing of this ice loss. Enhanced ocean‐driven melt is required during the Early‐to‐Mid Holocene to replicate geological records of deglaciation, possibly indicating that warm ocean waters were once present in this region. On multi‐centennial timescales, ocean temperature drove, while bed topography controlled, nonlinear rates of ice mass loss.

Cosmogenic-nuclide surface-exposure data provide important constraints on the thickness, extent and behaviour of ice masses in the geological past. A number of online calculators provide the cosmogenic nuclide community with a means of easily calculating surface-exposure ages. Here we provide a platform for plotting and analysing such data. This paper describes a suite of freely accessible numerical tools for visualising, evaluating and correcting surface-exposure data that are used to reconstruct past glacier and ice sheet geometries. iceTEA (Tools for Exposure Ages) is available as an online interface ( http://ice-tea.org ) and as MATLAB© code. There are 8 tools, which provide the following functionality: 1) calculate exposure ages from 10Be and 26Al data, 2) plot exposure ages as kernel density estimates and as a horizontal or vertical transect, 3) identify and remove outliers within a dataset, 4) plot nuclide concentrations on a two-isotope diagram and as a function of depth, 5) correct exposure ages for cover of the rock surface, 6) correct ages for changes in relative elevation through time, and estimate 7) average and 8) continuous rates of ice margin retreat or thinning. Three of the tools (1, 5 and 6) perform exposure age calculations, which are based on the framework of CRONUScalc. Results are available as printed text, tables and/or raster (.png) and vector (.eps) graphics files, depending on the tool. These tools are intended to enable users to evaluate complex exposure histories, assess the reliability of exposure ages, explore potential age corrections, and better analyse and understand spatial and temporal patterns within their data.

Any future changes in the volume of Antarctica’s ice sheets will depend on the dynamic response of outlet glaciers to shifts in environmental conditions. In the Transantarctic Mountains, this response is probably heavily dependent on the geometry of the system, but few studies have quantified the sensitivity of these glaciers to environmental forcings. Here we investigated the controls, along-flow sensitivity and time-dependent dynamics of Skelton Glacier. Three key outcomes were: i) present-day flow is governed primarily by surface slope, which responds to reduced valley width and large bed undulations, ii) Skelton Glacier is more susceptible to changes in atmospheric temperature than precipitation through its effect on basal sliding near the grounding line, and iii) under conditions representative of Pliocene and Quaternary climates large changes in ice thickness and velocity would have occurred in the lower reaches of the glacier. Based on these new quantitative predictions of the past and present dynamics of Skelton Glacier, we suggest that similar Transantarctic Mountain outlet glaciers could experience greater ice loss in their confined, lower reaches through increased basal sliding and ocean melt under warmer-than-present conditions. These effects are greatest where overdeepenings exist near the grounding line.

Understanding past changes in the Antarctic ice sheets provides insight into how they might respond to future climate warming. During the Pliocene and Pleistocene, geological data show that the East Antarctic Ice Sheet responded to glacial and interglacial cycles by remaining relatively stable in its interior, but oscillating at its marine-based margin. It is currently not clear how outlet glaciers, which connect the ice sheet interior to its margin, responded to these orbitally-paced climate cycles. Here we report new ice surface constraints from Skelton Glacier, an outlet of the East Antarctic ice sheet, which drains into the Ross Ice Shelf. Our multiple-isotope (10Be and 26Al) cosmogenic nuclide data indicate that currently ice-free areas adjacent to the glacier underwent substantial periods of exposure and ice cover in the past. We use an exposure-burial model driven by orbitally-paced glacial–interglacial cycles to determine the probable ice surface history implied by our data. This analysis shows that: 1) the glacier surface has likely fluctuated since at least the Pliocene; 2) the ice surface was >200 m higher than today during glacial periods, and the glacier has been thicker than present for ∼75–90% of each glacial–interglacial cycle; and 3) ice cover at higher elevations possibly occurred for a relatively shorter time per Pliocene cycle than Pleistocene cycle. Our multiple-nuclide approach demonstrates the magnitude of ice surface fluctuations during the Pliocene and Pleistocene that are linked to marine-based ice margin variability.

This study evaluated the use of sugammadex for reversal of profound neuromuscular blockade induced with rocuronium or vecuronium in dogs. Anaesthesia was induced and maintained with isoflurane in oxygen in eight dogs on two occasions. Neuromuscular blockade was monitored using peroneal nerve stimulation and acceleromyography. Rocuronium 0.6 mg/kg or vecuronium 0.1mg/kg was administered intravenously (IV), followed 5 min later by sugammadex 8 mg/kg IV. Lag and onset time of rocuronium and vecuronium, lag time from sugammadex injection to recovery of first twitch response, recovery of T1/T0 to 25% and 75%, recovery index, and time to recovery of the train-of-four ratio (T4/T1) to 0.9 were recorded. Cardiovascular and respiratory parameters were also noted. Statistical analysis was performed using one-way ANOVA. Onset time for rocuronium (37 ± 18s; [mean ± SD]) was significantly shorter than for vecuronium (62 ± 15s) (P

The application of the Alternant Molecular Orbital method to solids has been hampered both by the need to use a cubic Fermi volume as the reference system and by the belief that the AMO state is always an insulating state. We demonstrate here, however, that a simple relabeling of the AMO “occupied” and “virtual” states in an extended zone scheme allows one to use any Fermi volume for the reference state. Furthermore, the AMO state will now represent a metallic or insulating system depending on the presence of partially filled bands. We have applied the method to the interacting electron gas with BCC symmetry and find a metal-insulator transition at approximately rs = 50.

Effective, explicitly density-dependent (i.e., orbital-free) approximations to the Kohn–Sham kinetic energy functional Ts remain elusive. In the course of developing such functionals in collaboration with Frank Harris, various issues have arisen that have gone unaddressed. We consider four of them here: positivity of the KS kinetic energy density, supposed requirements on its functional dependence, the use of cutoffs to insure positivity, and the role of the Coulomb virial theorem in the asymptotic analysis of Ts. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009

Objective A clinical trial to determine whether continuous infusion administration technique was suitable for maintaining neuromuscular blockade with rocuronium bromide in dogs. Animals Twenty-two dogs, 10 males and 12 females, median age 2 years 4 months, median weight 32 kg undergoing elective surgical procedures under general anaesthesia: ASA classification I or II. Materials and methods After induction of anaesthesia, neuromuscular function was evaluated using train-of-four (TOF) stimulation of the dorsal buccal branch of the facial nerve. A bolus dose of 0.5 mg kg−1 rocuronium was administered intravenously and an infusion of 0.2 mg kg−1 hour−1 was started immediately. Neuromuscular blockade was assessed visually by counting the number of twitches observed during TOF stimulation repeated at 10-second intervals. Results The bolus dose of rocuronium abolished the response to TOF stimulation in 21 of the 22 dogs. The median onset time of neuromuscular blockade (complete loss of all four twitches) was 82 seconds (range 38–184 seconds). Median infusion duration was 76 minutes (range 20.3–146 minutes). Conclusions and clinical relevance This protocol of rocuronium administration was considered to be effective in dogs. Constant infusion of rocuronium is easily applicable to clinical practice and further work is required on infusion titration.

Outlet glaciers grounded on a bed that deepens inland and extends below sea level are potentially vulnerable to ‘marine ice sheet instability’. This instability, which may lead to runaway ice loss, has been simulated in models, but its consequences have not been directly observed in geological records. Here we provide new surface-exposure ages from an outlet of the East Antarctic Ice Sheet that reveal rapid glacier thinning occurred approximately 7,000 years ago, in the absence of large environmental changes. Glacier thinning persisted for more than two and a half centuries, resulting in hundreds of metres of ice loss. Numerical simulations indicate that ice surface drawdown accelerated when the otherwise steadily retreating glacier encountered a bedrock trough. Together, the geological reconstruction and numerical simulations suggest that centennial-scale glacier thinning arose from unstable grounding line retreat. Capturing these instability processes in ice sheet models is important for predicting Antarctica’s future contribution to sea level change., Nature Communications, 6, ISSN:2041-1723

Objective To evaluate the non-depolarizing neuromuscular blocking drug cis-atracurium in dogs with porto-systemic shunts, and to compare it in clinically normal animals. Animals Thirteen dogs of mixed breed and sex, aged between 3 and 31 months old, weighing 2.2–25.5 kg, with ASA physical status II–IV, and undergoing surgical attenuation of porto-systemic shunt. A control group of 11 bitches of mixed breed, between 8 and 60 months old, and weighing 4.5–41.0 kg, all ASA physical status I, undergoing routine ovarohysterectomy were also studied. Materials and methods Pre-anaesthetic medication was an opioid analgesic, given either alone or in combination with acepromazine. Following induction of general anaesthesia with intravenous (IV) propofol and oro-tracheal intubation, anaesthesia was maintained using isoflurane in either oxygen or oxygen and nitrous oxide. Ventilation was controlled. The train of four (TOF) technique was used to monitor neuromuscular blockade. An initial dose of 0.1 mg kg−1cis-atracurium was given IV and additional doses of 0.03 mg kg−1cis-atracurium were administered when at least one twitch of the TOF was present. Results Except for one dog that was killed during surgery because its anomaly was inoperable, all animals recovered satisfactorily from anaesthesia and surgery. In dogs with porto-systemic shunt, onset of neuromuscular blockade was 3.1 ± 1.1 minutes (mean ± SD) and in control dogs was 3.4 ± 0.7 minutes (not significantly different). Neuromuscular blockade lasted 34 ± 13 minutes in dogs with porto-systemic shunt and 29 ± 17 minutes in control dogs (not significantly different). Conclusions The presence of porto-systemic shunt did not affect the rate of onset or duration of action of cis-atracurium. Clinical relevance cis-Atracurium may have a use in veterinary anaesthesia for producing neuromuscular blockade in dogs with hepatic insufficiency, including those with porto-systemic shunt.

Antarctic Science, 26 (6), ISSN:0954-1020, ISSN:1365-2079

Objective To compare the induction dose requirements of thiopental using two different infusion rates for induction of anaesthesia in dogs. Study design Prospective, randomized study. Animals Fifty, healthy (ASA I or II) client-owned dogs with a mean age of 4.1 years and a mean mass of 20.4 kg undergoing elective surgery. Materials and methods Animals were randomly assigned to receive an infusion of 2.5% thiopental at a rate of either 0.1 ml kg −1 minute −1 or 0.4 ml kg −1 minute −1 , 30–40 minutes after pre-anaesthetic medication with intramuscular acepromazine (0.025 mg kg −1 ) and pethidine (3.5 mg kg −1 ). Thiopental administration was controlled by a precision syringe driver. Statistical analyses of the results, using the outcome ‘mg kg −1 required for induction’ (log-transformed) included unpaired t -tests for all categorical data (thiopental infusion rate, breed, sex, obesity, sedation quality) and univariable linear regression for continuous variables (mass, age). All variables were then considered in a multivariable linear regression model. The quality of induction with the two different infusion rates was also assessed. Results After controlling for quality of sedation, the thiopental induction dose requirement was significantly less ( p −1 ; range 4.9–13.7) compared with the faster infusion rate (median =11.0 mg kg −1 ; range 6.6–18.0). The quality of sedation also affected the dose required ( p = 0.03). The slower infusion rate was associated with a significantly poorer induction quality ( p = 0.3). Conclusions Slow thiopental infusion (0.1 ml kg −1 minute −1 ) for anaesthesia induction after acepromazine/pethidine pre-anaesthetic medication reduced the induction dose requirement, although the quality of induction was inferior. Clinical relevance The induction dose of thiopental was reduced with a slower administration rate and so slow administration is recommended in thiopental-sensitive animals.

A juvenile female black rhinoceros (Diceros bicornis) was successfully treated after overdose of drugs used for chemical restraint. Subsequent general anaesthesia for surgical reduction of a recurrent rectal prolapse was uneventful. Over a 25-minute period before transportation to the veterinary hospital, the animal received a total dose of 1.225 mg etorphine, 30 mg acepromazine and 30 mg detomidine. Based on an estimated mass of 200 kg, these corresponded to doses of 6.1 microg kg(-1) etorphine, 150 microg kg(-1) acepromazine, and 150 microg kg(-1) detomidine which constitutes considerable overdose for each drug given separately, notwithstanding the synergy that probably resulted when the three drugs were present concurrently. The estimated body mass may have substantially overestimated the actual body mass and exacerbated overdosage. The animal was recumbent and apnoeic on arrival at the hospital. Heart sounds were auscultated and a weak peripheral pulse was palpated; no pulse deficits were detected, although the heart rate was low. The trachea was intubated, inspired breath was enriched with oxygen and the lungs ventilated manually. Diprenorphine (1.5 mg) was given intravenously and spontaneous breathing resumed 11 minutes later. After induction of general anaesthesia using isoflurane, emergency surgery for correction of rectal prolapse was performed, from which the animal recovered uneventfully. The case highlights some of the practical problems that may be encountered in dealing with dangerous and unfamiliar species.

After being anaesthetised for between one hour 40 minutes and seven hours, five adult horses developed acute neurological signs and extensive cerebrocortical necrosis. Four of them had had abdominal surgery for colic and one had had repeated orthopaedic interventions. Between five hours and seven days after the surgery, all five horses suddenly developed severe signs of a predominantly prosencephalic disturbance: bilateral blindness with normal pupillary light responses, abnormal behaviour varying from propulsive pacing to head pressing, profound lethargy and generalised seizures. They were euthanased between 24 hours and three weeks after the onset of these signs. In three of the cases a gross examination of the brain revealed patchy malacia of the cerebral grey matter and some discolouration of the adjacent white matter. Microscopical examination revealed lesions that varied from laminar neuronal necrosis in the grey matter of the cerebral cortex to more diffuse necrosis of the cortex and underlying white matter. Four of the five cases had had a period of hypercapnea while anaesthetised, and two of them (and possibly a third) had also had hypoxaemia.

Objective To review the evidence regarding the reversal of neuromuscular block (NMB) in companion animals with emphasis on the development and use of newer agents. Database used Data sources include scientific reviews and original research publications in both human and veterinary literature using Pubmed and Scopus as search data bases. Unpublished and locally published data on reversal of NMB are presented. Conclusions Residual NMB has been shown to increase morbidity and mortality in humans and needs to be avoided. It can be detected only by adequate neuromuscular monitoring. The proper use of reversal agents avoids residual NMB and recurarization should not occur. Anticholinesterase inhibitors, such as edrophonium and neostigmine have been used to reverse NMB when the need for this has been established. Reversal is influenced by several factors and a number of undesirable side- effects of these drugs have been reported. Sugammadex, a γ-cyclodextrin, which was designed specifically to encapsulate rocuronium, is more rapid in its actions, has fewer side effects and can reverse profound NMB induced by aminosteroidal muscle relaxants.

Objective This clinical trial attempted to evaluate the potency, onset and duration of action of cis-atracurium in dogs. Animals Twenty dogs aged between 1 and 15 years and weighing between 15 and 85 kg admitted for a variety of elective, surgical procedures under general anaesthesia. Materials and methods Following induction of general anaesthesia, the effects of an intravenous loading dose of cis-atracurium (0.1 mg kg-1) were evaluated by counting visual responses to train of four (TOF) nerve stimulation. Incremental doses of 0.02 or 0.04 mg kg-1 cis-atracurium were administered when the first of four responses to TOF stimulation was present. Results An initial dose of 0.1 mg kg-1 eliminated all four TOF responses in 18 out of 20 dogs. The same dose, repeated 10 minutes later in two animals in which blockade was incomplete, abolished all responses. In dogs receiving 0.1 mg kg-1 cis-atracurium neuromuscular blockade lasted 27.2 ± 9.3 minutes. Up to six incremental doses were given in individual animals; incremental doses appeared to be noncumulative. No untoward side-effects were observed with the use of this drug. There was considerable variation between individuals in response to cis-atracurium. Conclusions Cis-atracurium is an effective neuromuscular blocking agent in the dog, although its potency varies. Clinical Relevance Further studies are required to determine whether observed differences in potency are related to age, breed or sex. Cis-atracurium may prove useful in dogs with impaired renal and or hepatic function.

Summary Background Dose limiting acute toxicity from chemoradiation for pancreatic cancer occurs in 15%–20% of patients treated with post-operative adjuvant therapy. Reported here is a pilot study using chronomodulated infusional 5-fluorouracil (5-FU) chemoradiation (CIC) for pancreatic cancer, a treatment designed to reduce normal tissue toxicity and maintain efficacy, with specific evaluation of acute and late morbidity, patterns of disease progression, and survival. Patients and methods Twenty-three patients with adenocarcinoma of the pancreas were treated with 5-FU CIC between January 1997 and September 1999. The median age was 64, and there were 9 males and 14 females. Six patients were considered unresectable and seventeen others were treated post-operatively. The median external beam irradiation dose was 50.4 Gy. 5-FU infusion was given five days per week (300 mg/m2/d) and the median total dose was 8.4 g/m2. The chronomodulated 5-FU infusion consists of a low basal infusion rate for 16 hours followed by an eight-hour escalating-deescalating infusion peaking at 10 p.m. All patients were followed from the time of initial diagnosis until last follow-up or death; the median follow-up was 16 months. Results No RTOG grade 3 or 4 hematologic toxicity occurred. Twelve of seventeen patients treated postoperatively have been controlled locally, and seven patients have no evidence of disease. The median survival is 28 months and one-year actuarial survival is 88% in the group of resected patients. The 6 patients treated for unresectable disease have a median survival of 13 months. Conclusions Acute toxicity of 5-FU CIC appears to be less frequent and less severe than that reported with flat infusional or bolus 5-FU based chemoradiation used for adjuvant postoperative therapy for pancreatic cancer. This method may warrant further examination, as it may be attractive for the elderly or those who cannot tolerate the toxicity associated with standard post-operative treatment protocols.

We have studied retrospectively 37 hips in 36 children at an average of 91 months after simultaneous open reduction and Salter innominate osteotomy for developmental hip dysplasia. At the latest review 97.3% were clinically and 83.8% radiologically good or excellent. In three hips (8%) there were signs of avascular necrosis, but only one had been symptomatic. There were no cases of recurrent posterior displacement.

Six adult female chimpanzees (Pan troglodytes) were anaesthetised for the placement of intrauterine contraceptive devices, microchips for identification, routine blood sampling, and physical measurements. Anaesthesia was induced with medetomidine in combination with ketamine administered by intramuscular injection with a projectile syringe. Induction was smooth and rapid, but five of the animals were insufficiently relaxed for orotracheal intubation. The plane of anaesthesia was deepened by administering isoflurane delivered in oxygen and nitrous oxide, and general anaesthesia was maintained for up to 74 minutes. The action of medetomidine was reversed at the end of each procedure with atipamezole, and the animals recovered smoothly and uneventfully.

Objective To compare acid–base balance and incidence of hyperchloraemic metabolic acidosis following administration of three crystalloid solutions to dogs undergoing anaesthesia for orthopaedic surgery. Study design Prospective, randomised, clinical study. Animals Sixty dogs. Methods During a non–standardised anaesthetic, 0.9% saline (S), Hartmann's solution (H) or a polyionic glucose–free maintenance solution (M) was administered IV at 10 mL kg−1 hour−1. Venous blood pH, PCO2, PCV, total protein, urea, sodium, potassium and chloride concentrations were measured at induction of anaesthesia (T0) and after 2 hours of fluid therapy (T2). Base excess (BE), bicarbonate, corrected chloride concentration (corrCl), osmolality, change in plasma volume (PV) and strong ion gap (SIG) were calculated. Changes in variables within groups (1–sample Student's t–test/Wilcoxon signed rank test) and between groups (1–way anova /Kruskal–Wallis) were assessed. Data are presented as median (interquartile range). Significance was set at p Results No significant differences existed between groups for pH, PCO2, PCV, total protein, urea, potassium, corrCl, PV and SIG. Potassium significantly increased in all groups. Significant differences existed between groups S and M for BE, sodium, chloride, bicarbonate and osmolality, and between groups H and M for sodium and osmolality. Chloride concentration significantly changed from 116 (114–117) to 117 (116–119) mmol L−1 in group S, 116 (115–118) to 115 (113–117) mmol L−1 in group H and 116 (115–118) to 114 (113–118) mmol L−1 in group M. In groups H and M, sodium and osmolality decreased, and BE and bicarbonate concentration increased significantly. Plasma volume increased by 28 (14–44)%, 25 (5–40)% and 24 (13–33)% in groups S, H and M, respectively. Conclusion and clinical relevance Hyperchloraemic metabolic acidosis did not develop after intraoperative 0.9% saline, Hartmann's solution or maintenance solution at 10 mL kg−1 hour−1 for 2 hours in dogs undergoing elective orthopaedic surgery. Bicarbonate and BE increased after Hartmann's and maintenance solutions. Increases in potassium concentration were unexplained.

Quantifying the ex vivo growth of complex multispecies dental biofilms using cross-polarization 1310-nm optical coherence tomography (CP-OCT) system was investigated.Bacterial microcosms, which were derived from plaque samples of paediatric subjects, were incubated in a biofilm reactor system containing discs of different dental materials for 72 h with daily sucrose pulsing (5×). CP-OCT analysis of biofilm mass was validated with crystal violet (CV) assays at various growth stages of these complex biofilms. CP-OCT was able to filter out the back-reflected signals of water layers in the hydrated biofilm and allowed for direct biofilm quantification. The overall depth-resolved scattering intensity of the biofilm showed very strong positive correlation with CV assay quantification (Spearman's ρ = 0.92) during the growth phase of the biofilm.CP-OCT was able to quantify the mass of the biofilm by measuring the overall depth-resolved scattering of the biofilm.CP-OCT has the ability to nondestructively monitor biofilm growth and elucidate the growth characteristics of these microcosms on different dental material compositions.

Medetomidine 10 μg/kg, was combined with butorphanol 0.1 mg/kg and administered intramuscularly to 27 dogs requiring sedation for various diagnostic or therapeutic procedures. All the dogs became deeply sedated. Heart rate fell by a mean of 55 per cent. Eighteen dogs showed signs of pain as the combination was injected. Sedation was sufficient for the intended procedure to be carried out in 25 of the dogs. General anaesthesia was induced in four dogs — the mean dose of thiopentone required for induction of anaesthesia was 2 mg/kg. Administration of atipamezole at the end of the procedure produced rapid and sudden recoveries in all the dogs, with a mean time to standing of nine minutes.

Medetomidine, either 5, 10 or 20 (μg/kg, was administered together with pethidine, 2 mg/kg, by either the intramuscular or subcutaneous route to 88 dogs from a clinical population. Administration of all the drug combinations consistently produced profound sedation in the dogs, accompanied by dramatic reductions in heart rate. The degree of sedation was similar to that seen after 40 μg/kg medetomidine is administered on its own to dogs. Intramuscular administration produced more reliable sedation, but was associated with more pain than subcutaneous administration. In a number of dogs, sedation permitted the completion of various diagnostic or therapeutic procedures. Several dogs were anaesthetised with thiopentone and the induction doses required were characteristically low (mean doses between 2 to 3·3 mg/kg depending on the dose of medetomidine and the route of administration). Administration of atipamezole at the termination of sedation or anaesthesia, produced a rapid and full recovery (mean time to standing between seven and 11 minutes).

As is typical of Polycomb-group loci, the Enhancer of zeste [E(z)] gene negatively regulates the segment identity genes of the Antennapedia (ANT-C) and Bithorax (BX-C) gene complexes. A second class of loci, collectively known as the trithorax group, plays an antagonistic role as positive regulators of the ANT-C and BX-C genes. Molecular analysis of the E(z) gene predicts a 760-amino-acid protein product. A region of 116 amino acids near the E(z) carboxy terminus is 41.2% identical (68.4% similar) with a carboxy-terminal region of the trithorax protein. This portion of the trithorax protein is part of a larger region previously shown to share extensive homology with a human protein (ALL-1/Hrx) that is implicated in acute leukemias. Over this same 116 amino acids, E(z) and ALL-1/Hrx are 43.9% identical (68.4% similar). Otherwise, E(z) is not significantly similar to any previously described proteins. As this region of sequence similarity is shared by two proteins with antagonistic functions, we suggest that it may comprise a domain that interacts with a common target, either nucleic acid or protein. Opposite effects on transcription might then be determined by other portions of the two proteins.

Assembly of type C retroviruses such as Moloney murine leukemia virus (M-MuLV) ordinarily occurs at the plasma membranes of infected cells and absolutely requires the particle core precursor protein, Pr65gag. Previously we have shown that Pr65gag is membrane associated and that at least a portion of intracellular Pr65gag protein appears to be routed to the plasma membrane by a vesicular transport pathway. Here we show that intracellular particle formation can occur in M-MuLV-infected cells. M-MuLV immature particles were observed by electron microscopy budding into and within rough endoplasmic reticulum, Golgi, and vacuolar compartments. Biochemical fractionation studies indicated that intracellular Pr65gag was present in nonionic detergent-resistant complexes of greater than 150S. Additionally, viral RNA and polymerase functions appeared to be associated with intracellular particles, as were Gag-beta-galactosidase fusion proteins which have the capacity to be incorporated into virions. Immature intracellular particles in postnuclear lysates could be proteolytically processed in vitro to mature forms, while extracellular immature M-MuLV particles remained immature as long as 10 h during incubations. The occurrence of M-MuLV-derived intracellular particles demonstrates that Pr65gag can associate with intracellular membranes and indicates that if a plasma membrane Pr65gag receptor exists, it also can be found in other membrane compartments. These results support the hypothesis that intracellular particles may serve as a virus reservoir during in vivo infections.

OBJECTIVE: The purpose of this research was to study the correlation between bile secretion and the liver regeneration in the partially hepatectomized rat. SUMMARY BACKGROUND DATA: Significant alteration in bile formation and secretion is expected in the liver after hepatectomy. There is scant literature, however, about the effects of liver regeneration in bile secretion. METHODS: The work was done in rats with 50% hepatectomy, 75% hepatectomy, and sham operation as the control. A chronic common bile duct fistula and a duodenal cannula were established for bile collection and the sample analysis on days 1, 3, 5, 7, and 9. RESULTS: With size reduced in the liver after 50% and 75% hepatectomy, the total bile volume decreased 45.9% and 51.5%, bile salt independent flow decreased 59.3% and 64.9%, bile salt secretion rate decreased 36.1% and 43.4%, bile salt basal synthesis rate decreased 52.3% and 56.4%, phospholipid secretion rate decreased 52.6% and 68.0%, and cholesterol secretion rate decreased 54.3% and 72.4% from control on day 1, respectively. All changes returned to the control level in 3 to 9 days with accompanying increasing liver size during regeneration. CONCLUSION: Alterations of total bile flow, bile salt independent flow, bile salt secretion rate, bile salt basal synthesis rate, and biliary lipid secretion after partial hepatectomy correlate with the liver regeneration rate in rats. Partial hepatectomy reduces the bile salt independent fraction calculated as per 100 g body weight rather than the dependent fraction. The study of bile salt and biliary lipid secretion is a useful method for monitoring synthetic function in liver regeneration in vivo.

OBJECTIVE: This experiment determined the effects of liver transplantation on bile salt kinetics and biliary lipid secretion. SUMMARY BACKGROUND DATA: Depression of bile secretion in the three main components and bile cholesterol supersaturation with a high incidence of cholesterol stone formation have been documented in patients with end stage liver diseases after transplantation. However, physiologic changes of bile salt and lipid secretion in recipients remain unclear. METHODS: The study was done using a rat liver transplant model with 1 and 6 hours of donor liver cold preservation in saline. A chronic common bile duct fistula and a duodenal cannula were established for bile collection and the sample biochemical study for 6 days. RESULTS: Altered bile salt kinetics in liver grafted rats included depressed bile flow for 1-3 hours after the revascularization, decreased bile salt concentration and outputs, reduced bile salt basal synthesis rate, and reduced bile salt pool size during the early postoperative period. Phospholipid concentration and secretion rate depressed for 1-3 days without altered cholesterol level. The uncoupling change of the cholesterol and the other bile components resulted in an increased lithogenic indices in bile on days 2 and 3. CONCLUSION: Alterations of bile composition and bile salt kinetics occur in liver transplanted rats. The changes may result from injuries of the liver microcirculation and parenchymal cells caused by cold preservation. The study of bile secretion is helpful for evaluation of the initial graft function. The changed ratio of three bile components may be important for cholesterol stone formation in the liver transplant recipient.

The generation of the steady rectilinear flow of an Oldroyd B fluid in a rectangular duct is considered. The Laplace transform is used to separate out the time dependence from the governing equations and a Fourier series is used to solve the resulting Poisson problem in the space variables. It is seen that the presence of elasticity in the fluid gives rise to velocity ‘overshoot’. The solution of Waters and King for the planar channel is recovered at large aspect ratios.