Continuous paravertebral block for thoraco-abdominal oesophageal surgery.
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Abdomen↗
Biomedical subjects
D J Sanders
Publications and source records attributed to D J Sanders.
Sequence analysis and resistance to pepsin hydrolysis as part of an assessment of the potential allergenicity of ice structuring protein type III HPLC 12.
The recently published WHO/FAO guidelines on the assessment of allergenicity of novel food proteins provide a strategy with which to approach the determination of the potential of novel proteins in foods to be allergens. Key to this strategy are the assessment of sequence similarity to known allergens and the assessment of the resistance to pepsin hydrolysis. Ice structuring proteins (also commonly referred to as anti-freeze or thermal hysteresis proteins) are a group of naturally occurring proteins that bind to ice and structure ice crystal formation. The amino acid sequence of the ice structuring protein (ISP) type III HPLC 12 (ISP type III) was compared in silico with the sequences of known allergens. Secondly, the resistance to pepsin hydrolysis of ISP type III and its glycoconjugates (produced in recombinant baker's yeast) was assessed. The results indicate that ISP type III has no sequence similarity with known allergenic proteins. Both ISP type III and ISP type III glycoconjugates contained within the fermentation product were hydrolysed readily by pepsin (50% loss in <10 min at pH 1.5) to give peptide fragments that were too small to be allergenic or to trigger cross-linking to IgE. In an accompanying study, we demonstrated that IgE from fish-allergic individuals did not bind ISP Type III. Therefore, in accordance with the WHO/FAO strategy, the assessment of ISP type III and ISP type III glycoconjugates by sequence analysis together with lack of resistance to pepsin hydrolysis and the absence of IgE binding supports the conclusion that both are unlikely to present a potential sensitisation hazard.
Allergens↗
The long Bain breathing system: an investigation into the implications of remote ventilation.
A long version of the Bain breathing system is commonly used when remote anaesthesia is required, such as during magnetic resonance imaging or radiotherapy. We compared the static compliance and distal pressures over a range of flows in a 1.6 and 9.6 m Bain system. We examined the effect on ventilation of increasing the length of the Bain system in lung models for 10, 20 and 70 kg patients. We found that static compliance was increased in the long Bain system. We found that with matched peak inspiratory ventilator pressures there was a reduction in peak inspiratory pressures at the patient end with the longer system (p < 0.001). A reduction in tidal volume was found with the 9.6 m Bain (p < 0.001), and positive end-expiratory pressure was increased (p = 0.01). Although the effect on tidal volume was proportionally small in the 70 kg simulation (660 and 617 ml in 1.6 and 9.6 m systems, respectively) it increases in significance in children, with a 23% reduction in tidal volume in the 10 kg mock lung (95 and 73 ml in 1.6 and 9.6 m systems, respectively). Anaesthetists should be aware of the reduction in tidal volume and increased positive end-expiratory pressure. During remote anaesthesia with a long Bain system, the ventilator should be adjusted to compensate.
Adult↗
Two kinds of transient outward currents, I(A) and I(Adepol), in F76 and D1 soma membranes of the subesophageal ganglia of Helix aspersa.
Transient outward currents were characterized with twin electrode voltage clamp techniques in isolated F76 and D1 neuronal membranes (soma only) of Helix aspersa subesophageal ganglia. In this study, in addition to the transient outward current (A-current, I(A)) described by Connor and Stevens (1971b), another fast outward current, referred to as I(Adepol) here, is described for the first time. This is similar to the current component characterized in Aplysia (Furukawa, Kandel & Pfaffinger, 1992). The separation of these two current components was based on activation and steady-state inactivation curves, holding potentials and sensitivity to 4-aminopyridine (4-AP). In contrast to I(A), I(Adepol) did not require hyperpolarizing conditioning pulses to remove inactivation; it was evoked from a holding potential of -40 mV, at which I(A) is completely inactivated. I(Adepol) shows noticeable activation at around -5 mV, whereas I(A) activates at around -50 mV. The time courses of I(Adepol) activation and inactivation were similar but slower than I(A). It was found that I(Adepol) was more sensitive than I(A) to 4-AP. 4-AP at a concentration of 1 mm blocked I(Adepol) completely, whereas 5-6 mm 4-AP was needed to block I(A) completely. This current is potentially very important because it may, like other A currents, regulate firing frequency but notably, it does not require a period of hyperpolarization to be active.
4-Aminopyridine↗
The absorption, distribution and excretion of 1- and 2-.
Human breast milk is rich in 2-palmitoyl 1,3 unsaturated triacyglycerols and during the neonatal period, when milk is the sole source of nutrients, their role could be particularly important. Betapol is a novel triacylglycerol mix resembling human breast milk in its high palmitic acid content and positional distribution. The total fat absorption from Betapol has been shown to be higher than fat from conventional infant milk formulas and closer to human breast milk in infants. However, the relative fate of purified palmitic acid esterified to glycerol in the 1-, 3- and 2-positions in neonatal and young animals has not previously been established. Therefore, the fate of orally administered 1-[1-14C]palmitoyl, 2,3 dioleoyl glycerol ([14C]POO) and 1,3 dioleoyl,2-[1-14C]palmitoyl glycerol (O[14C]PO) was investigated in suckling and weanling rats using liquid scintillation counting of tissues and expired air and whole-body autoradiography. The results obtained indicate that orally administered [14C]POO and O[14C]PO are extensively absorbed from the gut, probably either as palmitic acid or as a palmitoyl glyceride in both suckling and weanling rats. Radioactivity initially concentrated in brown fat with apparent migration to the white fat of weanling rats by 96 h. Levels of 14C were low in blood, brain and other tissues. Excretion of 14C was mainly by expiration of CO(2) (approximately 72% in 96 h), indicating beta-oxidation as a major route of metabolism. Urine and faeces accounted for only approximately 6% of the excreted radioactivity. The design and size of the experiment did not allow tests of statistical significance between the absorption and excretion of OPO and POO to be conducted. However, the absorption, distribution, beta-oxidation and excretion appeared to be similar.
Animals↗
Reducing unnecessary blood cross-matching.
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Blood Grouping and Crossmatching↗
Single-lung ventilation via a tracheostomy using a fibreoptically-directed 'steerable' endobronchial blocker.
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Aged↗
Effect of calcium and calcium channel blockers on transient outward current of F76 and D1 neuronal soma membranes in the subesophageal ganglia of Helix aspersa.
Twin-electrode voltage-clamp techniques were used to study the effect of calcium and calcium channel blockers on the transient outward current in isolated F76 and D1 neurones of Helix aspersa subesophageal ganglia in vitro (soma only preparation with no cell processes). On lowering extracellular Ca(2+) concentration from 10 to 2 mm or removing extracellular calcium from the bathing medium, the threshold for this current shifted in a negative direction by 11. 5 and 20 mV, respectively. On the other hand, increasing the extracellular Ca(2+) concentration from 10 to 20 and to 40 mm shifted the steady-state inactivation curves in positive directions on the voltage axis by 7 and 15 mV, respectively. Upon application of calcium channel blockers, Co(2+), La(3+), Ni(2+) and Cd(2+), transient potassium current amplitude was reduced in a voltage-dependent manner, being more effective at voltages close to the threshold. The current was elicited even at a holding potential of -34 mV. The specific calcium channel blockers, amiloride and nifedipine did not shift the activation and steady-state inactivation curves and did not reduce the transient outward current amplitude. It was concluded that the transient outward current is not dependent on intracellular Ca(2+) but that it is modulated by Ca(2+) and di- and trivalent ions extracellularly. The effects of these ions are very unlikely to be due to a surface charge effect because the addition of La(3+) (200 microm) completely reverses the shift in a hyperpolarizing direction when the extracellular Ca(2+) concentration was reduced from 10 to 1 mm and additionally shifts the kinetics further still in a depolarizing direction. The responses seen here are consistent with a specific effect of di- and trivalent ions on the transient outward current channels leading to a modification of gating.
Amiloride↗
The safety evaluation of phytosterol esters. Part 6. The comparative absorption and tissue distribution of phytosterols in the rat.
As part of an extensive safety evaluation programme, a series of studies has been conducted to determine the fate of phytosterols in the rat. Rats were dosed by oral gavage with 14C-labelled samples of cholesterol, beta-sitosterol or beta-sitostanol or (3)H-labelled samples of beta-sitostanol, campesterol, campestanol or stigmasterol dissolved in sunflower seed oil. Urine and faeces were collected for up to 96 hours after dosing. There was no quantification of biliary excreted material in these studies. Animals were sacrificed and either prepared for whole body autoradiography or tissues and carcass remains were assayed for 14C or (3)H. The overall absorption of phytosterols was low as judged by tissue and carcass levels of radioactivity. Elimination from the body was mainly in the faeces and was initially very rapid, but traces of material were still being excreted at 4 days after dosing. While total absorption of the phytosterols could not be fully quantified without biliary excretion data, it was clear that cholesterol was absorbed to the greatest extent (27% of the dose in females at 24 hours). Campesterol (13%) was absorbed more than beta-sitosterol and stigmasterol (both 4%) which were absorbed more than beta-sitostanol and campestanol (1-2%). The absorption of phytosterols was slightly greater in females than males. For each test material, the overall pattern of tissue distribution of radioactivity was similar, with the adrenal glands, ovaries and intestinal epithelia showing the highest levels and the longest retention of radioactivity.
Animals↗
Morphological and electrophysiological features of F76 and D1 neurones of the sub-oesophageal ganglia of Helix aspersa in vitro and in culture.
Identified neurones F76 and D1 of the suboesophageal ganglia of Helix aspersa were studied in the isolated ganglia in vitro and in culture. The neurones were examined electrophysiologically with current clamp and morphologically either with intracellular injections of Lucifer Yellow or biocytin. These nerve cells had very similar resting membrane potentials and responses to injected current. The projections of D1 and F76 have been characterised, with both neurones having two main axons. The F76 neurones project to the left pallial, right pallial, anal, and visceral nerves as well as to the left and right pleural ganglia. The D1 neurones have similar projections except that they do not project to the anal and visceral nerves. The bilateral symmetry to the pallial nerves and pleural ganglia is discussed. These cells were also studied electrophysiologically after mechanical isolation and culture. F76 and D1 neurones were separated by dissection (no enzymes) and cultured in three ways. In normal snail Ringer they remained viable for up to two weeks with no development. In Ringer preincubated with a ganglia or containing endothelial growth factor, neurite outgrowths were seen. Membrane potentials were significantly lower in cultured neurones than in vitro and the after hyperpolarization never went below resting in cultured cells but it did in vitro.
Action Potentials↗
Pulmonary haemorrhage after percutaneous paravertebral block.
We describe the management of a 65-yr-old woman anaesthetized for thoracotomy. The patient suffered a pulmonary haemorrhage after percutaneous paravertebral injection performed using the loss of resistance to saline technique. Thoracotomy at a later date revealed that the lung tissue had become adherent to the chest wall and that the paravertebral space was fibrosed secondary to previous surgery. This particular complication of percutaneous paravertebral block has not been reported previously and raises the question of risk vs benefit of this pre-emptive analgesic technique.
Aged↗
Membrane properties of mouse dorsal cochlear nucleus neurons in vitro.
Intracellular recordings were made from neurons of the mouse dorsal cochlear nucleus (DCN) in vitro using current clamp techniques in the presence or absence of different ion channel blocking drugs. Four electrophysiologically distinct cell groups were identified in the DCN. The groups were characterized on the basis of their spontaneous firing properties, the shape of the action potential (AP) and the pattern of firing, the shape of the current-voltage (I/V) relationship and the effects of channel blocking agents. By comparison with known histology, three of the four DCN groups were postulated to be cartwheel-like, fusiform-like, or tuberculoventral-like cells. The fourth group was postulated to be a stellate-like as it had similar properties to the spike train (stellate) cell of the AVCN. DCN stellate-like cells were spontaneously active, the action potentials (APs) were always followed by a large, brief hyperpolarization and the cells had linear current voltage relationships. The fusiform-like cells were spontaneously active and spontaneous IPSPs were also observed. The I/V relationship was linear for these cells. Tuberculoventral-like cells were not spontaneously active, but APs could be elicited by inward current injection. The I/V relationships for tuberculoventral-like cells were linear. Cartwheel-like cells were spontaneously active. These cells were characterized by the distinctive shape of their APs which were single, large amplitude, short duration APs sometimes followed by a series of complexes consisting of small, long duration APs. Cartwheel-like cells were the only cell type in the DCN which had non-linear I/V relationships. All cells in the DCN had APs which were abolished by tetrodotoxin. Different calcium dependent channels play a role in the formation of both the fast single AP and the slow complex AP in the cartwheel-like cells since all APs were abolished by the use of high concentrations of verapamil. Verapamil dramatically increased the duration of APs in fusiform-like cells and had no effect on tuberculoventral-like cells. In both tuberculoventral-like cells and cartwheel-like cells, 4-aminopyridine (4AP) depolarized the cells and all APs were abolished. Tetraethylammonium chloride (TEA) had a similar effect in cartwheel-like cells. In stellate-like, tuberculoventral-like and fusiform-like cells, the hyperpolarization which followed the AP was abolished by TEA. The AP duration in these cells was also increased by TEA. 4AP had a similar effect in stellate-like and fusiform-like cells. The data for DCN suggest that electrophysiological properties can be used to distinguish and identify neurons.
Action Potentials↗
Membrane properties of complex spike firing neurons of the mouse dorsal cochlear nucleus in vitro.
Intracellular recordings were made from complex spike firing neurons of the mouse dorsal cochlear nucleus (DCN) in vitro. The whole cochlear nucleus was dissected out and maintained submerged in rapidly flowing artificial cerebrospinal fluid (CSF). Recordings were made with current clamp techniques in the presence or absence of ion channel blocking drugs tetrodotoxin (TTX, 1 microM), tetraethylammonium (TEA, 20 mM), 4-aminopyridine (4-AP, 5 mM) or verapamil (50, 100, 150, 250 microM). The cells showed both spontaneous firing and responses to injections of depolarising current consisting of a mixture of a tall single action potential and complexes of 2 to 3 smaller wider action potentials superimposed on a plateau depolarisation. The membrane properties were: resting membrane potential -68.8 +/- 8.5 mV, cell resistance 54.1 +/- 26.5 M omega, time constant 9.6 +/- 5.4 ms and capacitance 0.25 +/- 0.5 nF; the first three variables had bimodel distributions. The current/voltage (I/V) relationship at membrane below resting was non-linear. Previously published histological evidence from the mouse DCN has shown that both cartwheel cells and Purkinje-like neurons are present. Both DCN cartwheel cells and cerebellar Purkinje cells are known to fire both tall single action potentials and complexes of smaller wider action potentials. It is therefore possible that the recordings shown here were made from these neuron types. TTX (1 microM) abolished both the tall single and the complexes of smaller action potentials, suggesting that the tall single action potentials are sodium dependent and possibly that a TTX sensitive sodium channel is responsible for the plateau as is suggested for Purkinje cells in the cerebellum. Verapamil (100 microM) abolished only the complex action potentials and the plateau leaving the tall narrow action potentials intact, which is consistent with the smaller complexes being calcium dependent. Higher concentrations abolished all spiking activity. TEA and 4-AP used separately both caused marked depolarisation to around -20 mV, suggesting that there is a large potassium current active at and near resting.
4-Aminopyridine↗
Membrane properties of mouse anteroventral cochlear nucleus neurons in vitro.
Intracellular recordings were made from neurons of the mouse anteroventral cochlear nucleus (AVCN) in vitro. The whole cochlear nucleus was dissected out and maintained submerged in rapidly flowing artificial CSF. This preparation has the advantages of maintaining cell-to-cell connections and dendritic trees whereas slices and enzymatically separated preparations do not. Recordings were made using current clamp technique in the presence and absence of the ion channel blockers, tetrodotoxin (TTX 1 microM), tetraethylammonium (TEA 20 mM), 4-aminopyridine (4-AP 5 mM) or verapamil (150 microM). Two distinct types of neurons were observed when tested with depolarizing current pulses: one which fired only a single action potential at the onset of stimulation followed by a relative depolarization for the remainder of the stimulus period, and the other which fired a sustained train of action potentials, each followed by a large undershoot, then a rapid recovery phase and the slower depolarization to threshold. The single spike cells (n = 24) had resting membrane potentials of -63.4 +/- 4.7 mV, resistance of 48.4 +/- 29.6 M omega, time constant of 3.47 +/- 3.1 ms, capacitance of 0.081 +/- 0.079 nF. The I/V plot was non-linear above the resting membrane potential and linear below. Spike train cells (n = 24) had resting membrane potentials of -64.2 +/- 4.54 mV, resistance of 69.8 +/- 28.9 M omega, time constant of 6.51 +/- 3.09 ms, capacitance of 0.11 +/- 0.087 nF. The I/V plot was linear both below resting membrane potential and up to threshold for spike firing. TTX abolished spike firing in both cell types. TEA significantly increased the spike duration in both cell types. 4-AP increased the spike duration in spike train cells but not in single spike cells. Verapamil had no effect on the firing properties of both cells but it significantly increased the spike duration of spike train cells. The single spike cells are known to fire rapidly and repetitively in vivo. Injection of sine wave currents caused rapid and repetitive firing suggesting that these cells require hyperpolarization to allow for removal of inactivation. There was a linear relationship between injected depolarizing current and the rate of action potential firing in spike train cells.
4-Aminopyridine↗
Neostriatal modulation of motor cortex excitability.
The influence of the basal ganglia motor loop on motor cortex function was examined by pharmacologically altering neostriatal activity while monitoring the electrical stimulation thresholds for eliciting movements of the ipsilateral and contralateral motor cortex in ketamine anesthetized rats. Repeated unilateral intraneostriatal infusions (1-3) of the glutamate agonist, kainic acid (0.1 microliter, 75 ng), or glutamate (0.3 microliter, 1.65 micrograms) reliably increased ipsilateral but not contralateral cortical thresholds. Single infusions of kainic acid (0.3 microliter, 150 or 225 ng) elevated ipsilateral cortical thresholds for 30-45 min; with glutamate (0.3 microliter, 1.65 micrograms), the change lasted less than 10 min. Antidromically identified striatonigral projection neurons (n = 8) located approximately 500 microM from the infusion cannula, showed either increased firing (n = 4) for less than 10 min following glutamate infusion or no change from their non-firing state (n = 4). Non-antidromically activated neurons (n = 3) were all excited by the infusion, although an interval of inhibition preceded or followed the excitation in two cases. Infusions (0.3 microliter) of inhibitory agents (GABA, 31 and 310 ng; muscimol 34.2 ng; and DNQX 34.2 ng) did not alter cortical threshold, nor did saline vehicle. Lesion of the ventrolateral but not ventromedial thalamic nucleus prevented the modulation of cortical thresholds following intraneostriatal infusion of 225 ng kainic acid. Thus the neostriatal alteration of cortical thresholds indicates a modulation of cortical excitability via thalamic projections and not the outcome of competing descending cortical and neonstriatal influences converging on motorneurons. These results suggest that tonic feedforward modulation of the motor cortex and the pyramidal tract by the basal ganglia can be inhibitory.
Animals↗
Subthalamic nucleus and globus pallidus lesions alter activity in nigrothalamic neurons in rats.
Lesions of the subthalamic nucleus or the globus pallidus altered the response of substantia nigra pars reticulata neurons (antidromically identified as projecting to the thalamus) to electrical stimulation of the frontal agranular cortex. In intact animals, cortical stimulation evokes three independent responses (excitation, inhibition, excitation) that may occur singly or in various combinations. The independence of the various responses, especially the temporally coincident excitatory and inhibitory responses, suggests that the net inhibitory and excitatory pathways carrying these signals from the cortex may converge to varying degrees on individual nigrothalamic neurons. Subthalamic lesions increased total response duration (from 28.4 to 39.7 ms), increased the duration of inhibition (from 18 to 30 ms), decreased the occurrence of excitatory responses, and decreased the intensity of the second excitation (from 1.1 to 0.6 spikes/s). Lesion of the globus pallidus also increased total response duration (up to 38 ms), but by increasing the duration of the second excitation (from 15.1 up to 23.8 ms). The intensity of the second excitation (from 1.1 to 1.5 spikes/stimulus) and the number of cells showing the first and second excitations also increased. The incidence, but not the duration, of the inhibition increased. The mean firing rate increased after subthalamic nucleus lesion (34.2 spikes/s) as compared to intact (27.0) or globus pallidus lesion (25.6). These changes may reflect changes in the relative contribution of the five different pathways transmitting information from the cortex to the substantia nigra. In all cases the cortico-striato-nigral pathway is largely intact.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of humidification on inhalation induction with isoflurane in children.
A well practised technique is important in achieving quiet induction of anaesthesia in children, but the volatile agent used also influences the process. Isoflurane results in more airway problems than halothane but recent studies have described several ways of improving the acceptability of isoflurane for inhalation induction of anaesthesia. We have studied the effect of humidification of inspired gases on respiratory complications and hypoxic episodes during induction. Forty-one children undergoing inhalation induction of anaesthesia with isoflurane and nitrous oxide in oxygen were allocated randomly to receive either humidified or non-humidified gas. Humidification did not result in a lesser incidence of problems. These findings are contrary to the results in a similar study in a predominantly adult sample which demonstrated a significantly lower incidence of complications using humidified gases.
Anesthesia, Inhalation↗
Does the potency of fentanyl vary with different inhalational agents?
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Administration, Inhalation↗