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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lung recruitment at birth does not improve lung function in immature lambs receiving surfactant.

BACKGROUND: In mature animals with surfactant deficiency induced by lung lavage, the therapeutic effect of exogenous surfactant is enhanced by a lung recruitment maneuver. We then tested whether a lung recruitment maneuver at birth immediately before surfactant treatment would improve lung function also in preterm lambs with surfactant deficiency due to immaturity. METHODS: Ten newborn lambs with a gestational age of 127 days were randomized to receive surfactant either before the first breath or immediately after a lung recruitment maneuver consisting of five sustained inflations of 8, 16 or 32 ml/kg. Functional residual capacity was measured by sulfur hexafluoride washout, and inspiratory capacity as well as maximal compliance were obtained from a static expiratory pressure-volume curve after the lungs had been inflated to 35 cm H2O. In addition, blood gases were obtained. Measurements were made at 15, 45, 175, 135, 170 and 230 min after birth. Post mortem histological examinations of the lungs were performed in a blinded fashion. RESULTS: The lung recruitment maneuvers did not improve oxygenation. Inspiratory capacity, static compliance and functional residual capacity at 4 h, as well as post mortem intrapulmonary air volume, had an inverse relation to the size of inflations given at birth. There was also a negative correlation between size of inflations at birth and response to surfactant therapy, as assessed by lung microscopy. CONCLUSION: Lung recruitment at birth does not improve the response to surfactant in immature lambs, but may instead have an adverse effect on lung function and morphology.

Animals↗
PubMed2001

Trypanosoma brucei brucei crosses the blood-brain barrier while tight junction proteins are preserved in a rat chronic disease model.

African trypanosomiasis, sleeping sickness in humans, is caused by the systemic infection of the host by the extracellular parasite, the African trypanosome. The pathogenetic mechanisms of the severe symptoms of central nervous system involvement are still not well understood. The present study examined the routes of haematogenous spread of Trypanosoma brucei brucei (Tbb) to the brain, in particular on the question whether parasites can cross the blood-brain barrier, as well as their effect on tight junction proteins. Rats were infected with Tbb and at various times post-infection, the location of the parasite in the central nervous system was examined in relation to the brain vascular endothelium, visualized with an anti-glucose transporter-1 antibody. The tight junction-specific proteins occludin and zonula occludens 1, and the possible activation of the endothelial cell adhesion molecules ICAM-1 and VCAM-1 were also studied. At 12 and 22 days post-infection, the large majority of parasites were confined within blood vessels. At this stage, however, some parasites were also clearly observed in the brain parenchyma. This was accompanied by an upregulation of ICAM-1/VCAM-1. At later stages, 42, 45 and 55 days post-infection, parasites could still be detected within or in association with blood vessels. In addition, the parasite was now frequently found in the brain parenchyma and the extravasation of parasites was more prominent in the white matter than the cerebral cortex. A marked penetration of parasites was seen in the septal nuclei. In spite of this, occludin and zonula occludens 1 staining of the vessels was preserved. The results indicate that the Tbb parasite is able to cross the blood-brain barrier in vivo, without a generalized loss of tight junction proteins.

Animals↗
PubMed2001

The Cav2.1/alpha1A (P/Q-type) voltage-dependent calcium channel mediates inhibitory neurotransmission onto mouse cerebellar Purkinje cells.

The effects of voltage-dependent calcium channel (VDCC) antagonists on spontaneous inhibitory postsynaptic currents (sIPSCs) in mouse Purkinje cells were examined using in vitro cerebellar slices. The inorganic ion Cd2+ reduced sIPSC amplitude and frequency. No additional block was seen with the Na+ channel antagonist tetrodotoxin (TTX) suggesting that all action potential-evoked inhibitory GABA release was mediated by high-voltage-activated VDCCs. No evidence was found for involvement of Cav1/alpha1C and alpha1D (L-type), Cav2.2/alpha1B (N-type) or Cav2.3/alpha1E (R-type) high-voltage-activated VDCCs or low-voltage-activated Cav3/alpha1G, alpha1H and alpha1I (T-type) VDCCs in mediating presynaptic GABA release. Blockade of sIPSCs by 200 nM omega-agatoxin IVA implicated the Cav2.1/alpha1A (P/Q-type) subtype of high-voltage-activated VDCCs in mediating inhibitory transmission. Inhibition by omega-agatoxin IVA was similar to that seen with Cd2+ and TTX. Selective antibodies directed against the Cav2.1 subunit revealed staining in regions closely opposed to Purkinje cell somata. Cav2.1 staining was colocalized with staining for antibodies against glutamic acid decarboxylase and corresponded well with the pericellular network formed by GABAergic basket cell interneurons. Antibody labelling of Cav2.3 revealed a region-specific expression. In the cerebellar cortex anterior lobe, Cav2.3 staining was predominantly somatodendritic; whilst in the posterior lobe, perisomatic staining was seen primarily. However, electrophysiological data was not consistent with a role for the Cav2.3 subunit in mediating presynaptic GABA release. No consistent staining was seen for other Cav (alpha1) subunits. Electrophysiological and immunostaining data support a predominant role for Cav2.1 subunits in mediating action potential-evoked inhibitory GABA release onto mouse Purkinje cells.

Action Potentials↗
PubMed2001

Computerized image analysis of bubbles in gastric aspirate for prediction of respiratory distress syndrome.

UNLABELLED: Gastric aspirates were obtained from 80 newborn babies (gestational age 24-34 wk). Fifteen of these babies developed respiratory distress syndrome (RDS). Bubbles were generated in the samples by vigorous suctioning and the number and size distribution of the bubbles were determined in random fields by computer-aided image analysis. Sensitivity and specificity for prediction of RDS were 87% and 78% for average diameter of bubbles (cut-off points >45 microm) and similar for the proportion and total number of microbubbles (diameter <20 microm). CONCLUSION: Computerized image analysis of bubbles in gastric aspirate can be used for non-biased prediction of RDS in newborn babies.

Gases↗
PubMed2001

Long-term physical impairment and functional outcomes after complex facial fractures.

To develop an understanding of the expected functional outcomes after facial trauma, a retrospective cohort study of patients with complex facial fractures was conducted. A cohort of adults aged 18 to 55 years who were admitted to the R. Adams Cowley Shock Trauma Center between July of 1986 and July of 1994 for treatment of a Le Fort midface fracture (resulting from blunt force) was retrospectively identified. Outcomes of interest included measures of general health status and psychosocial well being in addition to self-reported somatic symptoms. General health status was ascertained using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). The Body Satisfaction Scale was used to define patient concerns about altered body image and shape. To determine whether complex maxillofacial trauma and facial fractures contributed to altered social interactions, the Social Avoidance and Distress scale was used. In addition, information about a patient, his or her injury, and its treatment were ascertained from the medical records. Using the methods described above, 265 patients with Le Fort fractures were identified. These individuals were matched to a similar group of 242 general injury patients. A total of 190 of the Le Fort patients (72 percent of those eligible for the study) and 144 (60 percent) general injury patients were successfully located, and long-term interview data were acquired.Le Fort fracture patients as a group had similar health status outcomes when compared with the group of general injury patients. However, when outcomes were examined by the complexity of the Le Fort fracture, the authors found that study subjects with severe, comminuted Le Fort injuries (group D) had significantly lower SF-36 scores (worse outcomes) for the two dimensions related to role limitations: role limitations due to physical problems and role limitations due to emotional problems (p < 0.05). SF-36 scores for all other dimensions except physical function were also lower for comminuted versus less complex Le Fort fractures, although differences were not statistically significant.Specifically, there was a direct relationship between severity of facial injury and patients reporting work disability. Of group C and D Le Fort patients (severely comminuted fractures) only 55 and 58 percent, respectively, had returned to work at the time of follow-up interview. These figures are significantly lower than the back-to-work percentage of patients with less severe facial injury (70 percent). When study participants were asked if they were experiencing specific somatic symptoms at the time of the interview that they had not experienced before the injury, a significantly larger percent of the Le Fort fracture patients (compared with the general injury patients) responded in the affirmative. Differences between the Le Fort fracture and general injury groups were statistically significant (p < 0.05) for all 11 symptoms. The percentage of patients reporting complaints increased with increasing complexity of facial fracture in the areas of visual problems, alterations in smell, difficulty with mastication, difficulty with breathing, and epiphora, and these differences reached statistical significance. Patients sustaining comminuted Le Fort facial fractures report poorer health outcomes than patients with less severe facial injury and substantially worse outcomes than population norms. It is also this severely injured population that reports the greatest percentage of injury-related disability, preventing employment at long-term follow-up. The long-term goal of centralized tertiary trauma treatment centers must be to return the patient to a productive, active lifestyle.

Activities of Daily Living↗
PubMed2001

Total intravenous versus inhalational anaesthesia for colonoscopy: a prospective study of clinical recovery and psychomotor function.

A randomized, prospective study was conducted on 69 patients comparing recovery after two different anaesthetic techniques for ambulatory colonoscopy. Thirty-five patients received an intravenous fentanyl (1 microg/kg), midazolam (0.05 to 0. 075 mg/kg) and propofol (10 to 20 mg boluses as required) combination. 34 patients received sevoflurane in 67% nitrous oxide. Drug administration was titrated to clinical signs. At baseline and 30, 60, 90 and 120 minutes after the procedure patient performance on a comprehensive battery of psychomotor tests was recorded. Emergence times were noted. Depth of sedation was assessed at 5 minute intervals for 30 minutes after the end of the procedure. Emergence times were faster in the fentanyl/midazolam/propofol group by 2.2 minutes. A lower sedation score was detected at 20 minutes in the sevoflurane/nitrous oxide group. Psychomotor impairment was of a greater magnitude and more prolonged by 30 to 90 minutes in the fentanyl/midazolam/propofol group. It is concluded that a sevoflurane/nitrous oxide anaesthetic has a suitable recovery profile for ambulatory colonoscopy and results in faster recovery of cognitive function compared with a fentanyl, midazolam and propofol combination.

Adolescent↗
PubMed2001

Resistance of different surfactant preparations to inactivation by meconium.

A disease similar to acute respiratory distress syndrome may occur in neonates after aspiration of meconium. The aim of the study was to compare the inhibitory effects of human meconium on the following surfactant preparations suspended at a concentration of 2.5 mg/mL: Curosurf, Alveofact, Survanta, Exosurf, Pumactant, rabbit natural surfactant from bronchoalveolar lavage, and two synthetic surfactants based on recombinant surfactant protein-C (Venticute) or a leucine/lysine polypeptide. Minimum surface tension, determined with a pulsating bubble surfactometer, was increased >10 mN/m at meconium concentrations >or=0.04 mg/mL for Curosurf, Alveofact, or Survanta, >or=0.32 mg/mL for recombinant surfactant protein-C, >or=1.25 mg/mL for leucine/lysine polypeptide, and >or=20 mg/mL for rabbit natural surfactant. The protein-free synthetic surfactants Exosurf and Pumactant did not reach minimum surface tension <10 mN/m even in the absence of meconium. We conclude that surfactant activity is inhibited by meconium in a dose-dependent manner. Recombinant surfactant protein-C and leucine/lysine polypeptide surfactant were more resistant to inhibition than the modified natural surfactants Curosurf, Alveofact, or Survanta but less resistant than natural lavage surfactant containing surfactant protein-A. We speculate that recombinant hydrophobic surfactant proteins or synthetic analogs of these proteins can be used for the design of new surfactant preparations that are relatively resistant to inactivation and therefore suitable for treatment of acute respiratory distress syndrome.

Animals↗
PubMed2001

Dynamic holography for optical interconnections. II. Routing holograms with predictable location and intensity of each diffraction order.

An analysis of dynamic phase-only holograms, described by fractional notation and recorded onto a pixelated spatial light modulator (SLM) in a reconfigurable optical beam-steering switch, is presented. The phase quantization and arrangement of the phase states and the SLM pixelation and dead-space effects are decoupled, expressed analytically, and simulated numerically. The phase analysis with a skip-rotate rule reveals the location and intensity of each diffraction order at the digital replay stage. The optical reconstruction of the holograms recorded onto SLM's with rectangular pixel apertures entails sinc-squared scaling, which further reduces the intensity of each diffraction order. With these two factors taken into account, the highest values of the nonuniform first-order diffraction efficiencies are expected to be 33%, 66%, and 77% for two-, four-, and and eight-level one-dimensional holograms with a 90% linear pixel fill factor. The variation of the first-order diffraction efficiency and the relative replay intensities were verified to within 1 dB by performing the optical reconstruction of binary phase-only holograms recorded onto a ferroelectric liquid crystal on a silicon SLM.

Journal Article↗
PubMed2000

Very low surfactant protein C contents in newborn Belgian White and Blue calves with respiratory distress syndrome.

We have studied a respiratory distress syndrome (RDS) occurring in newborn calves of the Belgian White and Blue (BWB) breed that represents the large majority of beef cattle in Belgium. Pulmonary surfactant isolated from 14 BWB newborn calves that died from RDS and from 7 healthy controls was analysed for composition and surface activity. An extremely low content or, in some instances, an absence of surfactant protein C (SP-C) was detected in the RDS samples by Western blotting and differential amino acid analysis [0.03+/-0.01% (w/w) relative to total phospholipids, compared with 0.39+/-0.06% for healthy controls (means+/-S.E.M., P < 0.001)]. The contents of surfactant protein B (SP-B) were similar in RDS and control samples. The crude surfactant samples isolated from RDS calves had higher ratios of total protein to total phospholipid, altered phospholipid profiles and lower SP-A contents. Both crude and organic extracts of RDS surfactant samples showed increased dynamic surface tension compared with healthy controls when evaluated with a pulsating-bubble surfactometer. The addition of purified SP-C to organic extracts of RDS surfactant samples lowered surface tension. Strongly decreased levels of mature SP-C associated with fatal RDS and altered surface activity in vitro have, to the best of our knowledge, not been previously reported. The mechanisms underlying RDS and the decrease in SP-C in BWB calves remain to be established.

Animals↗
PubMed2000

Driven DNA transport into an asymmetric nanometer-scale pore.

To understand the mechanism by which individual DNA molecules enter nanometer-scale pores, we studied the concentration and voltage dependence of polynucleotide-induced ionic-current blockades of a single alpha-hemolysin ion channel. We find that the blockade frequency is proportional to the polymer concentration, that it increases exponentially with the applied potential, and that DNA enters the pore more readily through the entrance that has the larger vestibule. We also measure the minimum value of the electrical potential that confines a modified polymer inside the pore against random diffusion and repulsive forces.

Bacterial Toxins↗
PubMed2000

Hyperpolarization-activated currents in presynaptic terminals of mouse cerebellar basket cells.

Using patch-clamp techniques, a hyperpolarization-activated current (I(h)) was recorded from synaptic terminals of mouse cerebellar basket cells. Ih was blocked quickly and reversibly by 2 mM Cs(+), and subtraction revealed a rapidly activating and deactivating I(h) current. Similar gating and block of presynaptic I(h) were also seen with the more selective inhibitor ZD 7288 (10 microM). The time constant of activation (tau (a))of presynaptic I(h) current became faster with membrane hyperpolarization, being approximately 74 ms at -130 mV, changing e-fold for a 33 mV change in membrane potential. Whole-cell recordings from basket cell somata also revealed an I(h) current, which was similarly sensitive to block by ZD 7288. Inhibition of I(h) by 10 microM ZD 7288 reduced the frequency ( approximately 34 %) and amplitude ( approximately 26 %) of spontaneous IPSCs (sIPSCs) recorded in Purkinje cells, one of the principal synaptic targets of basket neurones. This is the first report of an I(h) current in mammalian inhibitory presynaptic terminals, which may be an important target for neuromodulation in the cerebellum. Comparing the biophysical properties and distribution of cloned hyperpolarization-activated cation channels, we also suggest a molecular candidate underlying I(h) at these synapses.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Analysis of post-translational modification of mycobacterial proteins using a cassette expression system.

A recombinant expression system was developed to analyse sequence determinants involved in O-glycosylation of proteins in mycobacteria. By expressing peptide sequences corresponding to known glycosylation sites within a chimeric lipoprotein construct, amino acids flanking modified threonine residues were found to have an important influence on glycosylation. The expression system was used to screen mycobacterial sequences selected using a neural network (NetOglyc) trained on eukaryotic O-glycoproteins. Evidence of glycosylation was obtained for eight of 11 proteins tested. The results suggest that sites involved in O-glycosylation of mycobacterial and eukaryotic proteins share similar structural features.

Alkaline Phosphatase↗
PubMed2000

Interferon-gamma-responsive neuronal sites in the normal rat brain: receptor protein distribution and cell activation revealed by Fos induction.

Constitutive expression of the interferon-gamma receptor protein (IFN-gammaR), and the distribution of cells in which Fos, a marker of cell activation, is induced by intracerebroventricular administration of IFN-gamma, were studied in the rat brain by immunohistochemistry. IFN-gammaR immunopositivity was found in neuronal elements, which exhibited a selective distribution being concentrated in the piriform and entorhinal cortex, midline thalamus and medial hypothalamic structures, brainstem nociceptive relays (including the periaqueductal gray, the parabrachial nuclei and the caudal part of the spinal trigeminal nuclei), and circumventricular organs such as the median eminence and area postrema. IFN-gamma-induced Fos expression mostly corresponded to neuronal sites of receptor distribution. Because of its topographical distribution, it is suggested that activation of the IFN-gammaR in neurons may play a role to limit spread of infections in the brain and, in concert with other proinflammatory cytokines, to modulate adaptive responses to an antigen challenge mediated by the central nervous system.

Animals↗
PubMed2000

A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons.

Cerebellar granule neurons (CGNs) are one of the most populous cells in the mammalian brain. They express an outwardly rectifying potassium current, termed a "standing-outward" K(+) current, or IK(SO), which does not inactivate. It is active at the resting potential of CGNs, and blocking IK(SO) leads to cell depolarization. IK(SO) is blocked by Ba(2+) ions and is regulated by activation of muscarinic M(3) receptors, but it is insensitive to the classical broad-spectrum potassium channel blocking drugs 4-aminopyridine and tetraethylammonium ions. The molecular nature of this important current has yet to be established, but in this study, we provide strong evidence to suggest that IK(SO) is the functional correlate of the recently identified two-pore domain potassium channel TASK-1. We show that IK(SO) has no threshold for activation by voltage and that it is blocked by small extracellular acidifications. Both of these are properties that are diagnostic of TASK-1 channels. In addition, we show that TASK-1 currents expressed in Xenopus oocytes are inhibited after activation of endogenous M(3) muscarinic receptors. Finally, we demonstrate that mRNA for TASK-1 is found in CGNs and that TASK-1 protein is expressed in CGN membranes. This description of a functional two-pore domain potassium channel in the mammalian central nervous system indicates its physiological importance in controlling cell excitability and how agents that modify its activity, such as agonists at G protein-coupled receptors and hydrogen ions, can profoundly alter both the neuron's resting potential and its excitability.

Animals↗
PubMed2000

Electrophysiological characterization of voltage-gated K(+) currents in cerebellar basket and purkinje cells: Kv1 and Kv3 channel subfamilies are present in basket cell nerve terminals.

To understand the processes underlying fast synaptic transmission in the mammalian CNS, we must have detailed knowledge of the identity, location, and physiology of the ion channels in the neuronal membrane. From labeling studies we can get clues regarding the distribution of ion channels, but electrophysiological methods are required to determine the importance of each ion channel in CNS transmission. Dendrotoxin-sensitive potassium channel subunits are highly concentrated in cerebellar basket cell nerve terminals, and we have previously shown that they are responsible for a significant fraction of the voltage-gated potassium current in this region. Here, we further investigate the characteristics and pharmacology of the voltage-dependent potassium currents in these inhibitory nerve terminals and compare these observations with those obtained from somatic recordings in basket and Purkinje cell soma regions. We find that alpha-DTX blocks basket cell nerve terminal currents and not somatic currents, and the IC(50) for alpha-DTX in basket cell terminals is 3.2 nM. There are at least two distinct types of potassium currents in the nerve terminal, a DTX-sensitive low-threshold component, and a second component that activates at much more positive voltages. Pharmacological experiments also reveal that nerve terminal potassium currents are also markedly reduced by 4-AP and TEA, with both high-sensitivity (micromolar) and low-sensitivity (millimolar) components present. We suggest that basket cell nerve terminals have potassium channels from both the Kv1 and Kv3 subfamilies, whereas somatic currents in basket cell and Purkinje cell bodies are more homogeneous.

4-Aminopyridine↗
PubMed2000

Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide.

OBJECTIVE: To evaluate the efficacy of surfactant and inhaled nitric oxide (iNO) in endotoxin-induced acute lung injury (ALI). DESIGN: Prospective, randomised, controlled experimental study. SETTING: A medical university hospital research laboratory. INTERVENTION: Twenty-nine adult rabbits (2.4-3.4 kg) were given two doses of intravenous endotoxin (Escherichia coli) (0.01 mg/kg and, 12 h later, 0.1 mg/kg), and then subjected to mechanical ventilation. After 8 h these animals were allocated to four treatment groups: (1) control, (2) iNO at 20 ppm (NO), (3) surfactant at 100 mg/kg (Surf) and (4) both surfactant and iNO as in groups 2 and 3 (SNO), and ventilated for a further 6 h followed by broncho-alveolar lavage (BAL), analysis of surfactant contents in BAL fluid and histological examination of the lungs. MEASUREMENTS AND RESULTS: All the animals had developed ALI with respiratory failure 8 h after the second dose of endotoxin as evidenced by a decrease of PaO2/FIO2 from 520 +/- 30 to 395 +/- 19 mmHg and dynamic compliance (Cdyn) from 1.20 +/- 0.11 to 0.73 +/- 0.05 ml/ cmH2O x kg, and an increase of intrapulmonary shunting (Qs/Qt) from 7.5 +/- 0.8% to 12.9 +/- 1.0% (all measurements p < 0.01 versus baseline). In the SNO group, values for PaO2/FIO2, Cdyn and Qs/Qt after 6 h were 301 +/- 15 mmHg, 0.67 +/- 0.05 ml/cmH2O x kg and 16.5 +/- 0.8%, compared to 224 +/- 26 mmHg, 0.53 +/- 0.04 ml/ cmH2O x kg and 24.1 +/- 2.0%, respectively, in the control group (all measurements p < 0.01). Both Surf and NO groups showed intermediate levels of these parameters. In both Surf and SNO groups, the minimum surface tension of BAL fluid was lower, and the content of disaturated phosphatidylcholine/total protein higher, than in the control and NO groups (p < 0.01). Histological features of lung injury were less prominent and wet/dry lung weight ratio lower in the NO, Surf and SNO groups. Decreased surfactant protein A (SP-A) and its mRNA expression were found in all endotoxin-exposed groups, but the SP-A content of the SNO group was moderately improved in comparison to the control group. Surfactant aggregate size was not affected. CONCLUSION: Early application of surfactant and iNO moderately mitigated ALI as reflected by improvement of lung mechanics, pulmonary perfusion and morphology.

Administration, Inhalation↗