Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 19 recordsLinked to original sources

PubMed2007

Population pharmacokinetics of mefloquine in military personnel for prophylaxis against malaria infection during field deployment.

OBJECTIVE: The purpose of this study was to determine the population pharmacokinetics of mefloquine in healthy military personnel during prophylaxis for malaria infections. METHODS: The subjects were 1,111 Australian soldiers participating in two studies: a randomised double-blinded study (group A, 161 subjects) and an open-label study (group B, 950 subjects). Following a loading dose (250 mg mefloquine base daily, 3 days), subjects received an oral weekly maintenance dose of 250 mg over 6 months. Blood was collected after the last split loading dose then at weeks 4, 8 and 16 for group A, and at weeks 13 and 26 for group B. Plasma mefloquine concentrations were measured by high-performance liquid chromatography (HPLC). Pharmacokinetic modelling was performed using NONMEM. RESULTS: A two-compartment model with inter-occasion variability (IOV) for clearance satisfactorily described the pharmacokinetics. Typical values were clearance (CL/F, 2.09 l/h), central volume of distribution (V1/F, 528 l), absorption rate constant (KA, 0.24 h(-1)), inter-compartmental clearance (Q/F, 12.5 l/h), peripheral volume of distribution (V2/F, 483 l) and elimination half-life (t (1/2), 14.0 days). Weight had a positive influence on central volume but was insufficient to warrant dosage adjustments. The inter-individual variability (coefficient of variation, CV%) for CL/F and V1/F was 24.4% and 29.6%, respectively. The IOV for CL/F was 17.8%. The proportional residual error (CV%) for groups A and B was 11.5% and 19.5%, respectively, and the additive error standard deviation (SD) was 57 ng/ml and 149 ng/ml, respectively. CONCLUSION: The typical parameter values were comparable with those estimated in much smaller cohorts of healthy subjects and in malaria patients treated with single-dose mefloquine. The lower unexplained variability in the blinded study suggested these subjects may have been more compliant in taking their medication than soldiers in the open-label study.

Adolescent↗

PubMed2006

Lung morphology after late fetal tracheal ligation in rats.

Pulmonary hypoplasia and persistent pulmonary hypertension are the main causes of mortality and morbidity in congenital diaphragmatic hernia (CDH). Prenatal tracheal occlusion accelerates lung growth, but the mechanism remains unknown. In order to be able to establish the accuracy of our experimental model for further molecular biological examinations, we evaluated the histologic structure of 1. fetal lungs subjected to tracheal occlusion compared to 2. normal fetal lungs, 3. hypoplastic lungs in CDH, and 4. normal neonatal lungs. One group of Sprague-Dawley rat fetuses were subjected to intrauterine tracheal ligation (TL) on gestational day 19 (n = 7). Control fetuses were obtained from the same litters as those subjected to TL (n = 8). Another group of pregnant Sprague-Dawley rats were given 100 mg nitrofen on gestational day 9.5 to create CDH (n = 8). All fetuses were delivered by cesarean section on day 21. Lungs from 1-day-old, healthy, non-operated, newborn Sprague-Dawley rats were also examined (n = 6). Lung weight to body weight ratio was significantly higher in the TL lungs (5.0 +/- 0.36 %), compared to control lungs (2.8 +/- 0.15 %), CDH lungs (1.9 +/- 0.12 %), and normal neonatal lungs (4.2 +/- 0.18 %). Volume density of alveolar air space and radial alveolar count (RAC) in TL lungs (52 +/- 1.4 %) (3.3 +/- 0.25) were significantly higher than in control lungs (34 +/- 3.4 %) (2.2 +/- 0.17) and in CDH lungs (16 +/- 1.7 %) (1.7 +/- 0.07). No significant differences were found between the TL and the normal neonatal group (59 +/- 1.4 %) (3.6 +/- 0.11). Fetal lungs after TL showed evidence of growth stimulation with increased volume density of alveolar air space and increased RAC, comparable to findings in normal neonatal lungs.

Age Factors↗

PubMed2005

Biophysical and physiological properties of porcine surfactant enriched with polymyxin B.

OBJECTIVE: We examined whether the biophysical and physiological properties of Curosurf were improved by the cyclic amphipathic decapeptide polymyxin B (PxB). METHODS: Curosurf was diluted to 1-5 mg/ml with PxB added at 1, 2 or 3% (w/w). Albumin was added at 40 mg/ml. Minimum surface tension (gammamin) during surface compression was determined for each mixture with pulsating bubble. Immature newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32 mg/ml with or without 2% PxB and ventilated for up to 5 h. RESULTS: At surfactant concentration 2 mg/ml, gammamin was high (17 +/- 8.9 mN/m) but remained low (2.7 +/- 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5 mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax in comparison with controls but had no significant effect on lung-thorax compliance or alveolar expansion. CONCLUSION: Addition of 2% PxB improves surface activity of Curosurf at low concentration, increases its resistance to inactivation by albumin, and reduces the incidence of pneumothorax in immature newborn rabbits undergoing prolonged ventilation.

Administration, Inhalation↗

PubMed2005

Online optimization of fuzzy-PID control of a thermal process.

A constrained optimization of a simple fuzzy-PID (PID-proportional integral derivative) system is designed for the online improvement of PID control performance during productive control runs. The cost function design yields a desirable balance between rise time, setpoint overshoot, and settling time to the setpoint. The constraints determined by simulation yield control performance no worse than the existing control performance during online optimization. The optimized fuzzy-PID system is compared to a similarly optimized PID controller and a benchmark model predictive controller.

Journal Article↗

PubMed2004

Lipid peroxidation of lung surfactant in experimental neonatal group B streptococcal pneumonia.

Group B streptococcal (GBS) pneumonia, with neutrophilic granulocytes immigrating into the lungs, may occur in neonates. The incidence is particularly high among preterm infants, who often are treated with exogenous surfactant. We have previously demonstrated in vitro that neutrophils stimulated by GBS cause lipid peroxidation (LPO) and functional impairment of lung surfactant. The present study aimed at evaluating LPO of exogenous lung surfactant (Curosurf) and the protective effect of the natural antioxidant, vitamin E in immature ventilated newborn rabbits with experimental neonatal GBS pneumonia. There was a prominent proliferation of GBS in the lungs of animals treated with surfactant and ventilated for 5 h. GBS-infected rabbits had a higher LPO of lung lavage fluid than non-infected ones. The LPO could be diminished using vitamin E, which, however, did not affect bacterial proliferation. During the 5-h incubation period, mean lung-thorax compliance values were significantly lower in GBS-infected than in noninfected animals. We speculate that addition of vitamin E to exogenous surfactant preparations may improve their resistance to LPO and make them more suitable for treatment of neonates with pneumonia.

Animals↗

PubMed2004

Dendrotoxins: structure-activity relationships and effects on potassium ion channels.

Dendrotoxins are small proteins isolated from mamba (Dendroaspis) snakes. The original dendrotoxin was found in venom of the Eastern green mamba, Dendroaspis angusticeps, and related proteins were subsequently found in other mamba venoms. The dendrotoxins contain 57-60 amino acid residues cross-linked by three disulphide bridges, and they are homologous to Kunitz-type serine protease inhibitors, such as aprotinin (BPTI). The dendrotoxins have little or no anti-protease activity, but they block particular subtypes of voltage-dependent potassium channels of the Kv1 subfamily in neurones. Alpha-dendrotoxin from green mamba Dendroaspis angusticeps and toxin I from the black mamba Dendroaspis polylepis block cloned Kv1.1, Kv1.2 and Kv1.6 channels in the low nanomolar range; toxin K, also from the black mamba Dendroaspis polylepis, preferentially blocks Kv1.1 channels and is active at picomolar concentrations. Structural modifications and mutations to dendrotoxins have helped to define the molecular recognition properties of different types of K+ channels, although more work is needed to characterise the chemical features of the toxins that underlie their selectivity and potency at particular subtypes of channels. Dendrotoxins have been useful markers of subtypes of K+ channels in vivo, and dendrotoxins have become widely used as probes for studying the function of K+ channels in physiology and pathophysiology. With some pathological conditions being associated with voltage-gated K+ channels, analogues of dendrotoxins might have therapeutic potential.

Amino Acid Sequence↗

PubMed2003

Distribution of antinociceptive adenosine A1 receptors in the spinal cord dorsal horn, and relationship to primary afferents and neuronal subpopulations.

Adenosine can reduce pain and allodynia in animals and man, probably via spinal adenosine A1 receptors. In the present study, we investigate the distribution of the adenosine A1 receptor in the rat spinal cord dorsal horn using immunohistochemistry, in situ hybridization, radioligand binding, and confocal microscopy. In the lumbar cord dorsal horn, dense immunoreactivity was seen in the inner part of lamina II. This was unaltered by dorsal root section or thoracic cord hemisection. Confocal microscopy of the dorsal horn revealed close anatomical relationships but no or only minor overlap between A1 receptors and immunoreactivity for markers associated with primary afferent central endings: calcitonin gene-related peptide, or isolectin B4, or with neuronal subpopulations: mu-opioid receptor, neuronal nitric oxide synthase, met-enkephalin, parvalbumin, or protein kinase Cgamma, or with glial cells: glial fibrillary acidic protein. A few adenosine A1 receptor positive structures were double-labeled with alpha-amino-3-hydroxy-5-methyl-4-isoaxolepropionic acid glutamate receptor subunits 1 and 2/3. The results indicate that most of the adenosine A1 receptors in the dorsal horn are located in inner lamina II postsynaptic neuronal cell bodies and processes whose functional and neurochemical identity is so far unknown. Many adenosine A1 receptor positive structures are in close contact with isolectin B4 positive C-fiber primary afferents and/or postsynaptic structures containing components of importance for the modulation of nociceptive information.

Adenosine↗

PubMed2003

Pulmonary surfactant from healthy Belgian White and Blue and Holstein Friesian calves: biochemical and biophysical comparison.

The biochemical composition and biophysical behaviour of pulmonary surfactant samples isolated from healthy Belgian White and Blue (BWB) and Holstein Friesian (HF) calves have been investigated and compared. Interesting differences in composition have been demonstrated. In particular, a higher level of total hydrophobic surfactant-associated proteins (SP) (due to higher levels of SP-B and SP-C) is reported in HF calves compared to BWB calves. Higher levels of phosphatidylcholine (PC) and especially the disaturated form of PC were also found in HF as compared to BWB calves. No immediate effect on the surface tension properties evaluated by the pulsating bubble surfactometer was found between the surfactant samples of the two breeds under physiological conditions. However, since a high content of disaturated PC and the presence of the SP-B and SP-C are thought to be essential for the surface activity, we propose that the reported modifications could contribute to the apparently lower resistance of the BWB calves to respiratory troubles in comparison with HF calves.

Animals↗

PubMed2003

A lung recruitment maneuver immediately before rescue surfactant therapy does not affect the lung mechanical response in immature lambs with respiratory distress syndrome.

BACKGROUND: In animals with acquired surfactant-deficiency, a recruitment maneuver by increased tidal volumes enhances the effect of exogenous surfactant. In contrast, in the preterm lamb model, hyperinflation early after birth impairs the effect of surfactant prophylaxis. Here we examined whether a lung recruitment maneuver just before surfactant would affect the response to rescue treatment in immature lambs with established respiratory distress syndrome (RDS). METHODS: Five pairs of preterm twin lambs with gestational age 127 days were delivered by cesarean section and supported by pressure-limited mechanical ventilation for 4 h. At 30 min of age, when all the lambs were in severe respiratory failure, they were treated with porcine surfactant, 200 mg x kg-1. One lamb in each pair was subjected to a lung recruitment maneuver consisting of five sustained inflations of 20 ml x kg-1 just before surfactant instillation. RESULTS: At 10 min after surfactant treatment, all the lambs showed a large improvement in oxygenation and an increase in inspiratory capacity and static compliance. Except for a transiently better oxygenation after surfactant therapy in the recruitment group (P < 0.05), there was no significant between-group differences in gas exchange or lung mechanics at any time point during the study. There was no difference in post mortem intrapulmonary air volume or alveolar expansion in histologic lung sections between groups. CONCLUSION: This small study does not show any positive or negative effect of a lung recruitment maneuver on the response to rescue surfactant therapy in immature animals with RDS.

Animals↗

PubMed2003

Prediction of respiratory distress syndrome by the microbubble stability test on gastric aspirates in newborns of less than 32 weeks' gestation.

AIM: There is a need for a rapid method to identify infants who will develop respiratory distress syndrome (RDS) soon after birth, to allow early treatment of affected infants with surfactant. The microbubble stability test (MST) may be one such method, but clinical experience is sparse. METHODS: The MST was performed on gastric aspirates from 188 infants with a mean gestational age of 29 (range 23-31) wk. RESULTS: 87 infants developed moderate to severe RDS, corresponding to a prevalence of 46%. The sensitivity, specificity and predictive values for identification of infants with moderate to severe RDS were determined for the average diameter of bubbles, the proportion of microbubbles with different diameters and the total number of microbubbles. The proportion of microbubbles with diameters <20 or 25 microm gave the best prediction, with a sensitivity of 78-79%, a specificity of 57-58%, a positive predictive value of 62% and a negative predictive value of 76%. Early treatment with nasal continuous positive airway pressure probably mitigated the development of RDS in some infants with a low-degree surfactant deficiency and this may explain the relatively low specificity. CONCLUSION: In infants of <32 wk gestation RDS can be predicted by computerized image analysis of the size distribution of microbubbles generated in gastric aspirates.

Gestational Age↗

PubMed2003

Cladocera fauna composition in a river-lagoon system of the Upper Paraná River floodplain, with a new record for Brazil.

Cladocera communities were studied in lotic and lentic environments of the Upper Paraná River floodplain, State of Mato Grosso do Sul, Brazil. A total of 63 species of Cladocera were identified in 108 samples. Of these, 24 species are considered new records for that floodplain, and one is a new record for Brazil. Chydoridae was the most representative family with 19 genera and 39 species.

Animals↗

PubMed2002

Case-control studies of sporadic cryptosporidiosis in Melbourne and Adelaide, Australia.

Few studies have assessed risk factors for sporadic cryptosporidiosis in industrialized countries, even though it may be numerically more common than outbreaks of disease. We carried out case-control studies assessing risk factors for sporadic disease in Melbourne and Adelaide, which have water supplies from different ends of the raw water spectrum. In addition to examining drinking water, we assessed several other exposures. 201 cases and 795 controls were recruited for Melbourne and 134 cases and 536 controls were recruited for Adelaide. Risk factors were similar for the two cities, with swimming in public pools and contact with a person with diarrhoea being most important. The consumption of plain tap water was not found to be associated with disease. This study emphasizes the need for regular public health messages to the public and swimming pool managers in an attempt to prevent sporadic cryptosporidiosis, as well as outbreaks of disease.

Adolescent↗

PubMed2002

Surfactant improves oxygenation in infants and children with pneumonia and acute respiratory distress syndrome.

AIM: Pneumonia in childhood may be associated with surfactant dysfunction and severe acute respiratory distress syndrome (ARDS). The aim of this study was to investigate the effects of surfactant treatment on oxygenation in 8 infants (age range: 1 mo to 13 y) with severe respiratory failure owing to viral, bacterial or Pneumocystis Carinii pneumonia. METHODS AND RESULTS: Instillation of a modified porcine surfactant (Curosurf) improved gas exchange immediately. Median paO2/FiO2 increased from 66 to 140 mmHg (8.8-18.7 kPa; p < 0.01) within 1 h of surfactant treatment. Seven of the 8 patients received multiple surfactant doses. Four patients (50%) died 3-62 d after surfactant treatment. However, 6 patients (75%) were immunodeficient, so that the observed mortality rate was mainly due to the underlying disease. CONCLUSION: Surfactant dysfunction probably plays a role in the pathophysiology of severe paediatric ARDS triggered by pneumonia, as it was found that surfactant instillation rapidly improved gas exchange in the majority of the affected infants in our study. Larger randomized controlled studies are necessary to evaluate the effects of surfactant treatment on morbidity and mortality.

Adolescent↗

PubMed2001

Polyethylene glycol/surfactant mixtures improve lung function after HCl and endotoxin lung injuries.

Addition of nonionic polymers such as polyethylene glycol (PEG) and dextran ameliorates inactivation of Survanta by a variety of substances in vitro. Addition of polymers to Survanta also improves pulmonary function when used to treat rats with lung injury caused by instillation of human meconium. To find whether this approach is effective in lung injuries that more closely resemble adult respiratory distress syndrome (ARDS), we have compared the use of Survanta with Survanta + PEG in two additional models of lung injury caused by either lipopolysaccharide (LPS) or HCl in adult rats. Significant improvement of serial measures for arterial oxygenation and of postmortem pressure-volume measurements were found after treatment with Survanta + PEG compared with Survanta alone. PEG added to Survanta increased resistance to inactivation caused by tracheal fluid taken from animals injured with HCl. Other work suggests that PEG promotes surfactant aggregation, separates surfactant from surfactant inhibitors, and enhances access of surfactant to the gas-liquid interface. The addition of polymers to surfactants may also be useful in the treatment of lung injury where inactivation of surfactant has already occurred.

Animals↗

PubMed2001

Genomics: leprosy - a degenerative disease of the genome.

Analysis of the genome of the leprosy bacillus uncovers evidence of extensive deletion and inactivation of genes. Secluded in a specialised niche, it has discarded much of its genetic heritage, though retaining just enough to be a major human pathogen.

Genome, Bacterial↗

PubMed2001

Simultaneous multianalyte detection with a nanometer-scale pore.

It was recently shown that naturally occurring, genetically engineered or chemically modified channels can be used to detect analytes in solution. We demonstrate here that the overall range of analytes that can be detected by single nanometer-scale pores is expanded using a potentially simpler system. Instead of attaching recognition elements to a channel, they are covalently linked to polymers that otherwise thread through a nanometer-scale pore. Because the rate of unbound polymer entering the pore is proportional to its concentration in the bulk, the binding of analyte to the polymer alters the latter's ability to thread through the pore, and the signal that results from individual polymer translocation is unique to the polymer type; the method permits multianalyte detection and quantitation. We demonstrate here that two different proteins can be simultaneously detected with this technique.

Bacterial Toxins↗

PubMed2001

Frequency response of alternating currents through the Staphylococcus aureus alpha-hemolysin ion channel.

Alternating currents were measured through transmembrane ion channels formed by Staphylococcus aureus alpha-hemolysin proteins in planar bilayer membranes as part of an investigation to determine the channel's frequency response and the appropriateness of an equivalent circuit commonly used to model electrical interactions at the surface of cells. The experimental approach includes a novel method for separating the alternating current through one or more channels, which is conductive in nature, from the capacitively coupled current through the membrane. Separation of the conductive and capacitive alternating currents made it possible to measure the frequency response of the alpha-hemolysin channels. The results of the study are consistent with an equivalent circuit of a membrane capacitor in parallel with one or more channel resistors over the frequency range 30-120 Hz. The possible usefulness of frequency response data for ion channels in cell membranes during investigations of biological effects of time-varying magnetic fields is briefly discussed.

Bacterial Toxins↗

PubMed2001

Effect of surfactant and specific antibody on bacterial proliferation and lung function in experimental pneumococcal pneumonia.

OBJECTIVE: To investigate the effect of surfactant and specific antibody on bacterial proliferation in experimental pneumococcal pneumonia. METHODS: Near-term newborn rabbits received a standard dose (10(7)) of type 3 pneumococci via the airways. Control animals were sacrificed 1 minute later. Other animals were ventilated for 5 hours and treated via the tracheal cannula with surfactant (Curosurf 200 mg/kg), a mixture of surfactant and a polyclonal antipneumococcal antibody, the antibody without surfactant, or saline. RESULTS: There was a significant bacterial proliferation in lung tissue in all animals ventilated for 5 hours. Bacterial growth, expressed as log10 colony forming units (CFU) per gram of lung tissue was less prominent in animals treated with a mixture of surfactant and specific antibody than in animals treated with antibody alone (median, 7.51, range, 6.80--7.70 vs. median, 7.92, range, 7.07--8.50; P < 0.05). Dynamic lung-thorax compliance was improved with surfactant or surfactant plus antibody in comparison with saline or antibody alone. CONCLUSIONS: The data suggest that the suppressive effect of the antibody on bacterial proliferation becomes evident only when surfactant is administered together with the antibody.

Animals↗