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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Biophysical activity of an artificial surfactant containing an analogue of surfactant protein (SP)-C and native SP-B.

Natural surfactant preparations containing phospholipids and the hydrophobic surfactant proteins B and C (SP-B and SP-C) are effective in the treatment of respiratory distress syndrome in premature infants. The limited supply, and the risk of infectious agents and immunological reactions have promoted the evaluation of synthetic peptides in surfactant preparations. However, the folding of synthetic SP-C into an alpha-helix is inefficient and alpha-helical SP-C analogues with Val-->Leu substitutions form oligomers. In order to circumvent these problems we have synthesized an SP-C analogue, named SP-C(LKS), which differs from SP-C mainly by the exchange of most of the Val residues in positions 16-28 with Leu residues to promote an alpha-helical conformation, and by the introduction of Lys residues at positions 17, 22 and 27 in order to locate positive charges around the helical circumference and thereby avoid self polymerization. CD spectroscopy showed a spectrum typical for alpha-helical peptides and SDS/PAGE disclosed a single band. The biophysical activity of artificial surfactant preparations containing SP-C(LKS) and phospholipids, with and without native SP-B, was measured using a Wilhelmy balance and a pulsating bubble surfactometer. SP-C(LKS) (3%, w/w) in a mixture of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/phosphatidylglycerol/palmitic acid (68:22:9, by wt.) suspended in 150 mM NaCl, showed rapid spreading at the air-liquid interface and produced a surface tension of <1 mN/m at minimum bubble size (gammamin) and 42 mN/m at maximum bubble size (gammamax) in the pulsating bubble surfactometer. The addition of 2% (w/w) SP-B to the preparation reduced the maximum surface tension to 33-35 mN/m, i.e. both gammamin and gammamax values were similar to those of natural surfactant preparations. Optimal in vitro characteristics were also obtained from a preparation containing SP-C(LKS), SP-B, DPPC and phosphatidylglycerol, i.e. when palmitic acid was omitted from the lipid mixture. SP-B containing surfactant preparations made up in Hepes buffer at pH 6.9, instead of in 150 mM NaCl, had similar biophysical activity provided that palmitic acid was omitted, but decreased activity in the presence of palmitic acid.

Amino Acid Sequence↗
PubMed1999

[Lung function in premature infants can be improved. Surfactant therapy and CPAP reduce the need of respiratory support].

Randomised trials have shown exogenous surfactant therapy to reduce mortality and morbidity among very low birthweight (VLBW) infants with respiratory distress syndrome (RDS). Surfactant therapy is normally given to infants on mechanical ventilation. In the Stockholm area, 12 VLBW infants born after 27-30 gestational weeks and suffering from RDS were recently treated using the INSURE (Intubation-SURfactant-Extubation) approach--i.e., surfactant therapy during brief intubation, immediately followed by extubation and continuous positive airway pressure (CPAP) treatment. The treatment was successful in all 12 cases, the mean (+/- SD) a/A ratio increasing significantly from 0.17 +/- 0.04 before the INSURE procedure to 0.46 (0.12 after (P < 0.001). Only one infant later needed mechanical ventilation for RDS.

Blood Gas Analysis↗
PubMed1999

Computerized image analysis of lung expansion patterns in surfactant treated immature newborn rabbits.

This study evaluates the alveolar stereological profile of immature rabbit lungs after treatment with various surfactant preparations, deliberately modified to represent different rates of film adsorption, minimum surface tension and compressibility. Surfactant was isolated from porcine or bovine lungs, and some of these preparations were enriched with dipalmitoylphosphatidylcholine and other synthetic lipids. Alveolar stereological parameters were evaluated in histological lung sections by computerized interactive image analysis. Surfactant treatment enhanced lung expansion, with a significant correlation coefficient between dynamic compliance and alveolar volume density in all groups of animals. Surfactant treatment also significantly increased alveolar image area. Enrichment of surfactant with synthetic lipids did not improve stereological parameters, but caused a significant increase in the coefficient of variation for alveolar perimeter and image area, suggesting more heterogeneous expansion pattern. Experimental evaluation of exogenous surfactants in immature newborn animals should include assessment of alveolar stereological parameters to detect deviations from the uniform expansion pattern seen after treatment with an optimal surfactant substitute.

Animals↗
PubMed1999

Genetic matches and the logic of the law.

In a recent article Levine and Kobilinsky (1997) point out that current methods in forensic DNA 'identification' are inadequate because the commercial kits commonly used in forensic practice do not detect the true genotype, but rather a genotype based on convenient categorization. For this reason, Levine and Kobilinsky argue that statistics attached to such categorizations are invalid. The authors believe that the arguments of Levine and Kobilinsky are logically flawed.

Criminal Law↗
PubMed1999

Combined effects of high-frequency ventilation and surfactant treatment in experimental meconium aspiration syndrome.

BACKGROUND: Deterioration of lung function in meconium aspiration syndrome may in part be due to inactivation of endogenous surfactant. We evaluated the efficacy of high-frequency ventilation (HFV) and the combination of HFV and surfactant therapy in the management of respiratory failure induced by experimental meconium aspiration in adult rats. METHODS: Animals were anesthetized and tracheotomized, and received via the tracheal cannula a suspension of human meconium (25 mg/ml, dose 4 or 5 ml/kg). After 30 min of conventional ventilation (CV) with 100% oxygen, animals were in respiratory failure as indicated by a decrease in lung-thorax compliance of > or = 30% and PaO2 < 10 kPa. They were then ventilated for an additional 3 h with either CV (frequency 40/min, inspiration time 50%) or HFV (frequency 15 Hz, inspiration time 50%) using comparable mean airway pressures (about 20 cmH2O) and variable FiO2. Subgroups of animals were treated with Curosurf (80 mg/ml, dose 200 mg/kg) 30 min after meconium aspiration; no additional material was instilled in controls. RESULTS: From 30 min onwards, values for PaO2/FiO2 were significantly higher in animals ventilated with HFV without receiving surfactant than in control animals subjected to CV alone (at 120 min; 18 +/- 7.3 vs. 7.4 +/- 0.8 kPa, P < 0.05). Additional improvement in oxygenation was seen in HFV-treated animals receiving Curosurf (at 120 min: 39 +/- 16 kPa: P vs. HFV alone < 0.01). Relative lung volumes at a deflation pressure of 10 cmH2O, expressed as percent of maximum volume, were larger in animals ventilated with HFV than in those undergoing CV (41 +/- 12 vs. 33 +/- 10%; P < 0.05), and were further increased in the groups of animals treated with surfactant and ventilated with HFV (55 +/- 9.9%; P vs. animals ventilated with HFV not receiving surfactant < 0.01) or CV (49 +/- 9.6%; P vs. animals ventilated with CV without receiving surfactant < 0.05). Hyaline membranes, granulocytes in cytospin preparations from lung lavage fluid, and vascular-to-alveolar leak of albumin were less prominent in the HFV than in the CV group, particularly in animals treated with surfactant. CONCLUSION: Our data indicate that HFV, especially in combination with surfactant therapy, may be superior to CV for treatment of respiratory failure in this animal model of meconium aspiration syndrome.

Air Pressure↗
PubMed1999

Identification of residues in dendrotoxin K responsible for its discrimination between neuronal K+ channels containing Kv1.1 and 1.2 alpha subunits.

Dendrotoxin (DTX) homologues are powerful blockers of K+ channels that contain certain subfamily Kv1 (1.1-1.6) alpha- and beta-subunits, in (alpha)4(beta)4 stoichiometry. DTXk inhibits potently Kv1.1-containing channels only, whereas alphaDTX is less discriminating, but exhibits highest affinity for Kv1.2. Herein, the nature of interactions of DTXk with native K+ channels composed of Kv1.1 and 1.2 (plus other) subunits were examined, using 15 site-directed mutants in which amino acids were altered in the 310-helix, beta-turn, alpha-helix and random-coil regions. The mutants' antagonism of high-affinity [125I]DTXk binding to Kv1. 1-possessing channels in rat brain membranes and blockade of the Kv1. 1 current expressed in oocytes were quantified. Also, the levels of inhibition of [125I]alphaDTX binding to brain membranes by the DTXk mutants were used to measure their high- and low-affinity interactions, respectively, with neuronal Kv1.2-containing channels that possess Kv1.1 as a major or minor constituent. Displacement of toxin binding to either of these subtypes was not altered by single substitution with alanine of three basic residues in the random-coil region, or R52 or R53 in the alpha-helix; accordingly, representative mutants (K17A, R53A) blocked the Kv1.1 current with the same potency as the natural toxin. In contrast, competition of the binding of the radiolabelled alphaDTX or DTXk was dramatically reduced by alanine substitution of K26 or W25 in the beta-turn whereas changing nearby residues caused negligible alterations. Consistently, W25A and K26A exhibited diminished functional blockade of the Kv1.1 homo-oligomer. The 310-helical N-terminal region of DTXk was found to be responsible for recognition of Kv1.1 channels because mutation of K3A led to approximately 1246-fold reduction in the inhibitory potency for [125I]DTXk binding and a large decrease in its ability to block the Kv1.1 current; the effect of this substitution on the affinity of DTXk for Kv1.2-possessing oligomers was much less dramatic (approximately 16-fold).

Amino Acid Sequence↗
PubMed1999

Effects of sciatic nerve injuries on delta -opioid receptor and substance P immunoreactivities in the superficial dorsal horn of the rat.

The aim of the present study was to examine the effects of transection combined with tight ligation, and crush of the sciatic nerve on delta -opioid receptor and substance P immunoreactivities in the superficial spinal dorsal horn at different time points after injury. Both the delta -opioid receptor and substance P are primarily localised to primary afferent fibres and terminals. Seven days following transection and ligation, a slight decrease in both delta -opioid receptor and substance P levels was seen in laminae I and II. The maximal reduction appeared to take place around 4 weeks. Restoration of immunoreactivity was observed by 32 weeks, and by 1 year the levels were almost back to normal. Regarding crush injury, the reduction in both delta -opioid receptor and substance P immunoreactivities were less pronounced and recovery was faster than after transection injury. Already by 16 weeks, the levels were almost back to normal.These results show that peripheral nerve injuries dramatically reduce the levels of delta -opioid receptor and substance P immunoreactivities in the superficial dorsal horn after short survivals and demonstrate recovery after long survivals. Whether the marked reduction of delta -opioid receptors in the dorsal horn is involved in the decreased ability of opioid analgesics to alleviate neuropathic pain remains to be studied. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed1999

Nitric oxide synthase and interferon-gamma receptor immunoreactivities in relation to ascending spinal pathways to thalamus, hypothalamus, and the periaqueductal grey in the rat.

The retrograde tracer fluoro-gold was injected into the periaqueductal grey, thalamus or hypothalamus, and spinal cord sections were processed for neuronal nitric oxide synthase (nNOS) immunohistochemistry to investigate the relationships of nNOS immunoreactive, and spinomesencephalic, spinothalamic and spinohypothalamic projection neurones. In addition, in the lateral spinal nucleus the relationship between spinomesencephalic, -thalamic and -hypothalamic projection neurones, and nNOS and interferon-gamma receptor immunoreactive structures was investigated at the lumbar level. No single retrogradely labelled spinomesencephalic, -thalamic or -hypothalamic neurone showed nNOS immunoreactivity. In the lateral spinal nucleus, however, many fluoro-gold-labelled neurones were closely apposed by both nNOS and interferon-gamma receptor immunoreactive structures, especially prominent in the hypothalamic injection cases. This study gave no evidence for nNOS immunoreactivity in spinal neurones projecting to the periaqueductal grey, thalamus or hypothalamus, but suggests that in the lateral spinal nucleus such neurones are contacted by both nNOS- and interferon-gamma receptor-containing axon terminals.

Animals↗
PubMed1999

Evidence for multiple promoter elements orchestrating male-specific regulation of the her-1 gene in Caenorhabditis elegans.

The sex-determining gene her-1 is required for male development in Caenorhabditis elegans. In XO males, two her-1 mRNAs, her-1a and her-1b, are transcribed from two separate promoters: P1, located in the 5'-flanking region, and P2, located in the large second intron. In XX hermaphrodites, accumulation of both her-1 transcripts is repressed by the sdc genes, which in turn are negatively regulated by the xol-1 gene. When introduced into a xol-1(y9) background, transgenic arrays, including 3.4 kb of her-1 intron 2 sequence (P2), result in phenotypes that mimic those of sdc(lf) mutants, including suppression of XO lethality and masculinization of both XX and XO animals. The masculinization, but not the suppression of XO lethality, is dependent on endogenous her-1 activity. These effects could therefore result from sequestration (titration) of sdc gene products by sequences in the arrays, causing derepression of her-1 (masculinizing effect) and disruption of the dosage compensation machinery (allowing survival of XO animals). We used these effects as an assay in a deletion analysis of the two her-1 promoter regions to define potential cis-regulatory sites required for the putative titration. Several regions in P2 contributed to these effects. P1 was effective only in combination with certain P2 sequences and only if a particular P1 site previously implicated in her-1 repression was intact. These results suggest that normal repression of transcription from P1 in XX animals may involve cooperative interaction with sequences in the P2 region. In experiments to test for a possible role of the her-1b transcript in regulation of sdc genes, no significant effects could be demonstrated.

Animals↗
PubMed1999

Homologs of the Caenorhabditis elegans masculinizing gene her-1 in C. briggsae and the filarial parasite Brugia malayi.

The masculinizing gene her-1 in Caenorhabditis elegans (Ce-her-1) encodes a novel protein, HER-1A, which is required for male development. To identify conserved elements in her-1 we have cloned and characterized two homologous nematode genes: one by synteny from the closely related free-living species C. briggsae (Cb-her-1) and the other, starting with a fortuitously identified expressed sequence tag, from the distantly related parasite Brugia malayi (Bm-her-1). The overall sequence identities of the predicted gene products with Ce-HER-1A are only 57% for Cb-HER-1, which is considerably lower than has been found for most homologous briggsae genes, and 35% for Bm-HER-1. However, conserved residues are found throughout both proteins, and like Ce-HER-1A, both have putative N-terminal signal sequences. Ce-her-1 produces a larger masculinizing transcript (her-1a) and a smaller transcript of unknown function (her-1b); both are present essentially only in males. By contrast, Cb-her-1 appears to produce only one transcript, corresponding to her-1a; it is enriched in males but present also in hermaphrodites. Injection of dsRNA transcribed from Cb-her-1 into C. briggsae hermaphrodites (RNA interference) caused XO animals to develop into partially fertile hermaphrodites. Introducing a Cb-her-1 construct as a transgene under control of the C. elegans unc-54 myosin heavy chain promoter caused strong masculinization of both C. briggsae and C. elegans hermaphrodites. Introduction of a similar Bm-her-1 construct into C. elegans caused only very weak, if any, masculinization. We conclude that in spite of considerable divergence the Cb gene is likely to be a functional ortholog of Ce-her-1, while the function of the distantly related Bm gene remains uncertain.

Amino Acid Sequence↗
PubMed1999

The MCFONTZL classification system for soft-tissue injuries to the face.

A review of the literature and case records reflected a need for the development of a clinically applicable assessment scheme and classification system for soft-tissue laceration injuries to the face. Herein, a systematic approach for assessing facial lacerations is proposed based on location, depth of penetration, branching, directionality, size, presence of soft-tissue defect, and translation of such injuries into the current procedural terminology (CPT) code. Moreover, a new classification system for facial laceration injuries is presented that may serve as the basis for simplification of current billing codes. Prospective clinical application of this classification system may lead to standardization of facial injury assessment and improvement in the incomplete and inconsistent patient record. This system will establish a reliable database that may identify factors in soft-tissue injuries that contribute to poor aesthetic results or secondary functional deformities. These data will lead to the modification of established treatment plans.

Facial Injuries↗
PubMed1999

Experimental neonatal respiratory failure induced by lysophosphatidylcholine: effect of surfactant treatment.

The purpose of this study was to characterize the toxic effects of lysophosphatidylcholine (lyso-PC) on neonatal lung function. Various doses of lyso-PC (from 0 to 40 mg/kg) were administered to near-term newborn rabbits. Lung-thorax compliance during mechanical ventilation was significantly decreased by doses >/=10 mg/kg, and static lung volumes during deflation were decreased by doses >/=20 mg/kg. Using the same experimental model, we investigated the effects of modified porcine surfactant (Curosurf, 200 mg/kg). Animals exposed to lyso-PC at birth and treated simultaneously with surfactant showed a satisfactory therapeutic response, whereas those treated after 30 min failed to respond. These animals also had a much larger leak of albumin into the air spaces and an elevated minimum surface tension of the lavage fluid in a pulsating bubble surfactometer, suggesting inactivation of the exogenous surfactant. Timing of surfactant administration may thus be essential for the therapeutic effect in this experimental model of acute lung injury.

Acute Disease↗
PubMed1999

Combined treatment with surfactant and specific immunoglobulin reduces bacterial proliferation in experimental neonatal group B streptococcal pneumonia.

Neonates suffering from group B streptococcal (GBS) pneumonia often lack type-specific opsonizing antibodies. We studied the influence of combined intratracheal treatment with surfactant and a specific antibacterial polyclonal antibody (IgG fraction) on bacterial proliferation and lung function in an animal model of GBS pneumonia. Near-term newborn rabbits received an intratracheal injection of either the specific IgG antibody, nonspecific IgG, surfactant, a mixture of surfactant and the antibody, or 0.9% saline. At 30 min the rabbits were infected with a standard dose (10(8)) of the encapsulated GBS strain 090 Ia. After 5 h of mechanical ventilation the mean estimated increase in bacterial number in lung homogenate (log10 colonies/g) was 0.76 in the antibody group, 0.92 in the nonspecific IgG group, 0.55 in the surfactant group, and 1.29 in the saline group. A mean decrease in bacterial number (-0.05) was observed in the group that received combined treatment with surfactant and antibody (p < 0.05 versus all other groups). Lung-thorax compliance was significantly higher in both groups of surfactant-treated animals compared with saline or IgG treatment. We conclude that in experimental neonatal GBS pneumonia combined treatment with surfactant and a specific immunoglobulin against GBS reduced bacterial proliferation more effectively than either treatment alone.

Animals↗
PubMed1999

Nasal continuous positive airway pressure and early surfactant therapy for respiratory distress syndrome in newborns of less than 30 weeks' gestation.

OBJECTIVE: To determine whether early versus late treatment with porcine surfactant (Curosurf) reduces the requirement of mechanical ventilation in very preterm infants primarily supported by nasal continuous positive airway pressure (nasal CPAP). DESIGN: Multicenter randomized, controlled trial. PATIENTS: The study population comprised 60 infants <30 weeks' gestation with respiratory distress syndrome (RDS) who had an arterial to alveolar oxygen tension ratio (a/APO2) of 0.35 to 0.22. The cohort from which the study population was generated comprised 397 infants. RESULTS: The need for mechanical ventilation or death within 7 days of age was reduced from 63% in the late-treated infants to 21% in early-treated infants. Increasing numbers of antenatal steroid doses also improved the outcome, especially in the early-treated infants. Six hours after randomization mean a/APO2 rose to 0.48 in the early-treated infants compared with 0.36 in the late-treated. The need of mechanical ventilation before discharge was reduced from 68% in the late-treated to 25% in the early-treated infants. CONCLUSIONS: Nasal CPAP in combination with early treatment with Curosurf significantly improves oxygenation and reduces the subsequent need for mechanical ventilation in infants <30 weeks' gestational age with RDS.

Biological Products↗
PubMed1999

Subunit principles in midface fractures: the importance of sagittal buttresses, soft-tissue reductions, and sequencing treatment of segmental fractures.

The patterns of midface fractures were related to postoperative computed tomography scans and clinical results to assess the value of ordering fracture assembly in success of treatment methods. A total of 550 midface fractures were studied for their midface components and the presence of fractures in the adjacent frontal bone or mandible. Preoperative and postoperative computed tomography scans were analyzed to generate recommendations regarding exposure and postoperative stability related to fracture pattern and treatment sequence, both within the midface alone and when combined with frontal bone and mandibular fractures. Large segment (Le Fort I, II, and III) fractures were seen in 68 patients (12 percent); more comminuted midface fracture combinations were seen in 93 patients (17 percent). Midface and mandibular fractures were seen in 166 patients (30 percent). Midface, mandible, and nasoethmoid fractures were seen in 38 patients (7 percent). Frontal bone and midface fractures were seen in 131 patients (24 percent). Split-palate fractures accompanied 8 percent of midface fractures. Frontal bone, midface, and mandibular fractures were seen in 54 patients (10 percent). The midface, because of weak bone structure and comminuted fracture pattern, must therefore be considered a dependent, less stable structure. Its injuries more commonly occur with fractures of the frontal bone or mandible (two-thirds of cases) and, more often than not (>60 percent), are comminuted. Comminuted and pan-facial (multiple area) fractures deserve individualized consideration regarding the length of intermaxillary immobilization. Examples of common errors are described from this patient experience.

Facial Asymmetry↗
PubMed1999

Footprints of the globe: a practical look at the mechanism of orbital blowout fractures, with a revisit to the work of Raymond Pfeiffer.

Multiple mechanisms of orbital blowout fractures have been proposed since the fracture was described at the beginning of this century. The original theory of direct globe-to-wall contact was abandoned long ago for the more contemporary hydraulic and bone conduction theories. Although the more widely accepted theories play an obvious role in fracture generation and its associated complications, it is our contention that direct globe-to-wall contact is an important and largely unrecognized mechanism in orbital blowout fracture production. By means of a critical review of the historical literature and an analysis of patient computed tomography scans, support is presented for the original theory first proposed by Raymond Pfeiffer in 1943.

Humans↗
PubMed1998

Principles of surfactant replacement.

Surfactant therapy is an established part of routine clinical management of babies with respiratory distress syndrome. An initial dose of about 100 mg/kg is usually needed to compensate for the well documented deficiency of alveolar surfactant in these babies, and repeated treatment is required in many cases. Recent experimental and clinical data indicate that large doses of exogenous surfactant may be beneficial also in conditions characterized by inactivation of surfactant, caused by, for example, aspiration of meconium, infection, or disturbed alveolar permeability with leakage of plasma proteins into the airspaces. The acute response to surfactant therapy depends on the quality of the exogenous material (modified natural surfactants are generally more effective than protein-free synthetic surfactants), timing of treatment in relation to the clinical course (treatment at an early stage of the disease is better than late treatment, and may reduce the subsequent need for mechanical ventilation), and mode of delivery (rapid instillation via a tracheal tube leads to more uniform distribution and is more effective than slow airway infusion). Treatment with aerosolized surfactant improves lung function in animal models of surfactant deficiency or depletion, but is usually associated with large losses of the nebulized material in the delivery system. Furthermore, data from experiments on immature newborn lambs indicate that treatment response may depend on the mode of resuscitation at birth, and that manual ventilation with just a few large breaths may compromise the effect of subsequent surfactant therapy. The widespread clinical use of surfactant has reduced neonatal mortality and lowered costs for intensive care in developed countries. The hydrophobic surfactant proteins SP-B and SP-C are probably essential for optimal biophysical and physiological activity of exogenous surfactants isolated from mammalian lungs, and the dose-effectiveness (in part reflecting resistance to inactivation) can be further improved by enrichment with SP-A. The development of new artificial surfactant substitutes, based on synthetic analogues of the native surfactant proteins, is an important challenge for future research.

Biological Products↗