Biomedical subjects
B Robertson
Publications and source records attributed to B Robertson.
Correlations between radiological and cytological findings in early development of bronchopulmonary dysplasia.
Sequential chest radiographs from 40 newborn infants requiring assisted ventilation for respiratory distress syndrome or other conditions were evaluated with a new scoring system aiming at identifying abnormal expansion patterns and interstitial infiltrates representing an early stage of bronchopulmonary dysplasia (BPD). Age at examination ranged from 3 to 23 days. Tracheal effluent samples obtained from the babies during the same period of observation were examined cytologically for evidence of regenerating airway epithelium with squamous metaplasia, indicating BPD. According to the radiological scoring system 24 babies (60%) developed BPD, first diagnosed at a median age of 9 days. By cytological criteria 20 babies (50%) developed BPD, first diagnosed at a median age of 10.5 days. The results from radiological and cytological diagnosis of BPD were concordant in 16 babies (P < 0.05 by chi-square test). Using oxygen dependency at the age of 28 days as evidence of established BPD, the radiological scoring system alone had a sensitivity of 93% and a specificity of 53%. The corresponding figures for cytological assessment alone were 73% and 58%, respectively. By combining radiological and cytological findings, values for sensitivity and specificity were 67% and 68%, respectively.
Ambulatory nursing. The handmaiden/specialist dichotomy.
Will ambulatory nursing roles change sufficiently to cope with the healthcare demands of the next century or should they be taken over by administrative personnel? The authors analyze traditional and clinical nurse specialist ambulatory nursing activities and highlight the dichotomy between menial handmaiden and professional nursing activities that must be bridged if ambulatory nursing is to survive.
Molecular characterization of the her-1 gene suggests a direct role in cell signaling during Caenorhabditis elegans sex determination.
We have characterized two transcripts from the male-determining her-1 locus in Caenorhabditis elegans. The larger transcript, which appears more important for male development, is predicted to encode a novel 175-amino-acid, cysteine-rich polypeptide with an apparent amino-terminal signal sequence and potential cleavage and glycosylation sites. Expression of a full-length cDNA construct for the larger transcript driven by a body-wall-myosin promoter causes extensive masculinization of all sexually dimorphic tissues in XX (normally hermaphrodite) animals. This activity is dependent on the presence of the her-1 signal sequence or a substitute synthetic signal sequence in the encoded polypeptide. These results suggest that a secreted product of the her-1 gene dictates male development.
Pharmacology of a cloned potassium channel from mouse brain (MK-1) expressed in CHO cells: effects of blockers and an 'inactivation peptide'.
1. Chinese hamster ovary cells (CHO), maintained in cell culture, were stably transfected with DNA for the MK-1 voltage-activated potassium channel, previously cloned from a mouse brain library. 2. Voltage-activated currents were recorded by the whole cell patch clamp method. In CHO cells transfected with the vector only, there were no significant outward voltage activated currents. However, large outward voltage-activated potassium currents were always observed in those cells which had been transfected with the vector containing the DNA encoding for MK-1. 3. These potassium currents activated from -40 mV, and reversed at the potassium equilibrium potential. The half-maximal conductance of MK-1 was at -10 mV and had a slope factor of 11 mV when fitted with a Boltzmann function. There was only very slight (< 10%) inactivation of MK-1 even at very large positive voltages. 4. MK-1 was reversibly blocked by: 4-aminopyridine (4-AP, 0.1-4 mM), Toxin I 10-100 nM), mast cell degranulating peptide (1 microM), tetraethylammonium (TEA, 4-10 mM), tedisamil (100 microM), quinine (100 microM) and ciclazindol (100 microM); all applied to the outside of the cell from a 'U tube' rapid perfusion system. 4-AP may block closed as well as open MK-1 potassium channels. 5. A synthetic 20 amino acid peptide derived from the N-terminus sequence of the Shaker B potassium channel (the 'inactivation peptide') produced dramatic inactivation of MK-1 when applied to the inside, but not the outside of the cell. Reducing peptide concentration or 'degrading' the peptide produced less inactivation. 6. The block of MK-1 by the synthetic inactivation peptide was quite different in time dependence from block by internal TEA (0.4-4 mM), which probably blocks much more quickly but less potently than the peptide.
Surfactant inhibition in experimental meconium aspiration.
Human meconium components were separated into a water-methanol soluble phase containing mainly proteins and bilirubin and a chloroform soluble phase containing free fatty acids, triglycerides and cholesterol. Various amounts of original meconium, the water-methanol soluble fraction or the chloroform soluble fraction were added to standard suspensions of porcine surfactant (Curosurf). In a pulsating-bubble or Wilhelmy-balance system, meconium and its subfractions inhibited surfactant activity, but the chloroform soluble fraction had the highest specific inhibitory activity. Original meconium in saline (130 or 65 mg/ml) was instilled into the airways of ventilated near-term newborn rabbits (dose 6 ml/kg). Lung-thorax compliance was reduced by 38% in animals aspirating the higher dose and by 27% in the low-dose group. Histological sections showed intra-alveolar accumulation of fine meconium particles in experimental animals, but no plugging of larger airways. We conclude that respiratory failure from meconium aspiration may be mediated, in part, by inactivation of surfactant.
Surfactant improves lung function and morphology in newborn rabbits with meconium aspiration.
Nearly mature newborn rabbits (gestational age 29.5 days) were tracheotomized at birth and received, via the tracheal cannula, 6 ml/kg body weight of a filtered saline suspension of human meconium, 65 or 130 mg/ml. Animals were kept in body plethysmographs and ventilated for 60 min with standardized tidal volume (8-10 ml/kg). Aspiration of meconium caused, in both groups, a statistically significant reduction in lung-thorax compliance, elevated PCO2 in heart blood and reduced alveolar volume density (VV) in histological sections. Both groups responded to treatment with exogenous surfactant (Curosurf, 200 mg/kg) with a moderate, statistically significant improvement in lung-thorax compliance, PCO2 and alveolar VV. Our data indicate that respiratory failure after neonatal meconium aspiration may be influenced favorably by treatment with exogenous surfactant.
Replacement therapy with porcine natural surfactant--current status and future challenges. Report from the 8th International Workshop on Surfactant Replacement, Oslo, May 20-22, 1993.
Explore the source record for details and available documents.
Randomized multicentre trial of treatment with porcine natural surfactant for moderately severe neonatal respiratory distress syndrome. The Collaborative European Multicentre Study Group.
A randomized trial comparing outcome of babies treated with a natural surfactant (Curosurf) for moderately severe respiratory distress syndrome (RDS) with corresponding data from babies treated at a more advanced stage of the disease is reported. A total of 182 newborn babies (mean gestational age 29.8 weeks) requiring mechanical ventilation and a fraction of inspired oxygen (FiO2) in the range of 0.40-0.59 for RDS were randomized to immediate ("early") treatment (No = 86) with surfactant (200 mg/kg), or to a control group (No = 96). According to the protocol 49 controls (51%) qualified for a "late" surfactant treatment at an FiO2 requirement of > or = 0.60. In both groups of treated patients administration of surfactant led to a rapid improvement of oxygenation, but the peak value for PaO2 and the variability of the response tended to be lower in babies given immediate treatment. In comparison with the total control group, babies treated immediately had lower incidence of grade III-IV intraventricular hemorrhage (7% vs 18%; p < 0.05), lower mortality (9% vs 23%; p < 0.05), and lower incidence of unfavourable outcome--defined as death or bronchopulmonary dysplasia--(18% vs 34%; p < 0.05) at 28 days. Also significant reductions of time in oxygen > 21% and time on mechanical ventilation were observed. Our data suggest that treatment with surfactant when RDS is moderately severe prevents or reverses the natural progression of the disease in at least 50% of the cases and lowers the risk of serious complications.
Corticosteroids and surfactant for prevention of neonatal RDS.
Two main strategies are available for the prevention of neonatal respiratory distress syndrome (RDS) in cases of preterm delivery: antenatal administration of hormones that accelerate fetal lung maturation, and prophylactic treatment with surfactant soon after birth. The efficacy of each of these therapeutic regimens has been well documented in large randomized clinical trials, and recent data furthermore indicate that, in preterm babies with lowered risk of RDS after antenatal corticosteroid treatment, the odds for developing RDS are not further reduced by prophylactic treatment with surfactant. Corticosteroids and surfactant operate by clearly different mechanisms. The steroids stimulate (via the fibroblast-pneumonocyte factor) production of surfactant phospholipids by alveolar type II cells, enhance the expression of surfactant-associated proteins, reduce microvascular permeability, and accelerate overall structural maturation of the lungs. However, the increment in pool size of surfactant resulting from antenatal treatment with corticosteroids is trivial relative to the dose of exogenous surfactant required for successful prophylaxis at birth. Data from animal experiments indicate that antenatal corticosteroids and postnatal surfactant treatment have synergistic beneficial effects on neonatal lung function, and that these effects can be further potentiated by adding antenatal administration of thyrotrophin releasing hormone (TRH). Promising results have been obtained in recent clinical trials combining antenatal treatment with corticosteroids and TRH for prevention of RDS.
Comparison of prophylaxis and rescue treatment with Curosurf in neonates less than 30 weeks' gestation: a randomized trial.
OBJECTIVE: The aim of this randomized clinical trial was to evaluate the immediate effects of prophylactic administration of Curosurf and to compare outcomes after prophylactic or expectant management. STUDY DESIGN: Porcine surfactant (Curosurf, 200 mg/kg body weight) was administered intratracheally within 10 minutes of birth to preterm neonates with a gestational age of 26 to 29 weeks (n = 75); rescue-eligible neonates (n = 72) were initially subjected to a sham maneuver. The primary end points of the trial, evaluated at the age of 6 hours, were to obtain (1) a 40% decrease in the ratio between transcutaneous oxygen tension (tcPO2) (kPa) and fraction of inspired oxygen (FIO2), and (2) a 50% decrease in the incidence of radiologically verified respiratory distress syndrome (RDS). After 6 to 24 hours, a similar dose of surfactant was given to the neonates of both the prophylaxis and the rescue-eligible group, if they needed mechanical ventilation with an FIO2 > or = 0.6. RESULTS: At 6 hours the prophylaxis group had, in comparison with the rescue-eligible group, significantly higher tcPO2/FIO2 ratios (mean +/- SD: 39.7 +/- 15.3 vs 28.1 +/- 18.1; P < .001) and less severe RDS by radiological scoring (chi 2 = 14.9; P = .005). Severe RDS was present in 19% of the prophylactically treated neonates versus 32% in the rescue-eligible group (P < .05). The prophylaxis group needed shorter periods of FIO2 > 0.40 than the rescue-eligible neonates (P < .01), and eight neonates of the prophylaxis group (11%) versus 23 of the rescue-eligible group (32%) qualified for rescue treatment with surfactant in the interval 6 to 24 hours (P < .01). There were no differences in the incidence or severity of pneumothorax, pulmonary interstitial emphysema, cerebral hemorrhage, periventricular leukomalacia, patent ductus arteriosus, in the duration of mechanical ventilation or time in supplemental oxygen, or in mortality. CONCLUSIONS: Subgroup analysis revealed (1) that administration of corticosteroids reduced the risk of developing neonatal RDS as effectively as did surfactant prophylaxis at birth, and (2) that prophylaxis was effective especially in neonates with gestational age < 28 weeks or birth weight < 1000 g, in male neonates, and in neonates who had received no antenatal treatment with corticosteroids. Our data indicate that prophylactic treatment with surfactant should be considered in high-risk neonates fulfilling these latter criteria.
[Effect of 2 different dosages of a porcine surfactant on pulmonary gas exchange of premature infants with severe respiratory distress syndrome].
BACKGROUND: Doses between 20 and 200 mg/kg body weight (bw) of different surfactant preparations have been recommended in clinical trials for the treatment of neonatal RDS; an optimal dose regimen of surfactant replacement therapy has not yet been defined. Aim of the present pilot study was the evaluation of pulmonary gas exchange in infants with severe RDS following the application of either a high (200 mg/kg bw) or a low (100 mg/kg bw) dose of a natural porcine surfactant (Curosurf). METHODS: 15 neonates were randomized to a high dose regimen, 17 infants to a low dose of surfactant. Apart from a lower 1 minute Apgar in the 100 mg/kg bw group, birth weight, gestational age, sex, 5 minute-Apgar and disease severity (arterial to alveolar oxygenation ratio (a/A-ratio): 0.10 +/- 0.03 [high dose], 0.11 +/- 0.06 [low dose], mean +/- SD) were well matched in both groups. RESULTS: Following surfactant instillation there was a rapid improvement in oxygenation in both groups. The a/A-ratio was slightly higher in the 200 mg/kg bw group during the first 12 hours following surfactant replacement, but statistically this was significantly higher only 4 hours after treatment (0.38 +/- 0.11 vs. 0.24 +/- 0.13, mean +/- SD, p < 0.05). CONCLUSION: The dose of 100 mg/kg bw Curosurf resulted in a rapid improvement in oxygenation and ventilatory requirements; only during the first hours following surfactant replacement there was a slight further improvement with the higher dose of 200 mg/kg bw. The impact of different dose regimens on outcome parameters still has to be defined by a larger clinical trial.
Antinociception from the administration of beta-endorphin into the periaqueductal gray of rat is enhanced while that of morphine is inhibited by barbiturate anesthesia.
Pentobarbital anesthesia causes about a 10-fold increase in the antinociceptive potency of beta-endorphin microinjected into the periaqueductal gray (PAG) region of the rat brain. The antinociceptive response to PAG morphine was markedly attenuated during anesthesia, but returned as the rats regained consciousness. As they recovered from anesthesia, muscular rigidity and body stiffness (catalepsy) also occurred in the pentobarbital treated animals receiving morphine. These results are consistent with the activation of separate and distinct descending pain inhibitory neuronal systems by these two opioid agonists, and the differential modulation of the systems by pentobarbital. They also suggest that the mechanism underlying muscular responses to morphine is sensitive to pentobarbital, and is not shared by beta-endorphin.
WGA-HRP and choleragenoid-HRP as anterogradely transported tracers in vagal visceral afferents and binding of WGA and choleragenoid to nodose ganglion neurons in rodents.
The axonal and terminal labelling pattern in the brain stem resulting from the injection of horseradish peroxidase (HRP) conjugate of wheat germ agglutinin (WGA) or choleragenoid into the nodose ganglion of guinea pigs was examined. In addition, the binding profiles of WGA and choleragenoid in the nodose ganglion of guinea pig and rat were examined. The results show that WGA-HRP and choleragenoid-HRP (B-HRP) produce almost identical distribution of axonal and terminal labelling, the difference being some contralateral fibre labelling present only with B-HRP. However, WGA-HRP shows the strongest labelling at short survival times, whereas B-HRP requires longer postoperative survival times to reach maximum labelling intensity. All nodose ganglion neurons appear to bind WGA as well as choleragenoid although to a varying degree. The results of this and previous studies support the view that visceral sensory ganglion cells and the large light subpopulation of somatic dorsal root ganglion cells both bind choleragenoid, whereas the small dark somatic cells show affinity for WGA but rarely for choleragenoid.
IL-4 enhances programmed cell death (apoptosis) in stimulated human monocytes.
Because IL-4 down-regulates several proinflammatory functions associated with human monocytes/macrophages, we explored the possibility that IL-4 also decreases monocyte survival. IL-4 caused a concentration-dependent decrease in viability of IL-1 or LPS stimulated, but not unstimulated, monocytes. Nonviable cells demonstrated classic features of programmed cell death or apoptosis, in that they were condensed and contained oligonucleosome-sized (200 bp) DNA fragments. When compared with several other cytokines commonly associated with inflammatory lesions, IL-4 was uniquely effective in enhancing cell death. We found that IL-4 enhanced death more quickly in IL-1-stimulated cells than in LPS-stimulated cells, that stimulated monocytes did not become resistant to the effects of IL-4 during culture, and that the effects of IL-4 on viability were antagonized by IFN-gamma. Enhanced cell death was stimulus-specific in that monocyte viability maintained by certain activating agents, such as Con A or CSF, was unaffected by IL-4. These findings represent the first evidence of cytokine-enhanced programmed cell death in monocytes and suggest that the antiinflammatory effects of IL-4 are mediated in part by reducing survival of stimulated monocytes in chronic lesions.
Interpretation of the effect of an oscillating electric field on membrane enzymes.
Theoretical expressions for the frequency and amplitude dependence of the rate of a catalyzed reaction are fitted to the data of Graziana et al. (1990) [Graziana, A., Ranjeva, R., & Teissié, J. (1990) Biochemistry 29, 8313-8318] for Ca2+ uptake by carrot protoplasts in an oscillating electric field. This uptake is a direct (linear) measure of the rate of increase of ATP caused by a plasma membrane enzyme in the oscillating field. The fit gives 20 ms and 33 microseconds for the relaxation times of the enzyme and roughly 3 for the effective number of elementary changes displaced across the membrane by a conformational change of the enzyme in its catalytic cycle. Additional experiments are suggested to define further the mechanism of the enzymatic reaction.
A 2-year follow up of babies enrolled in a European multicentre trial of porcine surfactant replacement for severe neonatal respiratory distress syndrome. Collaborative European Multicentre Study Group.
The postnatal growth, respiratory status and neurodevelopmental outcome of surviving babies enrolled in the first European multicentre trial of porcine surfactant (Curosurf) replacement for severe neonatal respiratory distress syndrome, were assessed at corrected ages of 1 and 2 years. Follow up rates of survivors were 93% at 1 year and 89% at 2 years. Treated and control groups were similar at both 1 and 2 years in terms of physical growth, the prevalence of persistent respiratory symptoms and the occurrence of major and minor disability. Serum antibodies recognising Curosurf and surfactant-anti-surfactant immune complexes were detected in both treated and control babies, the titres showing no difference between groups. Examination of histological lung sections from non-survivors revealed a higher incidence of severe pulmonary interstitial emphysema in control babies than in those treated with surfactant. Surfactant treatment for severe respiratory distress syndrome reduces neonatal mortality and air leaks and is not associated with an increase in disability 2 years later.
Opioid receptors mediating antinociception from beta-endorphin and morphine in the periaqueductal gray.
beta-Endorphin and morphine produce an increase in the latency of the tail-flick reflex when administered into the PAG of awake rats. The antinociceptive effect of both opioid agonists was blocked by the sequential local injection of either CTP (D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2), a selective mu opioid receptor antagonist, naltrexone, or beta-endorphin (1-27), a putative epsilon opioid receptor antagonist, with minimal selectivity. When either CTP or naltrexone was used as the antagonist, the dose-inhibition curves generated for beta-endorphin and morphine were not parallel, suggesting the involvement of separate and distinct receptors. Also, synergism occurred when a dose of morphine producing submaximum antinociception was administered simultaneously with either a submaximal or ineffective dose of beta-endorphin. Inhibition of the antinociceptive response to beta-endorphin by mu antagonists and the non-selective antagonism of both beta-endorphin and morphine by beta-endorphin (1-27) suggested that epsilon opioid receptors were not involved. Additionally, a mu/delta opioid receptor complex was not involved, since ICI 174,864 (Allyl2-Tyr-Aib-Aib-Phe-Leu-OH), a selective delta opioid receptor antagonist, did not alter the response to beta-endorphin. Thus, although additional characterization is required, beta-endorphin and morphine appear to act (at least in part) through different opioid receptors, demonstrable using selected mu opioid receptor antagonists.