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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 19 recordsLinked to original sources
PubMed1992

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.

Analgesics↗
PubMed1992

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.

Animals↗
PubMed1992

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.

Cell Death↗
PubMed1992

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.

Adenosine Triphosphate↗
PubMed1992

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.

Antibodies↗
PubMed1992

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.

Amino Acid Sequence↗
PubMed1992

A method for assessing the quality of life of cancer patients: replication of the factor structure.

The psychometric properties of a method of measuring the quality of life of cancer patients based on multiple linear analogue scales have been assessed in a group of 294 patients with breast cancer attending one clinical unit. The method was found to be readily managed by patients although a small number of scales presented difficulties of understanding to patients and difficulties of analysis. The scales distinguished readily between patients of different disease and treatment status. Factor analysis revealed a 5 factor structure which we interpret as relating to physical activities of everyday living, emotional disturbance, alimentary disturbances, appearance and cosmetic problems and a fifth factor which is more difficult to interpret and includes impairment of speech, writing and concentration. We feel the essential factors determining quality of life in cancer patients have been demonstrated in this and our earlier studies and there is now a substantial level of agreement in the factors that have been identified by groups taking quite different approaches. The major factors determining quality of life in cancer patients are now known and should be assessed in clinical research and clinical trials. The method by which they should be assessed is not as yet so clear.

Adult↗
PubMed1992

Exogenous porcine surfactant (Curosurf) is inactivated by monoclonal antibody to the surfactant-associated hydrophobic protein SP-B.

A monoclonal antibody to the surfactant-associated hydrophobic protein SP-B was added at various concentrations to a standard preparation of porcine surfactant (Curosurf 10 mg/ml), and surface properties were evaluated with pulsating bubble. Retarded adsorption of surfactant was observed at antibody concentrations > or = 0.5 mg/ml and significantly increased values for minimum surface tension were observed at antibody concentrations > or = 1 mg/ml. In vivo effects of the antibody were tested in immature newborn rabbits ventilated with a standardized sequence of insufflation pressures. Animals receiving 0.1 ml surfactant (80 mg/ml) mixed with antibody at concentrations > or = 4 mg/ml had low tidal volumes, poor lung stability in pressure-volume recordings, poor alveolar expansion in histological sections and widespread epithelial necrosis in peripheral airways. Admixtures of IgG had no such effects. We conclude that this monoclonal antibody inactivates exogenous porcine surfactant, probably by preventing fast adsorption of surfactant lipids to the alveolar air-liquid interfaces.

Adsorption↗
PubMed1992

Bubbles and computer-aided image analysis for evaluation of surfactant inhibition.

Surfactant (Curosurf, diluted to 5 mg/ml) was suspended in normal saline with 3 mM CaCl2 and mixed with different concentrations of albumin or fibrinogen. The samples were vortexed to generate microbubbles, and the equivalent circle diameter of these bubbles was determined with computer-aided image analysis. Bubbles in the original surfactant suspension had an average diameter of 27 microns after 2 min, and their size increased only little during a 15-min period of observation. The diameter of bubbles generated in the presence of albumin (4 or 40 mg/ml) or fibrinogen (4 mg/ml) was 4-5 times larger, indicating surfactant inhibition. We conclude that evaluation of microbubble stability with image analysis provides an objective and rapid assessment of surfactant inhibition, and we speculate that the method could also be used for quantification of surfactant activity in airway samples.

Animals↗
PubMed1992

Factors influencing morbidity and mortality in infants with severe respiratory distress syndrome treated with single or multiple doses of a natural porcine surfactant.

In an international multicenter trial infants with clinical and radiological signs of severe RDS (age 2-15 h, birthweight 700-2,000 g, mechanical ventilation, FiO2 greater than or equal to 0.6, no complicating disease) were randomized to receive either a single dose (n = 176) or up to three subsequent doses (n = 167) of a natural porcine surfactant (Curosurf). Using a logistic regression model, the effects of therapy, birthweight, sex, hospital and other clinical factors on survival and various outcome parameters were evaluated. Mortality (13 vs. 21%, p less than 0.05) and the incidence of pneumothorax (9 vs. 18%, p less than 0.01) were significantly lower in the multiple-dose group. Low birthweight, hospital allocation, low Apgar score and initial disease severity were associated with an increased mortality. Low birthweight, hypothermia (admission temperature less than 36 degrees C) and acidosis (pH less than 7.25) prior to surfactant treatment could be identified as risk factors for the development of intracranial hemorrhage.

Biological Products↗
PubMed1992

Raised plasma hypoxanthine levels as a prognostic sign in preterm babies with respiratory distress syndrome treated with natural surfactant.

Plasma hypoxanthine concentration was measured in twelve preterm babies with respiratory distress syndrome (RDS) treated with 200 mg/kg of a porcine surfactant (Curosurf). Five of the babies died within one week and seven survived the neonatal period. Surviving babies had no significant changes in plasma hypoxanthine concentration throughout a one hour study period following the administration of surfactant. By contrast, in nonsurvivors the mean plasma hypoxanthine concentrations increased from 6.8 mumol/l before surfactant administration to 14.2 mumol/l 15 minutes after surfactant treatment. Survivors had a mean maximal increase in plasma hypoxanthine of 1.9 mumol/l 15-30 min factor surfactant treatment compared with 9.4 mumol/l in nonsurvivors (p < 0.05). The babies who developed intracranial hemorrhage had significantly higher maximal plasma hypoxanthine increase (mean 9.6 mumol/l) compared with babies who did not develop intracranial hemorrhage (mean 1.1 mumol/l) (p < 0.01). The combination of high PaO2 and high hypoxanthine concentration could lead to an increased production of oxygen radicals which might be harmful. We conclude that plasma hypoxanthine concentration may serve as an indicator of the prognosis in preterm babies treated with natural surfactant. Further, it seems important to reduce oxygen supplementation as soon as surfactant is given to possibly limit oxygen radical production.

Biomarkers↗
PubMed1992

The impact of nausea and vomiting upon quality of life measures.

The measurement of quality of life in cancer patients has achieved prominence in recent years. This results from recognition of the limitations of available therapies and a clearer view of the goals of treatment in patients whose diseases may not be curable. Many different approaches to the measurement of quality of life have been proposed and these will be reviewed. In a recent survey of available methods, the Medical Research Council's Working Party on Quality of Life Measurement systematically analysed available instruments for measuring quality of life specifically in cancer patients and commented on a number of instruments of general purpose that may be used in oncology. It was concluded that no instrument is entirely satisfactory for all purposes and that available instruments have to be selected carefully for a particular study or a particular aspect of clinical practice. However, among the existing instruments, the Rotterdam Symptom Checklist for a general assessment of many facets of quality of life and the Hospital Anxiety and Depression Scale, for detecting psychosocial morbidity quickly and easily, were useful. In our own studies we have used a multiple linear analogue scale system to measure aspects of quality of life in breast cancer patients and have recently addressed the determinants of overall quality of life. Our studies identify the importance of evaluating the psychometric properties of measurement instruments in quality of life. Reliability and validity and the ability to discriminate changes with time and between clinically distinct groups have to be carefully assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anxiety↗
PubMed1992

[Treatment of preterm neonates with severe respiratory distress syndrome using exogenous natural surfactants of porcine origin].

From September 1989 to September 1990, a total of 25 newborn infants with severe RDS (on mechanical ventilation and with a FiO2 above 0.6) were treated with porcine surfactant (Curosurf), since its efficacy has been demonstrated in a prior clinical trial (Pediatrics 1988; 82: 683-91). The mean birth weight and gestational age were 1,327 +/- 566 g and 29.5 +/- 3.8 weeks, respectively. Twenty-four percent of the babies had an arterial pH below 7.1. At a mean postnatal age of 9.1 +/- 10.7 hours, a dose of 200 mg/Kg of Curosurf was given by the tracheal route. Mean paO2 rose from 47 +/- 14 mm Hg to 166 +/- 64 mm Hg (p less than 0.001). The paO2 increased in 24 of the 25 cases and in 20 (80%) the post-treatment paO2 was a least two times higher than the pre-treatment value. An hour after surfactant treatment, the paCO2 decreased from 58 +/- 21 mm Hg to 45 +/- 16 mm Hg (p less than 0.01) and the pH increased from 7.19 +/- 0.15 to 7.28 less than 0.11 (p less than 0.001). The following complications were observed: pulmonary interstitial emphysema (16%), pneumothorax (8%), patent ductus arteriosus (36%), intraventricular hemorrhage (28%) and bronchopulmonary dysplasia (24%). The neonatal survival rate and the survival rate after discharge from the hospital were 76% and 64%, respectively. The combined survival and absence of DBP was 32%. Nonsurvivors had lower birth weights and gestation ages, as well as lower paO2 5 min after treatment and higher FiO2 24 hours after surfactant treatment than did the survivors.

Animals↗
PubMed1992

Lung protein leakage in respiratory failure induced by a hybridoma making monoclonal antibody to the hydrophobic surfactant-associated polypeptide SP-B.

Adult mice were inoculated intraperitoneally with a hybridoma (8B5E) making monoclonal antibody to the porcine surfactant-associated polypeptide SP-B; this antibody cross-reacts with the corresponding polypeptide in the mouse surfactant system. Respiratory failure, developing 7-9 days after inoculation, was associated with a decrease in lung-thorax compliance determined during artificial ventilation, and an increase in the amount of protein including the specific antibody in lung lavage fluid. There was a statistically significant negative correlation between the compliance and the amount of protein as well as antibody recovered by lung lavage: r (log scale) = -0.69 and -0.82, respectively (P less than 0.01, both), but no decrease in the amount of phospholipids in lung lavage from animals inoculated with the hybridoma. Treatment with a large dose of porcine surfactant (about 320 mg phospholipids/kg body weight) had no positive effect on lung-thorax compliance during artificial ventilation; on the contrary, surfactant-treated animals showed a decrease in compliance similar to that seen in control animals after instillation of a similar volume of saline into the airways. We conclude that respiratory failure developing after inoculation with this hybridoma is probably at least in part mediated by flooding of the airspaces with antibody interfering with surfactant function.

Animals↗
PubMed1992

Randomized European multicenter trial of surfactant replacement therapy for severe neonatal respiratory distress syndrome: single versus multiple doses of Curosurf.

There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial effects of a single large dose of Curosurf (200 mg/kg) in babies with severe respiratory distress syndrome (arterial to alveolar oxygen tension ratio approximately 0.10) could be enhanced by using multiple doses of surfactant. Preterm neonates (birth weight 700 to 2000 g) with severe respiratory distress syndrome requiring artificial ventilation with fraction of inspired oxygen greater than or equal to 0.6 were randomized into two groups at an age of 2 to 15 hours. Both groups received the usual dose of Curosurf (200 mg/kg) immediately after randomization. In neonates randomized to receive multiple-dose treatment, two additional doses of Curosurf (100 mg/kg each) were instilled into the airways (12 and 24 hours after the initial dose) provided that the patients still needed artificial ventilation with fraction of inspired oxygen greater than 0.21. In both groups (single dose: n = 176, multiple doses: n = 167) there was a rapid improvement in oxygenation as reflected by a threefold increase in arterial to alveolar oxygen tension ratio within 5 minutes after surfactant instillation (P less than .001), and peak inspiratory pressure and mean airway pressure could be reduced significantly during the first 6 hours after surfactant treatment. In addition, ventilatory requirement (peak inspiratory pressure, ventilatory efficiency index) was reduced in the multiple-dose group 2 to 4 days after randomization (P less than .05 to .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Products↗
PubMed1991

The effects of serotonergic stimulation on hippocampal and neocortical slow waves and behavior.

The effect of central serotonergic stimulation on hippocampal and neocortical electrical activity and behavior was studied in freely moving rats by administering: (a) tranylcypromine followed by tryptophan, (b) fluoxetine followed by 5-hydroxytryptophan, or (c) p-chloroamphetamine alone. In all rats, scopolamine-resistant hippocampal rhythmical slow activity (RSA), thought to be dependent on brain serotonin, maintained its normal relation to behavior, occurring in close correlation with Type 1 behaviors (postural changes, turning of the head, walking). This RSA was generally absent during stereotyped behavior (head weaving, forepaw treading, hindlimb splaying and tremor). Scopolamine-resistant neocortical low-voltage fast activity (LVFA), also though to be dependent on brain serotonin, was present during Type 1 behaviors and also during stereotyped behavior. Most rats that developed a full stereotyped behavior syndrome had behavioral and electrocortical seizures which were associated with a reduction in the amplitude of hippocampal activity. These seizures were suppressed by methysergide or benserazide. Metergoline (and methysergide to a lesser extent) suppressed the stereotypic behaviors of the serotonin syndrome, resulting in a striking increase in the locomotion caused by central serotonergic stimulation. Such locomotion was accompanied by RSA and LVFA. It was concluded that increased serotonergic activity in the CNS causes an increase in motor activity and a correlated increase in scopolamine-resistant hippocampal RSA and scopolamine-resistant neocortical LVFA and suggested that metergoline blocks serotonin receptors mediating stereotyped behaviors, thereby permitting the expression of serotonin-mediated locomotion.

5-Hydroxytryptophan↗