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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1991

Canine hydrophobic surfactant polypeptide SP-C. A lipopeptide with one thioester-linked palmitoyl group.

The amino acid sequence and the posttranslational modification of the hydrophobic surfactant polypeptide SP-C from canine, rabbit and bovine lungs were established by direct sequence analysis and plasma-desorption time-of-flight mass spectrometry. The results reveal that canine SP-C has only one cysteine residue which, however, is palmitoylated, like the two Cys residues in other characterized SP-C molecules. In addition, canine SP-C is N-terminally truncated, with only 34 amino acid residues in its longest form. Thus, SP-C molecules can apparently vary to some extent in the N-terminal lipid-modified part, whereas the extremely hydrophobic middle and C-terminal parts are well conserved.

Amino Acid Sequence↗
PubMed1991

Populations of rat spinal primary afferent neurons with choleragenoid binding compared with those labelled by markers for neurofilament and carbohydrate groups: a quantitative immunocytochemical study.

A quantitative comparison was made of the population of L5 dorsal root ganglion neurons that bind choleragenoid and the population of neurons labelled by RT97, an anti-neurofilament antibody, SSEA3, an antibody to a globoseries carbohydrate group and 1B2, an antibody to a lactoseries carbohydrate group. Neurons with choleragenoid binding formed a population of 37% of all the cells and 94% of these were also immunoreactive to RT97. The choleragenoid-and RT97-positive groups of cells showed the same size distribution. Two small populations of cells existed which were choleragenoid negative/RT97 positive and choleragenoid positive/RT97 negative. SSEA3 immunoreactivity was found in 8% of the dorsal root ganglion neurons which were of all sizes. The 1B2 immunoreactivity was found in 32% of the dorsal root ganglion cells, the majority of which were in the small size range. More than half of the SSEA3-positive cells but only a few of the 1B2-positive neurons were labelled for choleragenoid. These results demonstrate that choleragenoid labels the majority of the light (RT97-positive) cell population and that light cells unlabelled by choleragenoid are small in number and spread across a wide size range.

Animals↗
PubMed1991

Capsaicin causes prolonged inhibition of voltage-activated calcium currents in adult rat dorsal root ganglion neurons in culture.

The effect of capsaicin on voltage-activated calcium currents was investigated in voltage-clamped somata of cultured adult rat dorsal root ganglion neurons. About half the neurons studied were sensitive to capsaicin, which induced an inward current at negative membrane potentials accompanied by an increase in membrane conductance. In the sensitive neurons capsaicin inhibited voltage-activated calcium current to an extent that depended on the size and duration of the capsaicin-induced inward current. Calcium channels were protected from the long-lasting inhibitory action of capsaicin by substituting extracellular Ca with Mg or Ba when capsaicin was applied, which suggests that the inhibition was dependent on the presence of extracellular Ca. Substituting Ca with Co did not prevent the prolonged block of calcium channels. It is concluded that the inhibition of voltage-activated calcium currents by capsaicin is secondary to increased intracellular Ca levels due to calcium entry through capsaicin-activated cation-specific ion channels in the plasma membrane. Long-lasting inhibition of voltage-activated calcium channels may contribute to the mechanism of the analgesic and anti-inflammatory effects of capsaicin through inhibition of neurotransmitter release from central and peripheral terminals of primary afferent nociceptive neurons.

Animals↗
PubMed1991

Anterograde horseradish peroxidase tracing and immunohistochemistry of trigeminal ganglion tooth pulp neurons after dental nerve lesions in the rat.

The peripheral reorganization of pulpal nerves after tooth injury was studied, in the rat, with anterograde horseradish peroxidase tracing techniques, and combined retrograde Fluorogold tracing and immunohistochemistry was employed to examine the effects of inferior alveolar nerve lesions or tooth injury on some cytochemical characteristics of pulpal trigeminal ganglion nerve cells, namely content of substance P, calcitonin gene-related peptide and the ganglioside GM1 (binding subunit of cholera toxin), as well as affinity to RT 97 (antibody to neurofilament protein) and the lectin Griffonia simplicifolia isolectin I-B4. Anterograde horseradish peroxidase tracing demonstrated that pulpal nerves either disappear or reinnervate novel targets after loss of pulpal tissue. There were no obvious signs of neuroma formation. Retrograde Fluorogold labelling with immunohistochemistry showed that after inferior alveolar nerve lesions with subsequent regeneration, a much higher proportion of Fluorogold cells (15%) were substance P-positive compared to normal (2%). In addition, 3% of the cells were Griffonia simplicifolia isolectin I-B4-positive. Such cells were very rare in controls. Proportions of calcitonin gene-related peptide-, GM1- and RT-97-positive cells were normal. After tooth lesions, the proportions of Fluorogold-positive substance P-, Griffonia simplicifolia isolectin I-B4-, GM1- and RT 97-labelled cells were similar to controls, while the proportion of calcitonin gene-related peptide-positive neurons was reduced. The results show that pulpal deafferentation may change the long-term cytochemical characteristics of affected trigeminal ganglion neurons.

Animals↗
PubMed1991

Relationships between emotional control, adjustment to cancer and depression and anxiety in breast cancer patients.

The possible relationship between psychological responses among breast cancer patients and disease outcome continues to be an area of controversy and debate. Two parallel findings are reported separately in the literature: first, that emotional control is more common among women with breast cancer than in women with benign breast disease or in healthy controls and second, that a helpless attitude towards the disease is related to a poor prognosis. These previously unrelated psychological responses are examined here in a group of women (N = 359) with early stage breast cancer, who were seen one to three months after diagnosis. The relationships between emotional control, adjustment to cancer and psychological morbidity were examined. Prevalence levels of 16 and 6% were observed for anxiety and depression respectively, which are lower than reported more generally in the literature. The results indicated a highly significant association between scores for the tendency to control emotional reactions and a fatalistic attitude toward cancer. A significant association was observed between anger control and a helpless attitude. Psychological morbidity was also linked to type of adjustment to cancer. The data are interpreted in terms of a process model of psychological responses which suggests that emotional control (an important component of the Type C behaviour pattern) fatalism, helplessness and psychological morbidity are linked.

Adaptation, Psychological↗
PubMed1991

Surfactant inactivation and surfactant replacement in experimental models of ARDS.

Lung structure and function, and the effect of surfactant replacement, were studied in three animal models of adult respiratory distress syndrome (ARDS): surfactant depletion by repeated lung lavage, proteinaceous pulmonary edema induced by prolonged exposure to hyperoxia, and inoculation with hybridoma making an antibody to the hydrophobic surfactant-associated protein, SP-B. Surfactant replacement therapy restored normal gas exchange in respiratory failure induced by repeated lung lavage but was ineffective in animals with severe lung parenchymal lesions induced by hyperoxia or antibody to SP-B. Lung edema fluid from animals exposed to hyperoxia inhibited surfactant function in a concentration-dependent manner. These observations indicate that, in experimental ARDS, the effect of surfactant replacement depends on the type of animal model and, especially, on the degree of lung injury present at the time of therapy.

Animals↗