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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 271 records · Page 15Linked to original sources
PubMed1988

Effects of antenatal hydrocortisone on tidal volumes in spontaneously breathing preterm newborn rabbits. Possible mediation by adrenal catecholamines.

Rabbit fetuses were injected on day 26 of gestation with hydrocortisone (2 mg) and delivered by hysterotomy 2 days later. The animals were tracheotomized at birth, and tidal volumes and esophageal pressures were recorded during spontaneous ventilation at standardized intervals from the first breath to the age of 2 h. In a subgroup of animals, the catecholamine content was measured in the adrenal glands. In comparison with littermate controls, tidal volumes were enlarged in hydrocortisone-treated neonates at the first breath and 60 min after birth; however, this effect was associated with an increased incidence of intra-alveolar hemorrhage. Hydrocortisone-treated animals also had a significantly increased adrenal content of adrenaline. Our data confirm a modest beneficial effect of antenatal hydrocortisone treatment on the fetal lung and suggest that this might in part be mediated by adrenal catecholamines. Stimulation of beta-adrenergic receptors could thus potentiate the effect induced by direct influence of glucocorticoids on fetal lung maturation.

Adrenal Glands↗
PubMed1988

[Treatment of severe respiratory distress syndrome in the premature infant with natural surfactant].

14 preterm infants with severe respiratory distress syndrome (birthweight 1170 +/- 369 g, mean +/- 1SD) have been treated with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg); follow up and outcome data were compared with matched controls (1200 +/- 288 g, n = 20). Treated infants showed improved oxygenation and gas exchange within minutes after surfactant application. Duration of intermittent positive pressure ventilation was significantly reduced in treated patients when compared to controls (surfactant treated: 16 d (mean value), controls 27 d, p less than 0.05). Similarly, total exposition in greater than 40% oxygen was 5.5 h in treated infants versus 79 h in controls (p less than 0.001). Pneumothorax occurred in 7 of the 20 control infants (35%), but in none of the treated patients (p less than 0.05). However, haemodynamically significant patent ductus arteriosus (PDA) occurred more often in the surfactant group (50% versus 30%, not significant). The incidence of PDA requiring treatment was the same in both groups. Occurrence of intracranial haemorrhage, bronchopulmonary dysplasia and retinopathy of prematurity was identical in both groups. Mortality was 25% in controls and 7% in treated babies. This study confirms the efficacy of surfactant treatment in neonates with severe respiratory distress syndrome.

Birth Weight↗
PubMed1987

Two hydrophobic low-molecular-mass protein fractions of pulmonary surfactant. Characterization and biophysical activity.

Hydrophobic low-molecular-mass proteins were isolated from minced pig lungs and separated into two fractions. Electrophoresis of protein fraction 1 showed two major bands. Calculations of molecular masses from the electrophoretic mobilities are unreliable because of the extreme hydrophobicity of the peptides. However, the two bands were at positions corresponding to apparent molecular masses of about 3 kDa and 14 kDa, while sequence degradation disclosed only one major structure. Electrophoretic separation of protein fraction 2 revealed one band, at an apparent molecular mass of about 6 kDa. Microheterogeneities at the N terminus of both fractions were observed. However, the two fractions had different N-terminal structures and amino acid compositions. Consequently they are concluded to represent different polypeptides without common segments. Bronchoalveolar lavage from humans also contains surfactant polypeptides and at least the fraction 2 peptide is highly similar in human and porcine surfactants. Artificial surfactant preparations, obtained by recombination of protein fraction 1 or 2 with a mixture of synthetic phospholipids, were evaluated with the pulsating bubble method and in experiments on artificially ventilated premature newborn rabbits. The addition of protein fraction 1 to the phospholipid mixture improved surface adsorption from more than 300 s to about 2 s and reduced minimum surface tension from more than 20 mN/m to nearly 0 as measured with a pulsating bubble. When this surfactant preparation was instilled into the airways of newborn rabbits, the tidal volumes at insufflation pressure 25 cm H2O was increased about twentyfold compared to the volumes obtained in non-treated controls. Preparations based on protein fraction 1 had better in vitro and in vivo properties than those based on protein fraction 2. Both these protein-based preparations were decidedly more effective than phospholipids alone.

Amino Acid Sequence↗
PubMed1987

Intraoperative cyanosis: a case of dapsone-induced methaemoglobinaemia.

Intraoperative cyanosis is most commonly caused by hypoxaemia. The anaesthetist is required to perform a rapid series of diagnostic manoeuvres and take remedial action. Occasionally methaemoglobin, sulfhaemoglobin, or haemoglobin M, undetected preoperatively, is the cause of the cyanosis. We report a case of methaemoglobinaemia secondary to dapsone ingestion that was diagnosed intraoperatively. Dapsone, a sulfone, is used therapeutically to treat leprosy and dermatitis herpetiformis. The differential diagnosis of cyanosis, and the origin and fate of methaemoglobin are discussed. In addition the diagnostic steps and the laboratory investigations required to make the diagnosis are listed.

Adolescent↗
PubMed1987

Nodular accumulation of type II cells and inflammatory lesions caused by inhalation of low cobalt concentrations.

Eight rabbits were exposed to 2 mg/m3 and eight to 0.4 mg/m3 of cobalt as CoCl2 for 14-16 weeks (5 days/week, 6 hr/day). Eight rabbits were used as controls. Light microscopic examination of the lungs showed nodular accumulation of alveolar type II cells in all cobalt-exposed rabbits. Abnormal macrophage reaction was observed in all eight rabbits exposed to the high dose and in five of the eight exposed to the low dose. Interstitial inflammation was present in all the rabbits exposed to the high dose and in half of the rabbits exposed to the low dose. Ultrastructural morphometric examination revealed no significant increase in the volume density of type II cells in the cobalt-exposed animals, as the nodular accumulation of these cells was balanced by an increased number of interjacent fields devoid of type II cells. In cobalt-exposed lungs, there was focal swelling of both type I and type II cells, and some of the latter lacked microvilli. The effect pattern after CoCl2 exposure was thus clearly different from those patterns seen after exposure to other toxic metals. We speculate that nodular accumulation of type II cells represents the primary lesion in CoCl2-exposed lungs and that the proliferation of such cells in interjacent areas might be suppressed by a feedback mechanism regulating surfactant production in the terminal airspaces.

Animals↗
PubMed1987

Alveolar macrophage abnormalities in rabbits exposed to low concentrations of trivalent chromium.

Rabbits were exposed by inhalation to a trivalent chromium compound (Cr(NO3)3) at a mean chromium concentration of 0.6 or 2.3 mg/m3 for about 4 months, 5 days/week and 6 hr/day. Light microscopic examination of the lungs revealed that both chromium levels induced a nodular intraalveolar accumulation of enlarged macrophages with granular, eosinophilic cytoplasm. Some macrophages were multinucleated and some showed advanced degenerative changes with disruption of cellular borders and nuclear pyknosis. The changes were most prominent in rabbits exposed to the high concentration and were in some areas associated with a mild interstitial infiltration of lymphocytes, neutrophils, and eosinophils. Electron microscopic examination of macrophages lavaged from the lungs revealed numerous enlarged lysosomes with membranous structures, distinct rounded inclusions, which by X-ray microanalysis were found to contain high amounts of chromium, and increased numbers of laminated inclusions probably representing ingested surfactant. The number of macrophages with a smooth surface was significantly increased. The macrophages in the lung tissue showed the same changes and in addition nodules of multinucleated "giant" cells were found. Morphometric estimation of the volume density of the type II cells did not reveal any significant differences between controls and rabbits exposed to the high concentration of chromium. In spite of the elevated number of laminated structures in the macrophages the amounts of phosphatidylcholine and 1,2-dipalmitoylphosphatidylcholine were not significantly increased in the lung. This indicates a reduced catabolism of surfactant by the alveolar macrophages.

Animals↗
PubMed1987

Endotracheal administration of surfactant in very low birth weight infants with respiratory distress syndrome.

This study was designed to evaluate whether the ventilatory maneuvers associated with surfactant replacement would, per se, influence oxygenation in newborn infants with severe respiratory distress syndrome. Eight patients (700 to 1400 g), all requiring mechanical ventilation with fraction of inspired oxygen greater than 0.6, were included in the trial; four were randomized to receive surfactant, and the others served as controls. Porcine surfactant (2 ml/kg; phospholipid concentration, 100 mg/ml) was instilled via a naso-endotracheal tube at end-expiration and dispersed into the lungs during a period of standardized "sighing" mediated by the ventilator: two prolonged ventilatory cycles (10 sec each) with an inspiration/expiration ratio of 4:1, followed by a 6-min ventilation with a frequency of 60 breath/min and an inspiration/expiration ratio of 4:1. Control babies received no surfactant but were otherwise subjected to the same ventilatory maneuvers. Surfactant-treated infants showed a rapid increase in transcutaneous oxygen associated with improved lung aeration in chest x-rays; the response was transient in three babies and persistent in one. No improvement was observed in control babies. We conclude that the beneficial effect of surfactant replacement cannot be attributed to the ventilatory maneuvers associated with the instillation procedure.

Critical Care↗
PubMed1987

In vivo administration of interleukin 1 to normal mice depresses their capacity to elicit contact hypersensitivity responses: prostaglandins are involved in this modification of immune function.

The administration of pyrogenic doses of interleukin 1 (IL-1) to normal mice before contact sensitization with dinitrofluorobenzene (DNFB) resulted in a significant reduction in the intensity of the elicited contact hypersensitivity (CH) responses. Adoptive transfer experiments established no difference between normal and IL-1-pretreated mice regarding their capacity to generate splenic suppressor-cell activity and lymph node effector-cell activity in response to DNFB. However, a marked reduction in the intensity of elicited responses was observed when primed CH-effector cells, obtained from normal donors, were adoptively transferred to IL-1-pretreated recipients. This finding was paralleled by a consistent reduction in the ability of the adoptively transferred cells to infiltrate the tissue sites of antigen challenge in the IL-1-pretreated animals. Treatment of mice with indomethacin, a potent inhibitor of prostaglandin production, abrogated the capacity of IL-1 to depress CH responses following skin sensitization with DNFB. Similarly, indomethacin was also capable of abrogating the ability of IL-1 to depress CH responses of adoptive recipients of primed CH-effector cells. Our results indicate that the capacity of IL-1 to depress CH responses in normal mice is due to an indomethacin-sensitive process, presumably mediated through the IL-1-induced generation and action of prostaglandins. This was supported by our finding that treatment of mice with arachidonic acid or prostaglandin E2 caused a similar type of inhibition. The mechanism(s) responsible for this effect appears to act at the efferent level of the CH response, as evidenced by the reduced capacity of CH-effector cells to infiltrate the tissue sites of antigen challenge.

Animals↗
PubMed1987

Severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant.

Ten newborn infants (795-1680 g) with severe respiratory distress syndrome (RDS) were treated with the isolated phospholipid fraction of bovine or porcine surfactant, which was administered via the airways (dose 200 mg/kg), at a median age of 10.5 h. Before receiving surfactant, all the infants were on artificial ventilation (FiO2 0.6-1.0). Within 2 h after surfactant replacement, the arterial-to-alveolar PO2 ratio increased from 0.1 to 0.35. There was a concomitant improvement in lung aeration on the chest roentgenograms and a significant reduction in the right-to-left shunt. Four patients died of cerebral hemorrhage; two of them also had a patent ductus arteriosus. One surviving infant developed bronchopulmonary dysplasia, and another succumbed 8 months later to the sudden infant death syndrome. No antibodies against surfactant were detected in the sera of the survivors. Since our results show a significant improvement in lung function after replacement therapy, the efficacy of this new surfactant preparation should be further tested in randomized clinical trials.

Chromatography, Gel↗
PubMed1987

On the action of ruthenium red and neuraminidase at the frog neuromuscular junction.

1. The actions of the polyvalent cationic dye Ruthenium Red and the enzyme neuraminidase were studied at the frog neuromuscular junction. 2. Both Ruthenium Red (0.5-40 microM) and neuraminidase (1, 2 and 4 u.) reduced the miniature end-plate potential (m.e.p.p.) amplitude irreversibly with little change in frequency. This effect could be attributed to the depressant action of these agents on the amplitude of extracellularly recorded miniature end-plate currents (m.e.p.c.s) coupled with their shortening effect on the duration of these m.e.p.c.s. For example, 10 microM-Ruthenium Red reduced the time constant of decay (tau D) of extracellular m.e.p.c.s to 35% of the control value. 3. Ruthenium Red (5, 10 and 15 microM) produced a pronounced reduction in the post-synaptic end-plate sensitivity to microiontophoretically applied acetylcholine. In some cases this effect was fully reversible on wash-out of the dye. 4. Amplitude histograms of m.e.p.c.s recorded under voltage clamp showed a similar shift of the modal value to lower levels in the presence of Ruthenium Red. Over the voltage range -70 to -110 mV the action of Ruthenium Red on the tau D was not voltage dependent. 5. The actions of Ruthenium Red on tau D were not affected by anaesthetic agents, such as the short-chain alcohols which increased tau D, or ketamine which decreased tau D. 6. Some possible modes of action of Ruthenium Red and neuraminidase are briefly discussed.

Action Potentials↗
PubMed1987

Renal recovery after release of experimental neonatal ureteric obstruction.

Partial obstruction of the left ureter was created in 2-day-old rats and released 2 days later. The effects were studied after 1, 2, 3 or 6 weeks. The obstruction resulted in prominent hydronephrosis, but the pelvic volume returned to normal already within 1 week after the release operation. In most of the previously obstructed kidneys there were small regions with moderately widened convoluted tubules and collecting ducts and minor areas with mild chronic pyelonephritis; these lesions were similar after 1 week as after 2-6 weeks, indicating that they were permanent. Judging from the parenchymal weight difference between the right and left kidney, there was slight reduction on the previously obstructed side at the 3rd week, balanced by hypertrophy on the contralateral side. At the 6th week the parenchymal weight reduction was no longer apparent but there was still evidence of contralateral hypertrophy. Thus, early release of the partial ureteric obstruction prevented persistent ipsilateral parenchymal weight reduction, without ensuring healing of the tissue lesions. The catch-up of parenchymal weight is probably due to the fact that the release was performed before the end of the period of postnatal nephron differentiation. Interference with this period seems to be the main cause of parenchymal weight reduction in permanent neonatal partial ureteric obstruction.

Animals↗
PubMed1987

Surfactant replacement in the management of the neonatal respiratory distress syndrome.

Several recent reports have documented the efficacy of surfactants replacement therapy in the neonatal respiratory distress syndrome (RDS). The surfactants tested in these trials were obtained from animal lungs or human amniotic fluid. In general, such natural preparations seem to be superior to entirely synthetic surfactants, although promising results have recently been obtained in animal experiments with artificial surfactant based on isolated apoproteins and synthetic phospholipids. Furthermore, surfactant replacement therapy seems to be more effective when the exogenous material is administered at birth, before the first breath, than when surfactant is instilled into the airways after a period of ventilation. This discrepancy may be due to maldistribution of the exogenous material, or to the rapid development of epithelial lesions in the immature lung, with leakage of surfactant-inhibiting proteins into the airspaces. A transient beneficial response to surfactant replacement may also be due to circulatory problems, especially reversal of the shunt through a patent ductus arteriosus, with overloading of the lung circulation leading to pulmonary oedema and recurrent respiratory failure. Additional, properly randomized clinical trials are required to evaluate the benefits and potential hazards of surfactant replacement therapy in neonatal RDS.

Amniotic Fluid↗
PubMed1987

Morphology and function of blood monocytes after incubation with lung surfactant.

Human blood monocytes were incubated for different periods of time with lung surfactant (phospholipid concentration 1-2.5 mg/ml). After short-term (30 min) incubation, there was an increase in the nitroblue tetrazolium (NBT) reduction of the monocytes both at rest and during stimulation with E. coli bacteria, and enhanced ingestion of fluorescein-labelled yeast particles. Electron microscopic examination of the same monocytes showed an active cell surface with numerous protrusions. Long-term (24 h) incubation with surfactant resulted in a reduced ability of the cells to adhere to plastic dishes. Although the NBT-reduction of resting monocytes was increased after long-term incubation with surfactant, the additional enhancement of NBT-reduction after stimulation with bacteria was decreased. These cells were rounded, usually devoid of surface structures, their nuclei were condensed, and their cytoplasm filled with surfactant material. Thus, monocytes are initially activated in the presence of surfactant, but if the cells become overfed with surfactant lipids their functional capacity decreases.

Animals↗
PubMed1987

Ultrastructure of the bronchial epithelium in adult patients with cystic fibrosis.

The respiratory epithelium of large airways was studied in biopsy specimens obtained by bronchoscopy in seven patients with cystic fibrosis (CF). All but one of these patients were chronically colonised with Pseudomonas aeruginosa. Biopsy specimens were also obtained from the large airways of 10 control patients with or without signs of chronic bronchitis. All samples were studied by transmission electron microscopy. Morphometry was applied to assess the volume density of various cell types and intercellular spaces and for quantification of microvilli of ciliated cells. In CF patients, the average number of microvilli per ciliated cell was decreased by 17% compared to patients with chronic bronchitis and by 34% compared to patients with apparently normal bronchi (p less than 0.02, respectively), but otherwise no abnormalities were found. In particular, the volume density of goblet cells was not increased. Thus the ultrastructure of the airway epithelium may be nearly normal in CF, even in adult patients with chronic respiratory infection.

Adult↗