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Biomedical subjects

D Royston

Publications and source records attributed to D Royston.

At least 109 records · Page 6Linked to original sources
PubMed1987

A comparison of 99mTc-DTPA and 113mIn-DTPA aerosol clearances in humans. Effects of smoking, hyperinflation, and in vitro oxidation.

As an index of permeability of the alveolar epithelium, the clearance of an inhaled aerosol of 99mTc-DTPA is increased in several disease states. However, the usefulness of the test to assess the severity of disease is limited because healthy smokers also have abnormally rapid rates of clearance. Because the stability of the 99mTc-DTPA bond might be a contributory factor, we tested the affinity of 99mTc for DTPA in vitro, and in groups of healthy smokers (n = 13) and nonsmokers (n = 7) we measured the clearances of 99mTc-DTPA and 113mIn-DTPA, which have a similar molecular shape and charge. In vitro, sodium hypochlorite or hydrogen peroxide released as much as 98% of free 99mTc from the 99mTc-DTPA complex. When incubated with human neutrophils stimulated with phorbol myristate acetate, between 4 and 7% of free 99mTc-DTPA was released after 30 min, and 12% was released after 60 min. In vivo, the clearances of both 99mTc-DTPA and 113mIn-DTPA in the smokers (n = 13) were faster than in the nonsmokers (n = 7) (p less than 0.05). Within the smokers, the mean 99mTc-DTPA clearance (T1/2 25 +/- 4 min) was faster than the mean 113mIn-DTPA clearance (34 +/- 6 min), (p less than 0.05). For nonsmokers, the difference was smaller (T1/2 99mTc-DTPA, 56 +/- 6; T1/2 113mIn-DTPA, 62 +/- 6) and not significant. During hyperinflation, smokers (n = 8) and nonsmokers (n = 8) both demonstrated an increase in 113mIn-DTPA clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

The effect of human antiendotoxin monoclonal antibodies on endotoxin-induced lung injury in the rat.

A model of endotoxin-induced lung injury was developed in the rat. We found that 24 h after intravenously administered endotoxin (3 mg/kg) there was increased clearance of the isotope 99mTcDTPA from the lung to blood, increased neutrophils in the lung in bronchoalveolar lavage, and increased levels of products of peroxidation of lipids and nucleic acid in the serum. Using this model, we evaluated the effect of pretreatment of rats with a human monoclonal antibody specific to the core glycolipid that is common to all endotoxins. We found that pretreatment prevented the increased clearance of 99mTcDTPA from the lung, as well as the increase in lipid peroxidation products in the serum. The antibody did not prevent increased neutrophil accumulation in the lung. The findings suggest that the administration of human antiendotoxin monoclonal antibodies prior to endotoxemia may prevent some of the changes in the lung associated with endotoxin.

Animals↗
PubMed1986

Infused salbutamol accentuates acid-induced lung injury in the rat.

The effect in the rat of salbutamol infusion (1 microgram min-1 kg-1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 +/- 2.6 min) compared with non-acid-treated rats (98.1 +/- 7.2) (P less than 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 +/- 1.9) than the acid and control infusion group (P less than 0.05). Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 +/- 0.3) compared with the non-acid-treated controls (5.4 +/- 0.2) (P less than 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 +/- 0.6) (P less than 0.001 vs acid and control infusion). Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include beta 2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant beta 1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.

Albuterol↗
PubMed1986

The non-steroidal anti-inflammatory agent, indoprofen, does not protect against hydrochloric acid induced lung injury in the rat.

The effects of pulmonary instillation of hydrochloric acid on solute flux from the lung (measured as the clearance of 99mTcDTPA) together with an index of oedema formation (the ratio of lung wet weight to lung dry weight) was measured in rats. There was a significant increase in 99mTcDTPA clearance (P less than 0.001) and also in lung wet:dry weight ratio (P less than 0.01) 4-5 h following acid challenge. There was no difference in the effects of challenge with acid of pH1 and pH2. In addition, intravenous injection of indoprofen (20mg/kg) a non-steroidal anti-inflammatory agent failed to produce any beneficial effect on the variables under study when given after acid (pH2) challenge. There was also histological evidence of an influx and sequestration of granulocytes into the lung. Despite this, the plasma concentration of thiobarbituric acid reactive material (used as an index of cell-derived, oxidant-free radical production) was significantly reduced in all acid-treated groups. These data show that hydrochloric acid will initiate a severe inflammatory response in the lung of the rat and that the non-steroidal anti-inflammatory agent indoprofen when given after the injury produced no evidence of a beneficial effect on this inflammatory response.

Acid-Base Equilibrium↗
PubMed1986

Effect of raised thoracic pressure and volume on 99mTc-DTPA clearance in humans.

Although positive airway pressure is often used to treat acute pulmonary edema, the effects on epithelial solute flux are not well known. We measured independently the effect of 1) positive pressure and 2) voluntary hyperinflation on the clearance of inhaled technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) in six nonsmokers and six smokers. Lung volumes were monitored by inductance plethysmography. Each subject was studied in four situations: 1) low end-expiratory volume (LO-), 2) low volume plus 9 cmH2O continuous positive airway pressure (LO+), 3) high end-expiratory volume (HI-), and 4) high volume plus continuous positive airway pressure (HI+). The clearance half time of 99mTc-DTPA for the nonsmokers decreased from 64.8 +/- 7.0 min (mean +/- SE) at LO- to 23.2 +/- 5.3 min at HI- (P less than 0.05). Positive pressure had no synergistic effect. The mean clearance half time for the smokers was faster than nonsmokers at base line but unaffected by similar changes in thoracic volume and pressure. We conclude that, in nonsmokers, positive airway pressure increases 99mTc-DTPA clearance primarily through an increase in lung volume and that smokers are immune to these effects.

Adult↗
PubMed1986

Comparison of lung vascular and epithelial permeability indices in the adult respiratory distress syndrome.

Measurements of pulmonary clearance of inhaled 99mTc-DTPA and transvascular 113mIntransferrin flux were made in 12 patients with established ARDS and 14 volunteer control subjects (7 smokers and 7 nonsmokers). Smokers had significantly increased 99mTc-DTPA clearance (clearance rate constant, 3.6 +/- 0.8; mean +/- SEM) compared with nonsmokers (1.2 +/- 0.1). All patients with ARDS had increased clearance of 99mTc-DTPA (5.2 +/- 0.9), but the finding was nonspecific in that increased clearance overlapped with the findings in normal smokers. Protein flux in smokers (protein flux units, 0.0 +/- 0.2) was similar to that in nonsmokers (0.3 +/- 0.2). In 9 of the 12 patients with ARDS, protein flux was increased, and as a group (3.2 +/- 1.0) they differed significantly (p less than 0.01) from the combined smoking and nonsmoking control subjects (0.2 +/- 0.1, n = 14). The parameters of DTPA clearance and transvascular protein flux correlated well in the patients with ARDS (Spearman's rank correlation = 0.71, p less than 0.01). Although 99mTc-DTPA clearance is a sensitive technique in ARDS, a single study in this context does not allow a diagnostic conclusion because of its non-specificity. Abnormal protein flux appears to be more specific for ARDS but was not a universal finding in the patients studied.

Adult↗
PubMed1986

Increased pulmonary transvascular protein flux after canine cardiopulmonary bypass. Association with lung neutrophil sequestration and tissue peroxidation.

We examined the hypothesis that increased pulmonary transvascular protein flux after cardiopulmonary bypass (CPB) is mediated in part by neutrophil-derived, oxygen-free radicals. Measurements of transvascular lung 113mIn-transferrin flux, transpulmonary neutrophil counts, and plasma concentrations of thiobarbituric acid (TBA) reactive substances were made in 8 dogs after CPB and in 6 dogs who underwent thoracotomy alone. The TBA reactivity is indicative of lipid peroxidation and was used as an index of oxygen-free radical release. All 14 dogs had a baseline measurement of lung protein flux 1 wk prior to thoracotomy. In the bypass dogs, lung protein flux was -0.2 +/- 0.3 protein flux units (mean +/- SEM) at baseline and increased significantly after bypass to 3.3 +/- 1.0 (p less than 0.01). The control thoracotomy group had baseline values similar to the baseline studies in the CPB dogs (0.2 +/- 0.3 units), but no significant difference was noted after thoracotomy. The CPB dogs showed initial significant parallel falls in left atrial (LA) and central venous (CV) neutrophil counts during bypass (baseline, 5.3 +/- 0.7 X 10(9) cells/L in both sample sites, falling to 3.0 +/- 0.5 and 2.9 +/- 0.5, respectively, p less than 0.001), but a significant CV-LA transpulmonary gradient existed only when pulmonary perfusion recommenced after a period of total asystole. Concentration of TBA reactive substances increased significantly during the course of bypass (baseline LA, 6.4 +/- 0.5 nmol/L, baseline CV, 6.4 +/- 0.5, increasing to 9.8 +/- 1.0 and 9.4 +/- 1.6 at the end of bypass, respectively, p less than 0.01), but likewise, there was a significant transpulmonary gradient only after reversal of asystole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Increased production of peroxidation products associated with cardiac operations. Evidence for free radical generation.

We investigated the degree and time course of neutrophil sequestration into human lungs during cardiac operations. At the same time, measurement of the concentration of peroxidation products in the plasma was used as an index of oxidant free radical activity. The study was performed in two groups of patients. Group A (n = 11) had studies extending over the entire operative period and showed a highly significant sequestration of neutrophils into the lung, together with a highly significant (p less than 0.001) rise in peroxidation products from 2.8 +/- 0.12 nmol/ml(mean +/- standard error of the mean)before bypass to a peak of 5.05 +/- 0.13 nmol/ml at the end of bypass. As these changes occurred only during the time after release of the aortic cross-clamp, we investigated this period in more detail in a second group of patients (Group B, n = 7). Results from this group showed that significant release of peroxidation products occurred at the same time as pulmonary neutrophil sequestration. This study has produced evidence of increased oxidant activity in the lung associated with cardiac operations. Nevertheless, it is not known whether the neutrophils sequestered into the lung alone induced the increased activity. Similarly, whether neutrophil-derived oxidant species are the sole cause of lung tissue injury remains unproved.

Cardiopulmonary Bypass↗
PubMed1985

Adult respiratory distress syndrome after allogeneic bone-marrow transplantation: evidence for a neutrophil-independent mechanism.

5 patients in whom the adult respiratory distress syndrome (ARDS) developed after bone-marrow transplantation (BMT) for chronic myeloid leukaemia are described. Donors in all cases were siblings who were matched for all major-histocompatibility-complex determinants. All patients were neutropenic to varying degrees at the onset of respiratory symptoms. Histological evaluation in all patients at necropsy showed diffuse alveolar damage with no evidence of intrapulmonary neutrophil sequestration. No patient had detectable levels of plasma peroxidation products, which were measured as an index of neutrophil oxidant function. Significantly increased clearance of inhaled 99mTc-diethylene-triamine-pentacetate was a uniform finding, suggesting impaired alveolar-capillary barrier function in keeping with ARDS. An increase in an index of lung epithelial permeability leading to ARDS may develop in neutropenic patients who have evidence of neither intrapulmonary neutrophil sequestration not tissue oxidant injury. ARDS after BMT is probably multifactorial in aetiology, but neutrophil-derived oxidant products play no part in its genesis.

Adult↗
PubMed1985

The effect of surgery with cardiopulmonary bypass on alveolar-capillary barrier function in human beings.

We measured the rate of clearance of technetium 99m-labeled diethylenetriamine pentaacetate (99mTcDTPA) (molecular weight, 492 daltons) from the lung into the blood (T1/2LB) in 9 patients before and after operation with cardiopulmonary bypass (CPB). Two hours postoperatively, T1/2LB fell from 49.3 +/- 13.6 minutes (mean +/- standard deviation) to 24.0 +/- 12.8 minutes (p less than 0.001). In addition, alveolar-arterial oxygen tension difference P(A-a)O2 had increased from 73 +/- 28 mm Hg to 164 +/- 37 mm Hg (p less than 0.001). The rates of clearance of 99mTcDTPA had returned to preoperative times by 7 days after operation, although there was still a significant (p less than 0.05) elevation in P(A-a)O2. Postoperative respiratory failure developed in 1 patient. The only abnormality of lung function detected preoperatively was an increased clearance rate for 99mTcDTPA (T1/2LB, 18 minutes). This study has shown an increased clearance from the lung of a low-molecular-weight molecule following operation with CPB. This finding should allow a more rational approach to elucidating the mechanisms of injury to the gas-blood interface in the lung following this type of operation.

Aged↗
PubMed1985

Pronounced, episodic oxygen desaturation in the postoperative period: its association with ventilatory pattern and analgesic regimen.

The respiratory effects of two postoperative analgesic regimens were compared in two groups of 16 patients each, recovering from general anesthesia and major surgery. One group received a pain-relieving dose of iv morphine (mean, 18.1 mg), with the same dose repeated as a continuous intravenous infusion over the subsequent 24 h. The other group received regional anesthesia using bupivacaine. The patients were monitored for 16 h after surgery. The two analgesic regimens provided patients with comparable analgesia throughout the study period, but there were quite different respiratory effects in the two groups. Ten patients receiving morphine infusions had a total of 456 episodes of pronounced oxygen desaturation (SaO2 less than 80%). These occurred only while the patients were asleep, and all were associated with disturbances in ventilatory pattern, namely, obstructive apnea (144 episodes in eight patients), paradoxic breathing (275 episodes in six patients), and period of slow ventilatory rate (37 episodes in one patient). In contrast, in patients receiving regional anesthesia, oxygen saturation never decreased below 87%. Central apnea, obstructive apnea, and paradoxic breathing occurred more frequently in patients in the morphine group (12, 10, and 10 patients, respectively) than patients in the regional anesthesia group (4, 3, and 5 patients, respectively). The interaction of sleep and morphine analgesia produced disturbances in ventilatory pattern, causing profound oxygen destruction. These results suggest that postoperative pain relief using regional anaesthesia has a greater margin of safety in terms of respiratory side effects than does the continuous administration of opiates.

Adult↗
PubMed1985

Changes in permeability of the alveolar-capillary barrier in firefighters.

The effect on alveolar-capillary barrier permeability of chronic exposure to a smoke produced by the partial combusion of diesel oil, paraffin, and wood was examined. An index of permeability was determined from the rate of transfer from the lung into the blood of the hydrophilic, labelled chelate 99mTc diethylene triamine penta-acetate (MW 492 dalton). The results of this test were expressed as the half time clearance of the tracer from the lung into the blood (T1/2 LB). The study was carried out at the Royal Naval Firefighting School, HMS Excellent. Permeability index was measured on seven non-smoking naval firefighting instructors who had worked at the school for periods of longer than two and a half months. Tests of airway function and carbon monoxide transfer factor were performed on four of these seven instructors. The results of the permeability index showed a T1/2 LB of 26 min +/- 5 (SEM) which differed significantly from that of normal non-smokers. By contrast all other lung function tests had values within the predicted normal range.

Adult↗
PubMed1985

Cigarette smoke induced changes in rat pulmonary clearance of 99mTcDTPA. A comparison of particulate and gas phases.

The rat model was developed to study the effects of cigarette smoke on pulmonary clearance of 99mTcDTPA. The method developed was sufficiently noninvasive to allow frequent repeat measurements to be made with a high degree of reproducibility. Animals exposed twice daily to 90 puffs of dilute whole cigarette smoke for 7 days showed an increase in 99mTcDTPA clearance from the lung which returned to normal within 3 wk of stopping exposure. Filtration of the smoke to remove all the particulate matter abolished the changes.

Animals↗
PubMed1985

Some short-term effects of changing to lower yield cigarettes.

The rate of clearance from the lung of the hydrophilic tracer molecule 99mTc DTPA was used to investigate the short-term effects on lung epithelial function when smokers switched to cigarettes with lower yields of tobacco smoke constituents. Two separate studies were performed. In the first study, subjects smoked conventional mid- and low-tar cigarettes. The second study used two specially manufactured cigarettes with similar tar and nicotine yields, but differing carbon monoxide yields. Neither study demonstrated any significant improvement in 99mTc DTPA clearance. The yields of carbon monoxide determined under standard machine smoking conditions implied that there would be a 44 percent reduction in exposure to carbon monoxide when subjects switched from smoking conventional mid-tar to low-tar cigarettes. However, measurements of carboxyhemoglobin showed that the smokers compensated for the lower yields and their exposure was reduced by only 11 percent. Similarly, in the second study, the subjects reduced their exposure by 7 percent instead of the expected 44 percent. Urine nicotine/cotinine excretion measurements in this study indicated that there was no complimentary increase in nicotine absorption suggesting the possibility that subjects may be able to regulate their intake of individual components of the cigarette smoke. Thus, the unexpected result from this study was the finding that cigarette smokers could, in some way, regulate their intake of smoke from cigarettes of different composition so as to maintain a constant exposure of smoke constituents.

Adolescent↗
PubMed1985

Amniotic fluid infection with intact membranes in relation to stillborns.

The role of transamniotic fetal infection in the presence of intact membranes has attracted widespread attention. The present study is a reexamination of the autopsy material from 145 cases of macerated stillbirth observed in the National Maternity Hospital from 1979 to 1982. The objective was to ascertain the incidence of congenital pneumonia. No more than five cases were discovered, and in only two of these was there convincing evidence that the membranes were intact. The amniotic fluid infection syndrome seemed to be of little importance in the causation of late intrauterine death.

Amniotic Fluid↗
PubMed1984

Histamine increases lung permeability by an H2-receptor mechanism.

The effect of specific H1 and H2 receptor antagonists on bronchial reactivity and increase in lung epithelial permeability in response to inhaled histamine was measured in 5 non-smoking men (age range 24-36 years). Inhaled histamine produced a short-lived but consistent increase in permeability to 99Tc-diethylenetriamine penta-acetate. An H1-receptor antagonist, terfenadine (60 mg), protected against the bronchoconstrictor effect but had no significant influence on the increase in permeability. The H2-receptor antagonist ranitidine (150 mg) significantly reduced the permeability response without having an effect on bronchial reactivity. These results demonstrate that the bronchoconstrictor effect of histamine is mediated by H1 receptors and permeability increase is mediated by H2 receptors. H2-receptor mediated increase in lung epithelial permeability may be important clinically.

Adult↗