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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Novel effects of dendrotoxin homologues on subtypes of mammalian Kv1 potassium channels expressed in Xenopus oocytes.

We have examined the effects of two DTX homologues, toxin I and toxin K, on Kv1.1, Kv1.2 and Kv1.6 channels expressed in Xenopus oocytes. Toxin I blocked all three channels; in contrast, toxin K was selective for Kv1.1. Both toxins slowed channel activation and inactivation kinetics with 10 nM toxin I approximately doubling activation and inactivation time constants of Kv1.1. For the first time, we have demonstrated the selectivity of a DTX homologue for a single cloned Kv1 channel and suggest that these toxins may sterically hinder the conformational changes that occur during channel gating.

Animals↗
PubMed1996

Cysteine-modifying reagents alter the gating of the rat cloned potassium channel Kv1.4.

The effects of cysteine-modifying reagents on the gating of rat cloned Kv1.4 channels expressed in HEK-293 cells were examined using the whole-cell patch-clamp technique. Cells transfected with Kv1.4 expressed a rapidly inactivating K+ current with a mid-point of activation of -31 mV and a slope factor of 5 mV measured with tail current protocols in 35 mM Rb+ external solutions. The cysteine-specific oxidizing agents 2,2'-dithiobis-5-nitropyridine (DTBNP, 50 microM) and chloramine-T (CL-T, 500 microM) removed inactivation of Kv1.4. These effects were reversed by the reducing agent dithiothreitol (DTT, 10mM). In addition, DTBNP and CL-T also slowed Kv1.4 deactivation and increased the voltage sensitivity of deactivation. The action of cysteine-modifying reagents on Kv1.4 suggests that redox state affects channel gating, with oxidation tending to stabilize the open state of the channel, both by removing inactivation and slowing deactivation.

Animals↗
PubMed1996

Treatment of severe meconium aspiration syndrome with porcine surfactant. Collaborative Surfactant Study Group.

UNLABELLED: This study is based on clinical data from a retrospective series of 54 infants with meconium aspiration syndrome treated with porcine surfactant at a median age of 14 h (range 1-176 h). Median arterial/ alveolar oxygen tension ratio (a/A PO2 ratio) before treatment was 0.08 (range 0.02-0.23) and oxygenation index 25 (range 6-110). After treatment with surfactant at an initial dose of 50-200 mg/kg there was a modest but statistically significant increase in a/APO2 ratio associated with a reduction of oxygenation index. Ten (18%) babies showed a 3-4 fold increase in a/APO2 ratio within 1-2 h of treatment. Twenty-four (44%) babies showed little or no response by 1-2 h with the remaining infants showing modest improvement in oxygenation. One third of babies required repeated doses of surfactant. Twenty-eight day survival was 81%, with two babies requiring extracorporeal membrane oxygenation. CONCLUSION: Natural surfactant treatment of severe meconium aspiration may prove to be a useful intervention and randomised controlled clinical trials should be undertaken.

Biological Products↗
PubMed1996

Long-term cycling of surfactant films in Wilhelmy balance.

Surface properties of porcine surfactant were observed during long-term cycling in Wilhelmy balance. Various amounts of surfactant were applied onto the surface as dry particles or droplets, or were suspended in the hypophase, and the films generated by this material were subjected to 50% cyclic compression at a rate of 1 cycle per min. Film spreading was faster from a droplet than from a particle of lyophilized surfactant, but the "stable period" during which minimum surface tension of the compressed film remained below 5 mN/m was significantly longer for the dry material. For surfactant suspensions the period of film "refinement", defined as the number of cycles required to reduce minimum surface tension to a level below 5 mN/m, was inversely correlated with the concentration of surfactant in the hypophase. Thirteen batches of porcine surfactant, used successfully in clinical trials for treatment of neonatal respiratory distress syndrome, were evaluated in the same system suspended in the hypophase at a concentration of 0.5 mg/ml. Films adsorbed from these batches had a median refinement period of 4 cycles, and a median stable period of 2160 cycles (36 h). In the same assay system, surfactant activity was inhibited in a dose-dependent manner by serum, fibrinogen, meconium, and bilirubin, but the specific inhibitory activity was significantly higher for bilirubin than for the other substances tested.

Analysis of Variance↗
PubMed1996

High-energy ballistic and avulsive facial injuries: classification, patterns, and an algorithm for primary reconstruction.

A 17-year experience from 1977 to 1993 with gunshot, shotgun, and high-energy avulsive facial injuries emphasizes the superiority and safety of "ballistic wound" surgical management: (1) immediate stabilization in anatomic position of existing bone, (2) primary closure of existing soft tissue, (3) periodic "second look" serial debridement procedures, and (4) definitive early reconstruction of soft-tissue and bony defects. The series contains 250 gunshot wounds, 53 close-range shotgun wounds, and 15 high-energy avulsive facial injuries. Four general patterns of involvement are noted for both gunshot and shotgun wounds and three for avulsive facial injuries. The treatment algorithm begins with identifying zones of injury and loss for both soft and hard tissue. Gunshot wounds are best classified by the location of the exit wound; shotgun and avulsive facial wounds are classified according to the zone of soft-tissue and bone loss. Treatment, prognosis, and complications vary according to four patterns of gunshot wounds and four patterns of shotgun wounds. Avulsive wounds have not been recommended previously for ballistic wound surgical management. The appropriate management of high-energy avulsive and ballistic facial injuries is best approached by an aggressive treatment program emphasizing initial primary repair of existing tissue, serial conservative debridement, and early definitive reconstruction.

Adult↗
PubMed1996

Surfactant treatment in experimental Escherichia coli pneumonia.

BACKGROUND: Deterioration of lung function in bacterial pneumonia may in part be due to inactivation of endogenous surfactant. We investigated the effects of surfactant treatment on gas exchange and lung morphology in an experimental model of pneumonia caused by Escherichia coli. METHODS: A total of 117 adult rats received via the trachea 2 ml/kg body weight of a standard suspension of Escherichia coli (4 x 10(9) bacteria/ml). After 2-3 days, 31 of the infected animals showed symptoms of respiratory failure with PaO2 < 27 kPa during ventilation with 100% O2. All these animals were kept in a multi-plethysmograph system and ventilated for 45 min with a tidal volume of 6 ml/kg, a frequency of 30/min, an inspiration/expiration ratio of 1:1, and a positive end-expiratory pressure of 0.2 kPa. After 15 min of mechanical ventilation, animals were divided in three treatment groups, receiving via the airways (1) no material, (2) normal saline (2 ml/kg), or (3) Curosurf, 80 mg/ml (2 ml/kg). Ten healthy animals served as controls. Lung-thorax compliance and blood gases were measured 15 and 30 min after surfactant treatment. After the period of ventilation, animals were killed, and the left lung was weighed and fixed in formalin for histological examination. The right lung was washed in situ with normal saline via the tracheal tube. Total phospholipids, and levels of phosphatidylcholine (PC) and protein in lavage fluid were determined. RESULTS: In comparison with pre-treatment values, average PaO2 at 30 min was increased by 76% in animals receiving Curosurf (P < 0.01), but did not improve in the other groups. The left lung weight/body weight ratio showed a nearly 3-fold increase in infected animals in comparison with normal controls. There was also a 3-fold increase in the protein content of lung lavage fluid from infected rats, but values for total phospholipids and PC content were unchanged in animals not receiving surfactant. Histological examination of the lungs showed wide-spread non-specific pneumonia in infected animals, but no difference in alveolar air expansion between surfactant-treated and non-treated ones. CONCLUSION: Surfactant replacement significantly improves oxygenation in rats with E. coli pneumonia, without affecting lung-thorax compliance during mechanical ventilation or alveolar expansion pattern in lungs fixed by conventional methods.

Animals↗
PubMed1996

Using a mailed survey to predict hospital admission among patients older than 80.

OBJECTIVE: To determine if the results of a questionnaire mailed to older patients can help identify those patients at greatest risk of hospital admission. DESIGN: A longitudinal cohort study. SETTING: A prepaid managed care plan in the Denver metropolitan area. PARTICIPANTS: Of the 4414 eligible patients at least 81 years old, 3745 (84.8%) responded. MEASUREMENTS: We studied the predictive power of self-reported demographic, health status, medical history, health habits, functional status (including Katz' activities of daily living and OARS instrumental activities of daily living), and socioeconomic status data to identify those older adults at greatest risk of hospitalization within 4.5 months of completing the survey. We derived our predictive model on one-half the subjects and tested its validity it on the other half. RESULTS: Univariate analysis revealed 25 variables significantly associated with hospital admission. In a logistic regression model, four significant variables successfully stratified the patients by risk of admission. These four variables are: the presence of heart disease, the presence of diabetes, need for help preparing meals, and limited physical independence (requiring the help of a person or mechanical aid to get around). In addition, there was an antagonistic interaction between the presence of heart disease and limited physical independence. The model stratified patients from low risk (4.5% chance of admission) to high risk (39% chance of admission). As measured by the Hosmer-Lemeshow statistic and the area under a receiver-operator characteristic (ROC) curve, this model fit both the derivation and validation subjects well. CONCLUSIONS: A mailed questionnaire achieved a high response rate, and the information collected produced an effective model predictive of hospitalization in the short term. Four easily ascertained pieces of information identify those patients older than age 81 at increased risk.

Activities of Daily Living↗
PubMed1996

Synthetic protein analogues in artificial surfactants.

Today, airway instillation of surfactant preparations is a generally used treatment for respiratory distress syndrome in premature infants. Most commercially available surfactants are purified from animal lungs and contain lipids, mainly phospholipids, and about 2% of the hydrophobic surfactant proteins B and C (SP-B and SP-C). During the last half-decade the main structural properties of these proteins have been clarified and this knowledge now makes it possible to design synthetic analogues for future use in artificial surfactants.

Drug Design↗
PubMed1996

Rapid reverse transcription-PCR detection of hepatitis C virus RNA in serum by using the TaqMan fluorogenic detection system.

We describe the application of a new fluorogenic probe-based PCR assay (TaqMan; Perkin Elmer Corp./Applied Biosystems, Foster City, Calif.) for the detection of hepatitis C virus RNA in serum and plasma. This assay allows for the direct direction of specific PCR products within minutes of completion of the PCR by monitoring the increase in fluorescence of a dye-labeled oligonucleotide probe. We evaluated this assay by comparing the results obtained by nested PCR with those obtained by TaqMan PCR. Test samples included two separate dilutions series of plasma samples from experimentally infected chimpanzees and a panel of 48 serum specimens from patients with community-acquired hepatitis C virus. The quantity of HCV RNA in each chimpanzee plasma sample was determined by using branched DNA (bDNA) signal amplification assay (Quantiplex HCV RNA assay; Chiron Corp., Emeryville, Calif.). Both PCR assays demonstrated similar levels of detection and could reliably detect 13 bDNA genome equivalents per sample. We found an overall concordance of 88% between results of two PCR assays with the community-acquired panel, which resolved to 100% when discrepant samples were retested by nested PCR. TaqMan compared favorably with nested PCR with key advantages of speed, increased throughput, and decreased opportunity for false-positive results because of elimination of second-round amplification.

Animals↗
PubMed1996

Antibody to surfactant protein A increases sensitivity of pulmonary surfactant to inactivation by fibrinogen in vivo.

It has been suggested that surfactant protein-A (SP-A) protects surfactant activity from inhibitors such as fibrinogen. Substantial evidence indicates that inhibition of surfactant activity is often important in the pathogenesis of acute respiratory failure. Studies on surfactant function in the pulsating bubble surfactometer imply that SP-A helps to maintain low surface tension in the presence of inhibitors such as fibrinogen. We tested whether SP-A acts in this way in vivo. Rabbit pups, 29 d gestational age, were treated with a monoclonal antibody to rabbit SP-A (R5) followed by fibrinogen, or with control preparations (normal IgG and saline, respectively). Lung compliance was measured during ventilation throughout these experiments. Air-space volume and pulmonary edema were quantitated morphometrically. Animals receiving anti-SP-A antibody + fibrinogen showed substantial and significant impairment in lung compliance compared with control littermates receiving normal IgG and/or saline. Lungs from these animals showed decreased pulmonary air-space volume and increased alveolar edema. We conclude that SP-A protects pulmonary surfactant from inhibition by fibrinogen in vivo. This protective activity may be important in the pathogenesis of both adult and neonatal respiratory distress syndromes, and it may also be useful in devising therapies for these diseases.

Animals↗
PubMed1996

Exogenous surfactant improves ventilation efficiency and alveolar expansion in rats with meconium aspiration.

The pathogenesis of neonatal meconium aspiration syndrome (MAS) may involve inactivation of endogenous surfactant, and data from clinical pilot studies indicate that treatment with exogenous surfactant may alleviate respiratory failure in babies with MAS. We studied ventilation efficiency after treatment with a modified porcine surfactant in experimental meconium aspiration. Adult rats were anesthetized and tracheotomized, and received via a tracheal cannula from 4 to 6 ml/kg body weight of a saline suspension of human meconium (25 mg [dry weight]/ml). After 30 min of ventilation with 100% oxygen, the animals were in respiratory failure, with dynamic lung-thorax compliance < 0.5 ml/cm H2O/kg and PaO2 < 8 kPa (60 mm Hg). Animals were then allocated to: (1) immediate treatment with surfactant (200 mg/kg); (2) treatment with surfactant (200 mg/kg 3 h later; or (3) a control group not receiving surfactant. All animals were ventilated for 6 h with variable FIO2 and peak inspiratory/positive end-expiratory pressure (PIP/PEEP). In the control group, six of 12 animals died of respiratory failure with hypoxemia and acidosis despite ventilation with 100% oxygen and high mean airway pressure (> 20 cm H2O). The lungs of all animals in this group showed severe atelectasis, influx of neutrophils, edema, and hyaline membranes. In contrast, animals allocated to immediate or late surfactant treatment had lower mortality (one of seven and two of eight, respectively), a reduction of oxygen supply by 30%, and a decrease in mean airway pressure of 3 to 4 cm H2O. This was associated with a > 50% increase in static lung volume at 40 cm H2O inflation and 10 cm H2O deflation pressure and improved alveolar expansion in histologic sections. Hyaline membranes tended to be less prominent in surfactant-treated animals than in controls. We conclude that both early and late treatment with surfactant is effective in this animal model of MAS.

Animals↗
PubMed1996

Hemodynamics and tissue blood flow after porcine surfactant replacement in surfactant-depleted newborn piglets.

In 22 newborn piglets we studied the effect of hypovolemia or hypoxemia on hemodynamics and regional blood flow after instillation of porcine surfactant. Surfactant deficiency was obtained by repeated lung lavage, and blood flow measurements were carried out using radioactive microspheres. Three groups of piglets were studied, controls (n = 8), hypovolemia (n = 7), and hypoxemia (n = 7). Three to five minutes after instillation of surfactant, mean arterial blood pressure decreased significantly in all three groups with a mean decrease (+/- SD) of 31(+/- 12), 33(+/- 9), and 29(+/- 9) mm Hg, respectively (p < 0.01 in all three groups). Systemic vascular resistance decreased significantly in all three groups immediately after surfactant instillation (p < 0.01) and returned to presurfactant level after 60 min. Blood flow did not change after surfactant instillation in any of the three groups, in neither skin, muscle, pancreas, brain, nor retina. In liver, kidney, intestine, and choroidea there was a decrease in blood flow immediately after instillation with return to presur-factant levels within 60 min. Hypoxemia or hypovolemia before surfactant instillation did not increase the hemodynamic instability. The decrease in mean arterial blood pressure was caused by a vasodilation and not by a reduced cardiac output.

Animals↗
PubMed1996

Pulmonary epithelial permeability. An animal study of inverse ratio ventilation and conventional mechanical ventilation.

STUDY OBJECTIVE: To compare pressure-controlled inverse ratio ventilation (PCIRV) with volume-controlled ventilation with positive end-expiratory pressure (VCV PEEP) at equal levels of end-expiratory alveolar pressure. The primary focus of the study was on pulmonary epithelial permeability. Histologic and gravimetric indicators of lung injury were also studied. DESIGN: Randomized animal study. SETTING: Experimental investigation at Södersjukhuset, Stockholm, Sweden. ANIMALS: Thirty-two New Zealand white rabbits. INTERVENTIONS: Ventilation with PCIRV or VCV PEEP for 6 h at an end-expiratory pressure level of 5 cm H2O. MEASUREMENTS AND RESULTS: Lung mechanics, heart rate, BP, and gas exchange. Measurement of pulmonary epithelial permeability by 99mTc-DTPA lung clearance. Extravascular lung water by gravimetric analysis. Morphology by light microscopy after a perfusion fixation procedure. Mean and peak airway pressures were 12.4 +/- 4.3 and 15.9 +/- 4.5 cm H2O with PCIRV and 8.6 +/- 0.8 (p < 0.001) and 19.9 +/- 4.1 cm H2O (p < 0.03) with VCV PEEP at 6 h. Mean systemic BP was lower with PCIRV (58 +/- 9 mm Hg) than with VCV PEEP (68 +/- 7 mm Hg) at 6 h (p < 0.003). At 6 h, PaCO2 was lower with PCIRV (3.2 +/- 0.6 kPa) than with VCV PEEP (4.1 +/- 0.8 kPa) (p < 0.02). There was no difference in blood oxygenation between PCIRV and VCV PEEP. 99mTc-DTPA lung clearance curves were monoexponential with both PCIRV and VCV PEEP. Mean lung clearance expressed as T 1/2 was 16 +/- 9 min with PCIRV and 107 +/- 74 min with VCV PEEP (p < 0.001). Morphologic examination revealed no differences between the groups and no evidence of significant lung injury. CONCLUSIONS: The observations reported in this article imply that PCIRV causes an alteration in lung epithelial or membrane function in comparison to VCV PEEP. This functional difference is most likely caused by the large time-adjusted lung volume produced by pressure control in combination with a prolonged inspiration. It remains to be established whether this early functional effect of PCIRV is relevant with regard to structural lung injury in mechanically ventilated subjects.

Animals↗
PubMed1996

Prophylaxis of respiratory distress syndrome by treatment with modified porcine surfactant at birth: a multicentre prospective randomized trial.

The objective of this prospective, multicentre trial, carried out at 18 third level hospitals in Italy, was to evaluate efficacy of modified porcine surfactant (Curosurf), administered at birth to prevent the development of respiratory distress syndrome (RDS) in premature infants. 287 babies with a gestational age of 24-30 weeks were randomized to prophylactic treatment with Curosurf (80 mg/ml; dose 20 mg/kg) or to a control group receiving no surfactant treatment in the delivery-room. Babies in both groups were eligible for rescue treatment with surfactant (200 mg/kg) if they developed clinical symptoms of RDS and required mechanical ventilation. The main end-point was to obtain, in the prophylaxis group, a 30% reduction in the incidence of grade 3-4 RDS. Median gestational age was 28 weeks in both groups and mean birth weight 1010 and 1002 g, respectively for prophylaxis and control babies. There was a 32% reduction in the incidence of grade 3-4 RDS in the prophylaxis group (p < 0.05). This was associated with a significant reduction in mean maximum fraction of inspired oxygen (0.57 vs 0.66%; p < 0.01), a decreased incidence of pulmonary interstitial emphysema (7 vs 14%; p < 0.05) and a lowered mortality (21 vs 35%; p < 0.01). Combined unfavourable outcome (mortality + bronchopulmonary dysplasia and/or grade 3-4 intraventricular hemorrhage and/or grade 2-4 retinopathy of prematurity) was significantly lower in the prophylaxis than in the second group (41 vs 58%; p < 0.01). The favourable effects of prophylactic treatment were equally recorded in all the age groups, including the babies with the lowest gestational age (24-25 weeks). Multiple and logistic regression analysis confirmed that high gestational age and surfactant prophylaxis were, independently, associated with a lower degree of RDS (p = 0.0001 and p = 0.0008, respectively) and a lower mortality (p = 0.0001 and p = 0.0045, respectively). We conclude that prophylaxis with modified natural surfactant effectively prevents RDS in newborn babies between 24 and 30 weeks' gestation.

Biological Products↗
PubMed1996

Concurrent-schedule performance in dairy cows: persistent undermatching.

Performance of dairy cows responding under concurrent variable-interval variable-interval schedules of food delivery was examined, with results analyzed in terms of the generalized matching equation. In Experiment 1, bias measures indicated that crushed barley was preferred over meatmeal when these foods were available under the alternative schedules. For whole-session data, substantial undermatching of response and time-allocation ratios to obtained reinforcement ratios was evident. Postreinforcement pause time ratios approximately matched obtained reinforcement rates. Subtracting these times from total time-allocation values yielded net time-allocation ratios that undermatched obtained reinforcement ratios to a greater degree than did whole-session time-allocation ratios. In Experiment 2, substantial undermatching was evident when the same foods (hay for 2 cows, crushed barley for 2 others) were available under the alternative schedules. Food-related activities and other defined behavior not related to food were quantified by direct observation, and were found to occupy a substantial proportion (roughly 40% to 80%) of experimental sessions. Subtracting the time spent in these activities from the time allocated to each component schedule did not reduce the degree of undermatching obtained. Across all conditions in both experiments, slopes of regression lines relating behavioral outputs to environmental inputs characteristically were below 0.6, which agrees with prior findings and suggests that, contrary to suggestions in the literature, undermatching in dairy cows is not the result of using different foods under alternative schedules or differential pausing under those schedules.

Animals↗