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Biomedical subjects

M J Bishop

Publications and source records attributed to M J Bishop.

At least 19 recordsLinked to original sources

Antibody against neutrophil adhesion improves reperfusion and limits alveolar infiltrate following unilateral pulmonary artery occlusion.

Relief of unilateral pulmonary arterial occlusion results in bilateral lung injury and results in only partial restoration of pulmonary blood flow distal to the site of occlusion. We hypothesized that the "no reflow" phenomenon was in part due to neutrophil adherence and aggregation in the pulmonary vasculature. The study was carried out in two phases. First, we studied the effect of neutrophil depletion on left lung blood flow following 24 hr of left pulmonary artery occlusion. Hydroxyurea was used to deplete circulating neutrophils to 77 +/- 18/mm3 (means +/- sem) (n = 6) as compared to 708 +/- 165/mm3 in control rabbits (n = 8). In both groups left lung blood flow immediately following reperfusion was markedly reduced at 6.4 +/- 2.2% of cardiac output in control rabbits and 7.3 +/- 2.3 in treated rabbits. However, at 4 hr, neutrophil-depleted animals had significantly greater flow (18.7 +/- 3.6 vs 8.4 +/- 2.3% for control rabbits, P less than 0.05). In both groups, flow remained substantially below the normal rabbit left lung blood flow of 39.8 +/- 2.2%. To test whether the improved reflow was due to decreased numbers of neutrophils limiting aggregation, or whether active neutrophil adherence played a role, we tested the effect of a monoclonal antibody that interferes with neutrophil adhesiveness (MoAb 60.3) on reflow and on neutrophil emigration into the alveoli. We found that MoAb 60.3 did not affect initial reflow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The UK Human Genome Mapping Project online computing service.

This paper presents an overview of computing and networking facilities developed by the Medical Research Council to provide online computing support to the Human Genome Mapping Project (HGMP) in the UK. The facility is connected to a number of other computing facilities in various centres of genetics and molecular biology research excellence, either directly via high-speed links or through national and international wide-area networks. The paper describes the design and implementation of the current system, a 'client/server' network of Sun, IBM, DEC and Apple servers, gateways and workstations. A short outline of online computing services currently delivered by this system to the UK human genetics research community is also provided. More information about the services and their availability could be obtained by a direct approach to the UK HGMP-RC.

Computer Communication Networks

Clustering cDNA sequences.

A set of programs has been written to quantify the similarities between large numbers of cDNA sequences. This information is used to cluster similar sequences together. The main program can cluster thousands of cDNA sequences per day using a novel, computationally inexpensive algorithm. The clustering information is kept in a small index file so that disk storage requirements are negligible. Using this index file, subsidiary programs create various views and statistical summaries of the entire cDNA sequence collection.

Algorithms

Pulmonary artery occlusion is sufficient to increase pulmonary vascular permeability in rabbits.

Unilateral pulmonary artery obstruction (PAO) for 24-48 h, followed by reperfusion, results in pulmonary edema and lung inflammation. We hypothesized that lung injury actually occurred during the period of PAO but, because of low microvascular pressures during the period of occlusion, was not detected until perfusion was reestablished. To test this hypothesis, we studied 14 rabbits divided into three groups: group I rabbits underwent sham occlusion of the left pulmonary artery for 24 h; group II rabbits underwent PAO but were not reperfused; and group III rabbits were subjected to PAO and then reperfused for 4 h. The fluid filtration coefficient measured during a zone 3 no-flow hydrostatic stress (pulmonary arterial pressure = pulmonary venous pressure, both greater than alveolar pressure) in group I lungs was less than that of lungs in either group II or III [0.52 +/- 0.02 (SE) ml.min-1.cmH2O.100 g wet wt-1 vs. 0.94 +/- 0.11 and 0.86 +/- 0.13 for groups II and III, respectively, P less than 0.05]. The wet-to-dry weight ratio of the left lung measured after the zone 3 stress was applied for 20 min was 6.90 +/- 0.09 in group I rabbits and 9.21 +/- 0.75 and 11.75 +/- 0.44 in groups II and III, respectively (P less than 0.05). Radiolabeled microspheres demonstrated that flow to the left lung was diminished after the period of PAO (38 +/- 4, 9 +/- 5, and 2 +/- 1% of cardiac output in groups I, II, and III, respectively; P less than 0.05 for group I vs. groups II and III).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pneumonia following closed head injury.

Pneumonia is common among patients with artificial airways in place. Most prior studies of such pneumonia involve a heterogeneous group of patients, usually with major medical or surgical illnesses. We studied the incidence of pneumonia in a group of patients with isolated closed head injury (CHI) in an effort to determine the pattern of the problem in the absence of other injuries and to determine whether the pattern of development of pneumonia in these patients was comparable to that in more heterogeneous groups of mechanically ventilated patients. We studied 109 initially comatose patients with isolated CHI who were ventilated 24 h or more. The mean age was 30.3 +/- 20.2 yr, 72% were male, and the admission Glasgow coma score was 4.9T +/- 1.4. Overall, 45 patients (41%) developed pneumonia, with the majority (29/45) occurring during the first 3 days of hospitalization. No patient developed pneumonia after the first week despite the fact that many were still ventilated, others remained intubated, and yet others were extubated but comatose. Patients who developed pneumonia experienced a longer ICU stay (10.5 +/- 5.4 days versus 7.2 +/- 4.3 days, p = 0.001) and hospital stay (34.8 +/- 27.6 versus 22.5 +/- 20.2 days, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Lidocaine effects on the laryngeal chemoreflex, mechanoreflex, and afferent electrical stimulation reflex.

The use of lidocaine hydrochloride as either a topical or intravenous agent has become a common practice for minimizing laryngospasm and the reflex cardiovascular effects resulting from upper airway manipulation. The efficacy and mechanism of action of lidocaine for this purpose remain unclear. We evaluated the effect of lidocaine on the laryngeal chemoreflex (LCR), mechanoreflex (LMR), and superior laryngeal nerve electrical stimulation adductor reflex (SLN-ESAR) in piglets. Cardiopulmonary responses were used to assess LCR and LMR. Latency following SLN stimulation was used to assess SLN-ESAR. Intravenous lidocaine hydrochloride at 3 mg/kg produced no suppression of the LCR, LMR, or latency (SLN-ESAR onset latency before lidocaine 11.7 +/- 0.7 milliseconds, after lidocaine 12.2 +/- 0.5 milliseconds; peak latency before lidocaine 13.2 +/- 0.2 milliseconds, after lidocaine 13.4 +/- 0.4 milliseconds). Topically applied lidocaine at the same dose eliminated both LCR and LMR responses in all animals, with return of reflex responses 15 minutes after application. No effect on the SLN-ESAR was seen with application of topical lidocaine. This study supports topical lidocaine as a suppressant of laryngeal mucosal neuroreceptors without central neural reflex effects. Intravenous lidocaine did not affect peripheral neuroreceptors, nor did it significantly affect the latency of the SLN-ESAR neural reflex arc. Intravenous and topical lidocaine differ in mechanism of action and efficacy with regard to modulation of reflex effects induced by laryngeal stimulation.

Administration, Topical

Interobserver variability in assessing pediatric postextubation stridor.

The reliability of parameters used to assess pediatric postextubation upper respiratory distress is unknown. We prospectively studied the interobserver reliability of six parameters commonly used to assess respiratory distress in children. Eligible patients were less than 15 years old and hospitalized for traumatic injuries at Harborview Medical Center between March and September 1989. At extubation, patients were examined independently by a physician, a nurse, and a respiratory therapist, each of whom evaluated respiratory rate (RR), stridor, air movement, flaring/retractions (F/R), level of consciousness (LOC), and oxygen saturation (O2 sat). Reliability was measured by percentage agreement and weighted kappa (Kw). The 25 children (27 extubations) had a median age of 7 years, and eight of the 27 required treatment for upper airway obstruction. Percentage agreement ranged from 82% (for air movement) to 96% (for O2 sat). Weighted kappas were excellent for RR and F/R (Kw greater than .6); moderate for LOC, stridor, and O2 sat (0.4 less than Kw less than .06); and poor for air movement (Kw less than .4). Further improvements in interobserver agreement are required to provide more consistent upper airway management in critically ill children.

Academic Medical Centers

Force applied during tracheal intubation.

This study quantitated the force applied during tracheal intubation to determine (a) whether the force differed among novice and experienced intubators, and (b) whether the force required differed when intubating patients' tracheas versus intubating the trachea of a commonly used training mannequin. We studied 27 tracheal intubations performed by 17 experienced (greater than 100 prior intubations) and 10 novice (less than 10 prior intubations) intubators. Each intubation was performed with a No. 3 Macintosh blade instrumented with strain gauges to determine force applied in the sagittal plane. The mean force applied was 24.6 +/- 2.9 N (mean +/- SEM) and the maximum force applied by each intubator was 47.6 +/- 3.8 N. There was no difference between groups in the mean force applied (28.8 +/- 6.1 N for the novice group vs 22.3 +/- 2.7 N for the experienced group, P = 0.27) nor in the maximum force applied (55.1 +/- 6.5 N for the novice group vs 43.2 +/- 4.7 N for the experienced group, P = 0.08). The only difference was in the impulse (force x duration), which was more for the novice group largely because of the longer average duration of intubation (40 +/- 12 s vs 19 +/- 4 s, P = 0.06). Among experienced intubators, we found that applied force correlated with patient weight and Mallampati class. Intubation of the Laerdal Airway Management Trainer required mean forces comparable to those required in patients (26.6 +/- 2.5 N vs 22.3 +/- 2.9 N), although the maximum force applied during the intubation effort was greater (58.3 +/- 4.7 N vs 43.2 +/- 4.7 N, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesiology

Efficacy of anticholinergic and beta-adrenergic agonist treatment of maximal cholinergic bronchospasm in tracheally intubated rabbits.

Cholinergically induced bronchoconstriction is thought to be a major cause of bronchospasm during anesthesia. We used tracheally intubated rabbits (4-mm endotracheal tube) stimulated with methacholine to assess the efficacy of beta-adrenergic agonist and anticholinergic treatment in reversing the increases in respiratory system resistance. Four groups were compared: (a) inhaled metaproterenol, 20 puffs via metered dose inhaler (0.65 mg/puff); (b) inhaled ipratropium bromide, 20 puffs from a metered dose inhaler (18 micrograms/puff); (c) 2 mg of intravenous atropine; and (d) no treatment after methacholine challenge as a control group. Methacholine increased respiratory system resistance from 0.041 +/- 0.001 (mean +/- SEM) to 0.098 +/- 0.006 cm H2O.mL-1.s-1 (P < 0.001). Whereas beta-adrenergic agonist treatment was ineffective in ameliorating bronchoconstriction, inhaled ipratropium bromide and atropine were highly effective, causing an 86%-88% reversal in the methacholine-induced increase in respiratory system resistance. Both these agents were also effective in improving dynamic compliance. We conclude that inhaled ipratropium bromide is effective in treating cholinergic bronchospasm even when administered via a small endotracheal tube and that the beta-adrenergic agonist metaproterenol is ineffective in rabbits in the face of maximal cholinergic stimulation.

Adrenergic beta-Agonists

Predictors of postextubation stridor in pediatric trauma patients.

OBJECTIVE: To determine which factors are the best predictors of postextubation stridor in pediatric trauma patients. DESIGN: Prospective cohort study. SETTING: The Burn and Trauma ICUs at Harborview Medical Center from March to September 1989. PATIENTS: Children were eligible for the study if they were less than 15 yr old, were intubated for greater than 12 hr, and did not have underlying cardiopulmonary disease. The study included 25 patients with 30 extubations. RISK FACTORS ASSESSED: Age, type of injury (burn vs. trauma), location of intubation ("field" vs. hospital), endotracheal tube size, length of intubation, and presence of an airleak around the tube at the time of extubation at 30 cm H2O pressure. MAIN OUTCOME MEASURE: Moderate to severe postextubation stridor requiring treatment with racemic epinephrine, helium-oxygen, reintubation, or tracheostomy. RESULTS: Treatment for postextubation stridor was required after 11 (37%) of 30 extubations, with five reintubations and one tracheostomy. The best predictor of postextubation stridor was absence of an airleak at the time of extubation (sensitivity 100%, positive predictive value 79%, p less than .001), followed by type of injury (facial burn vs. all others; sensitivity 64%, positive predictive value 88%, p less than .001). After controlling for these two factors, no other factor studied was a significant predictor of postextubation stridor. CONCLUSION: In pediatric trauma patients, mechanism of injury (facial burn vs. other) and absence of an airleak at the time of extubation are the strongest factors predicting postextubation stridor. Patients with one or both risk factors require special attention to airway management.

Adolescent

Complement activation is a secondary rather than a causative factor in rabbit pulmonary artery ischemia/reperfusion injury.

We have previously demonstrated that reperfusion of a rabbit lung in vivo after 24 h of unilateral pulmonary artery occlusion results in edema, transient leukopenia, and intravascular leukocyte aggregation. We hypothesized that complement was activated by reperfusion and that this in turn contributed to lung injury. In the preliminary phase of the study, we found that ischemia followed by reperfusion resulted in a drop in C3 to 15 +/- 10% (mean +/- SEM) of the prereperfusion value as compared with no change in a group of control animals that had undergone an identical thoracotomy but without pulmonary artery occlusion and reperfusion (p less than 0.05). We then studied three groups of animals to determine if complement depletion with cobra venom factor (CVF) prior to ischemia and reperfusion would prevent the injury. Rabbits treated with CVF but without occlusion and reperfusion did not develop significant lung edema, with left and right lung wet/dry ratios of 5.32 +/- 0.11 and 5.26 +/- 0.12, respectively. For rabbits that were not treated with CVF but underwent ischemia and reperfusion, the comparable numbers were 6.15 +/- 0.36 and 5.19 +/- 0.32 (p less than 0.05 for right versus left). For CVF-treated rabbits that underwent ischemia and reperfusion, the right/left difference persisted (6.77 +/- 0.48 versus 5.35 +/- 0.14, p less than 0.01). Immunocytochemistry documented C3 deposition in non-CVF rabbits that underwent ischemia and reperfusion but not in CVF-treated rabbits. We conclude that ischemia/reperfusion of the lung results in complement activation, but it is not a complement-dependent injury.

Animals

Complications of translaryngeal intubation.

The human larynx is complex and serves multiple functions. Unfortunately, endotracheal tubes do not reproduce all these functions. They serve well as air passages but cannot do so without damaging the mucosa of the posterior larynx. It appears that complications secondary to airway problems in the operating room are decreasing as the use of oximetry and capnometry becomes routine. It is hoped that this reduction in complications will carry over into the chronic care setting as such monitoring becomes the standard after intubations. Compared with malposition of the tube, most of the other complications of intubation are minor. However, knowledge of the various complications can ensure avoidance of many and early detection and correction of others.

Humans

Metered dose inhaler aerosol characteristics are affected by the endotracheal tube actuator/adapter used.

The authors studied the particle size of aerosols of metaproterenol produced by three different actuators designed for use in patients with endotracheal tubes in place. These were compared with the metaproterenol aerosol produced by the actuator (provided by Boehringer-Ingelheim [BI]) that was supplied by the manufacturer for use in patients whose tracheas are not intubated. The volume of particles in the respiratory size range (1.0-5.1 microns) delivered to the end of the endotracheal tube were measured using adapters designed by Intec (IT), Instrumentation Industries (II), and Monaghan (MAIS). Particle numbers were measured using a CSAS 100 scattering-aerosol laser spectrometer, and volumes were calculated by assuming the particles were spheres. The authors found that the volume of particles in the respiratory range with the IT, II, and MAIS adapters plus endotracheal tube were 11, 31, and 66%, respectively, of the volume produced in the respiratory range by the BI. When particles likely to impact before reaching the lower airways (greater than 5 microns) were measured, almost none was produced by the adapters plus endotracheal tube, whereas the majority of drug volume in the BI aerosol was in the greater than 5 microns range. It was concluded that the aerosol produced by different actuators differ from each other, that all three produced less drug in the respiratory range than was produced by the manufacturer-supplied actuator, and that large particles are effectively removed by the adapter plus endotracheal tube.

Administration, Inhalation

Problems associated with prolonged intubation in the geriatric patient.

The authors review problems associated with prolonged intubation. Laryngeal stenosis and injuries caused by the endotracheal tube itself are described. Postintubation laryngotracheal pathology, including signs and symptoms and the management of specific lesions, is described in detail. Other injuries associated with prolonged intubation, such as nasal ulceration, sinusitis, and oral ulcers, also are reviewed.

Aged

Alveolar hypoxia, inhibition of hypoxic pulmonary vasoconstriction, and permeability edema.

We previously reported that regional alveolar hypoxia reduces oleic acid-induced permeability edema formation [Cheney et al. (1987). J. Appl. Physiol. 62: 1690-1697]. In order to define the role of hypoxic pulmonary vasoconstriction (HPV) on this effect, we studied the effects of regional alveolar hypoxia on permeability edema formation with this response inhibited. Dogs weighing 25 +/- 1 kg in which the HPV response had been inhibited by the administration of minoxidil (1 mg/kg i.v.) were anesthetized, mechanically ventilated and had a bronchial divider placed so the left lower lobe (LLL) could be ventilated with an FIO2 = 0.05 or FIO2 = 1, while the right lung was continuously ventilated with an FIO2 = 1.0. In 10 study animals the LLL was ventilated with an FIO2 = 0.05 for 4 h after induction of bilateral permeability pulmonary edema with 0.05 ml/kg of intravenous oleic acid. In six control animals the LLL was ventilated with an FIO2 = 1 for 4 h after the same injury. Postmortem gravimetric analysis indicates that alveolar hypoxia of the LLL with the HPV response inhibited had no effect on pulmonary edema formation. We conclude that inhibition of HPV abolishes the protective effect of regional alveolar hypoxia on oleic acid-induced permeability edema formation.

Animals

Delivery efficiency of metered dose aerosols given via endotracheal tubes.

The authors studied the efficiency of delivery of the inhaled bronchodilator metaproterenol when delivered via an endotracheal tube (ETT) using a metered dose inhaler (MDI). They found that the percentage of drug exiting the ETT varied with tube size, ranging from 3.0 +/- 1.9 for a 6.0 mm ETT to 6.5 +/- 4.4 for a 9.0 mm ETT (mean +/- SEM, P less than 0.05). The efficiency of delivery was also affected by whether the MDI was activated before or after initiation of gas flow through the ETT, with activation into a flowing stream significantly more efficient. The authors conclude that an MDI can deliver a dose of drug to the trachea, but delivery efficiency is lower than reported for MDI delivery in spontaneously breathing patients.

Administration, Inhalation

Regional alveolar hypoxia does not affect air embolism-induced pulmonary edema.

We studied the effects of regional alveolar hypoxia on permeability pulmonary edema resulting from venous air embolization. Anesthetized dogs had the left upper lobe removed and a double-lumen tube placed so that right lung and left lower lobe (LLL) could be ventilated independently. Air was infused into the femoral vein for 1 h during bilateral ventilation at an inspiratory O2 fraction (FIO2) of 1.0. After cessation of air infusion the LLL was then ventilated with a hypoxic gas mixture (FIO2 = 0.05) in six animals and an FIO2 of 1.0 in six other animals. Lung hydroxyproline content was measured as an index of lung dry weight. LLL bloodless lobar wet weight-to-hydroxyproline ratio was 0.33 +/- 0.06 mg/micrograms in the animals exposed to LLL hypoxia and 0.37 +/- 0.03 mg/micrograms (NS) in the animals that had a LLL FIO2 of 1. Both values were significantly higher than our laboratory normal values of 0.19 +/- 0.01 mg/micrograms. We subsequently found in four more dogs exposed to global alveolar hypoxia before and after air embolism that the air injury itself significantly depressed the hypoxic vasoconstrictor response. We conclude that regional alveolar hypoxia has no effect on pulmonary edema formation due to air embolism. The most likely reason for these findings is that the air embolism injury itself interfered with hypoxic pulmonary vasoconstriction.

Animals