Search PubMed⌕ Search

Biomedical subjects

J A Orr

Publications and source records attributed to J A Orr.

At least 37 records · Page 2Linked to original sources
PubMed1993

Transient ventilatory responses to endotoxin infusion in the cat are mediated by thromboxane A2.

We tested the hypothesis that ventilatory responses to endotoxin infusion in the anesthetized cat are mediated by thromboxane A2 (TxA2). Intravenous infusion of endotoxin (1.6 mg/kg of E. coli, strain 05:B55, delivered over 1 min) in six cats elicited increases in right ventricular blood pressure (Prv) and a transient systemic hypotension. These hemodynamic changes were accompanied by an abrupt apnea, followed by a transient period of rapid, shallow breathing, Cardiorespiratory changes coincided with large increases (> 10-fold) in the plasma concentration of TxB2, the stable metabolite of TxA2. These effects and the release of TxA2 did not occur if endotoxin was infused a second time into the same animal. In addition, animals that were pretreated with either indomethacin (n = 3; 3.0 mg/kg) or the TxA2 receptor antagonist, daltroban, (n = 4; 7.5 mg/kg) exhibited no change in Prv, arterial blood pressure, or respiration when given equivalent doses of endotoxin. We conclude that the release of TxA2 is responsible for the early pulmonary hypertension and rapid, shallow breathing observed during endotoxin infusion in the anesthetized cat. These TxA2-mediated responses are severe but transient in nature.

Animals↗
PubMed1992

A parallel implementation of the backward error propagation neural network training algorithm: experiments in event identification.

An artificial neural-network-based (ANN) event detection and alarm generation system has been developed to aid clinicians in the identification of critical events commonly occurring in the anesthesia breathing circuit. To detect breathing circuit problems, the system monitored CO2 gas concentration, gas flow, and airway pressure. Various parameters were extracted from each of these input waveforms and fed into an artificial neural network. To develop truly robust ANNs, investigators are required to train their networks on large training data sets, requiring enormous computing power. We implemented a parallel version of the backward error propagation neural network training algorithm in the widely portable parallel programming language C-Linda. A maximum speedup of 4.06 was obtained with six processors. This speedup represents a reduction in total run-time from 6.4 to 1.5 h. By reducing the total run time of the computation through parallelism, we were able to optimize many of the neural network's initial parameters. We conclude that use of the master-worker model of parallel computation is an excellent method for speeding up the backward error propagation neural network training algorithm.

Algorithms↗
PubMed1992

Effects of the thromboxane A2 mimetic, U46,619, on pulmonary vagal afferents in the cat.

Release of thromboxane A2 (TxA2) or infusion of the TxA2 mimetic U46,619 in the cat elicits pulmonary hypertension and rapid shallow breathing (Shams et al., Respir. Physiol. 71: 169-183, 1988). The vagus nerve mediates the observed respiratory, but not the circulatory, effects (Shams and Scheid, J. Appl. Physiol. 68: 2042-2046, 1990). To identify the type of lung vagal afferent fibers involved in this respiratory response to TxA2, we have recorded the functional single-unit activity and its response to infusion of U46,619 in fine strands of the vagus nerve in the artificially ventilated cat and rabbit. The fibers were classified as originating from slowly adapting (SAR) or rapidly adapting (RAR) stretch receptors by their response to sustained pulmonary inflation (intrapulmonary pressure of 20-25 cmH2O) or as C-fibers, by their response to a bolus injection of phenylbiguanide. C-fibers responded variably to lung inflation. U46,619 infusion caused only a small increase in SAR or RAR activity along with increases in end-inspiratory tracheal airway pressure (Paw), but evoked a marked increase in the firing rate of C-fibers, independent of their response to lung inflation. This increase in C-fiber activity was unrelated to the increase in Paw, which accompanied the infusion of U46,619. Since these responses remained the same after indomethacin they appear to be due to a direct action of U46,619, and not to be mediated by prostanoids that might be released by U46,619. These data suggest that C-fibers are indeed involved in the respiratory effects of TxA2. Since the effects exerted on C-fibers by U46,619 were unrelated to increased Paw, TxA2 is likely to stimulate the nerve endings directly, rather than via smooth muscle contraction. On the other hand, the small stimulating effect of U46,619 on SAR and RAR may be mediated by bronchoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Intelligent alarms reduce anesthesiologist's response time to critical faults.

The proliferation of monitors and alarms in the operating room may lead to increased confusion and misdiagnosis unless the information provided is better organized. Intelligent alarm systems are being developed to organize these alarms, on the assumption that they will shorten the time anesthesiologists need to detect and correct faults. This study compared the human response time (the time between the sounding of an alarm and the resolution of a fault) when anesthesiologists used a conventional alarm system and when they used an intelligent alarm system. In a simulated operating room environment, we asked 20 anesthesiologists to resolve seven breathing circuit faults as quickly as possible. Human response time was 62% faster, decreasing from 45 to 17 s, when the intelligent alarm system was used. The standard deviations in response time were only half as large for the intelligent alarm system. It appears that the computer-based neural network in the intelligent alarm system diagnosed faults more rapidly and consistently than did the anesthesiologists. This study indicates that breathing circuit faults may be more rapidly corrected when the anesthesiologist is guided by intelligent alarms.

Anesthesiology↗
PubMed1992

Failure of pulmonary acidosis to increase respiratory drive.

Experiments were performed to determine whether increases in acidity isolated to the pulmonary circulation would stimulate hypothesized pulmonary chemoreceptors and increase respiratory drive in the anesthetized paralyzed mechanically ventilated cat (n = 9). Respiratory drive was assessed by measuring the frequency and amplitude of the integrated phrenic neurogram. To create an isolated pulmonary acidosis, blood returning to the lung was acidified by infusion of 0.3 M lactic acid (1.91 ml/min) into the inferior vena cava, while systemic arterial pH was restored to near normal levels by simultaneous infusion of base (0.3 M NaOH) into the left atrium. Six minutes after the start of this dual infusion of acid and base, right ventricular (pulmonary) pH decreased from 7.286 to 7.179 and PCO2 increased 7 Torr. Systemic arterial pH and PCO2 were unchanged from measurements immediately before the infusion. This level of pulmonary acidosis failed to increase respiratory drive as assessed by phrenic activity. To test the sensitivity of the preparation to known systemic arterial chemical stimuli, a combined pulmonary and systemic acidosis was elicited by infusion of 0.3 M lactic acid into the inferior vena cava and 0.3 M NaCl into the left atrium. This infusion significantly lowered both systemic arterial and pulmonary arterial pH (7.343 to 7.155 for systemic arterial pH and 7.286 to 7.067 for pulmonary pH) and increased phrenic efferent activity 45%. We conclude that phrenic efferent activity is unaffected by moderate reductions in the pH of the pulmonary circulation in the absence of a significant systemic arterial acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMed1992

Differential features for a neural network based anesthesia alarm system.

We have developed a neural network based alarm system that identifies 19 specific faults in the anesthesia breathing circuit, such as "Inspiratory Hose Leak," or "Y-Piece Disconnection." CO2, pressure, and expired flow waveforms, along with ventilator settings, were sampled by a personal computer. Fifty-two features, such as "maximum CO2" or "minimum pressure", were extracted from each breath, converted to "differential" features, normalized, and used as the inputs of a three layered feed-forward neural network. The network was trained, using backward error propagation with momentum, to classify each breath as normal or containing one of 19 faults. To collect the neutral network training set, seven dogs were anesthetized and ventilated using controlled ventilation. Each of 19 faults were created over a range of ventilator settings and fresh gas flows. The neural network correctly identified 83.1% of 550 events presented to it during testing. These preliminary results are an encouraging example of neural network applications in the field of clinical monitoring.

Anesthesia, Closed-Circuit↗
PubMed1991

Evaluation of a parallel implementation of the learning portion of the backward error propagation neural network: experiments in artifact identification.

Various methods have been proposed in an attempt to solve problems in artifact and/or alarm identification including expert systems, statistical signal processing techniques, and artificial neural networks (ANN). ANNs consist of a large number of simple processing units connected by weighted links. To develop truly robust ANNs, investigators are required to train their networks on huge training data sets, requiring enormous computing power. We implemented a parallel version of the backward error propagation neural network training algorithm in the widely portable parallel programming language C-Linda. A maximum speedup of 4.06 was obtained with six processors. This speedup represents a reduction in total run-time from approximately 6.4 hours to 1.5 hours. We conclude that use of the master-worker model of parallel computation is an excellent method for obtaining speedups in the backward error propagation neural network training algorithm.

Algorithms↗
PubMed1990

Fast neutron treatment for squamous cell carcinoma of the head and neck: final report of Edinburgh randomised trial.

OBJECTIVE: To compare neutron treatment and megavoltage (photon) radiotherapy in locally advanced squamous cell carcinoma of the head and neck. DESIGN: Randomised trial of patients stratified by site of primary tumour and presence or absence of lymph node metastases. Follow up of patients after treatment. SETTING: Department of clinical oncology, Western General Hospital, Edinburgh. PATIENTS: 165 Patients with untreated, histologically proved squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. All patients completed treatment, and no patient was lost to follow up. INTERVENTION: Treatment with either neutrons or photons. MAIN OUTCOME MEASURES: Disease state and morbidity (scored with the system of the European Organisation for Research on Treatment of Cancer) at each visit during follow up. RESULTS: Of the 165 patients, 85 were randomised to receive neutron treatment and 80 to receive photon treatment. Minimum follow up was five years. Local control of cancer remained similar in the two groups, being achieved in 37 (44%) patients after neutron treatment and 36 (45%) after photon treatment. Five year and actuarial 10 year survival rates were 24% (20/85) and 14% respectively in the group treated with neutrons and 34% (27/80) and 30% respectively in the group treated with photons. Five year survival rates without local disease were 19% (16/85) and 30% (24/80) respectively. Necrosis was more common after neutron treatment than after photon treatment. Seven patients in the neutron group who developed necrosis died whereas no deaths were associated with photon treatment. CONCLUSION: Rates of long term local control were similar in the two groups. Necrosis related to radiation was more common in patients treated with neutrons, and the mortality related to treatment was significantly higher in these patients.

Carcinoma, Squamous Cell↗
PubMed1989

Cardiopulmonary function in exercising bar-headed geese during normoxia and hypoxia.

To investigate possible physiologic mechanisms that allow the bar-headed goose to perform strenuous physical activity when flying at high altitude (e.g., above 9,000 m), we measured cardiopulmonary variables during running exercise (treadmill; 0.6 m.sec-1; 2 degrees incline) while the bird breathed either normoxic (21% O2) or hypoxic (7% O2) gases via a face mask. 1. During normoxic exercise, O2 uptake rate doubled and both ventilation and cardiac output increased. Blood gases and pH in arterial, mixed venous and blood from the leg, however, remained virtually unaltered. 2. Hypoxia at rest stimulated ventilation to rise but not cardiac output. The birds reached a steady state with virtually unaltered O2 uptake. 3. Exercise during hypoxia further stimulated ventilation, resulting in elevated arterial PO2 and O2 content compared to hypoxia at rest. However, O2 uptake increased only slightly, and cardiac output did not rise over the resting hypoxic value. The hyperventilation resulted in respiratory alkalosis and increased CO2 output, with R values being as high as 2.0. 4. It is concluded that neither ventilation nor pulmonary gas transfer were the limiting step in supplying O2 to the working muscles during hypoxic exercise in our experiments. It is more likely that muscle blood flow or diffusion from muscle capillaries to mitochondria, or both, determined the aerobic capacity under these conditions.

Animals↗
PubMed1989

A prototype gas exchange monitor for exercise stress testing aboard NASA Space Station.

A monitor was developed to track weightlessness deconditioning aboard the National Aeronautics and Space Administration (NASA) Space Station by measuring the O2 uptake (VO2) and CO2 production (VCO2) and calculating maximum VO2 and anaerobic threshold during an exercise stress test. The system uses two flowmeters in series to achieve a completely automatic flow calibration, and it uses breath-by-breath compensation for sample line transport delay. The accuracy of the system was measured over the range of VO2 and VCO2 from 100 to 800 ml/min by means of simulation. Accuracy was 0.54% for VO2 and 2.9% for VCO2. The system was further evaluated using two laboratory methods, the first method being comparison with a breath-by-breath system. As volunteers performed a maximum effort on a cycle ergometer, the mean difference in readings between the two systems was 17 ml/min for VO2 and 8.0 ml/min for VCO2. The correlation coefficient squared was greater than 0.96 for both. The second laboratory test was to use the system for 2 mo in a Human Performance Laboratory. Readings of maximum VO2 (VO2max) and anaerobic threshold were repeatable and consistent with the individual's activity level. The accuracy and convenience of operation will make this a valuable instrument aboard the Space Station.

Equipment Design↗
PubMed1988

Absence of CO2-sensitive venous chemoreceptors in the cat.

We tested for the presence of CO2-sensitive venous chemoreceptors in anesthetized, paralyzed, artificially ventilated cats (N = 8). Systemic venous PCO2 was elevated (venous CO2 loading) by continuously passing blood withdrawn from the femoral artery (20 ml/min) through an extracorporeal gas exchanger, ventilated with 50% CO2 and 50% O2, and returning this hypercapnic blood to the femoral vein. Respiratory output was assessed by means of the amplitude of the integrated phrenic neurogram. Results of venous CO2 loading were compared to those of airway CO2 loading in which inspired CO2 levels were adjusted to give the same arterial PCO2 (PaCO2) as in venous loading. Despite large differences in mixed venous PCO2 (PvCO2) during venous CO2 loading (PvCO2 = 55 Torr, PaCO2 = 37 Torr) compared to airway CO2 loading (PvCO2 = 45 Torr, PaCO2 = 37 Torr), phrenic output was unchanged. However, phrenic output was elevated 33% when PaCO2 was increased 6-7 Torr by raising inspired CO2 and reduced 50% when PaCO2 was lowered 6-7 Torr by lowering inspired CO2, thereby substantiating the responsiveness of the respiratory control system to changes in PaCO2. The respiratory output response to changes in venous CO2 was also tested at a higher PaCO2 (40 Torr, created by adding 1% CO2 to the inspired air) and, as before, no change in phrenic output occurred when PvCO2 was elevated at a constant PaCO2. These experiments provide direct evidence for the absence of chemoreceptors in the central veins, right heart, and pulmonary arterial system of the cat that would respond to changes in PvCO2.

Animals↗
PubMed1988

Cardiorespiratory responses to HCl vs. lactic acid infusion.

Previous reports indicate that intravenous infusion of HCl can alter breathing and blood pressure even if reductions in systemic arterial pH are prevented. To extend these findings, as well as to determine whether other acids elicit comparable results, this report compares the cardiopulmonary response between right atrial infusion of lactic acid and HCl in awake ponies. Lactic acid, infused at a dose of 1.5 mmol/kg over 18 min, lowered systemic and pulmonary arterial pH 0.062 and 0.092 U, respectively, and increased pulmonary arterial pressure (delta Ppa, 4 mmHg), heart rate (HR, 4/min), and tidal volume (delta VT, 190 ml/m2). HCl, infused at a reduced dose of 0.5 mmol/kg over 18 min, lowered systemic and pulmonary arterial pH 0.024 and 0.047 U, respectively, but produced increases in Ppa (delta 23 mmHg), HR (delta 42/min), and VT (delta 321 ml/m2) that were significantly greater than from the larger dose of lactic acid. These results indicate that cardiopulmonary responses to infusion acidosis differ between the type of acid infused. It is suggested that, in the unanesthetized pony, HCl-induced infusion acidosis has a unique cardiopulmonary-stimulating action unrelated to the pH changes imparted to the circulating arterial blood and that this response is absent during the infusion of lactic acid.

Animals↗
PubMed1987

Fast neutron therapy for squamous cell carcinoma in the head and neck region: results of a randomized trial.

A randomized trial of fast neuron therapy compared with 4MV photons for patients with head and neck cancer is reported. One hundred and sixty-eight patients were recruited between 1977 and 1984. The minimum follow-up is 2 years. Three patients were withdrawn before treatment began. Eighty-five were allocated to neutron therapy and 80 to receive photon therapy. All patients had squamous cell cancers in one of four primary sites: oral cavity, oropharynx, larynx, and hypopharynx. Local tumor control was similar in both groups: 44.7% after neutrons and 45.0% after photons. Salvage surgery was performed on 18 patients in each treatment group for residual or recurrent cancer. Acute radiation reactions of the mucous membranes were significantly more severe after photons. The number of patients with serious late reactions was greater after neutron therapy but the difference was not statistically significant. There were six deaths related to late morbidity after neutron therapy but none after photon therapy. Survival was better after photon therapy but the difference compared with the neutron group failed to reach statistical significance. When intercurrent deaths are excluded, the difference is less marked. Photon therapy was clearly better in terms of disease-free survival giving a 2-year local disease-free rate of 41.3% (s.e. 5.5%) compared with 29.4% (s.e. 4.9%) after neutrons.

Carcinoma, Squamous Cell↗
PubMed1987

An evaluation of fast neutron irradiation in the treatment of squamous cell carcinoma in cervical lymph nodes.

Analyses have been made of the response of metastatic cervical lymph nodes following neutron therapy, either as part of a randomized trial or in patients treated electively. In the trial patients, the overall regression and local control rates were similar after photons and neutrons. Mobile nodes, less than 3.0 cm, appeared to respond better to neutron therapy, and node masses greater than 3.0 cm had better control after photon therapy. The differences observed however were not statistically significant. There was a highly significant association between the control of the primary tumor and control of nodal disease. No survival advantage for neutrons was observed in association with apparently better control rates in cervical nodes.

Carcinoma, Squamous Cell↗
PubMed1987

Neutron therapy for malignant tumours of the salivary glands. A report of the Edinburgh experience.

A group of 28 patients with malignant tumours of the salivary glands have been treated by d(15) + Be neutron irradiation. Nineteen patients had inoperable cancers. Three had gross recurrent cancer and three had measurable residual cancer after surgery. Three patients were treated post-operatively for microscopic residual disease. Seven different histological types of tumour were included. Six out of 8 patients with adenoid cystic carcinomas have lasting local tumour control. 54.5% of the gross tumours were locally controlled. All three of those classified as microscopic residual disease have no evidence of local recurrence. 11/14 cancers given 16.0 Gy or more in 20 fractions in 4 weeks were controlled compared with only 1/8 given a lower dose. 12/19 cancers less than 10.0 cm maximum diameter were controlled. The radiation-related morbidity was similar to that observed after photon therapy.

Adult↗