Biomedical subjects
R J Leonard
Publications and source records attributed to R J Leonard.
The Banting Memorial Lecture 1973: Islet differentiation, organ culture, and transplantation.
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Pancreatic islet transplantation in the rat.
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Fetal rat pancreas: differentiation of the acinar cell component in vivo and in vitro.
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Studies on the biologic activity and mode of action of 7-deazainosine.
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On the mode of action of 7-deaza-adenosine (tubercidin).
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Design and evaluation of a new, low pressure loss, implantable artificial lung.
The authors designed and tested an artificial lung intended for intrathoracic implantation as a bridge to lung transplantation in chronic pulmonary insufficiency or as an alternative in the treatment of advanced acute respiratory failure. The prototype devices are comprised of 380 microns outer diameter polypropylene matted fibers with a blood path length of 3.5 cm, frontal area of 128 cm2, void fraction (porosity) of 0.53, and surface area of approximately 2.2 m2. Blood flow is external and approximately perpendicular to the fiber bundle, which fits in an extruded, flexible polyethylene terephthalate housing. Inflow and outflow anastomoses are made to the pulmonary artery and the left atrium, respectively, thereby avoiding a prosthetic blood pump. Inlet and outlet gas lines exit through the chest wall. Nine in vitro experiments of oxygen (O2) transfer performance by the device, with water, initially were done. Our previously described semiempirical mathematical model of convective O2 transfer in cross-flow, hollow fiber membrane lungs was applied to the results from the water tests to predict the transfer rates at any set of blood conditions. Five in vitro blood tests were conducted using a single-pass technique to evaluate O2 and carbon dioxide (CO2) transfer rates, measure pressure losses, and compare predicted and measured O2 transfer rates. O2 transfer rates of 150-200 ml/min, and CO2 transfer rates exceeding 200 ml/min, could be achieved at blood flow rates as great as 4 l/min. Pressure drops of approximately 10-20 mmHg were observed at blood flow rates of 2-4 l/min. Preliminary results of device implantation in two pigs indicate the feasibility of achieving clinically significant O2 and CO2 transfer rates with a low blood-side pressure loss.
Testing of an intrathoracic artificial lung in a pig model.
A low input impedance, intrathoracic artificial lung is being developed for use in acute respiratory failure or as a bridge to transplantation. The device uses microporous, hollow fibers in a 0.74 void fraction, 1.83 m2 surface area bundle. The bundle is placed within a thermoformed polyethylene terephthalate glucose modified housing with a gross volume of 800 cm3. The blood inlet and outlet are 18 mm inner diameter vascular grafts. Between the inlet graft and the device is a 1 inch inner diameter, thin-walled, latex tubing compliance chamber. These devices were implanted in Yorkshire pigs via median sternotomy with an end to side anastomosis to the pulmonary artery and left atrium. The distal pulmonary artery was occluded to divert the right ventricular output to the device. Pigs 1 and 2 were supported fully for 24 hrs and then killed. Pig 3 was supported partially for 20 hrs and died from bleeding complications. The first implant, in a 55 kg male pig, transferred an average of 176 ml/min +/- 42.4 of O2 and 190 ml/min +/- 39.7 of CO2 with an average blood flow rate of 2.71/min +/- 0.46. The normalized average right ventricular output power, Pn, was 0.062 W/(L/min) +/- 0.0082, and the average device resistance, R, was 3.5 mmHg/(L/min) +/- 0.62. The second implant, in a 60 kg male pig, transferred an average of 204 ml/min +/- 22.5 of O2 and 242 ml/min +/- 17.2 of CO2 with an average blood flow rate of 3.7 L/min +/- 0.45, Pn of 0.064 W/(L/min) +/- 0.0067, and R of 4.3 mmHg/(L/min) +/- 0.89. The third implant, in an 89 kg male pig, transferred an average of 156 ml/min +/- 39.6 of O2 and 187 ml/min +/- 21.4 of CO2 with an average blood flow rate of 2.5 L/min +/- 0.49, Pn of 0.052 W/(l/min) +/- 0.0067, and R of 3.4 mmHg/(L/min) +/- 0.74. These experiments suggest that such an artificial lung can temporarily support the gas transfer requirements of adult humans without over-loading the right ventricle.
Effects of stripping and laser excision on vocal fold mucosa in cats.
We compared the effects of stripping and laser excision on vocal fold mucosa in cats. Of particular interest were the comparative effects of each procedure on the mucosa's sensory structures. Mucosa was stripped from one vocal fold in three cats, lased in three additional cats, and histologically examined at 1-, 2-, and 3-week intervals postoperatively. Results indicate that both procedures produce unique and degenerative effects that are still apparent 3 weeks after operation; however, nervous elements in lased tissue samples appeared less disrupted than in stripped tissue. Unique effects on the composition of epithelial tissue also were noted for the two procedures. Implications for voice quality in human patients undergoing similar procedures are discussed.
A total heart/lung bypass simulator.
The often overlooked role of device design is the need to teach the optimal use of the device. A mathematical model was used in the development of the Sarns/3M SMO oxygenator, as presented at the 1985 ASAIO meeting. This model accepts inlet saturation, hemoglobin levels, and other variables, and returns output saturation, and has been verified in over 100 clinical cases. A patient oxygen consumption model including oxygen stores was developed, using clinical data based on size, temperature, and a term called "anesthesia level." This interesting factor accounts for differences between institutions. The two models were integrated with a heat exchanger model and a patient temperature model to allow accurate predictions of cooling and heating, and a hemoconcentrator model. The combination was programmed for IBM compatible computers to create a bypass simulator. A potential user can put a patient on bypass starting with any selected patient variables, track progress on a minute by minute basis, and adjust the circuit variables as dictated by his technique. The program runs in accelerated time, and accepts defaults to continue without changes as long as desired. Such a simulator is valuable for the initial introduction of the new device to experienced perfusionists, the training of potential new perfusionists, study of unusual or complex cases, the design of new devices, and even as a "track along" system during an actual clinical case.
Effects of repeated stripping on vocal fold mucosa in cats.
Repeated stripping of the vocal folds in patients with recurrent vocal nodules may produce permanent, negative effects on voice quality. Hoarseness can be present with no evidence of structural or functional disease on indirect laryngoscopy. A common assumption is that scar tissue has formed, though the relationship between scarring and voice quality is not clear. In the study reported here, cats were subjected to four strippings of the left vocal fold at 6- to 8-week intervals. Tissues obtained were examined for changes in the composition of the mucosa and its nervous network. Alterations observed over the four strippings included 1) an increasing component of fibrous tissue and 2) apparent changes in both the number and structure of nervous elements. Implications of the findings for voice production, clinical management, and further research are discussed.
Use of a mathematical model to predict oxygen transfer rates in hollow fiber membrane oxygenators.
A semi-empirical theoretical model of oxygen transfer is used to predict the rates of oxygen transfer to blood in hollow fiber membrane oxygenators over a wide range of inlet conditions. The predicted oxygen transfer rates are based on performance of the devices with water, which is more cost effective and easier to handle than blood for in vitro evaluations. Water experiments were conducted at three different flow rates to evaluate oxygen transfer performance in three commercially available membrane oxygenators. Data obtained from these experiments were used in a computer model to predict the rate of oxygen transfer to bovine blood at specified inlet conditions. Blood experiments were conducted at three different flow rates at a wide variety of inlet conditions, including different pH levels, hemoglobin concentrations, and oxyhemoglobin saturations for the three types of oxygenators. The measured and predicted oxygen transfer rates are closely correlated, which suggests that we have an accurate, reliable method for predicting oxygen transfer in hollow fiber membrane lungs.