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Biomedical subjects

J D Cooper

Publications and source records attributed to J D Cooper.

At least 145 records · Page 8Linked to original sources
PubMed1995

Lung transplantation for emphysema.

Lung transplantation is an established treatment option for patients with emphysema due to chronic obstructive pulmonary disease or alpha 1-antitrypsin deficiency. Operative mortality is low in experienced centers and functional results are acceptable. Morbidity associated with triple drug immunosuppression is significant. Constant annual death rates due to obliterative bronchiolitis and other complications result in a 50% 5-year survival; therefore, lung transplantation should only be offered to those ideal candidates who have no other treatment option.

Graft Rejection↗
PubMed1995

The international status of lung transplantation.

Lung transplantation has continued to increase yearly, but is now beginning to plateau possibly due to the stagnant donor pool. Emphysema/COPD continues to be the leading transplant diagnosis and infection, rejection and BO are the leading causes of recipient deaths. Actuarial survival statistics show that bilateral transplants have a slightly higher survival rate than single lung transplants with the difference widening the further out from transplantation one gets. The 6-year survival rate for all lung transplants was 40%.

Adolescent↗
PubMed1994

Automated sequential trace enrichment of dialysates combined with high-performance liquid chromatography and automated heart-cutting for the determination of the nucleoside 1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil and its metabolite 5-propynyluracil in urine.

The use of a new configuration to control the automated sequential trace enrichment of dialysate (ASTED) system has been used to estimate 1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil and its metabolite 5-propynyluracil in urine. The system employs "heart-cutting" as a means to improve the efficiency of sample preparation and reduce analysis time. Using this technique the mean within- and between-run imprecision (coefficient of variation) at three different urine analyte concentrations was found to be 1.6 and 3.6% and 1.7 and 3.3% for 5-propynyluracil and 1-(beta-D-arabinofuranosyl)-5-(1-propynyl)uracil, respectively.

Alkynes↗
PubMed1994

NMDA potentiates NGF-induced sprouting of septal cholinergic fibres.

Nerve growth factor (NGF) injected into the otherwise unlesioned adult rat septum induced sprouting of presumptive cholinergic fibres positive for p75NGFR and acetylcholinesterase (AChE). These fibres did not stain for tyrosine hydroxylase and therefore did not represent sympathetic ingrowth. Neurofilament staining on adjacent sections revealed fibres with similar morphology, suggesting new outgrowth in the form of sprouting rather than the upregulation of p75NGFR and AChE in pre-existing fibres. Simultaneous injections of subneurotoxic doses of N-methyl-D-aspartate (NMDA) significantly potentiated the effect of NGF on cholinergic fibre sprouting and caused pronounced glial fibrillary acidic protein (GFAP)-positive astrocytosis. Application of NMDA alone did not elicit sprouting of this type. These findings indicate that NGF can induce the sprouting of uninjured adult rat septal cholinergic fibres in vivo and suggest that reactive astrocytes are not inhibitory to cholinergic axonal outgrowth, and might serve as a substrate for growing axons in the presence of NGF.

Acetylcholine↗
PubMed1994

Changes in vascular permeability with ischemic time, temperature, and inspired oxygen fraction in isolated rabbit lungs.

The capillary filtration coefficient (Kf) is one of the most accurate measures of change in pulmonary vascular permeability and has been used in various models of acute lung injury. To evaluate the isolated effects of ischemia on Kf, we have developed an ex vivo rabbit lung model in which the influences of reperfusion are eliminated. The current study was designed to validate this model by determining the effect of cold flushing with low-potassium-dextran solution containing 1% glucose (LPDG), ischemic time, temperature, and inspired oxygen fraction on Kf. On completion of the ischemic period, the ventilated lungs, with the heart still attached, were suspended from a strain-gauge force transducer. After the lungs were flushed with 50 mL hetastarch solution (6% hetastarch solution with physiologic saline solution), the left atrial drainage cannula was occluded and the pulmonary artery pressure was incrementally increased by elevation of the reservoir. The Kf was calculated as the slope of the line relating the weight gain rate and pulmonary capillary pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Administration of prostaglandin E1 after lung transplantation improves early graft function.

Early graft dysfunction continues to be a major clinical problem after lung transplantation. The objective of this experiment was to determine whether continuous administration of prostaglandin E1 (PGE1) after lung transplantation has a beneficial effect on early graft function. Left lung allotransplantation was performed in 10 size-matched mongrel dogs (weight, 24.4 to 31.4 kg). Lung preservation consisted of a bolus injection of PGE1 (250 micrograms) into the pulmonary artery, followed by a pulmonary artery flush with 50 mL/kg of 4 degrees C modified Euro-Collins solution. The lungs were then stored at 1 degree C for 12 hours. Left lung transplantation was performed using standard technique. The right pulmonary artery and right bronchus were ligated prior to chest closure. Animals were placed in the supine position and ventilated for 6 hours with 100% oxygen at a rate of 20 breaths/min, a tidal volume of 550 mL, and a positive end-expiratory pressure of 5 cm H2O. Animals were randomly allocated to one of two groups. Group I animals (n = 6) received continuous PGE1 infusion from the onset of implantation. The dose was gradually increased and fixed when mean systemic pressure showed a 10% decrease (mean PGE1 dose, 31.7 +/- 6.9 ng.kg-1.min-1). Group II animals (n = 4) received no PGE1. After the 6-hour assessment period, arterial oxygen tension and alveolar-arterial oxygen pressure difference were preserved in group I compared with group II (group I versus group II: arterial oxygen tension, 255.8 +/- 37.6 mm Hg versus 64.7 +/- 7.9 mm Hg [p < 0.05]; alveolar-arterial oxygen pressure difference, 411.1 +/- 70.5 mm Hg versus 597.5 +/- 1.3 mm Hg [p < 0.05]).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1994

Pentoxifylline reduces lung allograft reperfusion injury.

Early graft dysfunction remains a significant problem in clinical lung transplantation. Pentoxifylline, a methylxanthine derivative, has been shown to have various beneficial effects on neutrophil-induced lung injury. We investigated effects of pentoxifylline on early posttransplantation lung function in a canine allograft model. Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution (50 mL/kg) and stored in an inflated state for 18 hours at 1 degrees C. In five experiments (group I), pentoxifylline was added to the flush and storage solutions (200 mg/L) at the time of harvest. The recipient animals received pentoxifylline (20 mg/kg intravenously) before reperfusion followed by pentoxifylline (0.1 mg.kg-1.min-1 intravenously) during the 6-hour posttransplantation assessment period. In group II, donors and recipients received no pentoxifylline. To evaluate only allograft function, the right main pulmonary artery and bronchus were ligated immediately after implantation. For 6 hours thereafter hemodynamics and gas exchange were assessed at 15-minute intervals while the animal was ventilated at an inspired oxygen fraction of 1.0. After 1 hour of assessment there was a significant difference in gas exchange between the groups, which persisted until the end of the study. By the end of the 6-hour assessment, the mean arterial oxygen tension was 236.7 mm Hg for group I versus 101.1 mm Hg for group II (p < 0.01), and the alveolar-arterial oxygen difference was 443.1 mm Hg versus 562.2 mm Hg (p < 0.015). Hemodynamics were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Predictors, frequency, and indications for cardiopulmonary bypass during lung transplantation in adults.

The records for 162 lung transplantations performed in 158 patients were reviewed with regard to the predictors for, frequency of, and indications for using cardiopulmonary bypass during the procedure. There were a total of 8 en bloc double-lung transplantations, 83 single-lung transplantations, and 71 bilateral single-lung transplantations. Bypass was used electively for all double en bloc and three of the bilateral sequential lung transplantation procedures and for 26 unilateral lung replacement procedures in patients with pulmonary hypertension. Of the remaining patients, 1 single-lung transplant recipient required bypass for correction of a surgical mishap and 18 bilateral single-lung recipients required bypass during replacement of the second lung. No preoperative predictors for the need of bypass could be identified. Among the bilateral sequential lung recipients, the use of bypass did not seem to adversely affect outcome, as expressed in terms of the time until extubation, the time spent in the intensive care unit, and the time required to reach a room air oxygen tension greater than 60 mm Hg.

Adult↗
PubMed1994

Respiratory responses to CO2 rebreathing in lung transplant recipients.

To evaluate the respiratory responses after lung transplantation, we studied the hypercarbic ventilatory response in 20 patients with severe obstructive pulmonary disease and compared it with that of 10 normal subjects. Eleven patients underwent bilateral lung transplantation and 9 patients had single-lung transplantation. All patients had preoperative hypercapnia (51.3 +/- 9.7 mm Hg) and blunted slopes of CO2 rebreathing curves for minute ventilation (0.39 +/- 0.20 L.min-1.mm Hg-1) and inspiratory occlusion pressure (0.35 +/- 0.30 s-1). The hypercapnia and blunted ventilatory responses persisted at the initial postoperative test (5.8 +/- 2.0 days) despite improved pulmonary function (preoperative forced expiratory volume in 1 second [FEV1], 0.57 +/- 0.16 L; initial postoperative FEV1, 1.83 +/- 0.65 L; p < 0.001). By the 15th to 30th postoperative day (21.3 +/- 6.0 days), compared with preoperative and initial postoperative values, end-tidal CO2 had normalized (40.6 +/- 6.9 versus 51.3 +/- 9.7 and 49.6 +/- 10.3 mm Hg; p < 0.005) and was coupled with enhanced ventilatory responses for the rebreathing curve for minute ventilation (1.26 +/- 0.7 versus 0.39 +/- 0.20 and 0.32 +/- 0.32 L.min-1.mm Hg-1; p < 0.005) and the inspiratory occlusion pressure curve (0.98 +/- 7.4 versus 0.35 +/- 0.30 and 0.41 +/- 0.29 s-1; p < 0.005). These respiratory responses developed without a change in postoperative pulmonary function (initial postoperative FEV1, 1.83 +/- 0.65 L versus last postoperative FEV1, 1.96 +/- 0.66 L; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Tidal volume and respiratory rate changes during CO2 rebreathing after lung transplantation.

To evaluate the contribution of the respiratory pattern to the ventilatory response after lung transplantation, we studied the changes in minute ventilation, tidal volume, and respiratory rate during CO2 rebreathing in 14 patients with severe obstructive pulmonary disease, and compared them with 10 normal subjects. Seven patients underwent a bilateral lung transplantation and 7 patients had single-lung transplantation. Single-lung transplant recipients increased their respiratory rate by the last postoperative test compared with either preoperative or initial test periods (0.38 +/- 0.13 versus 0.027 +/- 0.24 or 0.12 +/- 0.08 breaths.min-1.mm Hg-1; p < 0.005). Bilateral lung transplant recipients showed a diminished ability to augment their respiratory rate by the last postoperative test compared with either preoperative or initial test periods (0.13 +/- 0.23 versus 0.54 +/- 0.25 or 0.25 +/- 0.29 breaths.min-1.mm Hg-1; p < 0.06). The restored ventilatory response by the fourth postoperative week was due to a statistically significant increase in tidal volume for both single and bilateral lung transplant recipients. This study demonstrates that when lung transplant recipients have an appropriate ventilatory response to CO2 rebreathing, single-lung transplant recipients have a respiratory pattern similar to normal; whereas the bilateral lung transplant recipients show the effects of total pulmonary denervation. We conclude that the preserved ventilatory response in lung transplant recipients is composed of a respiratory pattern that is influenced by the presence or absence of vagal inputs.

Adult↗
PubMed1994

Differences in early results after single-lung transplantation. Washington University Lung Transplant Group.

Single-lung transplantation is an effective treatment for end-stage pulmonary failure caused by a variety of lung diseases. Although single-lung recipients may undergo a similar operative procedure, physiologic differences in the remaining native lung dictate differences in postoperative management and perhaps outcome. To examine these effects on the early results after single-lung transplantation, we retrospectively reviewed the course of 83 patients undergoing single-lung transplantation from September 1988 through July 1993. The cause of the lung disease was obstructive (OLD) in 43, idiopathic pulmonary fibrosis (IPF) in 16, and primary pulmonary hypertension (PPH) in 24 patients. The hospital mortality was 5% in OLD, 13% in IPF, and 8% in PPH. Gas exchange as demonstrated by alveolar-arterial oxygen gradients was worse after transplantation in patients with IPF (349 +/- 159 mm Hg) or PPH (270 +/- 171 mm Hg) compared with patients with OLD (174 +/- 105 mm Hg; p < 0.05). Mean pulmonary artery pressures were higher in patients with IPF (28 +/- 6 mm Hg) and PPH (26 +/- 7 mm Hg) compared with patients with OLD (22 +/- 5 mm Hg; p < 0.05). Peak airway pressures after transplantation were greater in patients with IPF (36 +/- 6 cm H2O) compared with patients with OLD (28 +/- 6 cm H2O; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Reduced transport of [125I]nerve growth factor by cholinergic neurons and down-regulated TrkA expression in the medial septum of aged rats.

Basal forebrain cholinergic neurons atrophy and degenerate in aging and Alzheimer's disease for unknown reasons. In this study, aged male Sprague-Dawley rats (26-30 months old) showed a significant 31% reduction in the number of septal cholinergic neurons which take up and retrogradely transport 125I-labelled nerve growth factor injected into their target hippocampus, as compared with young adult rats (three to six months old). In aged rats, cholinergic neurons not transporting nerve growth factor were severely atrophied and had a significant 60% reduction in mean cross-sectional area as compared with [125I]nerve growth factor transporting neurons. These changes were accompanied by a significant 43% decline in relative levels of messenger RNA encoding the high affinity nerve growth factor receptor TrkA, in the septal region of aged rats. There was no difference between young and aged rats in messenger RNA levels encoding the low affinity nerve growth factor receptor, p75NGFR. These findings suggest that aged basal forebrain cholinergic neurons exhibit a reduced capacity to sustain receptor mediated uptake and retrograde transport of target-derived neurotrophin. This reduced capacity is associated with severe neuronal atrophy and may contribute to the pronounced vulnerability of these neurons to degeneration in aging and Alzheimer's disease.

Aging↗
PubMed1994

Technique to reduce air leaks after resection of emphysematous lung.

Wedge excision of emphysematous lung tissue by means of a stapling device is frequently associated with prolonged air leakage. We have used bovine pericardial strips to buttress the staple line, preventing air leakage, which otherwise can occur at the staple holes when the lung is reinflated.

Biological Dressings↗
PubMed1994

Results of single and bilateral lung transplantation in 131 consecutive recipients. Washington University Lung Transplant Group.

We reviewed results of the first 131 recipients who received a single or bilateral sequential lung transplant at Barnes Hospital between July 1, 1988, and July 31, 1992. Follow-up data were complete as of January 1, 1993, for a minimum of 5 months' follow-up for all surviving recipients. There were 11 hospital deaths for an overall 92% hospital survival. Thirteen late deaths occurred and 107 (81%) recipients remain alive with a median follow-up period of 19 months. One hundred nineteen recipients survived at least 3 months after transplantation, and for this group factors that might influence long-term results were evaluated. The prevalence of pathologically proved bronchiolitis obliterans was 18.5%. Functional deterioration, which may not correlate with pathologic findings, was evaluated with a recently developed bronchiolitis obliterans syndrome staging system. Factors not influencing long-term outcome included the number of early rejection episodes, matching donor and recipient cytomegalovirus antibody status, or underlying diagnosis. Patients undergoing single lung transplantation for primary pulmonary hypertension or Eisenmenger's syndrome had results similar to those of other diagnostic groups. Furthermore, the hemodynamic improvement previously reported for this group of patients after single lung transplantation has been maintained at long-term follow-up. The shortage of donor organs and the need for improved methods for diagnosis and management of chronic rejection remain the most challenging problems in lung transplantation.

Actuarial Analysis↗
PubMed1993

Influence of temperature of flushing solution on lung preservation.

For lung transplantation the technique of flushing the donor pulmonary vascular bed may provide advantages in lung preservation such as rapid cooling and washout of blood. However, rapid cooling of the ischemic lung may also produce adverse effects. The aim of this study was to compare methods of cold flushing and topical cooling, and to evaluate the effect of temperature of the flushing solution on lung preservation. A total of 25 rabbit lungs were studied. Using an ex vivo rabbit lung model, postischemic function was assessed by the ability of the lung to oxygenate perfused blood and by measurement of pulmonary artery and airway pressures. The lungs in group I were preserved with simple immersion at 10 degrees C for 30 hours. The lungs in groups II through V were flushed with solution containing phosphate-buffered dextran (LPD) at different temperatures (groups II and IV, 10 degrees C; groups III and V, 23 degrees C) and stored at 10 degrees C for various ischemic periods (groups II and III, 30 hours; groups IV and V, 36 hours). Pulmonary vascular resistance during flushing at 10 degrees C was significantly higher than that at 23 degrees C (p < 0.001). Flushing resulted in better preservation than topical hypothermia. Flushing at 23 degrees C resulted in superior postischemic function compared with flushing at 10 degrees C. We conclude that in lung preservation, uniform flushing with LPD solution improves the ischemic tolerance as compared with topical hypothermia, and that flushing with solutions at too low temperatures may have adverse effects on lung preservation.

Animals↗
PubMed1993

Donor lung procurement: assessment and operative technique.

Given the relative scarcity of suitable donors and the widespread application of cardiac and pulmonary transplantation, it is imperative that a heart and two lungs be extracted from each donor. From increasing clinical experience and laboratory investigation in lung preservation, more flexible criteria for the assessment of potential lung donors are emerging. In this communication, we present our current criteria of donor lung suitability, and a simple and reliable technique of combined cardiopulmonary extraction that has provided suitable heart and lung grafts with excellent preservation, used in our last 150 donor organ procurements.

Dissection↗