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Biomedical subjects

J D Cooper

Publications and source records attributed to J D Cooper.

At least 19 recordsLinked to original sources

Pulmonary "twinning" procedure: use of lungs from one donor for single-lung transplantation in two recipients.

Since the introduction of lung transplantation as an option for patients with end-stage respiratory disease in the early 1980s, there have been substantial advances made in the technical aspects of transplantation as well as the early clinical results. With an ever-increasing number of patients being designated suitable candidates for transplantation, the volume of transplants in the foreseeable future will be limited more on the basis of donor lung supply than any other single factor. Pulmonary "twinning" provides an important step in ensuring that all suitable and available donor lungs are utilized whenever feasible. This report reviews the results of 20 single-lung transplantations carried out in five separate transplantation centers using organs retrieved from ten donors. The overall mortality rate in this group of patients was 5%, which compares very favorably with historical controls. No serious problem was noted with respect to increased perioperative morbidity or increased ischemic times in this group of patients. We suggest that this process should be considered and, wherever possible, adopted by all major lung transplant centers.

Adult

Management of dysfunction in the transplanted lung: experience with 7 clinical cases. Washington University Lung Transplant Group.

In a series of 34 lung transplant patients, donor lung dysfunction occurred on 7 occasions. One patient underwent retransplantation and the remaining 6 were treated conservatively. Survival was 100% in the donor lung dysfunction group. Percent predicted forced expiratory volume in 1 second, carbon monoxide diffusion, room air oxygen tension, and distance walked in 6 minutes were all lower (p less than 0.05) at 1 month after transplantation in those patients with donor lung dysfunction as compared with those without. These differences were not significant at 3 months after transplantation. We conclude that donor lung dysfunction can usually be managed conservatively with satisfactory results. Longer follow-up of this group of patients will be necessary to determine the long-term consequences of early graft injury.

Adult

Production and reversibility of right ventricular hypertrophy and right heart failure in dogs.

Combined heart-lung transplantation has been used for end-stage primary pulmonary hypertension. Experience with single-lung transplantation for other conditions suggested that associated severe right ventricular dysfunction resulting from increased afterload would recover after placement of a satisfactory lung allograft. Early experience with the application of single-lung transplantation for pulmonary hypertension supports this contention. We devised a reversible canine model of chronic progressive pressure-overloaded right heart failure by pulmonary artery banding to study the echocardiographic, hemodynamic, and pathological reversibility of the failing right heart. Clinical right heart failure was defined as the development of ascites and pleural effusions. Right heart failure developed in 23 dogs 67 to 348 days after banding, and they were divided into two groups to determine its early and long-term effects. Group 1 dogs (n = 11) were either sacrificed immediately after the onset of right heart failure (n = 5) or unbanded (n = 6); group 2 dogs (n = 12) were maintained in right heart failure for 3 months and then either sacrificed (n = 6) or unbanded. Unbanded dogs in both groups were observed for 4 additional months before sacrifice. A control group of 6 normal dogs was sacrificed for pathological comparisons. After unbanding, the right ventricular systolic pressure fell from 97 +/- 17 mm Hg (group 1) and 88 +/- 31 mm Hg (group 2) to 44 +/- 11 mm Hg and 47 +/- 13 mm Hg, respectively. Despite this persistent gradient across the pulmonary artery, echocardiographic and hemodynamic measures of right ventricular function returned to normal, albeit more slowly in the group 2 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Failure of prophylactic ganciclovir to prevent cytomegalovirus disease in recipients of lung transplants.

In an effort to prevent cytomegalovirus (CMV) pneumonitis, seven consecutive CMV-seronegative lung transplant recipients of organs from seropositive donors (D+/R-) were given ganciclovir, 2.5-5 mg/kg intravenously twice daily for the first 10-21 days after transplantation, and commercial polyvalent immune globulin, 200-400 mg/kg every 7-14 days intravenously, for the first 2-3 weeks after transplantation. This regimen was followed by oral acyclovir. Six patients developed CMV viremia and all developed CMV pneumonitis. Viremia occurred later in these patients compared with D+/R- patients who received alternative forms of CMV prophylaxis or CMV-seropositive recipients who received no specific prophylaxis (P = .023 and P = .021, respectively). There was no statistical difference in incidence or time to onset of CMV pneumonitis. When given as described, prophylactic ganciclovir and immune globulin followed by oral acyclovir may have delayed CMV viremia but did not prevent it or pneumonitis in high-risk lung transplant recipients.

Acyclovir

Omental flap in lung transplantation.

Some surgeons performing lung transplantation will wrap the bronchial anastomosis with omentum in an attempt to improve healing. The authors retrospectively reviewed the chest radiographs and computed tomographic (CT) scans of 31 patients who underwent lung transplantation with bronchial omentopexy to determine the CT appearance of the intrathoracic omentum and the frequency and type of chest radiographic manifestations created by the omental flap. The omental flap was seen at CT in all patients, was predominantly of fatlike attenuation, and contained linear areas of increased attenuation representing omental vessels. In 16 patients (52%), a total of 29 chest radiographic findings that corresponded to the omental flap were seen. There was no statistically significant correlation between the type of operative procedure and the presence of a chest radiographic correlate for the omentum. The results showed that the omental flap is a potential diagnostic pitfall on post-lung transplantation chest radiographs; when there is confusion, however, the omentum can be identified with CT because of its attenuation value and characteristic course.

Adolescent

Pulmonary vascular permeability after lung transplantation. A positron emission tomographic study.

We evaluated pulmonary vascular permeability in 15 patients after lung transplantation (21 allografts) by measuring the pulmonary transcapillary escape rate (PTCER) for Ga-68-labeled transferrin, using positron emission tomography. Seven recipients (four unilateral, three bilateral lung transplants) were studied within 3 days of transplantation, and each developed hypoxemia and allograft infiltrates consistent with the "reimplantation response." PTCER was higher in subjects studied within 1 day than in those studied at a later time, and fell in seven allografts studied serially. The initial PTCER also correlated (r = 0.77) with length of ischemic (preservation) time, even in the three subjects with bilateral allografts. Eight other recipients (five unilateral, three bilateral transplants) were evaluated for possible organ rejection at least 1 wk after transplantation. PTCER was normal in patients without clinical or histologic evidence of rejection, and it was elevated in recipients with rejection. PTCER fell each time after treatment for rejection with increased immunosuppression in the three patients studied serially. These data suggest that positron emission tomography measurements of PTCER might be a useful way to evaluate both the reimplantation response and organ rejection after lung transplantation.

Adult

NHLBI workshop summary. Biology of lung preservation for transplantation.

The types of animal models that are used for assessing lung preservation, and the types of interventions that are likely to prove of value, must be carefully selected. For example, the events of warm ischemia are not necessarily the same as those that occur during cold preservation. Warm ischemia has often been used as a means of accelerating the degree of ischemic injury, but the events may not be qualitatively the same. Nonetheless, the use of different types of lung injury models contributes to our overall understanding of mechanisms of lung injury associated with transplantation. Pathologic studies of lung injury ischemia and reperfusion may not prove helpful, as they may be nonspecific and insensitive. To compare results of different preservation methods, a standardized animal model would be most helpful if a universally accepted one could be identified. This would include standard measurements of lung function, standard techniques of transplantation, and follow-up studies of several days' duration after transplantation. Such a model could serve as the ultimate test of preservation methods following its development in a variety of the animal models. It must be emphasized that whereas animal models generally begin with a normal lung that is preserved, the clinical situation differs because the donor lungs may be far from normal at the outset due to the effects of brain death, hemodynamic instability, infection, trauma, and a host of other factors. Thus, the limits of safe preservation in a clinical situation may well be significantly less than the safe preservation time demonstrated in the laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage III unresectable non-small-cell lung cancer: results of the Toronto Phase II Trial.

PURPOSE: The 5-year survival rates with surgical resection for preoperatively identified stage IIIA N2 non-small-cell lung cancer (NSCLC) are less than 10%. A pilot study of mitomycin, vindesine, and cisplatin (MVP) induction chemotherapy was undertaken in an attempt to improve the curative potential of surgery in this group of patients. PATIENTS AND METHODS: Thirty-nine patients with mediastinoscopy stage IIIA N2 NSCLC received two cycles of MVP. Responding patients underwent thoracotomy for resection and two further courses of MVP. RESULTS: The overall response rate was 64% (25 of 39) with three complete and 22 partial responses. Twenty-two patients were resected, which included a radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no tumor remaining. Toxicity included two postoperative deaths secondary to a bronchopleural (BP) fistula, mitomycin pulmonary toxicity in two patients, and septic deaths in four patients. Twenty-eight patients have died; 20 have recurrent or progressive disease. Eight of the 18 patients completely resected have recurred, with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain), and one in both. Median survival of all 39 patients is 18.6 months, with a 3-year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%. CONCLUSIONS: We conclude (1) that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC; (2) the median survival seems to be prolonged; and (3) the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a phase III randomized trial to compare it with other treatment modalities.

Adult

The role of transbronchial lung biopsy in the treatment of lung transplant recipients. An analysis of 200 consecutive procedures.

STUDY OBJECTIVE: The purposes of this study were as follows: (1) to establish the positivity rate and complication rate of transbronchial lung biopsies in the treatment of lung transplant recipients; (2) to determine the sensitivity of transbronchial lung biopsy specimens for the diagnosis of clinically suspected acute rejection and cytomegalovirus pneumonia; and (3) to examine the results of surveillance transbronchial lung biopsies in clinically and physiologically stable recipients. DESIGN: Retrospective review and analysis of 203 consecutive procedures. SETTING: Washington University Lung Transplantation Program, Washington University School of Medicine and Barnes Hospital, St. Louis, Mo. PATIENTS: Fifty-five lung transplant recipients. INTERVENTIONS: Biopsies were done with 2-mm fenestrated forceps using fluoroscopic guidance. Two hundred three bronchoscopies with transbronchial lung biopsy were performed for clinical indications (n = 88), routine surveillance (n = 90), or follow-up of a previous biopsy (n = 25). Biopsy specimens showing acute allograft rejection were classified according to the scheme recommended by the Lung Rejection Study Group. MEASUREMENTS AND RESULTS: The positivity rate and complication rate were determined for the procedures. In procedures performed for clinical indications, the sensitivity for the diagnosis of acute rejection and cytomegalovirus pneumonia was calculated by a decision-to-treat analysis. A specific histologic diagnosis was detected in 69 percent of the clinical procedures, 57 percent of the surveillance procedures, and 64 percent of the follow-up procedures. For clinical indications, the sensitivity of transbronchial lung biopsy was 72 percent for the diagnosis of acute rejection and 91 percent for the diagnosis of cytomegalovirus pneumonia. Surveillance biopsy specimens often showed clinically inapparent rejection or cytomegalovirus pneumonia. The overall complication rate was 8.9 percent; none of the complications were life threatening. CONCLUSIONS: Transbronchial lung biopsy is a useful and safe procedure in the treatment of lung transplant recipients. When performed for clinical indications, the procedure proved to be sensitive for the diagnosis of acute rejection and cytomegalovirus pneumonia. When performed for surveillance in clinically and physiologically stable recipients, the incidence of rejection and cytomegalovirus pneumonia was unexpectedly high; the potential clinical implications of these findings will require further study.

Biopsy, Needle

Current status of lung transplantation--report of the St. Louis International Lung Transplant Registry.

There were 1,536 lung transplants reported to the St. Louis International Lung Transplant Registry as of September 1, 1992. The number of centers performing lung transplants increased each year. The 1- and 2-year actuarial survival statistics for all transplants were 68% and 60%, respectively. The most common indication for transplantation was chronic obstructive pulmonary disease, followed by idiopathic pulmonary fibrosis, emphysema secondary to alpha-1 antitrypsin deficiency, and cystic fibrosis. Among the total of 492 deaths reported (34%), sepsis was the leading cause of death.

Adolescent

Comparison of the University of Wisconsin preservation solution and other crystalloid perfusates in a 30-hour rabbit lung preservation model.

The University of Wisconsin solution, which contains a high potassium concentration (120 mmol/L), was evaluated for rabbit lung preservation by comparing it with a modified University of Wisconsin solution with low potassium (4 mmol/L), a low-potassium dextran solution (4 mmol/L), and simple surface cooling. In the first three groups rabbit lungs were flushed in situ with the solution (n = 5 in each group); then the lung-heart block was harvested and stored at 10 degrees C for 30 hours. In the surface cooling group the lungs were harvested without flushing and then simply immersed in saline and stored. For assessment, the stored lung was ventilated with room air and perfused with fresh venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function included gas analysis of effluent blood, mean pulmonary artery perfusion pressure, and peak airway pressure. Among these parameters, oxygen tension was most sensitive. Oxygen tension at 10 minutes' perfusion in the modified University of Wisconsin (95 +/- 6 mm Hg) and low-potassium dextran (99 +/- 4 mm Hg) groups was significantly higher than that in the surface cooling (61 +/- 7 mm Hg) and University of Wisconsin (51 +/- 7 mm Hg) groups. There was no difference between the modified University of Wisconsin and low-potassium dextran groups or between the surface cooling and University of Wisconsin groups. We conclude that the low-potassium University of Wisconsin solution is superior to the high-potassium University of Wisconsin solution and that the lactobionate and raffinose included in the University of Wisconsin solution as impermeants do not improve lung preservation in this model.

Adenosine

Epidemiology, clinical features, and diagnosis of Lyme disease.

Lyme disease is the most common vector-borne disease in the United States. Epidemiologic research has contributed to a better understanding of the factors involved in the geographic spread and increased incidence of the disease. Clinical features of Lyme disease, including skin, joint, cardiac, and neurologic involvement, are discussed here, along with recent studies that better characterize these clinical manifestations and more clearly define their immunopathogenesis. The diagnosis of Lyme disease is based on the clinical presentation. Laboratory testing may be helpful but has significant limitations, which we discuss in our review.

Humans

Single lung transplantation for pulmonary hypertension. Technical aspects and immediate hemodynamic results.

Donor availability has limited the clinical applicability of heart-lung transplantation in patients with end-stage pulmonary hypertension. Satisfaction with single lung transplantation in other patient groups prompted its extension to patients with pulmonary hypertension. Nine patients with end-stage pulmonary hypertension underwent single lung transplantation. Important technical considerations included routine use of cardiopulmonary bypass, simultaneous closure of significant associated cardiac defects (n = 4), and use of remaining thoracic donor organs in multiple recipients (total thoracic transplants from eight donors = 21). Analysis of immediate postoperative hemodynamics suggests that early relief of pulmonary hypertension and improvement in right ventricular function can be expected. There was one postoperative death. Eight patients have been discharged and are alive and well at a mean follow-up period of 1 year. All eight survivors have returned to New York Heart Association functional class I from their preoperative levels of III or IV. These results support the use of single lung transplantation as a transplant option in patients with end-stage pulmonary hypertension. The question of long-term durability remains unanswered.

Adult

The current status of lung transplantation.

The supply of donor organs remains extremely limited and improved methods to maintain the lungs of potential donors to allow for transplantation must be developed. Improved methods for preservation will increase the supply of suitable lungs and considerably simplify the logistics of transplantation, just as has occurred with liver transplantation. In the meantime, we continue to strive to utilize donor organs in the most efficient manner. On four occasions within the past 5 months, we have performed two simultaneous single lung operations and are prepared either to do this as a routine, or to offer the other lung to another center. Sufficient progress has been achieved to date to warrant the continued application of lung transplantation for end-stage pulmonary disease. With increasing experience, one can anticipate refinement of techniques and broader application of these procedures. Single lung transplantation, initially restricted to patients with end-stage pulmonary fibrosis, now has been applied successfully to patients with emphysema, pulmonary hypertension, and other conditions. We anticipate offering lung transplantation in the pediatric and even neonatal population in the very near future. This may prove to be particularly important in the group of children with so-called bronchopulmonary dysplasia, an end-stage interstitial fibrosis occurring in a small percentage of children born with what initially appears to be hyaline membrane disease and who require prolonged mechanical ventilation. Though currently transplantation can offer real benefit only to a limited number of individuals, it serves to create hope for many others. An additional benefit may prove to be the interest and attention that transplantation focuses on patients with end-stage lung disease and on the pathophysiology of chronic respiratory failure. Knowledge gained ultimately may result in the prevention of many of the disorders for which lung transplantation currently offers the only hope.

History, 20th Century

In a canine model, lung preservation at 10 degrees C is superior to that at 4 degrees C. A comparison of two preservation temperatures on lung function and on adenosine triphosphate level measured by phosphorus 31-nuclear magnetic resonance.

Techniques for organ preservation generally use hypothermia to retard metabolic requirements. However, excessive hypothermia may also produce injury. Using a canine left lung allotransplantation procedure, we compared two preservation temperatures (4 degrees and 10 degrees C) in terms of subsequent lung function measured by temporary occlusion of the right pulmonary artery after implantation of the preserved left donor lung. The lungs were flushed with low-potassium dextran electrolyte solution, inflated with 100% oxygen, and preserved for 18 hours. To investigate possible changes of energy stores at different temperatures, we performed phosphorus 31-nuclear magnetic resonance analyses of lung samples. Sequential determinations of adenosine triphosphate levels in lung tissue preserved at 4 degrees, 10 degrees, and 22 degrees C were studied. After transplantation, lungs preserved at 10 degrees C (n = 6) provided significantly better arterial oxygen tension than those preserved at 4 degrees C (n = 6), 451 +/- 46 mm Hg versus 243 +/- 86 mm Hg (p less than 0.05), and lower pulmonary vascular resistance, 581 +/- 68 dynes.sec.cm-5 versus 1006 +/- 157 dynes.sec.cm-5 (p less than 0.05). Adenosine triphosphate levels at 4 degrees and 10 degrees C were stable and did not differ from each other at the end of the 18-hour preservation period: 0.86 +/- 0.04 mumol/gm wet weight for control versus 0.86 +/- 0.07 mumol/gm wet weight for 4 degrees C and 0.93 +/- 0.06 mumol/gm wet weight for 10 degrees C after 18 hours of preservation. Preservation at 22 degrees C caused a 28% depression of adenosine triphosphate after 18 hours of preservation. These results lead us to conclude the following: (1) Optimal temperature for lung preservation is in the vicinity of 10 degrees C, and (2) lung dysfunction caused by excessive hypothermia is not due to a failure to maintain adenosine triphosphate levels. We suspect that adenosine triphosphate is generated by oxidative phosphorylation during lung preservation.

Adenosine Triphosphate

[Revascularization of tracheal transplants with omentum].

UNLABELLED: In a series of 6 dogs we performed an autotransplantation of a four-ring segment of the thoracic trachea. In 3 cases the omentum was brought into the chest and wrapped around the transplant (omentum group) and compared with the others (control group). After 20 days or at occurrence of severe tracheal stenosis the study was determined. In the omentum group all tracheal transplants healed with structural integrity. Microfil injection into the gastro-epiploic artery demonstrated revascularization through omental vessels. In the control group all transplants developed a severe stenosis due to chondromalacia within 2 weeks. IN CONCLUSION: The omentum can successfully revascularize a transplant of a four-ring segment of the thoracic trachea.

Animals

Morbidity, mortality, and early results of single versus bilateral lung transplantation for emphysema.

Both single lung transplantation and bilateral lung transplantation have been successful in patients with chronic obstructive pulmonary disease. Limited availability of donor lungs dictates wider use of single lung transplantation as long as this procedure provides a comparable functional result at less risk. Early morbidity, mortality rates, and functional results were compared in 32 consecutive patients undergoing either single or bilateral lung transplantation for end-stage chronic obstructive pulmonary disease. When pretransplantation and posttransplantation values of forced expiratory volume in 1 second, single breath diffusing capacity, total lung capacity, arterial oxygen tension, and 6-minute walking distance were compared, statistically significant improvement (p less than 0.01) was seen in both groups. However, significantly higher values (p less than 0.01) were attained for forced expiratory volume in 1 second, single breath diffusing capacity, and arterial oxygen tension in the bilateral transplantation group than in the single lung transplantation group. Patients receiving bilateral lung transplants were at greater risk for postoperative complications, especially cardiac arrhythmias and bronchial anastomotic defects. Actuarial survival for the single lung transplantation group was 93% at 1 year, versus 87% at 6 months and 71% at 1 year for the bilateral lung transplantation group. The optimal transplantation procedure for patients with chronic obstructive pulmonary disease has not been determined. Longer follow-up periods are needed to define better the roles of bilateral and single lung transplantation in this group of patients.

Age Factors

Biocompatibility of standard and silica-free silicone rubber membrane oxygenators.

Spiral coil membrane oxygenators made from either standard silicone rubber or silica-free silicone rubber were compared using three priming techniques. Standard priming, carbon dioxide priming, and denucleation priming were employed with each type of device. Four-hour venovenous membrane oxygenator perfusions were carried out on awake sheep anticoagulated with heparin. Virtually no differences were observed in any parameters measured between standard silicone rubber and filler-free silicone rubber membranes. Significantly greater platelet losses occurred during the first hour of perfusion with standard priming and with carbon dioxide priming than with denucleation priming, using either type of membrane. These experiments demonstrate that denucleation priming reduces platelet losses during extracorporeal membrane oxygenator perfusion, but that the use of filler-free silicone rubber does not improve the biocompatibility of the membrane.

Animals