Dominoes--pragmatism or piracy?
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Heart-Lung Transplantation↗
Biomedical subjects
J D Cooper
Publications and source records attributed to J D Cooper.
Bilateral sequential lung transplantation: the procedure of choice for double-lung replacement.
We recently described a technique for bilateral sequential lung transplantation that replaces the en bloc double-lung operation, a procedure that was accompanied by frequent problems with airway healing. Twenty-seven patients have undergone 28 bilateral sequential lung transplantations over the past 14 months. Eighteen patients had transplantation because of end-stage emphysema; 6, cystic fibrosis; and 1 each, obliterative bronchiolitis, usual interstitial pneumonitis with pulmonary fibrosis, and bronchiectasis. Cardiopulmonary bypass was used electively in the first 5 patients until it was recognized that the procedure could be done safely without it, and in only 3 additional recipients has it been employed. Mean ischemic time for the first lung was 276 +/- 43 minutes and for the second lung, 410 +/- 64 minutes. There have been five deaths, three in the postoperative period (11% operative mortality) and two late. The other patients are alive and well and do not require oxygen 2 to 15 months after transplantation. Mean forced expiratory volume in 1 second rose from 16% +/- 8% of predicted to 84% +/- 17% at 12 weeks. Six-minute walk values increased from a mean of 251 +/- 91 m to 666 +/- 42 m at 24 weeks. The excellent exposure afforded to both hemithoraces by the thoracosternotomy incision and the rare need of cardiopulmonary bypass have allowed us to offer the option of transplantation to patients who formerly would have been turned down because of previous pulmonary resection or pleurectomy. On four occasions, ventilator-dependent patients underwent successful transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Prophylactic cranial irradiation for lung cancer patients at high risk for development of cerebral metastasis: results of a prospective randomized trial conducted by the Radiation Therapy Oncology Group.
Beginning in February 1984, 187 evaluable patients with adenocarcinoma or large cell carcinoma of the lung clinically confined to the chest were randomized to receive either conventionally fractionated thoracic irradiation alone or thoracic irradiation with concurrent, prophylactic cranial irradiation. The study population included 161 patients treated for medically or surgically inoperable primary cancers, and 26 patients undergoing adjuvant postoperative mediastinal irradiation following attempted curative resection of primary cancers found to have metastasized to hilar or mediastinal lymph nodes. Elective brain irradiation was not effective in preventing the clinical appearance of brain metastases, although the time to develop brain metastases appears to have been delayed. Eighteen of 94 patients (19%) randomized to chest irradiation alone have developed brain metastases as opposed to 8/93 patients (9%) randomized to receive prophylactic cranial irradiation (p = .10). No survival difference was observed between the treatment arms. Among the 26 patients undergoing prior resection of all gross intrathoracic disease, brain metastases were observed in 3/12 patients (25%) receiving adjuvant chest irradiation alone, compared to none of 14 receiving prophylactic cranial irradiation (p = .06). In the absence of fully reliable therapy for the primary disease, and without effective systemic therapy preventing dissemination to other, extrathoracic sites, prophylactic cranial irradiation for inoperable non-small cell lung cancer cannot be justified in routine clinical practice. Further investigation in the adjuvant, postoperative setting may be warranted.
Adenocarcinoma↗
Closed mediastinal exploration in patients with persistent hyperparathyroidism.
Described are two patients with persistent hyperparathyroidism after unsuccessful neck explorations. Both had deep mediastinal parathyroid tumors located within the thymus gland. Formerly it had been the practice of the authors to perform a median sternotomy for the removal of such tumors. In the present cases, however, the neck was re-explored through a cervical incision and the entire thymus gland then was removed by the technique of "closed mediastinal thymectomy." An enlarged parathyroid gland was found embedded in the resected parenchyma of the thymus gland in each patient, and both were cured by the operation.
Adolescent↗
Trophic factor effects on septal cholinergic neurons.
The role of trophic factors in the adult central nervous system (CNS) is poorly understood. One system that may require trophic factors, particularly nerve growth factor (NGF) and brain-derived growth factor (BDNF), for normal function in the adult CNS is the cholinergic projection from the basal forebrain to the hippocampus. To study the nature of this requirement we ablated target neurons in the hippocampus that normally produce NGF and BDNF; we found no loss of cholinergic neurons or cholinergic phenotype in the medial septum in young adult rats. In similarly treated aged rats (24-33 months), some reduction in cholinergic phenotype was found, in the absence of cell death for up to 90 days. Thus, these cholinergic neurons either do not require trophic support for survival, or are able to obtain trophic factors from other sources for the duration of the experiments. In vitro, NGF withdrawal from septal neurons initially grown in the presence of NGF did not result in the death of old cholinergic neurons in these tissue cultures but did result in a down-regulation of transmitter-associated enzymes, accompanied by cholinergic cell shrinkage and a reduction in fiber density. Together, these findings suggest that target-derived factors may not be required for the survival of mature septal cholinergic neurons, but may be involved in maintenance of cholinergic and structural phenotype.
Alzheimer Disease↗
Lung transplantation for chronic obstructive lung disease.
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Humans↗
Single-lung transplantation for pulmonary hypertension. Three-month hemodynamic follow-up.
BACKGROUND: Shorter waiting times, relative technical simplicity, and satisfactory application to a broad spectrum of patients has made single-lung transplantation an attractive option in the treatment of patients with end-stage pulmonary hypertension. METHODS AND RESULTS: Seven patients with pulmonary hypertension underwent single-lung transplantation. Simultaneous closure of associated atrial septal defects was accomplished in two patients. Despite severely compromised pretransplant right ventricular function in all patients, there was no early or late mortality. Right ventricular functional recovery as characterized by hemodynamic assessment before and at a mean of 13 weeks posttransplant was nearly uniform and characterized by a drop in 1) pulmonary arterial systolic pressure from 92 +/- 7 mm Hg to 29 +/- 6 mm Hg (p = 0.001), 2) central venous pressure from 10 +/- 6 mm Hg to 1 +/- 2 mm Hg (p = 0.02), and 3) pulmonary vascular resistance index from 1,924 +/- 663 to 232 +/- 73 dyne.sec.cm-9 (p = 0.001). Radionuclide ventriculography before and at a mean of 17 weeks posttransplant documented a significant (p = 0.006) increase in right ventricular ejection fraction from 22 +/- 15% to 51 +/- 11%. Quantitative pulmonary perfusion scintigraphy at a mean of 17 weeks posttransplant demonstrated a significant (p = 0.001) increase in perfusion to the transplanted lung from 56 +/- 6% to 89 +/- 7%. There was a concomitant, slight but significant (p = 0.004) decrease in ventilation to the transplanted side from 56 +/- 6% to 49 +/- 8%. After transplantation, all patients returned to New York Heart Association functional class I or II from their preoperative levels of class III or IV. CONCLUSIONS: These early follow-up data cautiously support the option of single-lung transplantation in patients with pulmonary hypertension, although long-term durability of these hemodynamic changes deserves documentation before widespread application.
Follow-Up Studies↗
Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings.
Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure.
Aged↗
Analysis of referrals for lung transplantation. The Washington University Lung Transplantation Group.
In the first year of our lung transplantation program, 211 patients with end-stage pulmonary disease were referred for consideration. Over 50 percent of the patients had chronic obstructive pulmonary disease, and almost 20 percent had idiopathic pulmonary fibrosis. The referrals were screened according to predefined criteria of eligibility for single and double lung transplantation. After screening, 46 of the referred patients were admitted for an extensive inpatient evaluation, and 18 of these were accepted as candidates for transplantation. Although interest in lung transplantation is growing in both the medical and lay communities, a significant number of patients with endstage pulmonary disease were ineligible by our current criteria. As experience with these procedures is gained, criteria for selection may become less restrictive, and more patients may be candidates for transplantation.
Adult↗
[Does tissue pH measurement quantify circulation in the transplanted bronchus in lung transplantation].
Ischemia of the airway is the main cause of severe complications in lung transplantation. Tissue-pH is used as an indicator of ischemia in the myocardium and various other tissues. We developed a pH needle probe which can be applied through a bronchoscope to enable repeated measurements of the pH in the bronchus mucosa. In 8 conditioned mongrel dogs (20-25 kg) an autotransplant of a 4-ring segment of the thoracic trachea was performed and wrapped with an omental pedicle flap in 4 of them (omentum group vs control group). PH-measurements of the mucosa were performed at 3 points of the circumference of the normal trachea as well as the transplant. The measurements were done immediately postoperative and at day 3, 8, 14 and 20 using a modified MI 506 pH-needle electrode with an Ag-AgCl skin reference electrode and a Fisher accumet pH-meter (model 910). After 3 weeks or at occurrence of a severe tracheal stenosis macroscopic and histologic examination of the trachea was done. All animals in the omentum group finished the study. One developed severe stenosis due to tracheal malacia. Three of the four control-dogs had a severe tracheal stenosis at day 12, 13 and 16 which necessitated termination of the experiment. The pH-difference between trachea and transplant immediately postoperative was 0.16 +/- 0.02 in the 4 dogs with healed transplants and 0.15 + 0.03 in the 4 dogs with stenosis due to chondromalacia. Follow-up measurements at day 3 and 8 showed a pH-difference of 0.2 for the group with chondromalacia vs. 0.1 for the healed tracheas (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗
Current status of lung transplantation.
Techniques and indications for single and bilateral lung transplantation have evolved significantly in the past several years. Lung transplantation has entered a new era in which transplantation can be achieved with the same degree of success as that achieved with other major organ transplants. Many problems, common to organ transplantation remain to be solved including availability of suitable donor organs, improved immunosuppressive regimens, and the ability to properly diagnose and effectively treat organ rejection.
Bacterial Infections↗
The evolution of single lung transplantation for emphysema. The Washington University Lung Transplant Group.
Classic transplantation dogma mandated bilateral lung replacement for lung transplant candidates with end-stage emphysema to avoid air trapping in the native lung and subsequent crowding of the newly transplanted lung. During a recent 12-month period 11 patients with emphysema received a single lung transplant. There was no hospital mortality and only one patient had any notable degree of air trapping in the native lung. Substantial improvement in pulmonary function was seen as early as 2 weeks after transplantation, with significant functional improvement seen by 6 weeks, despite some residual ventilation-perfusion mismatch. We have demonstrated the utility and safety of single lung transplantation for patients with end-stage emphysema, and it is our operation of choice in recipients more than 50 years of age.
Exercise Test↗
Influence of intraalveolar oxygen concentration on lung preservation in a rabbit model.
We previously reported the use of an inexpensive screening model for lung preservation involving ventilation and perfusion of excised rabbit lungs after their preservation. We now have extended this model by perfusing the preserved lung in cross circulation with an anesthetized rabbit to permit stable reperfusion of the preserved lungs for 60 minutes. With this model we compared the results of lung preservation with the lungs inflated with nitrogen, room air, or 100% oxygen during 24 hours of hypothermic storage. Four groups of animals were studied: group 1, excision and immediate evaluation; group 2, inflation with room air and storage for 24 hours at 10 degrees C; group 3, same as group 2, with 100% oxygen for inflation during storage; group 4, same as group 2, with 100% nitrogen for inflation during storage. Assessment of the ex vivo perfused lung consisted of (1) blood gas analysis of inflow and outflow blood at 10-minute intervals; (2) continuous pulmonary artery and airway pressure monitoring; (3) measurement of pulmonary venous oxygen tension after 1 hour of reperfusion, with inflow oxygen tension adjusted to 15 mm Hg; (4) wet/dry weight ratio. We conclude that the paracorporeal circuit does not, in itself, cause lung injury over a 1-hour period; lungs preserved with nitrogen inflation rapidly became edematous and failed to function on reperfusion. Preservation with 100% oxygen inflation appears superior to inflation with room air.
Animals↗
A reevaluation of heparin requirements for cardiopulmonary bypass.
We wished to determine if reduction in the standard heparin administration for cardiopulmonary bypass could be accomplished safely with the use of membrane oxygenators. An experimental study was designed to evaluate two different heparin administration protocols for cardiopulmonary bypass with hollow-fiber membrane oxygenators. Two groups of six pigs were submitted to hypothermic cardiopulmonary bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed after 1 hour. In group I (control) heparin was administered to maintain the activated clotting time in excess of 450 seconds; in group II activated clotting time was maintained between 250 and 300 seconds. The mean total heparin administered was 41,000 units in group I and 25,000 units in group II. Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet count were determined before, during, and 1 hour after bypass. No significant difference in any of these coagulation parameters was observed between the groups. The performance of the oxygenators was similar in both groups, with no evidence of thrombosis. Thus reduced heparin administration, enough to keep activated clotting time between 250 and 300 seconds, was not related either to major coagulation factors and platelet consumption or to derangements in the oxygenator's performance.
Animals↗
The prevalence and management of bronchial anastomotic complications in lung transplantation.
The prevalence and management of bronchial anastomosis complications have been assessed in a series of 53 patients undergoing lung transplantation. Of the 50 patients subsequently at risk of airway complications, these problems occurred in seven (14%). Only one patient died as a direct result of the airway complication (2%). Four patients required airway stenting, and their management is discussed. Although airway healing is normal in the majority of patients undergoing lung transplantation (86%), when deficits occur they can usually be successfully managed with conservative treatment. Bronchial stenting may be required on either a temporary or a permanent basis.
Adult↗
Results of single-lung transplantation for bilateral pulmonary fibrosis. The Toronto Lung Transplant Group.
Between November 1983 and August 1989, we performed single-lung transplantation for end-stage pulmonary fibrosis in 20 patients. Nine patients (45 percent) who survived for more than one year form the basis of this report. Before surgery, the nine survivors had severe restrictive lung disease, with a mean (+/- SD) vital capacity (VC) of 43 +/- 9 percent, a forced expiratory volume in one second (FEV1) of 50 +/- 9 percent, and a single-breath diffusing capacity (DLCO) of 36 +/- 9 percent of predicted values. One year after transplantation, the patients' VC had reached 69 +/- 10 percent, FEV1 79 +/- 15 percent, and DLCO 62 +/- 16 percent of predicted values. Relative perfusion to the transplanted lung rose from 63 +/- 14 percent (three days after surgery) to 77 +/- 7 percent within three months and stayed constant or increased slightly thereafter. Before surgery, despite supplemental oxygen at flow rates varying from 1 to 9 liters per minute, none of the patients could exercise beyond stage 1/2 (2.7 km [1.7 miles] per hour, 5 percent grade) on a modified Bruce treadmill-exercise protocol. All eight patients tested one year or more after transplantation achieved at least stage 1 (2.7 km [1.7 miles] per hour, 10 percent grade), and usually a higher stage, without supplemental oxygen. Arterial oxygen tension returned to normal values in most patients (87 +/- 13 mm Hg), and supplemental oxygen, which all patients required before surgery, was no longer needed by any patient after transplantation. We conclude that in carefully selected patients with end-stage pulmonary fibrosis, single-lung transplantation is an effective treatment.
Adolescent↗
Projections to the rostral reticular thalamic nucleus in the rat.
Afferent pathways to the rostral reticular thalamic nucleus (Rt) in the rat were studied using anterograde and retrograde lectin tracing techniques, with sensitive immunocytochemical methods. The analysis was carried out to further investigate previously described subregions of the reticular thalamic nucleus, which are related to subdivisions of the dorsal thalamus, in the paraventricular and midline nuclei and three segments of the mediodorsal thalamic nucleus. Cortical inputs to the rostral reticular nucleus were found from lamina VI of cingulate, orbital and infralimbic cortex. These projected with a clear topography to lateral, intermediate and medial reticular nucleus respectively. Thalamic inputs were found from lateral and central segments of the mediodorsal nucleus to the lateral and intermediate rostral reticular nucleus respectively and heavy paraventricular thalamic inputs were found to the medial reticular nucleus. In the basal forebrain, afferents were found from the vertical and horizontal limbs of the diagonal band, substantia innominata, ventral pallidum and medial globus pallidus. Brainstem projections were identified from ventrolateral periaqueductal grey and adjacent sites in the mesencephalic reticular formation, laterodorsal tegmental nucleus, pedunculopontine nucleus, medial pretectum and ventral tegmental area. The results suggest a general similarity in the organisation of some brainstem Rt afferents in rat and cat, but also show previously unsuspected inputs. Furthermore, there appear to be at least two functional subdivisions of rostral Rt which is reflected by their connections with cortex and thalamus. The studies also extend recent findings that the ventral striatum, via inputs from the paraventricular thalamic nucleus, is included in the circuitry of the rostral Rt, providing further evidence that basal ganglia may function in concert with Rt. Evidence is also outlined with regard to the possibility that rostral Rt plays a significant role in visuomotor functions.
Animals↗
Improved technique for bilateral lung transplantation: rationale and initial clinical experience.
We previously described a technique for en bloc double-lung transplantation that was initially applied to select patients with cystic fibrosis and emphysema. This procedure is quite complex and associated with several limitations, including a substantial incidence of airway ischemia, postoperative myocardial depression, and cardiac denervation. To address these problems we have developed a simpler procedure for replacing both lungs. The operation is done through a transverse thoracosternotomy and involves sequential replacement of the two lungs. Positive features include separate bronchial anastomoses to reduce ischemic airway complications, elimination of the need for total cardiopulmonary bypass and a period of ischemic cardiac arrest, improved exposure to reduce intraoperative and postoperative hemorrhage, and maintenance of cardiac innervation. Additionally, the technique can be more easily mastered and widely applied. Details of the procedure and its initial clinical application in 3 patients having emphysema, cystic fibrosis, and bronchiolitis obliterans following previous double-lung transplantation, respectively, are described. All 3 patients recovered without complication. Postoperative function was excellent in spite of lung ischemic times ranging up to 91/2 hours.
Adult↗