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Biomedical subjects

G A Patterson

Publications and source records attributed to G A Patterson.

At least 19 recordsLinked to original sources

Pericardial repair of a tracheal laceration during transhiatal esophagectomy.

Transhiatal esophagectomy has recently been popularized for both benign and malignant esophageal disease. While we were performing a transhiatal esophagectomy for a squamous cell cancer of the upper third of the esophagus, a tear in the membranous trachea near the carina occurred. This was repaired through the cervical incision with a free pericardial patch. This solution to a potentially catastrophic complication of transhiatal esophagectomy gave a satisfactory result without early or late postoperative respiratory complications.

Aged

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

Maximal exercise testing in single and double lung transplant recipients.

Patients with end-stage pulmonary and pulmonary vascular disease can now be offered single-lung (SLT), double-lung (DLT), or heart-lung (HLT) transplantation. Long-term survival with greatly improved pulmonary function has been reported with all three procedures. Little has been reported of the exercise capacity after transplantation. This report documents Stage 1 exercise test results in six SLT (five males and one female; age 50.7 +/- 4.4; FEV1.0 75.5 +/- 6.7% of predicted) and seven DLT (three males and four females; age 37.3 +/- 6.7; FEV1.0 85.1 +/- 10.3% of predicted) recipients, early (3 months) and late (1 to 2 yr) following transplantation. The results show low work rates and VO2max in both SLT and DLT recipients at 3 months after transplant. Heart rate and minute ventilation did not appear limiting. There was no significant improvement when retested 1 to 2 yr after transplant. At 3 months, VO2max was 46% of predicted for SLT and 50% of predicted for DLT recipients. It is concluded that considerable exercise limitation persists after transplantation and does not appear to improve with time. These limitations are similar for both SLT and DLT and are not related to ventilation. The results may suggest chronic muscle deconditioning after long-term pretransplant debilitation.

Adult

Physiologic studies of tracheobronchial stents in airway obstruction.

When airway obstruction is due to extraluminal compression and/or dynamic collapse, metal and silicone rubber prosthetic stents may stabilize the affected airway. Through a rigid bronchoscope, we inserted three metal stents in two patients and 18 silicone stents in 15 adult patients with symptomatic tracheobronchial compression and dynamic airway collapse. The underlying cause was malignancy in three patients; benign tracheobronchial malacia in three patients, two of whom refused surgical resection; and tracheobronchial stenosis that developed at the anastomotic site following lung transplantation in 11 patients. Clinical status and lung function studies were analyzed before and after stent insertion. Following stent insertion, airway diameter at least doubled and near normal patency of the affected tracheobronchial tree was achieved in every patient using stents of axial length 4 to 5 cm. The stents were well tolerated clinically, and all patients noted immediate relief of dyspnea. Following stent insertion, the forced vital capacity (FVC) increased from 64 +/- 21% predicted (mean +/- 1 SD) to 73 +/- 19% predicted, p less than 0.1; the forced expiratory volume in 1 s (FEV1) from 49 +/- 25% predicted to 72 +/- 26% predicted, p less than 0.02; the ratio of the FEV1/FVC from 59 +/- 16% to 78 +/- 15%, p less than 0.01; and the maximum flow at 50% expired FVC from 38 +/- 26% predicted to 72 +/- 31% predicted, p less than 0.01.

Adult

Hypercapnic ventilatory response in recipients of double-lung transplants.

Ten survivors of double lung transplantation using a tracheal anastomosis underwent assessment of their ventilatory responses to hypercapnia (HCVR) at least 3 months postsurgery. At the time of HCVR testing, pulmonary functions were normal in four and abnormal in six patients who demonstrated degrees of obstruction, restriction, or mixed defects. Arterial blood gas measurements were normal. Postoperatively, hypercapnic responses were low or low normal. Mean changes in tidal volume and mean change in respiratory frequency in response to hypercapnia postoperatively were not different in patients with normocapnic versus hypercapnic preoperative blood gases. Neither postoperative resting PCO2 nor muscle strength (as measured by MIP) were predictive of the degree or character of the patients' ventilatory responses to hypercapnia. The factors resulting in the observed blunting of the hypercapnic response in this denervated population require further clarification; however, comparison of data between this patient population and recipients of heart-lung transplantation reported elsewhere suggests that alterations in pulmonary function correlate with the observed depression in HCVR.

Carbon Dioxide

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

Infectious complications following isolated lung transplantation.

STUDY OBJECTIVE: To ascertain the incidence, types, morbidity, and mortality of infectious episodes in isolated lung transplant recipients. DESIGN: Retrospective chart review of patients who have undergone transplants over a six-year period in one institution. PATIENTS: Twenty-three single and 17 double lung transplants followed up between 2 and 68 months. RESULTS: Fifty-one episodes of infection occurred in the group with a slight predominance in the double lung transplants. The 32 episodes of bacterial infection constituted the largest group of infection and more than half of these were pneumonias. Organisms identified were predominantly Gram negative. While bacterial processes made up the bulk of infections, fatalities were rare. Viral and fungal infections were less common, but more often fatal. Of six cases of viral pneumonitis, two were fatal; two of five cases of invasive fungal infection were also fatal. Overall, six patients died of infection. CONCLUSION: Our findings support previous reports from heart-lung centers documenting a high rate of infectious complications, particularly pneumonia, in recipients of lung grafts. In our experience, bacterial infections are the most common (two of three infections), but have the lowest mortality. Efforts should be directed toward establishing effective prophylaxis programs and early detection of infection.

Bacteria

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

The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation.

We have previously demonstrated that a low-potassium dextran solution provides superior and more reliable preservation of lungs for 12 hours than that provided by the commonly used Euro-Collins solution. This study was designed to examine the individual contributions of dextran 40 and a low (extracellular) potassium concentration to lung preservation. In a randomized, blinded study using an in vivo canine single-lung transplant model, lungs preserved with low-potassium dextran solution (K+, 4 mmol/L; dextran 40, 20 gm/L) were compared to lungs preserved with low-potassium, no-dextran solution (K+, 4 mmol/L) and high-potassium dextran solution (K+, 123 mmol/L; dextran 40, 20 gm/L). The lungs were assessed immediately and 3 days after transplantation. The low-potassium dextran solution provided excellent immediate pulmonary function with little variability (arterial oxygen tension, 519 +/- 12 mm Hg, measured on the transplanted lung alone, inspired oxygen fraction = 1.0, n = 6). Removing the dextran 40 from the flush solution (low-potassium group) led to a significant deterioration in pulmonary function (arterial oxygen tension, 243 +/- 78 mm Hg, n = 6, p less than 0.01). The high-potassium dextran solution provided extremely poor preservation (arterial oxygen tension, 176 +/- 79 mm Hg; n = 6; p less than 0.01). Two animals in this group died within 6 hours of operation. Viability of the transplanted bronchus was significantly improved with the two solutions containing dextran 40. These results indicate that dextran 40 and low potassium concentration both contribute significantly to the uniformly excellent 12-hour lung preservation seen with the low-potassium dextran solution.

Animals

Improved lung preservation with dextran 40 is not mediated by a superoxide radical scavenging mechanism.

Improved lung preservation with a low-potassium dextran-containing solution has been previously demonstrated. In a subsequent study, it was shown that dextran 40 contributes significantly to this improved preservation. In the current in vitro study, human neutrophils suspended in lung preservation solutions (low potassium with dextran and low potassium without dextran) were stimulated to produce superoxide radicals. The presence of dextran in the solution did not significantly alter the amount of superoxide measured in the assay (low potassium with dextran, 4.149 +/- 0.144 nmol/10(6) cells/20 min; low potassium without dextran, 3.896 +/- 0.215; p greater than 0.2). This suggests that dextran 40 did not appreciably scavenge superoxide radicals, nor did it alter the production of superoxide radicals by stimulated neutrophils. Thus the significantly improved lung preservation seen with the use of dextran 40 is probably not mediated by a superoxide radical scavenging process.

Dextrans

The effect of basic fibroblast growth factor and omentopexy on revascularization and epithelial regeneration of heterotopic rat tracheal isografts.

Donor airway ischemia is a significant problem after clinical lung transplantation despite the use of omentopexy for accelerated local bronchial revascularization. Several growth factors have been shown to induce angiogenesis in vitro and in vivo. In the present study the quantitative effects on tracheal revascularization and epithelial regeneration of omentopexy and continuous local administration of basic fibroblast growth factor were investigated in a heterotopic rat tracheal isograft model. Tracheas were harvested from donor rats and heterotopically implanted into the omentum of syngeneic recipient rats. Animals were randomly assigned to study groups differing only in treatment of the tracheal segments: omental wrap for 2, 7, or 14 days; omental wrap plus continuous local administration of basic fibroblast growth factor for 7 or 14 days; or omental wrap plus local application of saline for 7 or 14 days. Two, 7, or 14 days after the animals were put to death, the vascularity of the tracheal segments and attached omentum and the tracheal epithelial morphology were assessed in a blinded fashion with use of light microscopy and morphometric image analysis. Vascularity in tracheal segments treated with basic fibroblast growth factor was significantly (p less than 0.05) greater than in control tracheas after 7 and 14 days. Epithelial regeneration was also improved in the basic fibroblast growth factor-treated groups at days 7 and 14 (p less than 0.05). We conclude that continuous local administration of basic fibroblast growth factor enhances early revascularization of tracheal segments induced by omentopexy and accelerates epithelial regeneration in a heterotopic rat tracheal isograft model.

Animals

Equivalent eighteen-hour lung preservation with low-potassium dextran or Euro-Collins solution after prostaglandin E1 infusion.

Improved techniques of pulmonary preservation would help alleviate the critical shortage of donor organs in lung transplantation and would improve early graft function. A previous study demonstrated that cold pulmonary artery flush with low-potassium dextran solution was superior to Euro-Collins solution in preservation of canine lung allografts stored for 12 hours when no pulmonary vasodilator was used before donor lung flush. The present study was designed to determine whether donor pretreatment with prostaglandin E1 would affect the superiority of low-potassium dextran as a preservation solution. Prostaglandin E1 was infused (50 micrograms/min) in 12 donor dogs until potent vasodilation was demonstrated. Low-pressure pulmonary artery flush (50 ml/kg) with either Euro-Collins or low-potassium dextran solution (n = 6 for each group) was performed at 4 degrees C in a randomized, blinded fashion. Heart-lung blocks were extracted and stored at 4 degrees C for 18 hours before left lung allografting. Inflatable cuffs were placed around each pulmonary artery, allowing independent study of the native and transplanted lungs. All 12 recipient dogs survived the 3-day assessment period. Lungs flushed and stored in Euro-Collins or low-potassium dextran solution provided equivalent gas exchange function on day 0 (arterial oxygen tension: Euro-Collins 289 +/- 105 mm Hg versus low-potassium dextran 265 +/- 111 mm Hg; mean +/- standard error of the mean) and on day 3 (Euro-Collins 516 +/- 45 mm Hg versus low-potassium dextran 354 +/- 77 mm Hg; p = 0.10). Mean pulmonary artery pressures in the transplanted lung were not significantly different in the Euro-Collins and low-potassium dextran groups on day 0 (21.4 +/- 2 mm Hg versus 33.7 +/- 5 mm Hg, respectively; p = 0.09) or on day 3 (20.2 +/- 2.7 mm Hg versus 24.2 +/- 5.1 mm Hg, respectively; p = 0.50). We conclude that there was no advantage of low-potassium dextran over Euro-Collins as a flush solution in this 18-hour canine single lung allograft model in which prostaglandin E1 was administered before pulmonary artery flush.

Alprostadil

Reliable thirty-hour lung preservation by donor lung hyperinflation.

We examined the hypothesis that the degree of inflation of the lungs at the time of harvest may have an important role in postpreservation function. Lungs of donor dogs randomly assigned to groups 1 (n = 5) and 2 (n = 5) were ventilated with large tidal volumes (tidal volume, 25 ml/kg; positive end-expiratory pressure, 5 cm H2O; respiratory rate, 12 breaths/min, inspired oxygen fraction 1.0) and were inflated to 30 cm H2O for 15 seconds before pulmonary artery flush and again immediately before tracheal crossclamping. In group 3 (n = 5) donor lungs were normally ventilated (tidal volume, 12.5 ml/kg, positive end-expiratory pressure 0 cm H2O; respiratory rate 12 breaths/min, inspired oxygen fraction, 1.0) and were not hyperinflated before pulmonary artery flushing; the trachea was crossclamped at end-inspiration. In groups 1 and 3 a large bolus (25 micrograms/kg) of prostaglandin E1 was injected into the pulmonary artery before flushing and was also added to the pulmonary artery flush solution (500 micrograms/L). A rapid (approximately 50 seconds), high-volume mm Hg), hypothermic (4 degrees C) pulmonary artery flush was performed in all hypothermic (4 degrees C) pulmonary artery flush was performed in all groups with modified Euro-Collins solution. Heart-lung blocks were stored at 4 degrees C for approximately 29 hours before left single lung allografting. An inflatable cuff was placed around the recipient right pulmonary artery, allowing independent study of the transplanted lung. Hyperinflated lungs harvested with or without prostaglandin E1 provided equivalently excellent early posttransplant function (arterial oxygen tension [mean +/- standard deviation]: group 1; 503 +/- 45, vs group 2; 529 +/- 150 mm Hg; inspired oxygen fraction 1.0). Mean arterial oxygen tension was significantly lower in group 3 (116 +/- 78 mm Hg) than in either groups 1 or 2 (p < 0.0002 for either comparison). Copious reperfusion pulmonary edema was a constant feature in group 3 but was not seen in groups 1 and 2. All 10 recipients in groups 1 and 2 survived the 3-day assessment period without difficulty; two of the five recipients in group 3 died during initial unilateral perfusion of the transplanted lung. Donor hyperventilation and inflation to 30 cm H2O before hypothermic storage can help provide excellent posttransplantation lung function after 30-hour preservation, with or without prostaglandin E1 pretreatment. We speculate that this improvement may be due to effects of increased lung volume on pulmonary vascular tone and/or surfactant metabolism.

Alprostadil

Isolated lung transplantation.

A clinical reality since 1981, lung transplantation is now generally accepted as a useful procedure for patients with end-stage lung disease. Early attempts at lung transplantation were marked by infection, rejection, and, in particular, bronchial dehiscence. Obliterative bronchiolitis, an airway-targeted form of chronic rejection, continues to be a problem. It is associated with all types of lung transplantation and is an important cause of late death. In the past few years advances in surgical technique, organ preservation and postoperative management have all contributed to improved survival and preservation of lung function. The shortage of suitable organ donors remains the limiting factor in clinical programs worldwide and curtails more widespread application of lung transplantation.

Humans

Thymomas.

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Humans