Naturally acquired babesiosis in a reindeer (Rangifer tarandus tarandus) herd in Great Britain.

A provisional diagnosis of babesiosis was made in a reindeer herd in Scotland when seven animals died during 1997 and 1998. Additional clinical cases occurred, but the animals recovered after treatment. Thirty-one reindeer from the herd were tested for the prevalence of exposure to Babesia by the indirect fluorescent antibody test using a bovine isolate of Babesia divergens that had been passaged through gerbils. Infection rates were determined by Giemsa-stained blood smears. In addition, molecular identification of the infecting Babesiasp. was undertaken using SSU rRNA gene sequence analysis. It is likely that the organism causing babesiosis in this reindeer herd is B. divergens.

A prospective trial of inhaled nitric oxide in clinical lung transplantation.

BACKGROUND: Reperfusion injury (RI) is a major cause of mortality and morbidity among lung transplant recipients. We sought to determine if prophylactic administration of inhaled nitric oxide (NO) to lung transplant recipients at reperfusion would prevent RI. We also hypothesized that if prophylactic NO proves ineffective in preventing RI then it may improve pulmonary hemodynamics and gas exchange in the subset of patients who develop RI. METHODS: After informed consent, 28 consecutive, adult lung transplant recipients received NO at 20 ppm at reperfusion. NO was withdrawn for 15 min at 6 and 12 hr after reperfusion, and gas exchange and hemodynamics were measured. RESULTS: Five of the 28 lung transplant recipients (18%) developed RI. Withdrawal of NO for 15 min in this subset of patients resulted in a significant rise in mean pulmonary artery pressure and a reduction in oxygenation index. All five patients with RI were kept on inhaled NO until full functional recovery of the allograft and were then weaned from mechanical ventilation. None required extracorporeal membrane oxygenation support; the early mortality in this group was 20% (1/5). The remaining 23 patients without RI had uneventful early postoperative course and were weaned from NO and mechanical ventilation within 36 hr of transplantation. CONCLUSIONS: Prophylactic-inhaled NO does not prevent RI in human lung transplantation. However, inhaled NO, started at reperfusion, improves gas exchange and reduces pulmonary artery pressure in those patients who develop RI.

Lung volume reduction surgery: a cost and outcomes comparison of sternotomy versus thoracoscopy.

It remains unknown whether it is better to perform lung volume reduction surgery (LVRS) through video-assisted thoracoscopy (VATS) or sternotomy. This study compares both approaches in terms of surgical and patient outcomes as well as the associated costs. All patients undergoing LVRS from 1995 to 1997 at one institution by a single surgeon (PFW) were investigated. Preoperative, postoperative, and cost data were obtained from medical and financial records. A total of 42 patients with severe emphysema underwent LVRS (19 via sternotomy and 23 via thoracoscopy). Both groups were comparable preoperatively. Comparison of intraoperative times revealed VATS takes longer to perform (sternotomy, 118 +/- 29 minutes; thoracoscopy, 168 +/- 20 minutes). Postoperatively, the sternotomy patients had more days on the ventilator, more days in the intensive care unit, more days with an air leak, and longer hospital stays. In both groups, the majority of patients reported improvement in oxygen dependence as well as quality of life. Neither surgical approach conferred any long-term medical advantage; however, the average total hospital costs and charges were reduced in the VATS group (average cost: VATS, $27,178; sternotomy, $37,299). This study concludes that 1) LVRS seems to be beneficial for selected patients with end-stage emphysema; 2) postoperative morbidity and length of hospital stay are decreased in the VATS group; 3) long-term improvement in postoperative pulmonary function is not influenced by surgical approach; and 4) the overall charges and costs of the VATS approach is less than that of sternotomy.

Mycophenolate mofetil versus azathioprine immunosuppressive regimens after lung transplantation: preliminary experience.

BACKGROUND: Mycophenolate mofetil reduces episodes of biopsy-proven acute cellular rejection or treatment failure in the first year after kidney transplantation; however, limited data exist regarding the efficacy after lung transplantation. METHODS: In a 2-center, nonrandomized concurrent cohort study (level III evidence), we analyzed the incidence of biopsy-proven acute cellular rejection (International Society for Heart and Lung Transplantation grade > or=A2) and decrement in pulmonary function during the first 12 months after successful lung transplantation. All patients received induction immunosuppression with antithymocyte globulin (< or=5 days' duration), cyclosporine and prednisone, in addition to either mycophenolate mofetil (2.0 g/d) [n=11] or azathioprine (1 to 2 mg/kg per day) [n=11]. RESULTS: During the first 12 months after lung transplantation, the mycophenolate mofetil group experienced significantly fewer episodes of acute cellular rejection than the azathioprine group (0.26+/-0.34 vs 0.72+/-0.43 episodes/100 patient-days [mean+/-SD], p < 0.01; 95% CI for the difference=0.126 to 0.813). The change in forced expiratory volume -1 second [deltaFEV1] (liters) between the 3rd and 12th months after lung transplantation was analyzed for the two treatment groups. For this interval, deltaFEV1 for the mycophenolate mofetil group was +0.158+/-0.497 L vs -0.281+/-0.406 L for the azathioprine group (p < 0.05; 95% CI for difference=+0.0356 to 0.843). During the first year, there was 1 death in each group attributed to bronchiolitis obliterans syndrome with concurrent pneumonia. There were no differences in incidence of cytomegalovirus or bacterial infections between the treatment groups; however, a higher prevalence of aspergillus sp airway colonization in bronchoalveolar lavage fluid was observed for the mycophenolate mofetil group (p < .05). The prevalence of bronchiolitis obliterans syndrome at 12 months was 36% for the azathioprine group vs 18% for the mycophenolate mofetil group (p=NS). CONCLUSIONS: Our preliminary experience with mycophenolate mofetil after lung transplantation suggests a decreased incidence of biopsy-proven acute cellular rejection. Furthermore, less decline in FEV1 after 12 months may suggest a reduced incidence or delayed onset for development of bronchiolitis obliterans syndrome. Prospective randomized trials with low beta error (level I evidence) should be performed to assess the efficacy of mycophenolate mofetil vis-à-vis acute allograft rejection and bronchiolitis obliterans syndrome.

Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model.

BACKGROUND: Hypothermia is critical for proper lung preservation. Ideally, the lungs should be maintained at the optimal preservation temperature during the entire ischemic interval. Lung rewarming during implantation is commonly observed. This study was undertaken to investigate the severity of rewarming ischemia on preservation injury and the possibility of minimizing this by use of leukocyte depletion during initial reperfusion. METHODS: Four experimental groups were tested as follows: neonatal piglet heart-lung blocks were either (1) placed on an isolated, blood-perfused, working heart-lung circuit without intervening ischemia (control, n = 6), (2) reperfused on the circuit with whole blood (WB, n = 6) after 13 hours of preservation, (3) reperfused with WB after 12 hours of preservation and 1 hour of rewarming (RWB, n = 5), or (4) reperfused with leukocyte-depleted blood for an initial 10 minutes followed by WB, after 12 hours of preservation and 1 hour of rewarming (n = 6). All groups were studied for 4 hours. RESULTS: The partial pressure of arterial oxygen and lung compliance were significantly lower in the RWB group than in controls (113.8+/-33.1 vs 417.3+/-6.2 mm Hg, p < 0.01; and 0.8+/-0.2 vs 2.9+/-0.4 ml/cm H2O, p < 0.05, respectively). Pulmonary vascular resistance and lung wet/dry weight ratios were significantly higher in the RWB group than in controls (15884.1+/-11354.8 vs 6108.3+/-1309.9 dyne x sec x cm[-5], p < 0.05; and 7.13+/-0.24 vs 5.82+/-0.35, p < 0.05, respectively). The WB and leukocyte-depleted groups did not differ significantly from controls for any measured parameter. CONCLUSIONS: This model confirms that rewarming ischemia during lung implantation exacerbates reperfusion injury. Leukocyte-depleted reperfusion as tested for a short period of time (10 minutes) ameliorates this injury and therefore should be considered for clinical lung transplantation.

L-arginine administration during reperfusion improves pulmonary function.

BACKGROUND: Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of L-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury. METHODS: Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing L-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6). RESULTS: The partial pressure of oxygen in the whole blood group (113.8 +/- 33.1 mm Hg) was significantly less than in controls (417.3 +/- 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 +/- 0.2 mL/cm H2O) than in controls (2.9 +/- 0.4 mL/cm H2O; p < 0.01). The L-arginine and leukocyte-depleted blood groups showed no significant difference from controls. CONCLUSIONS: L-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.

Immunocytologic analysis of cells obtained from bronchoalveolar lavage in a model of rat lung allograft rejection.

Left lung transplantation (n = 30) between BN rat (RT1n) and LEW rat (RT1(1)) was performed to examine serial changes in the inflammatory cell profile and T-cell subsets occurring in bronchoalveolar lavage (BAL) obtained after transplantation. Transplanted animals were sacrificed on Days 1 to 7 post-transplantation. Previous studies show that lung allografts between these rat strains were strongly rejected within 7 days. The serial change in the cell profile of BAL showed a marked initial predominance of polymorphonuclear leukocytes, a decrease in macrophages, and a temporary increase in number of eosinophils on Day 2 post-transplantation. A gradual increase in lymphocytes coincident with progression of rejection was also noted. Immunocytologic studies using monoclonal antibodies specific for rat T-cell subsets and interleukin-2 receptor (IL-2R) showed significant increase in pan-T-cells on Days 3, 4, and 5 and T-suppressor/cytotoxic (CD8 positive) fraction on Days 4 and 5, whereas the T-helper (CD4 positive) fraction peaked on Day 2. The frequency of T-cells expressing IL-2R (55 kDa), indicating activated T-cells, significantly increased as early as Day 2 and maintained its high value thereafter. mRNA levels for IL-2R were detectable in the allografts on Day 2 and peaked on Day 5 post-transplantation. The value of CD4/CD8 T-cell ratios rose initially and then dropped below 1.0 on Days 4 and 5. These values differed markedly from those of syngeneic transplants (Lew-->Lew) examined on Day 5 post-transplantation. First, no significant changes in BAL cytology were seen when syngeneic transplants were compared with normal (Lew) lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional distribution of lung perfusion and ventilation at rest and during steady-state exercise after unilateral lung transplantation.

Cardiopulmonary exercise testing has previously demonstrated a reduced maximum oxygen uptake and anaerobic threshold, as well as abnormal wasted ventilation fraction and gas exchange after unilateral lung transplantation. To further explain the mechanisms of these abnormalities, we assessed the regional distribution of pulmonary blood flow and ventilation at rest and during steady-state exercise in nine recipients of unilateral lung transplants. Krypton-81 (81mKr) aerosol and technetium-99m (99mTc) were utilized to assess lung ventilation (V) and perfusion (Q), respectively. The digitalized images were trisected to analyze apical, mid-, and basilar lung perfusion and ventilation in both the transplanted and native lung, both at rest and steady-state upright exercise. Results were compared with previously reported data obtained in normal subjects in our laboratory using the identical technique. At rest, 75 +/- 13 percent of perfusion was directed to the transplanted lung; however, the corresponding fractional ventilation was only 67 +/- 14 percent. During exercise, there was no significant change in fractional perfusion or ventilation. Resting apical perfusion in the transplanted lung was higher than normal in four patients and comparable to normal in five patients. In contrast to the augmentation of apical perfusion observed in normal subjects during upright exercise, none of our patients increased the regional perfusion to the apices during exercise in either transplanted or native lungs. These unexpected responses suggest either more maximal allograft apical recruitment at rest due to the increased allograft perfusion or an abnormality in the apical pulmonary vasculature after transplantation. Furthermore, the relative mismatch in ventilation and perfusion in transplanted and native lungs suggests regions of high V/Q in the native, and low V/Q in the transplanted lung. This mismatch is most pronounced in recipients of single lung transplants for pulmonary vascular disease.

Hemodynamic responses to exercise after lung transplantation.

A reduced exercise tolerance, maximum oxygen uptake (VO2max), and anaerobic threshold have been reported after lung transplantation (LT). We prospectively assessed the hemodynamic responses to incremental cycle ergometry before and after LT in eight recipients. All recipients underwent a 6-week formal exercise training program. The VO2max increased after versus before LT (13.4 +/- 0.8 vs 9.2 +/- 0.8 ml/min/kg) (p < 0.01). No transition thresholds by analysis of arterial standard bicarbonate were discerned before LT, while the thresholds after LT were abnormally low (VO2 = 9.4 +/- 0.6 ml/min/kg or 35 +/- 3 percent of predicted maximum VO2). An early rise in arterial lactate was similarly observed after LT. Maximum stroke volume index increased in six of seven patients after versus before LT (51 +/- 4 vs 37 +/- 2 ml/beat/m2) (p < 0.05). Three patients demonstrated an increased mean pulmonary arterial pressure at rest, while pressures during exercise were elevated in six. Pulmonary vascular resistance was mildly elevated after LT but decreased appropriately during incremental exercise and was associated with normal cardiac output responses. We conclude that pulmonary vascular abnormalities occurred during hemodynamic exercise testing in the majority of LT recipients; however, exercise limitation was primarily attributed to cardiovascular limitation or to deconditioning in five of the recipients. In the remaining three, the exercise study was considered to be submaximal by virtue of low peak heart rates. A persistent state of deconditioning may have important implications with respect to exercise training regimens after LT.

Serum interleukin-2 levels in lung transplant recipients: correlation with findings on transbronchial biopsy.

Serum interleukin-2 (IL-2) levels were examined in the serum of 17 lung transplant recipients who underwent transbronchial biopsies to diagnose reasons for allograft dysfunction. Over 60 transbronchial biopsies were performed in these 17 patients in a 22-month observation period. Mean serum IL-2 levels were significantly elevated in patients experiencing allograft rejection (p less than 0.01), cytomegalovirus pneumonia (p less than 0.0006), and bacterial/fungal pneumonia (p less than 0.01), when compared with those with normal or nondiagnostic findings on transbronchial biopsies. Serum IL-2 levels were not extraordinarily elevated as seen in other types of allograft rejection and did not differentiate between infection and rejection. In addition, overlapping values were seen in the patient groups tested. Despite these limitations, elevated serum IL-2 levels in lung allograft recipients may provide supplemental information helpful in deciding when to perform transbronchial biopsies.

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.

Vascular rejection and graft eosinophilia in rat lung allografts.

Allogeneic lung transplantation was performed using a rat model in order to assess the pathologic changes that developed during the process of rejection. The left lungs of 38 BN rats (RT-1n) were orthotopically transplanted into LEW rats (RT-1). The allografts developed the well-known changes of perivascular, peribronchial, and interstitial lymphocytic infiltrates resulting in necrosis of the pulmonary parenchyma at 7-8 days after transplantation. In addition, we document two findings that have not been reported previously in lung transplantation: vasculitis and eosinophilic infiltrates. Vasculitis with swelling and vacuolization of the endothelial cells was observed in transplants as early as 3 days following transplantation. Vasculitis with fibrinoid necrosis of the vessel wall was prominent at 7-8 days after grafting. The allografts also exhibited eosinophilia at 2 to 4 days following transplantation. The density of eosinophils in the inflammatory infiltrate reached a peak of 20% on Day 3 post-transplantation. These findings suggest an important role of humoral immunity and a possible involvement of eosinophils in lung allograft rejection.

Technique of successful clinical double-lung transplantation.

Lung transplantation has become a successful method in the therapy for end-stage pulmonary disease. While single-lung transplantation provides benefit to patients with pulmonary fibrosis, bilateral lung transplants are required for septic or emphysematous lung disease. We describe the technique employed in 6 patients to transplant en bloc both lungs with the recipient heart left in place. The lungs are connected by a left atrial cuff, main pulmonary artery, and trachea. The completed implantation has a tracheal anastomosis securely wrapped in omentum, a left atrial anastomosis posterior to the heart, and a pulmonary artery anastomosis anteriorly. Airway ischemia resulted in the death of 1 patient. This procedure allows complete excision of all diseased pulmonary tissue, retention of the recipient's own heart, and separate excision of the donor heart for use in another recipient, thereby markedly increasing the supply of donor lungs for transplantation.

Esophagectomy for complex benign esophageal disease.

We evaluated the use of total thoracic esophagectomy and replacement with stomach in a group of 21 patients between 1976 and 1986 who had undergone multiple unsuccessful esophageal operations. All patients had between one and four unsuccessful operations for benign esophageal disorders. Sixteen patients had primary motor disorders: achalasia in nine and esophageal spasm in seven. Of these patients, 11 also had recurrent gastroesophageal reflux and peptic esophagitis. Complicated reflux disease characterized by severe esophagitis, stricture, and impaired peristalsis without primary motor disorder occurred in five patients. In one patient a functionally impaired long-segment colon interposition was removed and replaced with stomach. Total thoracic esophagectomy and cervical esophagogastric reconstruction was done in all patients. The transhiatal approach was chosen for resection in 16 patients and thoracotomy was used in the other five. There was one perioperative death (5%), from massive aspiration 4 days after transhiatal esophagectomy. Other complications included transient anastomotic leak (three patients), tracheoesophageal fistula (one), recurrent nerve palsy (one), and transient hoarseness (two). Follow-up is complete between 1 and 10 years and reveals the following functional results: 12 patients good to excellent, seven fair, one poor. In this patient group in which multiple prior procedures have failed to improve severe incapacitating symptoms, we believe further attempts at hiatal reconstruction are unlikely to succeed. For this circumstance, we recommend total thoracic esophagectomy with the use of stomach as the replacement organ of choice.

Extended cervical mediastinoscopy. A single staging procedure for bronchogenic carcinoma of the left upper lobe.

Despite a common misconception, bronchogenic carcinoma of the left upper lobe frequently metastasizes to lymph nodes not only in the anterior mediastinum (para-aortic and subaortic) but also in the superior mediastinum. Anterior (parasternal) mediastinotomy can be used to assess only the former compartment. This procedure alone, if not done in conjunction with standard cervical mediastinoscopy, will fail to disclose technically unresectable N2 or N3 disease of the left upper lobe involving the superior mediastinum. We have developed a technique to explore and sample nodes from both regions by extending a standard cervical mediastinoscopy, eliminating the need for a second incision when the anterior mediastinal compartment requires assessment. We have prospectively analyzed the first 100 procedures that we performed. This technique has been found to be accurate and exceptionally safe with one superficial wound infection as the only complication. We can recommend this single staging procedure for preoperative assessment of bronchogenic carcinomas of the left upper lobe.