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Biomedical subjects

W Weder

Publications and source records attributed to W Weder.

At least 55 records · Page 3Linked to original sources
PubMed1999

Efficacy and cost effectiveness of oral ganciclovir in the prevention of cytomegalovirus disease after lung transplantation.

BACKGROUND: Cytomegalovirus is the single most frequent pulmonary pathogen in lung transplant recipients who survive at least 2 weeks. Patients at increased risk are either seropositive or have received an allograft from a donor with latent infection. Morbidity and mortality caused by cytomegalovirus disease is still considerably high. METHODS: In an open, comparative study, we evaluated the efficacy, tolerance, and cost effectiveness of postoperative ganciclovir prophylaxis: intravenous dose of 2x5 mg/kg/day for 14 days, followed by either intravenous doses of 5 mg/kg]day (five patients), or oral doses of 3x 1000 mg (nine patients) up to 90 days. Oral ganciclovir was continued until prednisone was tapered below 15 mg/day. Prophylaxed groups were compared with a historical control (eight patients) in respect to cytomegalovirus disease, in-hospital stay, overall costs, and survival. Follow-up times and the net state of immunosuppressive therapy between groups were comparable. RESULTS: Six (75%) of the non-prophylaxed patients developed cytomegalovirus disease compared to none in the intravenous and one in the oral ganciclovir group (P=0.013). The non-prophylaxed patients had a longer cytomegalovirus-related in-hospital stay (P=0.018) and nonsignificantly higher cytomegalovirus-related costs. Bronchiolitis obliterans syndrome was less frequent with prophylaxis (P=0.039), and survival tended to be better (P=0.072). The only adverse effect was a subclavian vein thrombosis in the intravenous ganciclovir group. CONCLUSIONS: In lung transplant recipients, ganciclovir prophylaxis, either intravenous or oral, is safe, well tolerated, and effective in preventing cytomegalovirus disease. Moreover, ganciclovir prophylaxis seems likely to reduce the incidence of bronchiolitis obliterans syndrome. The oral formulation might be preferable because its convenience and possibly lower costs.

Administration, Oral↗
PubMed1999

Practicability and safety of dipyridamole cardiac imaging in patients with severe chronic obstructive pulmonary disease.

We tested the practicability of dipyridamole myocardial nitrogen-13 ammonia positron emission tomography (dipyridamole (13)NH(3 )PET) for the perioperative risk assessment of coronary artery disease (CAD) in a cohort of patients with severe chronic obstructive pulmonary disease (COPD) undergoing lung volume reduction surgery (LVRS). Twenty consecutive LVRS candidates, 13 men and 7 women (mean age 57+/-2 years), without symptoms of CAD were prospectively studied by dipyridamole (13)NH(3 )PET. Side-effects and overall tolerance were assessed by a questionnaire and visual analogue scale. Repeated pulmonary function tests were performed before and 4, 12, 16 and 30 minutes after dipyridamole injection. All dipyridamole (13)NH(3 )PET studies were negative for CAD. Seventeen patients underwent LVRS without cardiac complications; three patients did not undergo LVRS for other reasons. Nine patients suffered intolerable dyspnoea requiring i.v. aminophylline. Mean FEV(1) decreased significantly after dipyridamole infusion: in nine patients the reduction in FEV(1)exceeded 15% from baseline. We found that dipyridamole is not well tolerated and causes significant bronchoconstriction in patients with severe COPD. Although all dipyridamole-induced side effects can be promptly reversed by aminophylline, dipyridamole cannot be recommended as a pharmacological stress in this setting.

Ammonia↗
PubMed1999

8-Br-cGMP is superior to prostaglandin E1 for lung preservation.

BACKGROUND: Substitution of the nitric oxide (NO) pathway reduces ischemia/reperfusion injury after lung transplantation. 8-Br-cGMP is a membrane-permeable analogue of cGMP, the second messenger of NO. In this study, we evaluated the effect of administration of 8-Br-cGMP in the flush solution on early graft function. METHODS: Unilateral left lung transplantation was performed in 10 weight-matched pairs of outbred pigs (24 to 31 kg). Donor lungs were flushed with 1.5 L cold (1 degree C) low potassium dextrane (LPD) solution and preserved for 20 hours. In group I (n = 5), 8-Br-cGMP (1 mg/kg) was added to the flush solution. In group II (n = 5), 8 microg/kg prostaglandin E1 (PGE1) was injected into the pulmonary artery (PA) before flush. One hour after reperfusion, the recipients' contralateral right PA and bronchus were ligated to assess graft function only. cGMP levels in the PA and pulmonary vein were measured. Extravascular lung water index (EVLWI), pulmonary vascular resistance, mean PA pressure, and gas exchange (PaO2) were assessed during a 5-hour observation period. Lipid peroxidation (thiobarbituric acid-reactive substance) and neutrophil migration to the allograft (myeloperoxidase activity) were measured at the end of the assessment. RESULTS: In group I, a significant reduction of EVLWI (group I, 6.7 +/- 1.0 mL/kg vs group II, 10.1 +/- 0.6 ml/kg after 2 hours of reperfusion; p = 0.022), TBARS (group I, 65.6 +/- 10.0 pmol/g vs group II, 120.8 +/- 7.2 pmol/g, p = 0.0039), and MPO activity (group I, 0.8 +/- 0.1 change in optical density, (deltaOD)/mg/min vs group II, 1.7 +/- 0.3 deltaOD/mg/min, p = 0.036) was noted in comparison with group II. PaO2 levels tended to be higher in cGMP-treated animals, but the changes were not significant. Hemodynamic parameters did not differ between groups. CONCLUSIONS: In this large animal model of lung allograft ischemia/reperfusion injury, 8-Br-cGMP as additive to the flush solution improves posttransplant lung edema, lipid peroxidation, and neutrophil migration to the allograft. This effect is not attributable to improved flush by vasodilation, as we compared 8-Br-cGMP with PGE1 given before flush in control animals.

Alprostadil↗
PubMed1999

Two years' outcome of lung volume reduction surgery in different morphologic emphysema types.

BACKGROUND: Lung volume reduction surgery (LVRS) improves dyspnea, pulmonary function, and quality of life in selected patients with severe emphysema. We investigated the role of emphysema morphology in 37 patients as an outcome predictor for up to 2 years after operation. METHODS: Patients selected for bilateral thoracoscopic LVRS were divided, according to a simplified emphysema morphology classification, into three groups (homogeneous, moderately heterogeneous, and markedly heterogeneous) based on a preoperative chest computed tomogram. Pulmonary function, walking distance, and dyspnea were assessed. RESULTS: Functional improvement after LVRS was best in markedly heterogeneous emphysema with an increase from preoperative forced expiratory volume in 1 second of 31% +/- 2% (mean +/- standard error of the mean) to 52% +/- 4% of predicted postoperatively. It was significantly higher than in homogeneous emphysema (from 26% +/- 1% to 38% +/- 2% predicted) and in intermediately heterogeneous emphysema (from 29% +/- 2% to 44% +/- 45% predicted). At 24 months postoperatively, forced expiratory volume in 1 second and dyspnea score continued to be significantly better than preoperative levels in all three morphologic groups. The survival rate was highest in patients with markedly heterogeneous emphysema. CONCLUSIONS: Functional and subjective improvements were maintained after LVRS for at least 24 months in patients with heterogeneous or homogeneous emphysema type.

Adult↗
PubMed1999

The nitric oxide synthase cofactor tetrahydrobiopterin reduces allograft ischemia-reperfusion injury after lung transplantation.

OBJECTIVE: Exogenous nitric oxide reduces ischemia-reperfusion injury after solid organ transplantation. Tetrahydrobiopterin, an essential cofactor for nitric oxide synthases, may restore impaired endothelium-dependent nitric oxide synthesis. We evaluated whether tetrahydrobiopterin administration to the recipient attenuates lung reperfusion injury after transplantation in swine. METHODS: Unilateral left lung transplantation was performed in 15 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.5 L cold (1 degrees C) low-potassium-dextran solution and preserved for 20 hours. Group I animals served as controls. Group II and III animals were treated with a bolus of tetrahydrobiopterin (20 mg/kg). In addition, in group III a continuous infusion of tetrahydrobiopterin (10 mg/kg per hour over 5 hours) was given. One hour after reperfusion, the recipient right lung was occluded. Cyclic guanosine monophosphate levels were measured in the pulmonary venous and central venous blood. Extravascular lung water index, hemodynamic variables, lipid peroxidation, and neutrophil migration to the allograft were assessed. RESULTS: In group III a significant reduction of extravascular lung water was noted in comparison with the controls (P =.0047). Lipid peroxidation in lung allograft tissue was significantly reduced in group II (P =.0021) and group III ( P =. 0077) in comparison with group I. Pulmonary venous levels of cyclic guanosine monophosphate increased up to 23 +/- 1 pmol/mL at 5 hours in group II and up to 40 +/- 1 pmol/mL in group III (group I, 4.1 +/- 0.5 pmol/mL [I vs III]; P <.001), whereas central venous levels of cyclic guanosine monophosphate were unchanged in all groups. CONCLUSION: Tetrahydrobiopterin administration during lung allograft reperfusion may reduce posttransplantation lung edema and oxygen-derived free radical injury in the graft. This effect is mediated by local enhancement of the nitric oxide/cyclic guanosine monophosphate pathway.

Animals↗
PubMed1999

Donor and recipient treatment with the Lazaroid U-74006F do not improve post-transplant lung function in swine.

OBJECTIVE: U-74006F is the only Lazaroid which is currently in clinical use. A number of experimental studies demonstrate that Lazaroids reduce ischemia/reperfusion injury in various organ systems. We evaluated the effect of U-74006F on reperfusion injury in a large animal model of lung allo-transplantation. METHODS: Two different treatment modalities were evaluated and compared with corresponding control groups. Unilateral left lung transplantation was performed in 21 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.51 cold (1 degrees C) LPD solution and preserved for 20 h. In group I (n = 5), donor animals were pretreated with U-74006F (10 mg/ kg i.v.) 20 min before harvest. In addition U-74006F was added to the flush solution (10 mg/l). In group III (n = 6), the Lazaroid was given to the donor before flush and to the recipient before reperfusion (3 mg/kg i.v.). Group II and IV (n = 5) served as control. One hour after reperfusion, the recipient contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), mean pulmonary artery pressure, cardiac output, and gas exchange were assessed during a 5 h observation period. Lipid peroxidation (TBARS) and neutrophil migration (MPO activity) were measured at the end of the assessment in lung allograft tissue. RESULTS: A significant change of TBARS concentration was shown in group III (group III 78.7+/-4.6 pmol/g vs. group IV 120.8+/-7.2 pmol/g (P = 0.0065) normal lung tissue 41.3+/-4.2 pmol/g). MPO activity was reduced in group III 3.74+/-0.25 deltaOD/mg per min vs. group IV 4.97+/-0.26 deltaOD/mg per min (P = 0.027), normal lung tissue 1.04+/-0.27 deltaOD/mg per min). Pulmonary hemodynamics and gas exchange after reperfusion did not differ between groups. In group I and III, a tendency towards a reduced EVLWI was noted. CONCLUSION: We conclude that combined treatment of donor and recipient with U-74006F reduces free radical mediated injury in the allograft. However, this intervention did not result in a significant reduction of post-transplant lung edema or improvement of pulmonary hemodynamics. Donor pretreatment alone did not improve lung allograft reperfusion injury. These results indicate that the benefit of U-74006F is too small to consider clinical application in lung transplantation.

Animals↗
PubMed1999

Lung volume reduction surgery combined with cardiac interventions.

OBJECTIVE: Postoperative course and functional outcome were evaluated in patients who underwent lung volume reduction surgery (LVRS) or in combination with valve replacement (VR), percutaneous transluminal coronary angioplasty (PTCA), placement of a stent, or coronary artery bypass grafting (CABG). METHODS: Patients with severe bronchial obstruction and hyperinflation due to pulmonary emphysema were evaluated for lung volume reduction surgery. Cardiac disorders were screened by history and physical examination and assessed by coronary angiography. Nine patients were accepted for LVRS in combination with an intervention for coronary artery disease (CAD). In addition, three patients with valve disease and severe emphysema were accepted for valve replacement (two aortic-, one mitral valve) only in combination with LVRS. Functional results over the first 6 months were analysed. RESULTS: Pulmonary function testing demonstrates a significant improvement in postoperative FEV1 in patients who underwent LVRS combined with an intervention for CAD. This was reflected in reduction of overinflation (residual volume/total lung capacity (RV/TLC)), and improvement in the 12-min walking distance and dyspnea. Median hospital stay was 15 days (10-33). One patient in the CAD group died due to pulmonary edema on day 2 postoperatively. One of the three patients who underwent valve replacement and LVRS died on day 14 postoperatively following intestinal infarction. Both survivors improved in pulmonary function, dyspnea score and exercise capacity. Complications in all 12 patients included pneumothorax (n = 2), hematothorax (n = 1) and urosepsis (n = 1). CONCLUSION: Functional improvement after LVRS in patients with CAD is equal to patients without CAD. Mortality in patients who underwent LVRS after PTCA or CABG was comparable to patients without CAD. LVRS enables valve replacement in selected patients with severe emphysema otherwise inoperable.

Aged↗
PubMed1999

Complications in the native lung after single lung transplantation.

OBJECTIVES: Single lung transplantation is a viable option for patients with end-stage pulmonary disease; despite encouraging results, we observed serious complications arising in the native lung. We retrospectively reviewed 36 single lung transplants to evaluate the incidence of complications arising in the native lung, their treatment and outcome. METHODS: Between 1991 and 1997, 35 patients received 36 single lung transplants for emphysema (16), pulmonary fibrosis (14), lymphangioleiomyomatosis (4), primary pulmonary hypertension (1) and bronchiolitis obliterans (1). The clinical records were reviewed and the complications related to the native lung were divided into early (up to 6 weeks after the transplant) and late complications. RESULTS: Nineteen complications occurred in 18 patients (50%), leading to death in nine (25%). Early complications (within 6 weeks from the transplant) were bacterial pneumonia (1), overinflation (3), retention of secretions with bronchial obstruction and atelectasis (1), hemothorax (1), pneumothorax (1) and invasive aspergillosis (3); one patient showed active tuberculosis at the time of transplantation. Two patients developed bacterial pneumonia and invasive aspergillosis leading to sepsis and death. The other complications were treated with separate lung ventilation (1), bronchoscopic clearance (1), chest tube drainage (1) and wedge resection and pleurodesis (mechanical) by VATS (1). One patient with hyperinflation of the native lung eventually required pneumonectomy and died of sepsis. The patient with active tuberculosis is alive and well after 9 months of medical treatment. Late complications were recurrent pneumothorax (4), progressive overinflation with functional deterioration (2), aspergillosis (1) and pulmonary nocardiosis (1). Recurrent pneumothorax was treated with chest tube drainage alone (1), thoracoscopic wedge resection and/or pleurodesis (2) and pneumonectomy (1); hyperinflation was treated with thoracoscopic lung volume reduction in both cases; both patients with late infectious complications died. CONCLUSIONS: After single lung transplantation, the native lung can be the source of serious problems. Early and late infectious complications generally result in a fatal outcome; the other complications can be successfully treated in most cases, even if surgery is required.

Adolescent↗
PubMed1999

Combined treatment with endothelin- and PAF-antagonists reduces posttransplant lung ischemia/reperfusion injury.

BACKGROUND: Pathophysiologic changes of posttransplant lung ischemia/reperfusion injury are mediated by redundant cellular and humoral mechanisms. We investigated the protective effect of combined administration of platelet activating factor (PAF) and endothelin (ET) antagonists after prolonged ischemia in a small animal lung transplantation model. METHODS: Orthotopic left lung transplantation was performed after 20 hours cold ischemia in male Fischer (F344) rats weighing 200-250 g. Group I served as control. In Group II, donors received 1 mg/kg body weight of the endothelin antagonist TAK-044, and recipients 2 mg/kg. Group III was treated with the PAF antagonist TCV-309 (donor: 50 microg/kg; recipient: 100 microg/kg) (Takeda Chemicals Ltd.). Group IV received a combined treatment with both substances at the same dosage. Twenty-four hours after reperfusion, the native contralateral lung was occluded to assess gas exchange of the graft only, and 5 minutes later the thoracic aorta was punctured for arterial blood gas analysis (n = 5). In other animals (n = 5), lung tissue was frozen 24 hours after reperfusion and assessed for myeloperoxidase activity (MPO) and thiobarbituric acid reactive substances. RESULTS: Combined inhibition of PAF and ET-1 at the receptor level resulted in significantly improved graft function as compared to controls (Group I), and to groups treated with either TAK-044 or TCV-309. This was determined by a higher arterial oxygen content (112 +/- 9 mmHg, p = .00061 vs control, 48 +/- 5 mmHg), reduced MPO activity (0.35 +/- 0.02 deltaOD/mg/min, p = .000002 vs control, 1.1 +/- 0.1 deltaOD/mg/min) and reduced lipid peroxidation (59.5 +/- 2.5 pmol/g, p = .011 vs control, 78.5 +/- 4.1 pmol/g). The improvement of arterial oxygen (Group II 77 +/- 10 mmHg, p = .027 vs control; Group III 84 +/- 8 mmHg, p = .0081 vs control) and reduction of MPO activity (Group II 0.85 +/- 0.061 deltaOD/mg/min, p = .017; Group III 0.92 +/- 0.079 deltaOD/mg/min, p = .058) in groups treated with either a PAF antagonist or an ET antagonist was significantly less than in Group IV. CONCLUSIONS: Combined donor and recipient treatment with an ET antagonist and a PAF antagonist results in superior posttransplant graft function 24 hours after reperfusion, suggesting a synergistic role of ET-1 and PAF in the mediation of reperfusion injury in this model. Single treatment with either of the antagonists revealed only a slight improvement compared to untreated controls.

Animals↗
PubMed1999

[Surgical lung volume reduction--an option for treating severe pulmonary emphysema].

Lung volume reduction surgery is a novel operative concept, which may be applied in certain patients, who are severely handicapped by advanced pulmonary emphysema and suffer from dyspnea at minimal exercise despite optimal medical therapy. The most destroyed lung parts are resected by video-assisted thoracoscopy. This type of surgery has a surprisingly low morbidity and mortality at specialized centers. It improves symptoms by ameliorating lung function and exercise tolerance. Maximal functional improvement is observed and lung function starts to decline slowly within one to two years thereafter.

Endoscopy↗
PubMed1999

[Lung transplantation in advanced pulmonary emphysema].

Over the last 15 years lung transplantation developed from an experimental technique to a valid therapy for patients with end-stage pulmonary emphysema. The main reason for this progress are better defined selection criteria, improved operative technique and organ preservation, optimized peri- and postoperative management, and a more precise immunosuppressive and anti-infective therapy. Indications, technique, treatment and results of lung transplantation in emphysema patients are discussed.

Aged↗
PubMed1999

Functional and morphological heterogeneity of emphysema and its implication for selection of patients for lung volume reduction surgery.

Lung volume reduction surgery (LVRS) in patients with advanced pulmonary emphysema aims to alleviate symptoms and enhance quality of life by improving respiratory mechanics. The theoretical concepts of the operation predict the greatest functional benefit in patients with marked hyperinflation, and with airflow obstruction due to loss of elastic recoil. Consistent observations in several centres, have confirmed these expectations. To achieve maximal reduction in lung volume at the least cost of functional tissue, resection is targeted to the lung zones with the most severe destruction by emphysema, leaving zones with relatively well-preserved tissue intact. Heterogeneity in emphysema distribution as assessed by visual scoring of the chest computed tomography scan according to a simple grading system has been shown to correlate with LVRS outcome variables. Therefore, evaluation of lung volume reduction surgery candidates has to include the functional and morphological characteristics of the emphysema as well as a general assessment of perioperative risk. However, the knowledge of potential predictive factors of lung volume reduction surgery outcome is so far based on retrospective analysis of highly selected patients. Therefore, many questions in respect of the selection of ideal candidates for this procedure remain unanswered at the present time.

Elasticity↗
PubMed1999

Role of lung perfusion scintigraphy in relation to chest computed tomography and pulmonary function in the evaluation of candidates for lung volume reduction surgery.

Lung perfusion scintigraphy is employed to evaluate patients with severe emphysema who are candidates for lung volume reduction surgery (LVRS). Our purpose was to investigate the role of scintigraphy in relation to chest computed tomography (CT) and lung function in this setting. Six observers blinded to clinical data retrospectively scored preoperative scintigrams of 70 patients undergoing bilateral video-assisted LVRS according to the distribution of lung perfusion as homogeneous, intermediately heterogeneous, or markedly heterogeneous. Heterogeneity of emphysema distribution was also assessed by chest CT. Dyspnea and pulmonary function were measured preoperatively and 3 mo postoperatively. In 42 patients with markedly heterogeneous, in 18 with intermediately heterogeneous, and in 10 with homogeneous perfusion, mean (+/- SE) FEV1 increased by 57 +/- 8% (p < 0.0001), 38 +/- 9% (p < 0.001), and 23 +/- 9% (p = NS) (p = NS for intergroup comparisons). In a multiple regression analysis, functional improvement after LVRS was more closely correlated with preoperative hyperinflation and the degree of emphysema heterogeneity estimated by chest CT than with the degree of perfusion heterogeneity assessed by scintigraphy. In 16 of 22 patients with homogeneous emphysema distribution in the chest CT scintigraphy revealed intermediately or markedly heterogeneous perfusion. We conclude that lung perfusion scintigraphy has a limited role in prediction of outcome, but it may help to identify target areas for resection in LVRS candidates with homogeneous CT morphology.

Adult↗
PubMed1998

[Surgical pain therapy in inoperable metastatic epigastric tumor by bilateral thoracoscopic splanchnicectomy].

Patients with unresectable supramesenteric malignancies often suffer from intractable pain. The supramesenteric viscera are supplied by the greater splanchnic nerve. Surgical options to effectively denervate the supramesenteric area are coeliac ganglionectomy, open or percutaneous coeliac ganglion block or transhiatal bilateral splanchnicotomy. The surgical minimally invasive alternative is thoracoscopic splanchnicectomy. In 7 patients pain was scored on a scale from 1 (no pain) to 10 (maximal pain) before and after surgery and weekly thereafter. Five bilateral and 2 left-sided thoracoscopic splanchnicectomies were performed. Operation time was 17 +/- 3 min for each side. The mean pain score dropped from preoperatively (under morphine sulphate medication) 7.4 +/- 0.6 to 4.9 (2.5-8.25) 1 week postoperatively (p = 0.02) and to 4.9 (2.5-6.75) 7 weeks postoperatively (p = 0.02). The relief from back pain was immediate and complete, but abdominal pain tended to recur. Six of our 7 patients and their general practitioners rated the intervention as a success. Thoracoscopic splanchnicectomy affords excellent palliation in patients with unresectable supramesenteric tumour, offering reliable pain control.

Abdominal Neoplasms↗
PubMed1998

Prospective, randomized comparison of extrapleural versus epidural analgesia for postthoracotomy pain.

BACKGROUND: Thoracic epidural analgesia is considered the method of choice for postthoracotomy analgesia, but it is not suitable for every patient and is associated with some risks and side effects. We therefore evaluated the effects of an extrapleural intercostal analgesia as an alternative to thoracic epidural analgesia. METHODS: In a prospective, randomized study, pain control, recovery of ventilatory function, and pulmonary complications were analyzed in patients undergoing elective lobectomy or bilobectomy. Two groups of 15 patients each were compared: one received a continuous extrapleural intercostal nerve blockade (T3 through T6) with bupivacaine through an indwelling catheter, the other was administered a combination of local anesthetics (bupivacaine) and opioid analgesics (fentanyl) through a thoracic epidural catheter. RESULTS: Both techniques were safe and highly effective in terms of pain relief and recovery of postoperative pulmonary function. However, minor differences were observed that, together with practical benefits, would favor extrapleural intercostal analgesia. CONCLUSIONS: These results led us to suggest that extrapleural intercostal analgesia might be a valuable alternative to thoracic epidural analgesia for pain control after thoracotomy and should particularly be considered in patients who do not qualify for thoracic epidural analgesia.

Analgesia↗