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Biomedical subjects

A Boehler

Publications and source records attributed to A Boehler.

At least 19 recordsLinked to original sources

How does psychological processing relate to compliance behaviour after lung transplantation? A content analytical study.

Non-compliance is one of the crucial problems impairing outcome after transplantation. Fourteen lung transplant recipients were interviewed about their thoughts regarding transplant-related topics. Compliance was assessed by doctors. The psychological processing was investigated by content analysis. Highly compliant patients perceived more advantages by transplantation. In contrast, low-compliant patients reported either an emotional distance to the lung or a closer relationship to the donor. Furthermore, they showed a contradictory relationship to the medical staff. There are some indications that perception of advantages by transplantation is crucial to compliance. This experience takes place in the context of a good staff-patient relationship. Emotional distance to the lung or nearness to the donor are further contributing factors of non-compliance.

Adaptation, Psychological↗

Lung transplant recipients holding companion animals: impact on physical health and quality of life.

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

Adolescent↗

Mesothelioma after lung transplantation.

The case history is presented of a lung transplant recipient who developed malignant mesothelioma. This is thought to be the first such report. Mesothelioma should be suspected in lung transplant recipients with a haemorrhagic pleural effusion in the native lung when there is no convincing evidence for bronchogenic carcinoma or post transplant lymphoproliferative disease, even in the absence of exposure to asbestos.

Female↗

Multiple peripheral pulmonary artery stenoses in adults: a rare cause of severe pulmonary hypertension necessitating lung transplantation.

Stenoses of multiple peripheral pulmonary artery branches represent a rare cause of pulmonary hypertension in children, but the prognosis is very poor for such patients. Herein we describe 2 patients with multiple peripheral pulmonary artery stenoses (MPPAS) presenting with severe pulmonary arterial hypertension in adulthood, which has only once been described previously. Both patients lived without significant health problems for decades; however, after onset of symptoms, their medical condition declined rapidly, necessitating lung transplantation several months after the diagnosis despite vasodilator therapy. Because MPPAS mimics chronic thromboembolic pulmonary hypertension, this entity may being underdiagnosed, decreasing the possibility of adequate therapy.

Adult↗

[Lung transplantation--indication, evaluation, risks and complications].

To date, lung transplantation is an established therapy for advanced lung diseases such as chronic obstructive lung disease, cystic fibrosis, pulmonary fibrosis, and pulmonary arterial hypertension. This therapeutic option not only leads to increased survival but also to improvements in quality of life. To date, one-year survival rates at the Zurich Lung Transplant Program are 87% and five-year survival rates are 72%. It is of most importance that the referral to the transplanting center is not too late and that the right time point for transplant surgery is not missed. Progress has been made with regard to early detection and therapy of chronic allograft rejection thereby improving long-term survival substantially.

Graft Rejection↗

Valaciclovir for chronic hepatitis B virus infection after lung transplantation.

We report on a chronic asymptomatic hepatitis B surface antigen (HBsAg) carrier who developed an increase in aminotransferase and HBsAg levels 1 year after lung transplantation. During treatment for cutaneous herpes simplex virus (HSV) infection with oral valaciclovir there was a marked decrease in replicating hepatitis B virus (HBV)-DNA and aminotransferase levels, which was sustained for 9 months by continuing low-dose valaciclovir. A second rise in aminotransferase levels again responded to a valaciclovir dose increase and the HBV-DNA levels declined further. Although we cannot exclude a spontaneous variation of the serologic parameters, our observation suggests that valaciclovir may represent a valuable therapeutic option in the treatment of chronic hepatitis B after lung transplantation.

Acyclovir↗

Surfactant proteins in pulmonary alveolar proteinosis in adults.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised histologically by an intra-alveolar accumulation of fine granular eosinophilic and periodic acid-Schiff positive material. In a retrospective study, the composition of the intra-alveolarly accumulated material of adult patients with PAP was analysed by means of immunohistochemistry and Western blotting. In patients with PAP, the current authors found an intra-alveolar accumulation of surfactant protein (SP)-A, precursors of SP-B, SP-B, variable amounts of mono-, di-, and oligomeric SP-C forms, as well as SP-D. Only in one patient was a precursor of SP-C detected. By means of immuno-electron microscopy, the current authors identified not only transport vesicles labelled for precursors of SP-B and SP-C, but also transport vesicles containing either precursors of SP-B or SP-C in type-II pneumocytes in normal human lungs. It is concluded that pulmonary alveolar proteinosis in adults is characterised by an intra-alveolar accumulation of surfactant protein A, precursors of surfactant protein B, and surfactant proteins B, C and D. The current data provide evidence that not only an impairment of surfactant clearance by alveolar macrophages, but also an abnormal secretion of transport vesicles containing precursors of surfactant protein B (but not surfactant protein C) and an insufficient palmitoylation of surfactant protein C, which may lead to the formation of di- and oligomeric surfactant protein C forms, play a role in the pathogenesis of pulmonary alveolar proteinosis.

Adult↗

Post-transplant bronchiolitis obliterans.

Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischaemia/reperfusion injury and infections have made intermediate-term survival after lung transplantation an achievable goal. However, chronic allograft dysfunction in the form of bronchiolitis obliterans remains a major hurdle that threatens both the quality of life and long-term survival of the recipients. It affects up to 50-60% of patients who survive 5 yrs after surgery, and it accounts for >30% of all deaths occurring after the third postoperative year. This article discusses the alloimmune-dependent and -independent risk factors for bronchiolitis obliterans, the current understanding of the pathogenesis of bronchiolitis obliterans based on results of animal and human studies, the clinical staging of the complication, strategies that may contribute to the prevention and/or early detection of bronchiolitis obliterans, and suggestions for future research.

Animals↗

BAL findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF.

BACKGROUND: Idiopathic pulmonary alveolar proteinosis (PAP) has recently been recognised as a disease of impaired alveolar macrophage function caused by neutralising anti-granulocyte-macrophage colony-stimulating (anti-GM-CSF) autoantibodies. Subcutaneous recombinant human GM-CSF is a novel treatment for PAP, but its mechanism of action is unclear. METHODS: Clinical, functional, and bronchoalveolar lavage (BAL) findings were prospectively evaluated in a patient with PAP treated with daily subcutaneous GM-CSF 8 microg/kg for 12 weeks. RESULTS: Treatment resulted in improvements in dyspnoea, lung function, and peak cycle ergometry performance. In serum and BAL fluid the titre of anti-GM-CSF autoantibodies was raised at baseline and markedly reduced on treatment. At baseline the BAL fluid cellular profile showed a decrease in the absolute number and the percentage of macrophages (50%) and an increase in lymphocytes (45%), predominantly CD4+. This cellular distribution remained unchanged after 6 and 12 weeks of treatment while macrophages became morphologically normal and functionally improved. Extracellular proteinaceous material completely disappeared. CONCLUSIONS: Clinically successful treatment of PAP with GM-CSF was associated with a profound reduction in GM-CSF neutralising autoantibodies, improvement in alveolar macrophage morphology and function, but persistent BAL lymphocytosis.

Adult↗

Improved results after lung transplantation--analysis of factors.

Better recipient selection, sophisticated postoperative surveillance and new immunosuppressive and anti-infective regimens can improve the results of lung transplantation. We compared the results of lung transplants performed between 1992 and 1996 (early period; 47) and between 1997 and 2000 (recent period; 46) in a cohort study to assess which factors influenced survival. Estimates of relative hazards were adjusted for possible confounding effects with the use of Cox regression analysis. Overall 2-year survival was 70%. Survival by this time was significantly better in the recent period (82% vs. 60%; p = 0.0093). Acute rejection episodes and death due to BOS were less frequent in the recent period. There were no technical failures, and the cumulative incidence of BOS was low (34% at 5 years). The beneficial effect of the transplantation date 1997 or later at a hazard ratio of 0.33 (95% CI, 0.13-0.84) was materially changed only by the adjustment for ganciclovir prophylaxis (0.50; 95% CI, 0.09-2.91) and immunosuppression with mycophenolate mofetil (0.80; 95% CI, 0.27-2.36). After adjustment for both ganciclovir and mycophenolate mofetil, the beneficial time period effect was completely removed (1.24; 95% CI, 0.14-11.39). Immunosuppressive therapy with mycophenolate mofetil and use of ganciclovir prophylaxis in addition to careful postoperative surveillance and surgical expertise can lead to improved results after lung transplantation.

Adolescent↗

Recipient treatment with trimetazidine improves graft function and protects energy status after lung transplantation.

BACKGROUND: Ischemia-reperfusion injury remains an important obstacle to successful lung transplantation. Trimetazidine is an anti-ischemic drug that restores the ability of ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. The aim of this study was to assess the protective effect of trimetazidine after prolonged ischemia in lung transplantation. METHODS: Rat single-lung transplantation was performed in 4 experimental groups (n = 5 each). In all groups, transplantation was performed after 18 hours of cold (4 degrees C) ischemia. All donor lungs were flushed with low-potassium dextran-glucose (LPDG) solution that also contained 500 microg/liter prostaglandin estradiol (E(1)). Groups studied included: Group I: flush solution was administered containing 10(-6) mol/liter trimetazidine (TMZ), neither donor nor recipient treatment given; Group II: donors were treated with 5 mg/kg intravenous TMZ 10 minutes prior to harvest, but the flush solution did not contain TMZ; Group III: recipients treated with 5 mg/kg intravenous TMZ 10 minutes before reperfusion, and flush solution contained 10(-6) mol/liter trimetazidine; Group IV: ischemic control group. After 2 hours of reperfusion, oxygenation was measured and lung tissue was frozen and assessed for adenosine triphosphate (ATP) content, myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substances (TBARS). Peak airway pressure (PawP) was recorded throughout the reperfusion period. RESULTS: Group III showed significantly higher levels of ATP content (11.1 +/- 5.01 pmol vs Group I, 3.36 +/- 1.8 pmol, p = 0.008; vs Group II, 4.7 +/- 1.9 pmol, p = 0.03; vs Group IV, 0.7 +/- 0.2 pmol, p = 0.008), better oxygenation (442.5 +/- 26.5 mm Hg, vs Group I, 161.06 +/- 54.5 mm Hg; vs Group II, 266.02 +/- 76.9 mm Hg; vs Group IV, 89.4 +/- 14.7 mm Hg, p = 0.008) and reduced lipid peroxidation (TBARS) (0.15 +/- 0.03 nmol/g; vs Group I, 1.04 +/- 0.76 nmol/g; vs Group II, 0.69 +/- 0.4 nmol/g; vs Group IV, 2.29 +/- 0.4 nmol/g, p = 0.008). PawP and MPO activity were comparable in the 4 study groups. CONCLUSION: Recipient treatment with TMZ provided significant protection of energy status, better oxygenation and reduced lipid peroxidation. Our data suggest that TMZ may be an important adjunct in the prevention of post-transplant lung ischemia-reperfusion injury.

Animals↗

Lung transplantation for cystic lung diseases: lymphangioleiomyomatosis, histiocytosis x, and sarcoidosis.

Lung transplantation for respiratory failure due to lymphangioleiomyomatosis, histiocytosis X, and sarcoidosis is a therapeutic option in selected patients. These indications account for less than 6% of all lung transplant procedures, and experience is relatively scarce. Pulmonary function testing at evaluation usually shows an obstructive pattern in lymphangioleiomyomatosis, whereas histiocytosis presents with a mixed pattern, and sarcoidosis with a restrictive pattern. Lung diffusion capacity is similarly reduced, however, only histiocytosis and sarcoidosis are often associated with pulmonary hypertension. In all three diseases extrapulmonary manifestations, although of different kinds, are common and must be investigated before transplantation to avoid posttransplant diagnostic pitfalls. In all these diseases, single and bilateral transplantation show comparable results. Typical complications in lymphangioleiomyomatosis include intraoperative severe intrathoracic bleeding, posttransplant chylothorax, pneumothorax, and bleeding of angiomyolipomas. In histiocytosis, extrapulmonary manifestations in bones and pituitary gland may progress. These diseases typically recur in the allograft, leading to clinical symptoms in histiocytosis whereas recurrence in lymphangioleiomyomatosis and sarcoidosis is most often asymptomatic. Survival is similar to patients transplanted for other diseases.

Journal Article↗

Trimetazidine protects the energy status after ischemia and reduces reperfusion injury in a rat single lung transplant model.

BACKGROUND: Ischemia-reperfusion injury involves free radical generation and polymorphonuclear neutrophil chemotaxis. Trimetazidine is an anti-ischemic drug that restores the ability of the ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. We evaluated the effect of trimetazidine against ischemia-reperfusion injury after lung transplantation. METHODS: Rat single lung transplantation was performed in 3 experimental groups (n = 5): (1) the immediate transplantation group was defined as animals undergoing transplantation immediately after harvest without treatment; (2) the ischemic control group was defined as animals undergoing transplantation after 18 hours of cold (4 degrees C) ischemia without treatment; and (3) the trimetazidine-treated group was defined as animals undergoing transplantation after 18 hours of cold (4 degrees C) ischemia and donor and recipient treatment with 5 mg/kg intravenous trimetazidine 10 minutes before harvest and reperfusion, respectively. All donor lungs were flushed with low-potassium dextran-glucose solution. After 2 hours of reperfusion, oxygenation was measured, and lung tissue was frozen and assessed for adenosine triphosphate content, myeloperoxidase activity, and thiobarbituric acid-reactive substances. Peak airway pressure was recorded throughout the reperfusion period. RESULTS: The trimetazidine group showed significantly higher levels of adenosine triphosphate content (1.73 +/- 0.8 pmol vs 0.72 +/- 0.2 pmol [ischemic control], P =.008), better oxygenation (238.82 +/- 113.9 mm Hg vs 89.39 +/- 14.7 mm Hg [ischemic control], P =.008), and reduced lipid peroxidation (1.28 +/- 0.1 nmol/g vs 2.09 +/- 0.4 nmol/g [ischemic control], P =.008). Adenosine triphosphate levels of the trimetazidine group were comparable with those of the immediate transplantation group (1.73 +/- 0.8 pmol vs 1.89 +/- 0.5 pmol, respectively; P =.31). Peak airway pressure and myeloperoxidase activity were comparable among groups. CONCLUSION: Donor and recipient treatment with trimetazidine provided a significant protection of the energy status, better oxygenation, and reduced lipid peroxidation in this experimental model. Our data suggest that trimetazidine may be an important adjunct to prolong ischemic time safely and to decrease lung ischemia-reperfusion injury.

Adenosine Triphosphate↗

[Indications for lung transplantation in advanced cystic fibrosis].

Lung transplantation has become a valid therapeutic option for cystic fibrosis patients with end-stage lung disease. The indication for transplantation does not rely on strict criteria only but must be evaluated case by case. In particular, the dynamics of the clinical course need to be considered with regard to impaired physical performance, recurrent infections, decline in pulmonary function and weight loss. Important risk factors are a poor nutritional status, osteoporosis, liver involvement, previous pleurodesis and the occurrence of multiresistant bacteria. Management and assessment of cystic fibrosis patients for lung transplantation is complex. Therefore patients should be referred to specialised centres at an early stage.

Bacterial Infections↗

[Special problems after lung transplantation: walking a tightrope between infection and graft rejection].

Between November 1992 and September 1999 84 lungs have been transplanted at University Hospital Zurich. Currently the 1-year survival rate is up to 85%. However, long-term success is limited by the development of chronic rejection in the form of bronchiolitis obliterans. The risk factors are repeated episodes of acute rejection and infections, due to cytomegalovirus in particular. Both can occur in asymptomatic patients and are sometimes detected only by transbronchial lung biopsy. At the Zurich Lung Transplant Centre biopsies are performed as surveillance biopsies in asymptomatic patients in the first 6 months after transplantation, for clinical indications and as follow-up biopsies after a pathological result. Open lung biopsies are performed for special indications only. We evaluated 408 transbronchial biopsies taken between November 1992 and September 1999. Relevant findings were present in 46% of biopsies in symptomatic patients. Relevant acute rejection episodes were diagnosed in 15% of surveillance biopsies. Overall, 72% of acute rejection episodes requiring therapy and 33% of biopsies detecting cytomegalovirus were found in surveillance biopsies. 7 of 11 late (> 45 days postoperative) and 1 of 5 early (< or = 45 days postoperative) open lung biopsies revealed new diagnoses. Transbronchial biopsy after lung transplantation is at present the gold standard for diagnosis of acute rejection and cytomegalovirus pneumonia of the lung.

Adult↗

Osteonecrosis after lung transplantation: cystic fibrosis as a potential risk factor.

BACKGROUND: Osteonecrosis is a known complication after transplantation of solid organs. The incidence of osteonecrosis after lung transplantation is not well documented. METHODS: We investigated the incidence of symptomatic osteonecrosis in lung transplant recipients, transplanted between November 1992 and June 1998 at our institution. For the detection of osteonecrosis, all patients complaining of musculoskeletal pain underwent magnetic resonance imaging. Demographic characteristics, time after transplantation, etiology of underlying lung disease, and the number of steroid pulses for rejection episodes were compared for patients with and without osteonecrosis. RESULTS: Of 63 transplant recipients, all 49 with a follow-up of >3 months were included for analysis. Of seven symptomatic transplant recipients, five cases of osteonecrosis (10%) were detected at a median duration of 216 days (range 44-600) after transplantation. Patients with osteonecrosis have been treated with the same immunosuppressive regimen and with an equal number of steroid pulses for acute rejection episodes (1.4+/-1.1 vs. 1.4+/-1.5, P=0.69), but were younger (26+/-8 vs. 40+/-11 years, P<0.01) than other transplant recipients. Symptomatic osteonecrosis was detected in four of 14 patients (29%) with cystic fibrosis (CF), compared with one osteonecrosis among 35 patients (3%) with other underlying diseases (P<0.02). Within the group of CF patients, specific clinical and demographic characteristics correlating with the risk for subsequent osteonecrosis could not be found. CONCLUSION: In lung transplant recipients, CF may be a risk factor for the development of symptomatic osteonecrosis.

Adolescent↗

Transplant immunosuppression increases and prolongs transgene expression following adenoviral-mediated transfection of rat lungs.

BACKGROUND: Gene therapy provides the potential to modify donor organs to better withstand transplantation, but this has yet to be realized. In vivo gene transfer using adenoviral vectors has had limited success because of host immune response that induces inflammation and limits the amount and duration of transgene expression. We hypothesize that transplantation immunosuppression can attenuate the post-transfection host-immune response to allow for improved gene transfer following adenoviral-mediated transfection. METHODS: We intratracheally transfected with adenovirus containing the beta-galactosidase gene and randomized the rats to either the immunosuppression group, receiving daily cyclosporine, azathioprine, and methylprednisolone, or the control group, receiving no immunosuppression. We evaluated transgene expression and post-transfection inflammation at time points ranging from 1 day to 5 weeks. RESULTS: Following transfection, control rats showed relatively low levels of transgene expression, which rapidly decreased to non-detectable levels. In contrast, immunosuppressed rats demonstrated significantly higher levels of transgene expression overall (p < 0.00005), peaking at almost 3 times that of the control group (p < 0.02), and showing prolonged and elevated transgene expression at 5 weeks (p < 0.02). On histologic sections of the lungs, immunosuppressed rats exhibited overall lesser grades of post-transfection inflammation. CONCLUSIONS: Transplant immunosuppression provides the means to attenuate the severe immune response to adenoviral-mediated gene transfection and thereby increase and prolong transgene expression.

Adenoviridae↗