Posttransplant sinus surgery in lung transplant recipients with cystic fibrosis: a single institutional experience

Chronic rhinosinusitis is hypothesised to play a major role in lung transplant recipients with cystic fibrosis. Paranasal sinuses are considered to accumulate a significant bacterial load, potentially leading to lung allograft infection with ensuing complications such as bronchiolitis obliterans syndrome, i.e. allograft rejection. We therefore would like to present our combined medical and surgical treatment plan, which consists of an endoscopic fronto-spheno-ethmoidectomy as well as a meticulous daily nasal care program. The microbiological results show that our combined concept is effective, whereas especially daily nasal care with isotonic saline solution is the cornerstone in preventing significant colonisation of the sinuses and spreading bacteria to the lower respiratory tract causing lung allograft infection. Regarding the surgical part of our treatment, it should be emphasised that all sinuses and ethmoidal air cells should be widely opened. Edges such as bony overhangs should be smoothened to avoid mucus retention and consecutive bacterial recolonisation requiring subsequent revision surger

Extended Nitric Oxide Measurements in Exhaled Air of Cystic Fibrosis and Healthy Adults

In cystic fibrosis (CF) lung disease, exhaled nitric oxide (FeNO) is not raised, but rather is normal or even decreased when measured at a single expiratory flow. FeNO measurements at several flow rates allow differentiation between alveolar and bronchial nitric oxide (NO) production. Extended FeNO measurements therefore should be useful to localize the FeNO deficit in CF airways. FeNO was measured in stable CF adults with moderate lung disease and in healthy controls. Bronchial NO fluxes (JNO,Br) and alveolar NO concentrations (CAlv) were calculated from FeNO measurements at flow rates of 100, 150 and 200ml/s using a method previously described. Thirty-two adults were included in the study, 12 of whom had CF. CF adults had significantly lower FeNO values at all flow rates. The median JNO,Br was significantly lower in CF adults than in healthy controls [0.31nl/s (range=0.11-0.63) vs. 0.70nl/s (0.27-3.52); P<0.001], while the median CAlv was similar in both groups [1.7ppb (0.3-3.9) vs. 1.2 (0.1-5.2)]. Pulmonary NO exchange did not differ significantly between subgroups of CF patients with and without chronic Pseudomonas aeruginosa infection. No significant correlation was detectable between FEV1/VC and JNO,Br and CAlv, respectively. Extended FeNO measurements can separate alveolar and bronchial NO outputs in CF adults. The lower FeNO in adults with moderate to severe CF lung disease is likely to be the result of lower bronchial NO outpu

Ganciclovir/Valganciclovir Prophylaxis Decreases Cytomegalovirus-Related Events and Bronchiolitis Obliterans Syndrome after Lung Transplantation

Background. Until recently, cytomegalovirus (CMV) infection represented a major threat to lung transplant recipients. Preliminary studies have shown that antiviral prophylaxis might improve the outcome for these patients. Methods. We extended our initial pilot trial of prolonged prophylaxis with either oral ganciclovir (1 g 3 times per day) or valganciclovir (450 mg twice per day). The trial included 96 patients who were at risk for CMV-related events. Results. CMV prophylaxis resulted in a significant decrease in CMV-related events (i.e., active infection and disease), from 75% in a control group and for 274 cases from the literature who did not receive prophylaxis to a cumulative incidence of 27% (P<.001). Only 11% of the prophylaxis recipients experienced CMV disease (P<.001). Moreover, at 5 years, there was a significant decrease in the rate of bronchiolitis obliterans syndrome, from 60% to 43% (P=.002), and an improved rate of survival, from 47% to 73% (P=.036), irrespective of the immunosuppressive regimen received. CMV strains with UL97 mutations were recovered from 7 of 12 analyzed cases, but the presence of this mutation had no impact on the severity of CMV disease. Conclusions. A regimen of prolonged ganciclovir or valganciclovir prophylaxis decreased the rate of active CMV infection and disease, reduced the incidence of bronchiolitis obliterans syndrome, and improved the survival rate. Drug-resistant CMV strains may occur, but such strains appeared to have no impact on the outcome of CMV-related event

Lung transplantation for cystic fibrosis: a single center experience of 100 consecutive cases†

OBJECTIVE Lung transplantation is the ultimate treatment option for patients with end-stage cystic fibrosis (CF) lung disease. Despite poorer reports on survival benefit for CF patients undergoing lung transplantation, several centers, including ours were able to show a survival benefit. This study compares our center's experience with 100 consecutive recipients in two different eras. METHODS All CF patients who underwent lung transplantation at our center were included (1992-2009). Survival rates were calculated and compared between the earlier era (before 2000) and later era (since 2000). RESULTS CF patients constituted 35% of all transplantations performed at our institution. Mean age at transplantation was 27 years (range 12-52). Fifty-one percent of the patients were female. Waiting list time was lower in the earlier era compared to the later era (p=0.04). Lobar transplantation was performed in 10 cases. Thirty-four percent of the cases required downsizing of the graft. In 33% of the cases, transplantations were done on cardiopulmonary bypass. There were no anastomotic complications. Total intensive care unit stay was significantly lower in the later era compared to earlier era (p=0.001). The other parameters such as C-reactive protein at the time of transplantation, total cold ischemic time, and total operation time were comparable between the two eras. Overall 30-day mortality was 5%. The 30-day mortality was significantly lower in the second period (p=0.006). In the earlier era, 3-month, 1-year, and 5-year survival were 85±6%, 77±8%, and 60±9%, respectively, and in the later era improved to 96±2%, 92±3%, and 78±5% (p=0.03). CONCLUSION Improved results obtained in the early postoperative period since 2000 is most likely due to change in surgical management approach. Improved surgical outcome for CF patients can be obtained, especially in experienced transplant center

Moderate altitude but not additional endurance training increases markers of oxidative stress in exhaled breath condensate

Oxidative stress occurs at altitude, and physical exertion might enhance this stress. In the present study, we investigated the combined effects of exercise and moderate altitude on redox balance in ten endurance exercising biathletes, and five sedentary volunteers during a 6-week-stay at 2,800m. As a marker for oxidative stress, hydrogen peroxide (H2O2) was analyzed by the biosensor measuring system Ecocheck™, and 8-iso prostaglandin F2α (8-iso PGF2α) was determined by enzyme immunoassay in exhaled breath condensate (EBC). To determine the whole blood antioxidative capacity, we measured reduced glutathione (GSH) enzymatically using Ellman's reagent. Exercising athletes and sedentary volunteers showed increased levels of oxidative markers at moderate altitude, contrary to our expectations; there was no difference between both groups. Therefore, all subjects' data were pooled to examine the oxidative stress response exclusively due to altitude exposure. H2O2 levels increased at altitude and remained elevated for 3days after returning to sea level (p≤0.05). On the other hand, 8-iso PGF2α levels showed a tendency to increase at altitude, but declined immediately after returning to sea level (p≤0.001). Hypoxic exposure during the first day at altitude resulted in elevated GSH levels (p≤0.05), that decreased during prolonged sojourn at altitude (p≤0.001). In conclusion, a stay at moderate altitude for up to 6weeks increases markers of oxidative stress in EBC independent of additional endurance training. Notably, this oxidative stress is still detectable 3days upon return to sea leve

Tracers as Essential Tools for the Investigation of Physical and Chemical Processes in Groundwater Systems

In complex environmental systems, tracers are indispensable tools for the investigation of various physical, chemical, and biological processes. From the large variety of tracers employed by EAWAG in the aquatic environment, we present some examples relevant to groundwater research. Some tracers (e.g., 222Rn, 3H/3He, chlorofluorocarbons) allow the time since groundwater infiltration to be determined; this information can be used to quantify process rates such as flow velocities, recharge and reaction rates. Other tracers (e.g., conductivity, isotopes of oxygen or boron) can be used to quantify mixing ratios between waters of different origin, for instance, to study the admixture of leachate from a landfill to an aquifer. In contrast to these inert tracers, chemically reactive tracers (e.g., nitroaromatic compounds) can be used to study subsurface biogeochemical transformation processes, e.g. the reduction of contaminants under anaerobic conditions. The successful use of tracers in the study of environmental systems requires highly developed analytical facilities for a broad palette of tracer measurements and a careful choice of appropriate tracers for each specific problem

Characterization of the gaseous spacecraft environment of Rosetta by ROSINA

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90700/1/AIAA-2011-3822-983.pd

MTO1 mediates tissue specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention

Mitochondrial diseases often exhibit tissue-specific pathologies, but this phenomenon is poorly understood. Here we present regulation of mitochondrial translation by the Mitochondrial Translation Optimization Factor 1, MTO1, as a novel player in this scenario. We demonstrate that MTO1 mediates tRNA modification and controls mitochondrial translation rate in a highly tissue-specific manner associated with tissue-specific OXPHOS defects. Activation of mitochondrial proteases, aberrant translation products, as well as defects in OXPHOS complex assembly observed in MTO1 deficient mice further imply that MTO1 impacts translation fidelity. In our mouse model, MTO1-related OXPHOS deficiency can be bypassed by feeding a ketogenic diet. This therapeutic intervention is independent of the MTO1-mediated tRNA modification and involves balancing of mitochondrial and cellular secondary stress responses. Our results thereby establish mammalian MTO1 as a novel factor in the tissue-specific regulation of OXPHOS and fine tuning of mitochondrial translation accurac