Clemens Aigner

Increased levels and reduced catabolism of asymmetric and symmetric dimethylarginines in pulmonary hypertension

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) and has been implicated in endothelial dysfunction. ADMA is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), with DDAH2 representing the predominant endothelial DDAH isoform. Symmetric dimethylarginine (SDMA), also originating from arginine methylation by protein arginine methyltransferases, is an inhibitor of intracellular arginine uptake. In both chronic pulmonary hypertensive rats and patients suffering from idiopathic pulmonary arterial hypertension (IPAH; NYHA class III and IV), a marked increase in plasma ADMA and SDMA levels, as well as tissue levels of asymmetric and symmetric dimethylated proteins, was observed. Moreover, when comparing lung tissue from pulmonary hypertensive rats and IPAH patients to corresponding normal lung tissue, expression of DDAH2 was found to be reduced at both the mRNA and the protein level with no significant changes in DDAH1 expression. These findings were further supported by demonstrating a decrease in DDAH2 function in the experimental pulmonary hypertension model. Immunohistochemistry in human and rat control tissue demonstrated both isoforms of DDAH in the endothelial layer and in the alveolar epithelium. In contrast, in pulmonary hypertensive tissue, the immunoreactivity of DDAH2 in pulmonary endothelium was significantly decreased compared with DDAH1. Therefore, altogether we can conclude that enhanced dimethylarginine levels may contribute to vascular abnormalities in pulmonary arterial hypertension. Suppression of endothelial DDAH2 expression and function represents an important underlying mechanism.

A scale for decision making between whole lung transplantation or lobar transplantation

OBJECTIVEnIn lung transplantation, appropriate size matching is of crucial importance to achieve satisfactory outcomes. Tailoring of the lung has been repeatedly described as successful means of overcoming size disparities. The goal of this study was to define a parameter helping the surgeon in the decision whether a standard lung transplantation or a lobar transplantation should be anticipated.nnnMETHODSnWe retrospectively analysed the ratio between donor total lung capacity (TLC) and recipient TLC in all lung-transplant procedures performed in our institution from 1 January 2008 to 30 November 2008. The utility of this ratio using predicted recipient TLC (D/pR index) and real recipient TLC (D/rR index) in discriminating between whole lung transplantation and lobar transplantation was studied with the receiver operating characteristic (ROC) analysis.nnnRESULTSnThe median D/pR index in whole lung transplantations was 1.01 (range: 0.69-1.26) and 1.19 in lobar transplantation (range: 1.09-1.54). In the range between 1.12 and 1.14, sensitivity and specificity are both above 90%. The area under the ROC curve for D/pR index was 0.96. The median D/rR index in whole lung transplantations was 0.95 (range: 0.56-2.74) and 1.58 in lobar transplantation (range: 0.85-2.56). The area under the ROC curve was 0.73.nnnCONCLUSIONSnWe conclude that the D/pR index is more useful than D/rR index in discriminating between whole lung transplantation and lobar transplantation. With an area under the ROC curve of 0.96, this seems to be a suitable indicator in deciding between whole lung transplantation and lobar transplantation.

Cystic fibrosis and lung transplantation--determination of the survival benefit.

ZusammenfassungEinleitungZystische Fibrose (CF) ist eine anerkannte Indikation zur Lungentransplantation, jedoch ist der optimale Zeitpunkt für die Transplantation noch diskutabel. Liou et al. haben einen Score beschrieben, mit dem die 5-Jahres-Überlebenswahrscheinlichkeit für CF Patienten errechnet werden kann. Er schlussfolgerte, dass nur Patienten mit einer errechneten 5-Jahres-Überlebenswahrscheinlichkeit <30% einen Überlebensvorteil durch die Lungentransplantation haben. Jene zwischen 30% und 50% haben identische Überlebensraten und jene >50% haben schlechtere Überlebensraten mit Transplantation. Ziel dieser Studie ist es, die Gültigkeit und Anwendbarkeit dieses Models zu evaluieren.MethodikEs wurden die Daten von CF Patienten, welche von Jänner 1995 bis Juli 2001 transplantiert wurden, retrospektiv analysiert. Der Score nach Liou wurde anhand von Daten, welche vor der Transplantation erhoben wurden, errechnet. Die Patienten wurden anhand der errechneten 5 Jahresüberlebenswahrscheinlichkeit eingeteilt (Gruppe 1: <30%, Gruppe 2: 30–50%, Gruppen 3–5: >50%). Die Überlebensraten wurden für alle Gruppen ermittelt und mit der errechneten Überlebenswahrscheinlichkeit verglichen.ErgebnisseWährend des Beobachtungszeitraumes wurden 27 CF Patienten lungentransplantiert. 3 Patienten mussten aufgrund inkompletter Daten aus der Analyse ausgeschlossen werden. 15 Patienten fielen in Gruppe 1 und 9 Patienten in Gruppe 2. Kein Patient fiel in die Gruppen 3–5. In Gruppe 1 waren 9 weibliche und 6 männliche Patienten mit einem Durchschnittsalter von 22,1±4,9 Jahren. Durchschnittliche Überlebenszeit waren 918±787 Tage. 1-, 3- und 5-Jahres-Überlebensrate war 66,6%. 3 männliche und 6 weibliche Patienten fielen in Gruppe 2, Altersdurchschnitt waren 26,2±12,2 Jahre. Durchschnittliche Überlebenszeit in dieser Gruppe waren 701±617 Tage. 1-, 3- und 5-Jahres-Überlebensrate war 66,6%.SchlussfolgerungenIm Beobachtungszeitraum wurden nur Patienten mit einer errechneten 5-Jahres-Überlebenswahrscheinlichkeit <50% lungentransplantiert. Sowohl Patienten der Gruppe 1 als auch Gruppe 2 hatten eine 5-Jahres-Überlebensrate von 66,6%. Unserer Erfahrung nach haben demnach sowohl Patienten mit einer 5-Jahres-Überlebenswahrscheinlichkeit <30% als auch jene <50% einen klaren Überlebensvorteil durch die Lungentransplantation.SummaryIntroductionCystic fibrosis is a well acknowledged indication for lung transplantation; however, the optimal timing for transplantation remains debatable. Liou et al. described a score for calculating 5-year probability of survival for patients with cystic fibrosis and concluded that only patients with a probability of survival <30% gained a survival benefit from transplantation; those between 30% and 50% had equivocal survival effects from transplantation and those >50% suffered negative effects. The aim of the present study was to determine the validity and applicability of this model.MethodsData from patients with cystic fibrosis transplanted between January 1995 and July 2001 were retrospectively reviewed. Survival score according to Liou was calculated from data collected before transplantation. Patients were classified according to 5-year probability of survival (group 1: <30%, group 2: 30%–50%, groups 3–5: >50%). Actuarial survival rates were calculated separately for each group and compared with the predicted probability of survival.ResultsDuring the observation period 27 patients were transplanted for cystic fibrosis. Three patients had to be excluded from further analysis because of incomplete pretransplant data. Fifteen patients were classified as group 1 and nine patients as group 2. No patients were eligible for groups 3 to 5. There were nine female patients and six males in group 1, mean age 22.1±4.9 years. Mean survival time was 918±787 days; 1-, 3- and 5-year survival rates were 66.6%. Three male patients and six females were classified as group 2, mean age 26.2±12.2 years. Mean survival time for this group was 701±617 days, and 1-, 3- and 5-year survival rates were 66.6%.ConclusionWe found that only patients with a 5-year probability of survival <50% had been transplanted. For patients in groups 1 and 2 we report identical 5-year survival rates of 66.6%. According to our experience, cystic fibrosis patients with a 5-year probability of survival <30% and also those between 30% and 50% gain a clear survival benefit from bilateral lung transplantation.

Multimodale Therapie bei NSCLC

Behandlung und Prognose des nicht kleinzelligen Bronchuskarzinoms (NSCLC) sind abhängig vom Tumorstadium des Patienten. Das mediastinale Lymphknotenstaging ist entscheidend, um die optimale Th erapiestrategie festzulegen. Ein ipsilateraler mediastinaler Lymphknotenbefall (N2) bedeutet zumindest ein Stadium IIIA, in dem ein multimodales Th erapiekonzept mit Induktionschemotherapie bzw. –chemoradiotherapie mit nachfolgender Operation bei entsprechendem Downstaging das etablierte Standardverfahren ist. Die Identifi kation derjenigen Patienten, die bei operablem Primärtumor von einer Induktionstherapie profi tieren, ist eine der Herausforderungen des mediastinalen Stagings.

Cystic fibrosis and lung transplantation - determination of the survival benefit

Introduction nCystic fibrosis is a well acknowledged indication for lung transplantation; however, the optimal timing for transplantation remains debatable. Liou et al. described a score for calculating 5-year probability of survival for patients with cystic fibrosis and concluded that only patients with a probability of survival 50% suffered negative effects. The aim of the present study was to determine the validity and applicability of this model.