Background: In an attempt to monitor the pharmacodynamics of mycophenolate mofetil (MMF) we investigated the association of inosine morrophosphate clehydrogenase (IMPDH) activity in peripheral blood mononuclear cells with the expression of lymphocyte activation markers in stable cardiac transplant recipients treated with MMF.Methods: Twenty-four study patients were switched from azathioprine to MMF 7.2 +/- 4.1 years after heart transplantation.Results: While the MPA trough level remained unchanged, the mean activity of IMPDH declined from 890 to 462 pmol/10(6)PBMC/h three months after onset of MMF therapy, was almost completely inhibited at six months and partially restored to 160 pmol/10(6)PBMC/h 12 months after switch to MMF (p<.0001). We detected also significant changes in a number of activated lymphocyte subsets: CD4(+)/25(+), CD8(+)/38(+), CD19(+)/69(+), CD3(+)/16(+)/56(+), natural killer (NK) cells, and monocytes. Moreover, the IMPDH activity profile correlated positively with the number of CD8(+)/38(+) T cells (correlation coefficient (CC) +053), and inversely with NK cells (CC -0.52) and CD19(+)/ 69(+) cells (CC -0.61).Conclusions: We revealed a close association of IMPDH baseline activity in mononuclear cells with the expression of lymphocyte activation markers in stable heart transplant patients after introduction of MMF therapy. This supports the assumption of a rather immunomodulatory than immunosuppressive effect of MMF. (C) 2008 Elsevier B.V. All rights reserved.

BACKGROUND:Surgical methods for treatment of tricuspid valve (TV) endocarditis include complete TV excision, TV replacement, and the use of various reconstructive techniques even in cases of severe TV destruction and incompetence. This study summarizes our experience with TV reconstruction and replacement in patients with severe TV endocarditis.METHODS:Between October 1997 and July 2004, TV reconstruction was performed in 18 patients (mean age, 38 +/- 17 years; 7 women, 11 men), and TV replacement in 4 patients (mean age, 48 +/- 22 years; 2 women, 2 men). All patients presented with active endocarditis and severe TV incompetence. Reconstructive techniques included debridement of vegetations, complete resection of infected or destroyed leaflet tissue, leaflet reconstruction with pericardial tissue, sliding plasty of residual valve tissue and bicuspid valve formation with construction of a new commissure, and consecutive ring annuloplasty in all patients.RESULTS:There were no perioperative deaths. Late mortality was 0% for patients with TV reconstruction and 25% (n = 1) in the TV replacement group. At the latest follow-up (78% complete; mean, 53 +/- 18 months), 11 patients had no recurrent TV incompetence. Three patients presented with TV incompetence grade I or II. Two patients with TV reconstruction had recurrent TV endocarditis between 3 and 18 month postoperatively, including new vegetations in both patients and an additional pleural empyema in one. In all cases, conservative treatment was successful and no reoperation was required.CONCLUSIONS:The results of our study clearly demonstrate that in patients with severe TV endocarditis, complex reconstructive techniques yield excellent midterm results with regard to freedom of recurrence of endocarditis and valvular competence and should be considered as the primary surgical option in these patients. Tricuspid valve replacement should only be performed in cases of severe TV destruction that renders reconstructive techniques impossible.

BACKGROUND: Gastroesophageal reflux disease (GERD) affects approximately 20–40% of individuals in Europe and North America and represents a disorder associated with "losses" (loss of life quality, esophageal function and morphology). METHODS: Review of level of evidence III–IV papers on diagnosis of GERD. RESULTS: GERD symptoms (heartburn, regurgitation, dysphagia, cough, wheezing) are associated with pathologic acidic and/or nonacidic gastroesophageal reflux, impaired esophageal motility and lower esophageal sphincter function and pathologic morphology: stricture, ulcus, ring web formation; columnar lined esophagus (CLE); intestinal metaplasia (i.e. Barrett esophagus) which may progress towards dysplasia and adenocarcinoma of the esophagus. Symptom correlation with data obtained by combined pH- and intraluminal impedance monitoring represents a sensitive tool for assessment of presence or absence of GERD and should be offered to those with GERD symptoms and normal pH-monitoring. Endoscopy should include biopsy sampling of a normal appearing esophago-gastric junction for exclusion of microscopic CLE with or without intestinal metaplasia and/or dysplasia. The value of high-resolution manometry for diagnosis of GERD is still under investigation. CONCLUSIONS: Patient history, physical examination and assessment of life quality are of major importance for diagnosis of GERD. Novel technologies have profoundly contributed towards those responsible being able to ascertain whether symptoms are in fact being caused by gastroesophageal reflux.

Background. The objective of this study was to investigate purine nucleotide metabolism in peripheral blood mononuclear cells (PBMC) of cardiac transplant recipients switched from azathioprine to mycophenolate mofetil (MMF).Methods. Concentrations of guanosine 5'triphosphate (GTP) and adenosine 5'triphosphate (ATP), the activities of inosine monophosphate dehydrogenase (IMPDH), guanine phosphoribosyltransferase (GPRT), and hypoxanthine phosphoribosyltransferase (HPRT) were determined in PBMC of 27 cardiac transplant recipients before switch to MMF and 3, 6, and 12 months thereafter.Results. There was no difference in the activities of IMPDH and salvage pathway enzymes GPRT and HRPT as well as in intracellular GTP and ATP concentrations between the patients before switch to MMF and healthy controls. The GTP and ATP concentrations in PBMC of cardiac recipients did not change during the entire observation period. Although the MPA trough level remained similar, IMPDH activity declined from 897 to 316 pmol/10(6)PBMC/h 3 months after MMF onset, was almost completely inhibited after 6 months, and partially restored to 143 pmol/10(6)PBMC/h 12 months after switch to MMF. In contrast, GPRT activity increased after 3, 6, and 12 months of MMF therapy and HPRT activity 3 and 6 months after switch to MMF.Conclusions. We demonstrated for the first time an induction of salvage pathway enzyme activities in PBMC under MMF therapy. This probably accounts for the maintenance of intracellular purine nucleotide pools and prevents the GTP depletion.

This study assessed the value of haemostatic fleece (HF) in prevention of pleural adhesions in an experimental animal model. Forty rats were randomly assigned to four equal groups and underwent bilateral thoracotomy. In Group 1 standardized defects of 5 mm were generated in the visceral and the opposite parietal pleura without further coverage. In Group 2 a 5-mm piece of HF (TachoSil) was applied onto the intact pleura. In Group 3 a standardized pleural defect was completely covered by HF. The same kind of defect was only partially covered by HF in group 4 animals. Autopsy at 6 weeks (n=5, each group) revealed the fleece widely unchanged and covered by a smooth serous membrane. After 12 weeks (n=5, each group) the fleece had been completely resorbed. Histological studies revealed the area of the defect covered by regular mesothelium. In all animals pleural adhesions were detected only in the area without fleece coverage. In this experimental model HF prevented the development of pleural adhesions. This property may have clinical impact in patients with some probability of re-thoracotomy enabling to reduce the risk of pleural adhesions significantly.

a Abstract This study assessed the value of haemostatic fleece (HF) in prevention of pleural adhesions in an experimental animal model. Forty rats were randomly assigned to four equal groups and underwent bilateral thoracotomy. In Group 1 standardized defects of 5 mm were generated in the visceral and the opposite parietal pleura without further coverage. In Group 2 a 5-mm piece of HF (TachoSil ) was applied onto the intact pleura. In Group 3 a standardized pleural defect was completely covered by HF. The same kind of defect was only partially covered by HF in group 4 animals. Autopsy at 6 weeks (ns5, each group) revealed the fleece widely unchanged and covered by a smooth serous membrane. After 12 weeks (ns5, each group) the fleece had been completely resorbed. Histological studies revealed the area of the defect covered by regular mesothelium. In all animals pleural adhesions were detected only in the area without fleece coverage. In this experimental model HF prevented the development of pleural adhesions. This property may have clinical impact in patients with some probability of re-thoracotomy enabling to reduce the risk of pleural adhesions significantly. 2006 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

BACKGROUND:Our aim was to study the process of microcirculatory reconstitution in the bronchial stump after pneumonectomy.METHODS:Eighteen juvenile pigs (median weight 40.6 kg) were randomly assigned to three groups. In all animals left pneumonectomy was performed and the stapled bronchial stump (median length 3.8 cm) carefully denuded. Group I animals received coverage of the stump by intercostal flap. In group II, the stump was covered with TachoComb, an impermeable hemostatic fleece; and group III served as a control without any coverage of the stump. Animals were sacrificed at day 14 after surgery. Vascular density was evaluated in serial histologic sections at multiple levels stained with CD-31 antibody. One-way analysis of variance and the Wilcoxon test were used for data analysis.RESULTS:At autopsy, stumps of group III animals were totally covered by adjacent mediastinal structures. In group I, intercostal flaps were viable and completely healed to the bronchial stumps. There were no signs of infection or stump insufficiency in these groups. In all group II animals, empyema developed, and stumps were found necrotic at macroscopic and histologic evaluation. Statistical analysis revealed significantly lower vascular density of mature vessels in the area of the bronchial stump in group II compared with both other groups.CONCLUSIONS:Reconstitution of microcirculation of the denuded bronchial stump after pneumonectomy takes place in a centripetal way from adjacent viable tissue. Hence, the purpose of covering the bronchial stump is the improvement of blood supply rather than mechanical reinforcement.

Objective: To compare survival of patients with isolated synchronous and metachronous brain metastases from non-small cell lung cancer (NSCLC) after combined surgical treatment. Methods: A total of 991 patients underwent surgical resection of primary NSCLC between January 1994 and November 1999. Out of these, 32 patients (21 males and 11 females) were further treated for isolated brain metastases. In a retrospective survey, the outcome of patients with either synchronous (group 1, n = 16) or metachronous (group 2, n = 16) brain metastases was evaluated. Five patients out of each group received either adjuvant or neo-adjuvant chemotherapy. Data analysis includes descriptive statistics, Wilcoxon test, Kaplan-Meier method and Cox's proportional hazards model. Results: There was no significant difference in local tumour stage and histology of the primary turnout between both groups. Median of the disease free interval (DFI) after primary lung surgery (group 2) was 10 months, range 3-60 months. Median survival after lung surgery was 8.5 months in group 1 and 16.4 months in group 2 (P = 0.094). Median survival after cerebral procedures was 9.3 and 6.2 months, respectively (P = 0.127). Estimated survival rates by Kaplan-Meier method after cerebral procedures operation in group 1 were 37.5% at 1 year, 25.0% at 2 years and 18.8% at 5 years; in group 2 estimated survival rates were 31.3% at 1 year, 15.6% at 2 years and 0% at 5 years (P = 0.148). Calculated survival rates after lung surgery were identical in group 1; in group 2 survival rates were 62.5, 43.8 and 18.8% at 1, 2 and 5 years, respectively (P = 0.101). In the univariate model, none of the following variables had effect on survival: sex, age, T stage of the turnout, nodal status, timing of metastatic lesions, number of cerebral metastases, complete resection of primary tumour and histological type. Multivariate analysis did not reveal any risk factor, which significantly predicted survival. DFI did not correlate with survival of patients in group 2. Conclusions: Once isolated synchronous or metachronous brain metastases from NSCLC have developed, there is no difference in prognosis after combined surgery between analysed groups. This questions the value of lung resection in patients with isolated synchronous brain metastases. (C) 2004 Elsevier B.V. All rights reserved.

Cardiac Transplant Program of the University of Vienna: Experiences of 20 years. Since the beginning of the University of Vienna Cardiac Transplant Program in 1984, more than 900 heart

Background: Cytomegalovirus (CMV) has long been recognized as the most common opportunistic pathogen in transplant recipients. The use of post-detection antiviral treatment of CMV as a strategy to prevent disease in cardiac recipients is becoming the standard policy. Valganciclovir is an oral pro-drug of ganciclovir, with a 10-fold greater bioavailability than oral gancyclovir.Patients and Methods: We reported our first experience with 8 patients (3 female, 45.0 +/- 10.5 years old, non-CMV mismatched) who underwent cardiac transplantation and had positive results of CMV polymerase chain reaction (PCR) within first 6 weeks after transplantation without concomitant CMV disease. These patients received valganciclovir in dosage 450 to 900 mg daily depending on renal function for 3 weeks. Standard immunosuppressive regimen consisted of cyclosporin A, MMF and corticosteroids, and was not changed after detection of CMV infection. In,one patient we used sifolimus with respectively reduced dosage of cyclosporin A. Weekly measurements of CMV-PCR were performed to observe results of therapy.Results: After 1 week of valganciclovir therapy CMV-PCR plasma concentration in all patients decreased significantly (2,105 copies/ml vs 400 copies/ml; p < 0.0001). No relapse of CMV infection has been detected after completing of valganciclovir therapy with follow up duration of 9.0 +/- 0.92 months. The drug was generally well tolerated, and we did not observe any severe drug related adverse events.Conclusion: Oral valganciclovir as pre-emptive antiviral therapy administrated after detection of CMV infection seems to be an effective and safe treatment in cardiac transplant recipients. J Heart Lung Transplant.

HLA matching is associated with better graft survival in renal transplantation. Its role in cardiac transplantation (Tx) is still unclear. Nothing is known about the potential impact of induction therapy on outcome of well vs. poorly HLA matched cardiac recipients. The combined effect of histocompatibility and type of induction was analysed to determine their influence on graft survival, incidence of rejection and severe graft sclerosis in cardiac recipients.

Background: Cytomegalovirus (CMV) has long been recognised as the most common opportunistic pathogen in transplant recipients. The use of post-detection antiviral treatment of CMV as a strategy to prevent disease in cardiac recipients become the standard policy. Valgancyclovir is an oral prodrug of gancyclovir, with a 10-fold greater bioavailability than oral gancyclovir.

Background: Prolonged immunosuppression after solid-organ transplantation is associated with an increased risk for development of neoplasms. The purpose of this analysis was to investigate neoplasm incidence and outcome in patients with induction therapy.