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Biomedical subjects

Axel Haverich

Publications and source records attributed to Axel Haverich.

At least 19 recordsLinked to original sources
PubMed2007

Multicentered European study on safety and effectiveness of the On-X prosthetic heart valve: intermediate follow-up.

BACKGROUND: This study was performed to determine the safety and effectiveness of the On-X valve, a novel mechanical valve substitute. METHODS: Eleven centers participated in a European, multicentered, longitudinal, nonrandomized study of the On-X valve performance. Isolated aortic or mitral valve replacement with an On-X valve was studied in 301 patients. Aortic valve replacement was performed in 184 patients (average follow-up, 5.0 years), whereas mitral valve replacement was performed in 117 patients (average follow-up, 4.4 years). RESULTS: In patients with aortic valve replacement, mean transvalvular pressure gradients ranged from 8.3 to 4.7 mm Hg and effective orifice areas from 1.5 to 2.7 cm2, for 19-mm through 25-mm valves, respectively. After mitral valve replacement, mean gradient was 4.2 mm Hg and effective orifice area by pressure half-time was 2.6 cm2 regardless of valve size. Hemolysis was low, with postoperative serum lactate dehydrogenase at 225 +/- 41 IU (mean +/- standard deviation) or 253 +/- 65 IU, after aortic valve replacement or mitral valve replacement, respectively (upper normal value, 250 IU). At 1 year or greater postoperatively, 91.6% of patients after aortic valve replacement and 84.6% after mitral valve replacement were in New York Heart Association functional class I or II. Adverse event rates in percent per patient-year after aortic valve replacement or mitral valve replacement were thromboembolism, 0.88 or 1.76; thrombosis, 0.11 or 0.20; bleeding, 0.77 or 1.96, respectively. Late mortality was 1.97% or 2.55%, respectively. CONCLUSIONS: At the intermediate follow-up, the On-X valve exhibited improved hemodynamics, low hemolysis with in-range lactate dehydrogenase, and low adverse event rates, particularly in the aortic position.

Aged↗
PubMed2006

Potential of an injectable polymer to prevent hyperacute rejection of ex vivo perfused porcine lungs.

BACKGROUND: Removal of xenoreactive antibodies in pig-to-human lung transplantation by columns or organ perfusions proofed to be unsatisfactory and associated with adverse effects. In an ex-vivo lung perfusion model, we evaluated the potential of a soluble trisaccharide polymer (GAS914) to bind alpha-Gal antibodies and to protect a pulmonary xenograft from hyperacute rejection (HAR) and pulmonary xenograft dysfunction. METHODS: Porcine lungs were perfused with fresh human blood for 240 min. In the GAS914 treated group (n=6) the polymer was applied in three different concentrations. The control group (n=6) received no GAS914. Survival and function of perfused xenografts were monitored, and alpha-Gal antibodies as well as cytolytic anti-porcine antibodies analyzed. RESULTS: In the GAS-treated group survival of lungs was significantly prolonged, pulmonary vascular resistance reduced, pulmonary edema prevented, and oxygenation improved. On histopathological evaluation application of GAS resulted in minimal graft injury and significantly less deposition of the terminal complement complex C5b-9. Following application of GAS914, up to 89.8% of IgG alpha-Gal, 79.5% of IgM and 73.6% of anti-porcine antibodies in the human blood were bound by the polymer. Subsequent perfusion of porcine lungs resulted in absorption of only 3% of the baseline IgG alpha-Gal antibodies in the GAS914 group, compared to 87% in the controls. CONCLUSIONS: In this ex-vivo lung perfusion model, a trisaccharide polymer prevented immediate HAR, due to effective removal of alpha-Gal antibodies. In combination with additional strategies GAS914 may be a valuable tool in overcoming HAR and dysfunction of pulmonary xenografts.

Acute Disease↗
PubMed2006

Creatine kinase isoenzyme MB relative index as predictor of mortality on extracorporeal membrane oxygenation support for postcardiotomy cardiogenic shock in adult patients.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used as initial, biventricular circulatory support for patients with severe postcardiotomy cardiogenic shock (PCS). Due to its aggressiveness and limited weaning quote, concerns have been raised about maintenance of ECMO support regarding duration. However, it is frequently hazardous for physicians to make an individualized decision, whether and when discontinuation of ECMO support should be considered. We tried to find measurable values during ECMO support that could predict the patient mortality on ECMO support. METHODS: During a 9-year period, 32 patients (mean age 55.4+/-11.9; ranging from 30 to 75 years) with ECMO support for postcardiotomy cardiogenic shock were included in this study. RESULTS: Eighteen patients died without weaning (group I, 56.25%), while 14 patients could be weaned off the ECMO support (group II, 43.75%). In the group II, six patients (18.75%) died later in the postoperative course and eight patients (25%) survived to be discharged from hospital. The overall survival of all 32 patients at 30 days was 31.25% (n=10). At a follow-up period of 3.88+/-1.58 years, the overall survival rate was 12.5% (n=4). Mean duration of ECMO support was 2.7+/-1.7 days. The following variables were significantly different between the two groups: blood lactate level and the level of MB isoenzyme of creatine kinase (CK-MB) 48 h after ECMO initiation (p<0.01, p=0.001) as well as the CK-MB relative index as the ratio of CK-MB to total CK (p<0.001). Logistic regression identified that only the CK-MB relative index 48 h after ECMO initiation was associated with mortality on ECMO support (p=0.011, odds ratio=1.219, 95% confidence interval: 1.046-1.421). CONCLUSION: For adult non-transplantation patients with postcardiotomy cardiogenic shock, the CK-MB relative index 48 h after ECMO initiation can be a predictor of mortality on ECMO support. This might be a useful tool for considering a patient either for discontinuation of ECMO support or further treatment.

Adult↗
PubMed2006

Pravastatin prolongs graft survival in an allogeneic rat model of orthotopic single lung transplantation.

OBJECTIVE: MHC class II molecules play central roles in immune recognition and rejection. As statins have been shown to inhibit the production of these molecules, we analyzed the possible immunosuppressive effect of pravastatin, using our rat model of orthotopic lung transplantation. METHODS: Single orthotopic lung transplantation was performed in a Fischer 344-to-Wistar Kyoto strain combination. One group received pravastatin i.p. after transplantation, controls NaCl. Statin serum levels were analyzed by high performance liquid chromatography (HPLC). Animals were sacrificed on postoperative day (POD) 14 and 21. At sacrifice, samples were obtained for histology, immunhistochemistry, flow cytometry and real-time RT-PCR analysis of CD25, TNF-alpha, and MHC class II expression. Rejection was graded via histochemistry, using a system based on the working formulation of The International Society of Heart and Lung Transplantation. Immunohistochemistry was performed for expression of MHC class II, T-cell receptor, CD25, CD4/8 cell, NK cells, granulocytes and monocytes in naïve lungs and grafts from donor and recipient animals. Flow cytometric analysis of recipient peripheral blood mononuclear cells (PBMC) was used to analyze expression of CD3, CD4, CD8, and RT1B in both groups. In vitro analyses of MHC class II expression were performed in parallel. RESULTS: HPLC confirmed effective delivery of pravastatin. Recipients treated with pravastatin showed significantly less rejection on POD 14 and on POD 21, when compared to controls. Immunohistochemistry showed specific differences, suggesting a delay in rejection in the pravastatin group. Flow cytometric analyses showed a higher expression of CD4 in the control group on POD 21. Results of real-time RT-PCR analyses for MHC class II expression showed a significant decrease in expression in the statin-treated group. Flow cytometric analysis of gamma-IFN stimulated rat PBMC showed an inhibition of upregulation of MHC class II expression by pravastatin in vitro. CONCLUSIONS: Pravastatin prolongs graft survival in our allogeneic rat model of orthotopic lung transplantation. We assume that the underlying mechanism for this effect is the inhibition of upregulation of MHC class II molecule synthesis, thus blocking downstream effector mechanisms of the immune system.

Animals↗
PubMed2006

Hypothermic circulatory arrest with moderate, deep or profound hypothermic selective antegrade cerebral perfusion: which temperature provides best brain protection?

OBJECTIVE: Selective antegrade cerebral perfusion (SACP) seems to be associated with a better outcome compared to hypothermic circulatory arrest (HCA) alone. This study was undertaken to evaluate the influence of different SACP temperatures on the neurological integrity. METHODS: Twenty-six pigs were included in the study and assigned to 100 min HCA at 20 degrees C body temperature without (n = 6) or with either 10 degrees C (n = 6), 20 degrees C (n = 7) or 30 degrees C (n = 7) of SACP. Haemodynamics, metabolics and neurophysiology (EEG, SSEP, ICP, sagittal sinus saturation) were monitored. Animals were sacrified 4h after reperfusion and brains perfused for histological and molecular genetic assessment. RESULTS: There were no clinically relevant differences in haemodynamics between groups. The rise in ICP during SACP was significantly more marked in the 30 degrees C group (p < 0.05) and remained high during the entire experiment. In the 10 degrees C group the rise in ICP was postponed, but increased during reperfusion. The 20 degrees C group showed a slight increase of ICP over time, but remained significantly lower compared to HCA (p < 0.05). Sagittal sinus saturation decreased during SACP at 30 degrees C (p < 0.05). EEG recovery was most complete in the 20 degrees C group (p < 0.05). RT-PCR analysis of brain tissue revealed a reduction for heat shock protein (HSP-72) in 20 degrees C (p < 0.05) and 10 degrees C animals (p = 0.095). Histopathological evaluation showed a reduction of edema and eosinophilic cells in the groups treated with SACP. CONCLUSION: In this model, SACP is superior to HCA alone. Regarding the optimal temperature for SACP, it seems that 20 degrees C provides adequate brain protection in comparison to the potential detrimental effects of moderate (30 degrees C) and profound (10 degrees C) temperatures.

Animals↗
PubMed2006

Preoperative low-dose irradiation promotes long-term allograft acceptance and induces regulatory T cells in a porcine model of pulmonary transplantation.

BACKGROUND: A simplified conditioning protocol including single-dose preoperative thymic and low-dose whole body irradiation with or without subsequent donor bone marrow transplantation (BMTx) can be applied in porcine lung transplantation. We hypothesized that this protocol would prolong allograft survival. METHODS: Left-sided single lung transplantation from major histocompatibility complex (MHC)-mismatched donors was performed in 27 minipigs. Recipients received whole body (1.5 Gy) and thymic irradiation (7 Gy) before transplantation (IRR group, n=6), intravenous immunosuppression with methylprednisolone, cyclosporine, and azathioprine for 27 postoperative days (IS group, n=5) or both (IRR+IS group, n=10). BMTx group recipients were treated with irradiation, immunosuppression and a donor bone marrow infusion on postoperative day 1. Peripheral blood leukocyte phenotype and donor cell chimerism were monitored by flow cytometry. Purified CD25+ T cells from long-term survivors or rejecting animals were used for in vitro MLR suppression assays. RESULTS: Median graft survival was: IRR 12 days, IS 55 days, IRR+IS 239 days, and BMTx 80 days (P<0.0001). Early peripheral blood macrochimerism was substantial in both the IRR+IS and the BMTX group but was lost in all groups after day 80. The frequency and suppressive function of CD4+CD25+ T cells were enhanced in IRR+IS group long-term survivors. CONCLUSION: Although donor bone marrow infusion was not beneficial in our model, a substantial proportion of the animals treated with irradiation and a 28-day course of immunosuppression accepted their lung allografts long term. The mechanism involved in maintaining allograft tolerance may be based on peripheral T-cell regulation.

Animals↗
PubMed2006

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: is deep hypothermia required?

OBJECTIVE: To investigate whether deep (<20 degrees C) hypothermia is necessary in patients undergoing pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. METHODS: Between January 2004 and February 2005, 30 patients (New York Heart Association (NYHA) class III or IV) were randomly assigned to increasing (1 degrees C) levels of moderate (28-32 degrees C) hypothermic cardiopulmonary bypass (CPB), each study group including six patients. Primary study endpoint was adverse neurological outcome. Overall preoperative total pulmonary vascular resistance was 1110+/-192 dynes cm(-5). RESULTS: Mean CPB and cross-clamp times, and core temperature at the time of circulatory arrests were 129+/-39 min and 92+/-24 min, and 30.1+/-1.5 degrees C, respectively. Circulatory arrest was induced 2+/-0.7 times and its mean total duration was 10.3+/-5.2 min (range, 2-19 min). Postoperatively, three patients (10%) belonging to the 31 degrees C (n=1) and 32 degrees C (n=2) groups suffered from temporary neurological dysfunction. Postoperative mechanical ventilatory support and ICU stay were 26.3+/-18.9 h and 6.6+/-8.5 days, respectively, and uninfluenced by degree of hypothermia. There were no lung reperfusion injuries or any other major complications. All patients had a significant hemodynamic improvement. CONCLUSION: Results suggest that pulmonary endarterectomy can be safely performed with moderate hypothermia and short periods of circulatory arrests without the need of profound hypothermia.

Adult↗
PubMed2006

Clinical application of tissue engineered human heart valves using autologous progenitor cells.

BACKGROUND: Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. METHODS AND RESULTS: Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients. CONCLUSIONS: TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.

Adolescent↗
PubMed2006

Preclinical testing of tissue-engineered heart valves re-endothelialized under simulated physiological conditions.

BACKGROUND: The in vivo regeneration capacity of decellularized heart valve grafts is still controversial. The aim of this study was to evaluate function, morphological changes, and cellular composition of decellularized versus re-endothelialized ovine pulmonary valves (PV) after implantation into lambs for 1 or 3 months. METHODS AND RESULTS: PV (n=21) were decellularized using detergents. Twelve PV were repopulated with autologous jugular veins endothelial cells (ECs) in a dynamic pulsatile bioreactor under simulated physiological conditions. Morphological evaluation before implantation included histological stainings (H&E, Movat-pentachrome, von-Kossa, DAPI), immunostainings (anti-perlecan, anti-eNOS, anti-procollagen-I, anti-SM-alpha-actin), electron microscopy (EM), and DNA extraction. Decellularization led to cell-free scaffolds with preserved extracellular matrix (ECM) including basement membrane. Reseeded PV (n=5) were completely covered with ECs expressing endothelial nitric oxide synthase (eNOS) and von Willebrand factor (vWF). The function of orthotopically implanted decellularized and re-endothelialized PV (n=7, each) was analyzed after 1 and 3 months by echocardiography and revealed no differences in competence between both groups. A confluent EC monolayer expressing eNOS/vWF was only found in re-endothelialized PV but not in decellularized PV, whereas the valve matrices were comparable repopulated with interstitial cells expressing SM-alpha-actin and procollagen-I. More thrombotic and neointima formations were observed in decellularized PV. No signs of calcification were detected in both PV types. CONCLUSIONS: In vitro re-endothelialization of detergent-decellularized valves with autologous ECs under simulated physiological conditions significantly improves total EC valve coverage 3 months after implantation, whereas the valve repopulation with interstitial cells in vivo occurs most likely by cell migration inside the scaffold.

Animals↗
PubMed2006

In vitro re-endothelialization of detergent decellularized heart valves under simulated physiological dynamic conditions.

The production of viable biological heart valves is of central interest in tissue engineering (TE). The aim of this study was to generate decellularized heart valves with an intact ultra-structure and to repopulate these with endothelial cells (EC) under simulated physiological conditions. Decellularization of ovine pulmonary valve conduits was performed under agitation in detergents followed by six wash cycles. Viability of EC cultures exposed to washing solution served to prove efficiency of washing. Resulting scaffolds were free of cells with preserved extracellular matrix. Biomechanical standard tension tests demonstrated comparable parameters to native tissue. Luminal surfaces of decellularized valvular grafts were seeded with ovine jugular vein EC in dynamic bioreactors. After rolling culture for 48 h, pulsatile medium circulation with a flow of 0.1 L/min was started. The flow was incremented 0.3 L/min/day up to 2.0 L/min (cycle rate: 60 beats/min), while pH, pO2, pCO2, lactate and glucose were maintained at constant physiological levels. After 7 days, a monolayer of cells covered the inner valve surface, which expressed vWF, indicating an endothelial origin. A complete endothelialization of detergent decellularized scaffold can be achieved under simulated physiological circulation conditions using a dynamic bioreactor system, which allows continuous control of the culture environment.

Animals↗
PubMed2006

Generation and characterization of functional cardiomyocytes from rhesus monkey embryonic stem cells.

Embryonic stem cells (ESCs) from mice and humans (hESCs) have been shown to be able to efficiently differentiate toward cardiomyocytes (CMs). Because murine ESCs and hESCs do not allow for establishment of pre-clinical allogeneic transplantation models, the aim of our study was to generate functional CMs from rhesus monkey ESCs (rESCs). Although formation of ectodermal and neuronal/glial cells appears to be the default pathway of the rESC line R366.4, we were able to change this commitment and to direct generation of endodermal/mesodermal cells and further differentiation toward CMs. Differentiation of rESCs resulted in an average of 18% of spontaneously contracting embryoid bodies (EBs) from rESCs. Semiquantitative reverse transcription-polymerase chain reaction analyses demonstrated expression of marker genes typical for endoderm, mesoderm, cardiac mesoderm, and CMs, including brachyury, goosecoid, Tbx-5, Tbx-20, Mesp1, Nkx2.5, GATA-4, FOG-2, Mlc2a, MLC2v, ANF, and alpha-MHC in rESC-derived CMs. Immunohistological and ultrastructural studies showed expression of CM-typical proteins, including sarcomeric actinin, troponin T, titin, connexin 43, and cross-striated muscle fibrils. Electrophysiological studies by means of multielectrode arrays revealed evidence of functionality, electrical coupling, and beta-adrenergic signaling of the generated CMs. This is the first study demonstrating generation of functional CMs derived from rESCs. In contrast to hESCs, rESCs allow for establishment of pre-clinical allogeneic transplantation models. Moreover, rESC-derived CMs represent a cell source for the development of high-throughput assays for cardiac safety pharmacology.

Animals↗
PubMed2006

Fibroblasts of recipient origin contribute to bronchiolitis obliterans in human lung transplants.

RATIONALE: The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated. OBJECTIVES: This study analyzes whether circulating, bone marrow-derived, fibroblastic precursor cells contribute to the development of fibrosing lesions in human lungs, especially bronchiolitis obliterans. METHODS: The occurrence of in situ microchimerism in bronchiolitis obliterans lesions of human lung allografts (n = 12) as well as of autologous lung tissue from patients post-bone marrow transplantation (n = 2) was analyzed using laser-assisted microdissection after immunohistochemical labeling of leukocytes followed by short tandem repeat-polymerase chain reaction-based genotyping. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for independent confirmation in cases with appropriate sex mismatch (n = 2). MEASUREMENTS AND MAIN RESULTS: The bronchiolitis obliterans lesions of all 12 lung transplant patients contained considerable numbers of recipient-derived fibroblasts (mean, 32%). The fibrosing pulmonary lesions of the two bone marrow-transplanted patients also displayed clear in situ microchimerism. The in situ detection methodology confirmed these results, although to a lower degree (6-16%). CONCLUSIONS: These data clearly demonstrate the involvement of circulating fibroblastic precursor cells in the development of human fibrosing lung lesions and provide evidence that these cells are most probably bone marrow derived. These results may open new venues regarding the prevention of fibrosis in lung transplants and potentially in other organs.

Adult↗
PubMed2006

No evidence of transdifferentiation of human endothelial progenitor cells into cardiomyocytes after coculture with neonatal rat cardiomyocytes.

BACKGROUND: Recent studies have suggested the differentiation of human endothelial progenitor cells (huEPCs) isolated from peripheral blood into cardiomyocytes. This study investigates whether, when cocultured, neonatal rat cardiomyocytes (NRCMs) can induce transdifferentiation of huEPCs into cardiomyocytes. METHODS AND RESULTS: Coculture experiments with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI)-labeled huEPCs and NRCMs have been performed. Cocultures have been analyzed by means of flow cytometry, 3D confocal laser microscopy, species-specific reverse transcriptase-polymerase chain reaction for the expression of human cardiac marker genes, and electron microscopy. Although fluorescence-activated cell sorting (FACS) analysis and conventional wide-field fluorescence microscopy suggested the existence of DiIpos cardiomyocytes in cocultures, no convincing evidence of cardiac differentiation of huEPCs has been obtained. Apparently, DiIpos cardiomyocytes were identified as necrotic NRCMs or NRCM-derived vesicles with high levels of autofluorescence or, alternatively, as NRCMs lying on top of or below labeled huEPCs or huEPC fragments. Accordingly, no expression of human Nkx2.5, GATA-4, or cardiac troponin I was detected. CONCLUSIONS: No convincing evidence of transdifferentiation of huEPCs into cardiomyocytes was obtained. Although we cannot exclude that recent contrary data may be due to slightly different culture protocols, our study has revealed that recently applied standard analysis tools including FACS and wide-field fluorescence microscopy are not sufficient to demonstrate transdifferentiation in coculture settings and can lead to misinterpretation of the data obtained solely with these methods.

Animals↗
PubMed2006

Safety and efficacy of bioabsorbable magnesium alloy stents in porcine coronary arteries.

OBJECTIVE: We aimed to determine the safety and efficacy of biobasorbable magnesium alloy stents in porcine coronary arteries. Bioabsorbable magnesium stents carry the potential to overcome the limitations posed by permanent metallic stents such as chronic inflammation, late stent thrombosis, prolonged antiplatelet therapy, and artifacts when imaged by multislice-computed tomography or magnetic resonance imaging. METHODS: Magnesium alloy stents or stainless steel stents were randomly deployed in coronary arteries of domestic or minipigs. Domestic pigs were sacrificed at 3 days (n = 2) or 28 days, and minipigs at 3 months. RESULTS: At 3 days, magnesium alloy stents were intact, but started to show signs of degradation by 28 days. There was no evidence of stent particle embolization, thrombosis, excess inflammation, or fibrin deposition. At 28 days and 3 months, neointimal area was significantly less in magnesium alloy stent segments (2.44 +/- 0.88 mm(2) and 1.16 +/- 0.19 mm(2)) as compared with the stainless steel stent segments (5.03 +/- 1.5 mm(2) and 1.72 +/- 0.68 mm(2), P < 0.001 and 0.02). Quantitative coronary analysis indicates that percentage area stenosis and percentage diameter stenosis in magnesium alloy stent segments improved significantly at 3 months as compared to 28 days. Despite decreased neointimal hyperplasia, lumen area of the magnesium alloy stented vessels did not improve significantly. CONCLUSION: Magnesium alloy stents are safe and are associated with less neointima formation; however, reduced neointima did not result in larger lumen.

Absorbable Implants↗
PubMed2006

TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder characterized by manifestations in the cardiovascular, skeletal, ocular, and other organ systems. MFS type1 (MFS1) is caused by mutations in the gene encoding fibrillin (FBN1). Recently, the transforming growth factor-beta receptor-2 gene, TGFBR2, has been shown to be associated with a second type of this disorder with typically mild or absent ocular involvement (MFS type 2; MFS2). Several point mutations were found in the highly conserved serine/threonine kinase domain of TGFBR2. Mutations in both TGFBR1 and TGFBR2 are associated with Loeys-Dietz aortic aneurysm syndrome (LDS). We searched for TGFBR1 and TGFBR2 mutations in 41 unrelated patients fulfilling the diagnostic criteria of Ghent nosology or with the tentative diagnosis of Marfan syndrome, in whom mutations in the FBN1 coding region were not identified. In TGFBR1, two mutations and two polymorphisms were detected. In TGFBR2, five mutations and six polymorphisms were identified. Reexamination of patients with a TGFBR1 or TGFBR2 mutation revealed extensive clinical overlap between patients with MFS1, MFS2, and LDS.

Activin Receptors, Type I↗
PubMed2006

Anastomotic obstruction after magnetic vascular coupling after minimally invasive direct coronary artery bypass grafting.

We report a 61-year-old man who required reoperation 8 months after minimally invasive direct coronary artery bypass grafting after magnetic vascular coupling due to a symptomatic subtotal obstruction at the anastomotic site. It was also determined that the patient had been noncompliant in following the prescribed postoperative antiplatelet therapy.

Anastomosis, Surgical↗