PubMed Health⌕ Search

Biomedical subjects

Armin W Erasmi

Publications and source records attributed to Armin W Erasmi.

8 recordsLinked to original sources
PubMed2006

Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve.

The bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1-2% of the population. In a recent report, mutations in NOTCH1 a signaling and transcriptional regulator have been shown to cause BAV in two families. This study provides data on systematic sequencing in search for novel mutations in NOTCH1 gene in a large sample BAV. For the first time, we report results of a systematic mutation-analysis based on DNA-sequencing of all coding exons and adjacent splice consensus sequences of NOTCH1 gene. Our analyses revealed 57 NOTCH1 sequence variants. Twenty-one variants are located within exons and 36 within intronic or 5'-UTR sequences. Thirty-five variants were described previously as polymorphisms. The remaining 22, however, were neither listed in public SNP databases nor in the literature and were therefore considered novel. Seventeen variants were found only once (MAF = 1%), of these 15 were novel. Two sequence variants led to amino acid substitutions (p.T596M and p.P1797H) and are located in highly conserved regions of the NOTCH1 protein. In addition, these two mutations could not be detected in at least 327 healthy controls by using RFLP-analysis. The functional relevance of the other 13 novel and rare variants could not be proven without further functional examination. In this study, we provide a new evidence that the mutations in the NOTCH1 gene may trigger the underlying mechanism causing the valve calcification, especially in BAV. In conclusion, NOTCH1 gene mutations do not only play a role in familiar BAV, but can also be observed in approximately 4% of sporadic cases.

Adult↗
PubMed2006

Mitochondrial DNA deletions and the aging heart.

Mitochondrial DNA (mtDNA) mutations appear to be associated with a wide spectrum of human disorders and proposed to be a potential contributor of aging. However, in an age-dependent increase of the common 4977 bp deletion of human mtDNA still many unanswered questions remain. Comparing mtDNA copy levels in different tissues revealed that cardiac muscle had the highest, while the cortex cerebelli showed the lowest copy number of mtDNA in every donor. Intriguingly, mtDNA copy number showed no changes during aging. In heart tissue, the amount of 4977 bp mtDNA deletion increased in an age-dependent manner showing significant differences at the age of 40 years and older (p<0.005). In vitro studies analyzing human normal cells transfected with telomerase (BJ-T) revealed that oxidative stress (OS)--a well accepted promoter of aging--induced 4977 bp deletion and point mutations as demonstrated by real-time PCR and DHPLC analysis. Interestingly, OS induced apoptosis only in transformed human fibroblasts by activation of the intrinsic (mitochondrial-mediated) signalling pathway as indicated by morphological damage of mitochondria, DNA laddering and increase of the Bax/Bcl-2 ratio. In conclusion, in heart tissue, the amount of the 4977 bp deletion increased in an age-dependent manner and it was more detectable after the 4th decade of life, although there was some scatter in the data. Since, apoptosis was induced by the mitochondria-mediated pathway only in transformed cells, the role for apoptosis in normal tissue of the aging heart remains unclear.

Adolescent↗
PubMed2006

[Reconstructive surgery of the aortic valve: the Ross, David, and Yacoub procedures].

The aortic valve consists of three cusps attached to the wall of the aortic root. During the cardiac cycle, the aortic root undergoes complex movements that precede and aid opening and closing of the aortic valve. The aortic valve cusps themselves form thin-walled pocket-like structures, made from specialized tissue with fibrous, elastic, nervous, and muscular properties. The complex interactions of this tissue with the aortic root and within the cardiac cycle are only incompletely understood yet. In summary, the aortic valve is a complex structure which shows a perfect function in systole and diastole and under a wide range of hemodynamic conditions. No valve prosthesis (so far) can keep up with the function of the native aortic valve. Therefore, surgical techniques have been invented that aim at sparing the aortic valve or replacing it with very similar autologous tissue. Besides the resulting (near) normal valve function, one appealing advantage of these techniques is that oral anticoagulation can be abandoned completely. If the valve cusps themselves are normal, but the aortic root is aneurysmatic or dissected (with or without resulting secondary aortic insufficiency), the aortic valve can be spared by resecting the aortic root tissue and replacing it by a vascular graft. The aortic valve can then be implanted into the vascular graft in a way described by David, or can be remodeled into it (Yacoub technique) - in this case, the graft first needs to be incised at its base so that the three commissures of the valve can be sewn into the three incisions. This way pseudosinuses within the vascular graft are created. The sinuses within the aortic root are considered important for aortic valve function and coronary perfusion. On the other hand, incisions at the base of the vascular graft harbor the potential for redilatation of the aortic root because of a missing circular fixation. Such a fixation is achieved by the David technique. Therefore, there is a great debate in the surgical community which valve-sparing technique is the best and numerous modifications of the original techniques exist. A clear clinical advantage of one technique over the other could not be demonstrated so far, but many authorities advise that the David technique is to be used preferentially in patients with Marfan's syndrome (or other connective tissue disorders) and those with a very wide basal aortic root. If the aortic valve cusps themselves are diseased and cannot be reconstructed, the autologous pulmonary valve is the most physiological substitute. Replacing the aortic valve with the autologous pulmonary valve is named Ross procedure. The defect in the right ventricular outflow tract that is created while harvesting the autograft must be reconstructed during the same procedure; usually, a pulmonary valve allograft is used for this purpose. With all reconstructive surgical techniques and with all autologous replacements there is a risk of reoperation, mainly (besides technical issues) because it is feared that leaving autologous tissue in place leads to recurrence of the original illness. The published results, however, with aortic valve-sparing surgery and with the Ross procedure show that the risk of reoperation appears to be very acceptable. This statement is especially true for the Ross procedure for which more and longer experience exists worldwide. Echocardiographic studies show that the aortic valve function after valve-sparing techniques and - especially - after the Ross procedure is indeed excellent. Therefore, patients with aortic root pathologies or aortic valve diseases should be informed about valve-sparing aortic root reconstructive techniques or the Ross procedure. The choice of technique should be made in close contact between patient, cardiologist, and cardiac surgeon. However, the described techniques require extensive experience within the surgical team.

Aortic Aneurysm↗
PubMed2005

Mid-term findings on echocardiography and computed tomography after RVOT-reconstruction: comparison of decellularized (SynerGraft) and conventional allografts.

OBJECTIVE: The immune response against human-leucocyte-antigens on donor-cells may be an important factor contributing to the degeneration of allograft-valves. We have previously reported that the use of the decellularized allograft SynerGraft (CryoLife) reduces the immunologic response of the allograft-recipient. In this study we compare the echocardiographic and computed tomography angiographic (CTA) findings of SynerGrafts with conventional cryopreserved allografts. METHODS: 22 patients who received a pulmonary SynerGraft (SG-group) (21 during a Ross-procedure) underwent CTA and resting echocardiography (median: 10 months postoperatively). 47 randomly chosen patients who underwent a Ross-procedure served as controls (C-group) (median: 32 months postoperatively). RESULTS: Neither the pressure gradients (mean: SG=9+/-4 vs C=10+/-4mmHg; P=0.64) across the allograft, nor the effective orifice area (EOAI) (SG=0.93+/-0.80 vs C=0.93+/-0.42cm(2)/m(2); P=0.96) differed between the groups. The EOAI showed a significant correlation with the smallest allograft-conduit-area measured on CTA (r=0.81; P<0.001) which was most frequently (n=34) found in the proximal postvalvular tubular part of the conduit. Calcifications (n=11) or a fibroproliferative reaction (n=15) were rarely observed. Overall, there were no radiologic differences between the groups. On CTA, the smallest diameter of the allograft-conduits was significantly smaller than the diameter given on the cryopreservation protocol (SG=16+/-3 and C=17+/-3mm vs 25mm in both groups; P<0.001 each) whereas the diameter of the distal part of the allograft was not (SG=24+/-2, P=0.066, and C=25+/-3mm, P=0.82). CONCLUSIONS: Despite a significant shorter follow-up in the SynerGraft-group, no functional or radiologic differences were observed as compared to control-patients. The smallest diameter is located almost exclusively at the proximal level of allograft-conduits.

Adult↗
PubMed2003

Up to 7 years' experience with valve-sparing aortic root remodeling/reimplantation for acute type A dissection.

BACKGROUND: Aortic valve-sparing operations for acute type A dissection are appealing and innovative but less well defined surgical techniques requiring further evaluation. METHODS: We reviewed all consecutive patients with acute type A dissection who underwent either the remodeling (group 1, n = 21) or the reimplantation valve-sparing technique (group 2, n = 15) since October 1994. Patients were followed up clinically and echocardiographically for as long as 41.3 months (group 1) and 87 months (group 2). RESULTS: Hospital mortality was 19% (n = 4) for group 1 and 20% (n = 3) for group 2. Permanent new neurologic symptomatology occurred in 1 patient (3.6%). Three patients in group 1 required reoperation owing to redissection. No patient had an aortic insufficiency of more than grade 1. No late neurologic or thrombembolic events occurred. There was no statistically significant difference between both groups with respect to clinical and hemodynamic data. CONCLUSIONS: Remodeling and reimplantation aortic valve-preserving operations in acute type A dissection can be performed with adequate perioperative risk and excellent midterm aortic valve function. We found no evidence of one technique being superior to the other, however durability of the remodeling technique needs critical consideration especially in Marfan syndrome and when glue is used.

Acute Disease↗
PubMed2003

Histopathological grading of ascending aortic aneurysm: comparison of patients with bicuspid versus tricuspid aortic valve.

BACKGROUND AND AIMS OF THE STUDY: Bicuspid aortic valve (BAV) is a common inherited condition that is often accompanied by ascending aortic aneurysm. A high level of histological wall abnormalities was reported to be present in non-dilated aortas of patients with BAV. In patients with tricuspid aortic valve, there appears to exist a direct relationship between the diameter of the ascending aorta and degree of histopathological aortic wall abnormalities. Whether this situation exists in patients with BAV has not yet been investigated. METHODS: Surgical and medical records of all patients undergoing surgery of the ascending aorta were reviewed. A total of 65 patients was identified in whom an aortic wall specimen was obtained intraoperatively. These specimens were systematically re-evaluated, and graded according to the severity of seven histopathological conditions: fibrosis, atherosclerosis, medionecrosis, cystic medial necrosis, smooth muscle cell orientation, elastic fiber fragmentation, and inflammation. RESULTS: BAVs were present in 26 patients (40%). Patients with BAV had significantly less aortic wall alterations than patients with tricuspid aortic valves (p < 0.001) in all variables examined. The severity of aortic wall abnormalities was significantly dependent on aortic diameter in patients with BAV as well as tricuspid aortic valve (p = 0.036 and 0.019), but dependent on age (p = 0.009) only in patients with tricuspid aortic valve. CONCLUSION: The study results provide evidence that ascending aortic aneurysm in patients with BAV differs clinically and histologically from that in patients with tricuspid aortic valve. Further studies are needed to elucidate the impact of inherited and acquired aortic wall abnormalities on the development of aneurysms.

Adult↗