Adult heart procurement following circulatory determined death from a donor on venous-venous extracorporeal membrane oxygenation: A case report.

Donation after circulatory death in the context of heart transplants is attracting interest and becoming popular in clinical practice. Activity is growing in the United Kingdom, Australia, and the United States. We believe that a prolonged warm ischemic time (time from asystole to reperfusion of the heart on an ex vivo perfusion system) is a primary indicator of adverse outcomes. However, 1.5 liters of blood must be retrieved from the right atrium following sternotomy prolonging warm ischemic time. The patient in the following case report was supported by veno-venous extra-corporeal membrane oxygenation following drowning, further complicated by aspiration-related lung failure. Following circulatory death and a mandatory five-minute stand-off period, 1.5 liters of blood was drained from the circuit as sternotomy began. Surgeons then proceeded to direct procurement of the heart, aiming for least functional warm ischemic time. Following standard implantation, the patient's postoperative recovery has been unremarkable to date.

Inhibition of HDAC6 activity through interaction with RanBPM and its associated CTLH complex.

BACKGROUND: Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase that promotes many cellular processes that lead to cell transformation and tumour development. We previously documented an interaction between Ran-Binding Protein M (RanBPM) and HDAC6 and found that RanBPM expression inhibits HDAC6 activity. RanBPM is part of a putative E3 ubiquitin ligase complex, termed the C-terminal to LisH (CTLH) complex. Here, we investigated the involvement of the CTLH complex on HDAC6 inhibition and assessed the outcome of this regulation on the cellular motility induced by HDAC6. METHODS: Cell lines (Hela, HEK293 and immortalized mouse embryonic fibroblasts) stably or transiently downregulated for several components of the CTLH complex were employed for the assays used in this study. Interactions of HDAC6, RanBPM and muskelin were assessed by co-immunoprecipitations. Quantifications of western blot analyses were employed to evaluate acetylated α-tubulin levels. Confocal microscopy analyses were used to determine microtubule association of HDAC6 and CTLH complex members. Cell migration was evaluated using wound healing assays. RESULTS: We demonstrate that RanBPM-mediated inhibition of HDAC6 is dependent on its association with HDAC6. We show that, while HDAC6 does not require RanBPM to associate with microtubules, RanBPM association with microtubules requires HDAC6. Additionally, we show that Twa1 (Two-hybrid-associated protein 1 with RanBPM) and MAEA (Macrophage Erythroblast Attacher), two CTLH complex members, also associate with α-tubulin and that muskelin, another component of the CTLH complex, is able to associate with HDAC6. Downregulation of CTLH complex members muskelin and Rmnd5A (Required for meiotic nuclear division homolog A) resulted in decreased acetylation of HDAC6 substrate α-tubulin. Finally, we demonstrate that the increased cell migration resulting from downregulation of RanBPM is due to the relief in inhibition of HDAC6 α-tubulin deacetylase activity. CONCLUSIONS: Our work shows that RanBPM, together with the CTLH complex, associates with HDAC6 and restricts cell migration through inhibition of HDAC6 activity. This study uncovers a novel function for the CTLH complex and suggests that it could have a tumour suppressive role in restricting HDAC6 oncogenic properties.

Transapical Transcatheter Valve-in-Valve Implantation for Failed Mitral Valve Bioprosthesis.

UNLABELLED: Background: The rate of mitral bioprosthesis implantation in clinical practice is increasing. Transcatheter valve-in- valve implantation has been described for high risk patients requiring redo valve surgery. OBJECTIVES: To report our experience with transapical valve-in-valve implantation for failed mitral bioprosthesis. METHODS: Since 2010, 10 patients have undergone transapical valve-in-valve implantation for failed bioprosthesis in our center. Aortic valve-in-valve implantation was performed in one of them and mitral valve-in-valve implantation in nine. Mean age was 82 ± 4 years and 6 were female (67%). Mean time from original mitral valve (MV) replacement to valve-in-valve procedure was 10.5 ± 3.7 years. Follow-up was completed by all patients with a mean duration of 13 ± 12 months. RESULTS: Preoperatively, all patients presented with significant mitral regurgitation, two with mitral stenosis due to structural valve failure. All nine patients underwent successful transapical valve-in-valve implantation with an Edwards Sapien balloon expandable valve. There was no in-hospital mortality. Mean and median hospital duration was 15 ± 18 and 7 days respectively. Valve implantation was successful in all patients and there were no major complications, except for major femoral access bleeding in one patient. At last follow-up, all patients were alive and in NYHA functional class I or II. Echocardiography follow-up demonstrated that mitral regurgitation was absent or trivial in seven patients and mild in two. At follow-up, peak and mean gradients changed from 26 ± 4 and 8 ± 2 at baseline to 16.7 ± 3 and 7.3 ± 1.5, respectively. CONCLUSIONS: Transcatheter transapical mitral valve-in-valve implantation for failed bioprosthesis is feasible in selected high risk patients. Our early experience with this strategy is encouraging. Larger randomized trials with long-term clinical and echocardiographic follow-up are recommended.

Spatial ability and learning the use of an angled laparoscope in a virtual environment.

Little is known about the cognitive demands that underlie surgical performance. Several studies have suggested that spatial ability plays a substantial role in surgical skill. An example of a skill in which spatial cognition appears to be of importance is the use of the angled laparoscope. This paper describes a virtual environment designed to assess and train the use of the angled laparoscope. The learning rates of novices learning the skill for the first time in the virtual environment were measured. The rates were found to be highly variable and strongly correlated with spatial ability.

Developmental expression of protein kinase C subspecies in rat brain-pituitary axis.

We have examined the neonatal developmental expression of protein kinase C subspecies (PKCs) in rat brain, pituitary glands and cells by enzymatic activity assays, immunohistochemistry and Western blot analysis with type-specific antibodies. A very large increase (455%) was noticed in brain PKC activity during the first week of life with the particulate fraction (22% of total enzyme activity on day 1) increasing dramatically (900%) during the first week to 50% of enzyme activity. In contrast, the pituitary gland showed high activity on day 1 that decreased progressively to reach the lowest levels at 1 year of age. Paradoxically, the number of pituitary cells immunolabeled for PKC increases as a function of age. Western blot analysis showed only small changes in PKC alpha, PKC beta and PKC epsilon when brains from 6-day-old and 3-month-old female rats were compared, whereas PKC tau and PKC delta increased markedly during this period. On the other hand, brain PKC zeta decreased between 6 days and 3 months of age. Western blot analysis showed no major changes in pituitary PKC alpha, PKC beta and PKC zeta when 6-day-old and 3-month-old female rats were compared, while PKC tau was not detected. The major band of pituitary PKC delta (76 kDa) decreased markedly between 6 days and 3 months of age whereas the minor band (68 kDa) did not change.(ABSTRACT TRUNCATED AT 250 WORDS)