Outcomes of transcatheter aortic valve implantation in high surgical risk and inoperable patients with aortic stenosis: a single Australian Centre experience.

BACKGROUND: Degenerative aortic stenosis is the most common valvular heart disease in the elderly, and many patients are not suitable for aortic valve replacement surgery. Transcatheter aortic valve implantation (TAVI) is a new therapeutic option for selected patients at high risk for surgery. AIM: To evaluate the safety and efficacy of TAVI in Australian patients. METHODS: This is a prospective study of patients undergoing TAVI for severe symptomatic aortic stenosis at The Prince Charles Hospital, Brisbane, Australia between August 2008 and July 2013. Patients were at high risk of surgical aortic valve replacement, or inoperable, as deemed by a multidisciplinary 'heart team'. Outcomes include procedural success and complications, 30-day and 1-year mortality and stroke, combined end-points as outlined by the Valve Academic Research Consortium 2 consensus document. RESULTS: Two hundred and nine patients underwent TAVI during the study period. The mean age was 83.7 ± 6.7 years, and 101 (48%) were men. The valve systems utilised were as follows: Edwards-SAPIEN valve in 104 (49.5%), Medtronic CoreValve in 86 (41.2%) and Boston Scientific Lotus valve in 19 (9.3%) patients. Thirty-day and 1-year mortality rates were 5.7% and 11.5% respectively. Thirty-day and 1-year stroke rates were 4.3% and 6.2% respectively. The composite end-points of device success, early safety and clinical efficacy occurred in 80.4%, 27.3% and 68.4%. CONCLUSIONS: TAVI with various valve systems, delivered through several approaches, is feasible in high surgical risk and inoperable patients with severe aortic stenosis, with acceptable outcomes at short-term and intermediate-term follow up.

Plasma cell proliferation in the chicken harderian gland.

Studies to examine the percentages of proliferating plasma cells (PPC) in the Harderian gland (HG) were carried out in chicks between 5 and 12 weeks of age. Two methods, 5-bromo-2'-deoxyuridine (BrdUrd) incorporation into DNA and flow cytometric analysis of propidium iodide (PI) stained cells, were employed in control and emetine dihydrochloride treated birds. Flow cytometric analysis of PI stained cells showed the percentages of plasma cells in S phase were highest between 6 and 8 weeks of age. After this period of time, the number of S phase plasma cells decreased and remained low through 12 weeks of age. The lowest percentages of plasma cells in G0 + G1 were found at 6 and 8 weeks of age, and all ages had equal percentages of plasma cells in G2 + M phase. After administration of the protein synthesis inhibitor emetine dihydrochloride a common pattern of plasma cell depletion and repopulation in the HG was observed. At 3 and 5 days post-treatment the plasma cell population in the gland decreased and by 7 days post-treatment repopulation of the gland with plasma cells had taken place. Anti-BrdUrd staining of frozen sections revealed that the number of PPC were decreased at 3 days after emetine treatment but were as high as, or higher than, controls at 5 and 7 days post-treatment. Flow cytometric analysis indicated that some birds were more severely affected by emetine. Namely, the percentages of plasma cells in S phase were lower at 3 and 5 days post-treatment. Even though most birds were severely affected by emetine treatment during the experiments, they possessed a cell population with the proliferative capacity to quickly repopulate the HG by 7 days post-emetine treatment.

Immune cell proliferation in the harderian gland: an avian model.

Experimentation has been carried out to study proliferation of plasma cells in the chicken Harderian gland (HG) and to determine if a HG factor influences immune cell (i.e., B cell) proliferation. In young chickens, flow cytometric analysis of propidium iodide (PI)-stained plasma cells revealed that the percentages of cells in both the synthetic (S) and mitotic (G2M) phases of the cell cycle were highest between 6 and 9 weeks of age. A pattern of plasma cell depletion and repopulation in the HG was observed following administration of emetine dihydrochloride. At 3 and 5 days posttreatment the plasma cell population decreased, and by 7 days posttreatment repopulation of the gland with plasma cells occurred. This repopulation appeared as a result of plasma cell proliferation within the HG. Anti-5-bromo-2'-deoxyuridine (BrdUrd) staining of frozen sections showed that the numbers of plasma cells incorporating BrdUrd were low at 3 days posttreatment but were as high, or higher than, controls at 5 and 7 days posttreatment. These results were verified with flow cytometric data of PI-stained plasma cells. Data from bursal cell bioassays revealed proliferative activity influenced by a HG factor. Coculture of bursal cells with phorbol dibutyrate and diluted HG supernatants resulted in prolonged and increased proliferation of these cells. It is possible that the HG of chickens supports plasma cell proliferation through the elaboration of a factor which acts like a lymphokine.

Plasma cells of the chicken Harderian gland.

The chicken Harderian gland (HG) is densely populated in its subepithelial spaces with plasma cells (PC). These immune cells produce and secrete Ig of the IgA, IgG, and IgM classes. Such Ig secretion into the tears affords the upper respiratory tract with protective antibodies. The immunological role of the HG is quite interesting; yet this gland is a site of unusual PC proliferation. Studies of the gland utilizing bromodeoxyuridine (BrdUrd) incorporation into DNA and propidium iodide (PI) staining of PC DNA have verified previous suggestions in the literature that PC of the chicken HG proliferate. Both isolated PC suspensions and frozen sections of the HG from chicks aged 6 to 9 wk reveal that BrdUrd is incorporated into PC DNA. Furthermore, flow cytometric analysis of PI-stained PC indicates a relatively high percentage of PC in S phase of the cell cycle. Continued studies are examining possible mechanisms controlling proliferation and differentiation of PC in the HG. It is believed that the stromal elements of the HG produce and secrete a factor(s) that influences PC proliferation and differentiation. Isolation and characterization of this influencing factor(s) will allow for the possible systemic application of the factor(s) for enhancement of immune responses.