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Biomedical subjects

M F O'Brien

Publications and source records attributed to M F O'Brien.

At least 37 records · Page 2Linked to original sources

The SynerGraft valve: a new acellular (nonglutaraldehyde-fixed) tissue heart valve for autologous recellularization first experimental studies before clinical implantation.

The durability of current bioprosthetic heart valves is diminished by glutaraldehyde-associated leaflet calcification or by the associated absence of a cellular component capable of repair of wear-related damage. As a novel tissue engineering approach to improving replacement heart valve durability, we have developed a decellularization process to replace the use of cross-linking to limit xenograft antigenicity. The effectiveness of this process was assessed in a weanling sheep right ventricular outflow tract reconstruction model where valve function, calcification, and recellularization were examined. Porcine aortic valves were decellularized by a process designed to remove all histologically demonstrable leaflet cells. Stentless, bioprosthetic valves were fabricated from acellular tissues, cryopreserved, sterilized, and then implanted as pulmonary valve replacements in 4- to 6-month old female Suffolk sheep. Sheep aortic valves were implanted as allograft control subjects. After 150 days, the grafts were explanted and assessed histologically and by atomic absorption spectrophotometry for calcium content. All valves were hemodynamically functional at explant. Histological examination showed intact leaflets with in-growth of host fibroblastoid cells in all explanted porcine valves and no evidence of calcification. Porcine leaflet calcium content was unchanged over the duration of the implant (1.0+/-1.2 vs 1.5+/-1.8 mg/g dry weight, P = ns). Decellularization can stabilize xenogenic heart valves. Lack of calcification of acellular aortic leaflets suggests that prolonged durability of such valves is attainable without the use of cross-linking agents. The repopulation of the leaflet matrix offers additional promise of durability based on revitalization of the graft in vivo.

Animals↗

Allograft heart valve viability and valve-processing variables.

BACKGROUND: The impact of allograft valve viability on valve durability remains controversial. Analyses of our clinical results have demonstrated the superiority of the cryopreserved valve viable at the time of implantation over the 4 degrees C stored valve nonviable at the time of implantation. In this study, we quantitatively assessed the effects on viability of current and past valve-processing protocols at The Prince Charles Hospital. METHODS: The viability of pulmonary valves was quantitatively analyzed by thin-layer autoradiography to assess the effects of donor type, antibiotics, and valve storage. RESULTS: Control valve segments obtained from beating-heart donor valves had a higher initial viability (0.92+/-0.02) than nonbeating-heart donor valves (0.66+/-0.03). Cryopreservation after low-dose antibiotic sterilization significantly reduced viability to 50% to 60% of the control, and in the presence of amphotericin B, viability dropped further to 10% to 36% of the control. After 7 days' storage at 4 degrees C, viability was reduced to 2% of control and to 0% viability after 21 days. CONCLUSIONS: For maximal preimplantation viability, valves should be procured as soon as possible after cessation of heart beat and should be cryopreserved if they are not to be clinically implanted within 1 to 2 days. Amphotericin B should not be used in conjunction with cryopreservation if viability is to be maximized.

Amphotericin B↗

The stentless Cryolife-O'Brien aortic porcine xenograft: a five-year follow-up.

BACKGROUND: The 5-year follow-up of CryoLife-O'Brien stentless porcine aortic valve xenografts is presented. METHODS: From August 1991 to August 1996, the valve was used in 366 patients. Patients' ages ranged from 18 to 90 years (mean, 73+/-6 years). Survivors were monitored with Doppler echocardiography before discharge, at 6 months, and then annually by the referring cardiologist. Operative and long-term mortality and morbidity were collected using the Edmunds guidelines for reporting morbidity and mortality after cardiac valvular operations. RESULTS: The study was completed during a 6-month period with a 96.5% follow-up, comprising 999 patient-years for a mean follow-up period of 27 months (range, 3 to 64 months). Operative mortality was 6.5%. Linearized rates per patient-year for complications were as follows: structural valve deterioration (0%); thromboembolism (0.5%); prosthetic valve endocarditis (0.2%); valve reoperation (0.8%); and valve-related mortality (0.2%). Sixteen late deaths have occurred. The actuarial survival rate at 5 years was 83%+/-3.5%. CONCLUSIONS: The Cryolife-O'Brien stentless valve has given excellent early hemodynamic and 5-year results.

Actuarial Analysis↗

Histologic and immunohistochemical responses after aortic valve allografts in the rat.

BACKGROUND: Human aortic valve allografts elicit a cellular and humoral immune response. It is not clear whether this is important in promoting valve damage. We investigated the changes in morphology, cell populations, and major histocompatibility complex antigen distribution in the rat aortic valve allograft. METHODS: Fresh heart valves from Lewis rats were transplanted into the abdominal aorta of DA rats. Valves from allografted, isografted, and presensitized recipient rats were examined serially with standard morphologic and immunohistochemical techniques. RESULTS: In comparison with isografts, the allografts were infiltrated and thickened by increased numbers of CD4+ and CD8+ lymphocytes, macrophages, and fibroblasts. Thickening of the valve wall and leaflet and the density of the cellular infiltrate was particularly evident after presensitization. Endothelial cells were frequently absent in presensitized allografts whereas isografts had intact endothelium. Cellular major histocompatibility complex class I and II antigens in the allograft were substantially increased. A long-term allograft showed dense fibrosis and disruption of the media with scattered persisting donor cells. CONCLUSIONS: The changes in these aortic valve allograft experiments are consistent with an allograft immune response and confirm that the response can damage aortic valve allograft tissue.

Animals↗

Haemodynamics and left ventricular mass regression: a comparison of the stentless, stented and mechanical aortic valve replacement.

OBJECTIVE: Our objective was to compare the degree of change in hemodynamics and left ventricular mass (LVM) regression after aortic valve replacement (AVR) with stentless, stented and mechanical valves. METHODS: Patients greater than 59 years of age had AVR for aortic stenosis with the stentless xenograft (Cryolife-O'Brien, CLOB), stented xenograft (Carpentier-Edwards, C-E) or mechanical valve (ATS). One-hundred and forty-two patients received stentless, 40 stented, and 69 mechanical valves (mean age 74 +/- 6 vs. 72 +/- 7 and 67 +/- 6 years, respectively). Serial echocardiography was performed. RESULTS: The left ventricular outflow tract diameter was similar pre-operatively in the stentless versus the stented versus the mechanical groups (2.2 +/- 0.4 vs. 2.3 +/- 0.2 vs. 2.2 +/- 0.3 cm; P, n.s). The effective orifice area was larger immediately post-operatively in the stentless versus the stented or the mechanical group (2.4 +/- 0.4 vs. 2.0 +/- 0.6 vs. 2.0 +/- 0.7 cm2, P = 0.0001 for both comparisons). The peak aortic gradient at 6 months was significantly less in the stentless versus the stented and mechanical groups (15 +/- 7 vs. 25 +/- 9 vs. 22 +/- 9 mmHg, P < 0.0001). LVM regressed over 6 months in all subgroups: stentless 272 +/- 64 g vs. 220 +/- 72 g, P = 0.0001, stented 257 +/- 58 vs. 230 +/- 74 g, P = 0.02, and mechanical 267 +/- 95 vs. 204 +/- 54 g, P = 0.003. The reduction in LVM was greater in the stentless versus the stented (P = 0.05) but similar to the mechanical group. CONCLUSIONS: AVR with the stentless xenograft results in superior hemodynamics compared to the stented and mechanical valve replacements. AVR in all three groups leads to a significant regression of left ventricular hypertrophy within 6 months. However the reduction in LVM is greater in subjects with stentless and mechanical valves, which may have prognostic significance.

Aged↗

Apoptosis as a mechanism of neuronal cell death following acute experimental spinal cord injury.

The complex biochemical interactions following acute spinal cord injury have undergone considerable investigation recently. Progress has been made in discovering both primary and secondary injury cascades that combine to produce the ultimate neurologic insult. Traditionally, neuronal and supporting cell death following spinal cord injury have focused on necrotic death pathways resulting passively from the actual mechanical tissue damage and inflammatory processes which follow. However, the occurrence of programmed apoptotic cell death which is an actively mediated cellular process may occur following acute spinal cord injury and, if present, may play a role in the ultimate neurologic insult. In this study, we document a chronologically-specific course of apoptotic cell death by the TUNEL assay technique following an acute experimental spinal cord injury in the rat model. In this manner, apoptotic cell death following acute spinal cord injury may play a pivotal role in the secondary injury cascade which produces the ultimate neurologic insult and may allow potential for mediating neuronal survival via anti-apoptotic factors such as the protooncogene Bcl-2.

Acute Disease↗

Preoperative platelet dysfunction increases the benefit of aprotinin in cardiopulmonary bypass.

BACKGROUND: This study was designed to determine the benefit of aprotinin therapy in reducing bleeding during and after cardiopulmonary bypass in patients with preoperative platelet dysfunction. Platelet function involvement in the mechanism by which aprotinin acts was also investigated. METHODS: In a double-blind, randomized study, patients received high-dose aprotinin (n = 54) or placebo (n = 52). Whole blood aggregation was measured preoperatively. Platelet function and activation in both groups were assessed intraoperatively and postoperatively at five times. RESULTS: Aprotinin significantly reduced perioperative bleeding and postoperative blood transfusion. Placebo-treated patients with reduced preoperative platelet aggregation bled more postoperatively, but aprotinin reduced the bleeding in patients with normal or reduced platelet function to similar levels. Any cardiopulmonary bypass-induced changes in platelet aggregation, platelet activation as measured by P-selectin expression, and von Willebrand factor antigen and function were similar in aprotinin-treated and placebo-treated groups. CONCLUSIONS: The mechanism by which aprotinin reduced bleeding was independent of any effect on platelet function. However, aprotinin produced a greater reduction in bleeding among patients whose condition was hemostatically compromised by preoperative platelet dysfunction.

Aprotinin↗

An analysis of valve re-replacement after aortic valve replacement with biologic devices.

Biologic valve re-replacement was examined in a series of 1343 patients who underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve. A parametric model approach was used to simultaneously model the competing risks of death without re-replacement and re-replacement before death. One hundred eleven patients underwent a first re-replacement for a variety of reasons (69 patients with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and 14 patients with cryopreserved allograft valves). By multivariable analysis younger age at operation was associated with xenograft, 4 degrees C stored allograft, and cryopreserved allograft valve re-replacement. However, this effect was examined in the context of longer survival of younger patients, which increases their exposure to the risk of re-replacement as compared with that in older patients whose decreased survival reduced their probability of requiring valve re-replacement. In patients older than 60 years at the time of aortic valve replacement, the probability of re-replacement (for any reason) before death was similar for xenografts and cryopreserved allograft valves but higher for 4 degrees C stored valves. However, in patients younger than 60 years, the probability of re-replacement at any time during the remainder of the life of the patient was lower with the cryopreserved allograft valve compared with the xenograft valve and 4 degrees C stored allografts.

Adolescent↗

Allograft valves for aortic and mitral valve replacement.

Allograft valves have been used in cardiac valve replacement for 35 years. During much of this time, certain centers have used allograft aortic valves for aortic valve replacement and have reported excellent long-term results. After an initial period of failure using allograft mitral valves for mitral valve replacement, the technical problems of papillary muscle dehiscence and mitral regurgitation appear minimized by current investigators who now report encouraging early results. The current status of allograft use for aortic and mitral valve replacement is reviewed.

Aortic Valve↗

Intussuscepted partial-thickness ileal valve in continent urinary diversion.

OBJECTIVE: This study was undertaken to ascertain the feasibility of fashioning a nipple valve from partial-thickness ileum and to assess the competence and durability of that valve. The approach employed was designed to circumvent the necessity for considerable lengths of bowel to be committed to valve formation and to avoid the tendency for desusception, present with other forms of nipple valves. METHODS: A technique in which a subterminal segment of partial-thickness ileum was 'skinned' circumferentially of serosa and muscularis propria and then intussuscepted to form a continent nipple-valve mechanism was studied for up to 4 months in 10 dogs. The intussuscepted partial-thickness ileal valve was in continuity with a terminal ileal segment sutured flush with skin and, internally, with another segment laid open and anastomosed to the bladder. RESULTS: All valves were competent, withstanding intravesical pressures up to 90 cm H2O. Six dogs were catheterized, without difficulty, twice daily up to 104 days. The valve mucosal surfaces were smooth due to a loss of plicae circulares, and, between 'back-to-back' submucosal layers, a fine stroma developed. CONCLUSIONS: This simple technique, which is frugal in its use of bowel, provided a robust and effective ileal continence mechanism. Furthermore, because of denervation and interposing fibrous tissue, this nipple valve is considered most unlikely to desuscept subsequently. The intussuscepted partial-thickness ileal valve approach is recommended now for clinical evaluation.

Anastomosis, Surgical↗

Do consumer infant feeding publications and products available in physicians' offices protect, promote, and support breastfeeding?

The purpose of this study was to determine if consumer infant feeding publications and products distributed by physicians' offices protect, promote, and support breastfeeding. A total of 127 physician office practices completed a mailed questionnaire that measured the types of print and nonprint materials available and policies and practices regarding these resources. Commercially produced pamphlets were available in 114 (90%) of the offices surveyed, and were twice as likely to be routinely distributed as pamphlets from nonprofit agencies and government. Many publications contained outdated recommendations about breastfeeding; the most accurate publications were available in only 29 (23%) of practices surveyed. Magazines contravening the WHO Code were widely available (91 offices; 72%) and routinely distributed (58 offices; 46%). One hundred one offices (80%) accepted free formula and 48 (38%) routinely distributed it. Few offices had a policy (n = 25; 20%) or criteria (n = 17; 13%) for selecting infant feeding resources. Those with policies were less likely to distribute commercial pamphlets. In the majority of offices surveyed, physicians' offices accepted and routinely distributed publications and products which do not "protect, promote, and support" breastfeeding. Offices are encouraged to have policies guiding the distribution of infant feeding materials.

Adult↗

The CryoLife-O'Brien composite stentless porcine aortic xenograft valve in 118 patients.

The CryoLife-O'Brien stentless valve is a composite trileaflet porcine aortic valve. It is assembled from 3 non-coronary leaflets and has no foreign material support. It is therefore truly stentless. From December 1992 to January 1996, 118 patients with aortic valve replacement had a CryoLife-O'Brien stentless valve inserted at the Prince Charles Hospital, Brisbane. The mean age was 73 years (range 59-89) and 54% were men. Most patients had aortic stenosis secondary to a calcific degenerative valve. Follow-up is 100% with hematological and echocardiographic studies before discharge, at 6 months, and at 12-18 months. Five deaths (2 early and 3 late) have occurred and morbidity includes 3 strokes, 1 peripheral embolism, 3 perivalvular leaks, and 1 patient with late endocarditis. Valve performance has been good, with low transvalvular gradients and only a trace or no regurgitation in over 95% of patients after 18 months. No structural deterioration or hemolysis has occurred. Echocardiographic surveillance confirms a very effective central orifice. Short-term results show that the overall performance of the CryoLife-O'Brien stentless valve has been very satisfactory, with low mortality and morbidity in this elderly group of patients. The benefits include the absence of prosthetic material, wide leaflet coaptation, and a quick and easy insertion. Long-term anticoagulation is not necessary. It is particularly suitable for elderly patients with a symmetrical aortic root.

Aged↗

A novel technique for laminoplasty augmentation of spinal canal area using titanium miniplate stabilization. A computerized morphometric analysis.

STUDY DESIGN: Titanium miniplates are used to secure the posterior elements in the open position after expansive open-door laminoplasty. Preoperative and postoperative spinal canal dimensions are measured to assess the effectiveness of this technique. OBJECTIVES: To develop a simple yet effective technique to stabilize the posterior elements after laminoplasty and to compare preoperative and postoperative spinal canal dimensions to accepted normal values. SUMMARY OF BACKGROUND DATA: Expansive open-door laminoplasty has been offered as a simple alternative to laminectomy, which has been associated with postoperative kyphosis. Although the technique of laminoplasty is effective, a simple and reliable method of holding the posterior elements open has not been described. METHODS: Ten myelopathic patients with multilevel cervical canal stenosis secondary to spondylosis or ossification of the posterior longitudinal ligament were treated with an expansive open-door laminoplasty. The posterior elements were stabilized in the open position with titanium miniplates. Computer-assisted morphometric analysis was performed on preoperative and postoperative computed tomography scans to obtain spinal canal dimensions. Plain radiographs were used to monitor construct integrity. RESULTS: The preoperative sagittal canal diameter was 8.2 +/- 0.96 mm, and the canal area was 180.6 +/- 33.7 mm2. These dimensions increased after surgery to 16.6 +/- 1.5 mm and 321.9 +/- 29.7 mm2, respectively. The titanium miniplate constructs did not fail during the follow-up period (mean, 26.4 months), and the decompression was maintained. The single significant complication was transient C5 radiculopathy. CONCLUSIONS: Normal canal dimensions can be reestablished with open-door laminoplasty. Achieving and maintaining an increased sagittal canal diameter is probably the most important change in anatomic parameters to facilitate neurologic recovery. The use of titanium miniplates to stabilize the posterior elements after laminoplasty is a simple, durable, and effective technique to maintain the increased sagittal diameter of the spinal canal.

Adult↗

Internal mammary vein to coronary artery anastomotic fistula.

Two patients are presented where internal mammary artery grafting was performed for the relief of symptomatic coronary artery disease. At follow-up the internal mammary artery was occluded and a communication between the internal mammary vein and the native coronary artery was demonstrated. These patients were characterised by the early recurrence of angina or the appearance of a continuous murmur. Both patients were treated by re-operation with ligation of the arterio-venous fistula and saphenous vein grafting.

Adult↗

Human aortic valve allografts elicit a donor-specific immune response.

OBJECTIVE: The nature and magnitude of the immunologic response to implantation of human cryopreserved aortic valve allografts was investigated. METHODS: Twenty aortic valve allograft recipients were investigated for donor-specific antibody and T-cell-mediated responses with serial flow cytometric and microlymphocytotoxic crossmatch assays and one-way mixed lymphocyte cultures. RESULTS: Donor-specific immunoglobulin G antibodies to class I and II human leukocyte antigens were first detected in the serum of all aortic valve allograft recipients at 30 days after implantation and persisted in substantial amounts in all but one of the recipients at day 365. Recipient T-cell alloreactivity toward donor lymphocytes was significantly increased at day 30 compared with levels before and 10 days after operation. CONCLUSIONS: Cryopreserved aortic valve allografts elicit a substantial allogeneic response in recipients. This alloreactivity may contribute to the observed morphologic changes in aortic valve allografts and eventual long-term deterioration of allograft function.

Adult↗

Rifampicin antibiotic impregnation of the St. Jude Medical mechanical valve sewing ring: a weapon against endocarditis.

The Dacron sewing ring material of the St. Jude Medical mechanical heart valve (St. Jude Medical, Inc., St. Paul, Minn.) was passively impregnated with rifampicin (60 mg/ml) both in its unsealed state and after sealing by the methods of preclotting in blood, autoclaving in blood, and autoclaving in 20% albumin. Antistaphylococcal activity in the Dacron material was assessed immediately after rifampicin impregnation and at regular periods up to 5 days after implantation into the goat aorta. When the Dacron material had been sealed by autoclaving in blood and autoclaving in 20% albumin significant retention of antistaphylococcal activity was found after 5 days in vivo. Best results were obtained with the use of autoclaved blood (p < 0.05). We also compared these results with those obtained from impregnating commercially available gelatin-sealed (Gelseal) and collagen-sealed (Hemashield) Dacron material with rifampicin. Although antistaphylococcal activity was equivalent immediately after rifampicin impregnation, after 4 days in vivo the activity was negligible in Gelseal material (p < 0.05) and could not be demonstrated in Hemashield material. Rifampicin impregnation of the intact St. Jude Medical mechanical valve sewing ring may have an application in the prevention of prosthetic valve endocarditis and a clinical protocol is suggested.

Albumins↗