Homograft replacement of the mitral valve in young recipients: mid-term results.

OBJECTIVE: Mitral homograft (MH) can represent an interesting alternative for valve replacement in the young. However, concerns have been expressed about the durability of valve allografts in children. We report our experience with MH replacement in young patients. METHODS: From 1993 to 1997, 13 young patients aged 3-25 years (mean 15+/-6 years) underwent total mitral valve (MV) replacement with a cryopreserved homograft (CH). All but one had previously undergone one or more cardiac operations. The indications were rheumatic disease (6), acute and subacute endocarditis (2), congenital heart disease (4), and systemic lupus endocarditis (1). RESULTS: No in hospital deaths are reported. Discharge echocardiogram showed a well-functioning MH in all but one patient. One patient was lost to follow-up. Follow-up ranged from 0.7 to 6.6 years (4.1+/-2.2). On follow-up two patients were doing well. Two patients died without reoperation and both had MV stenosis. Seven patients (54%) required reoperation: mean delay 4.17 years (0.7-7). In all cases, thickening, shrinking and calcification of the allograft were present. None of these seven had contributive histopathologic changes. One patient presenting recurrent MV insufficiency will require a reoperation. CONCLUSION: MV homograft is a safe and reproducible technique, but does not provide durable results and should not be used in young patients.

Optimization of the resistance of arterial allografts to infection: comparative study with synthetic prostheses.

Arterial allografts can be used for in situ treatment of prosthetic graft infection. The purpose of this in vitro study was to compare the resistance of allografts and synthetic prostheses to infection by five strains of bacteria and to study antibiotic treatments designed to reduce allograft infection. Fresh and cryopreserved allografts were compared with synthetic prostheses made of various biomaterials including PTFE, plain Dacron, gelatine-sealed Dacron, and gelatine-sealed, rifampicine-bonded Dacron. Allografts were used with or without treatment using an antibiotic containing gentamycine, lincomycine, and vancomycine. The bacterial strains tested were Escherichia coli, Staphylococcus aureus, slime-producing Staphylococcus epidermidis, non-slime-producing Staphylococcus epidermidis, and Pseudomonas aeruginosa. Infection was evaluated by counting the number of adherent bacteria on the allograft or synthetic material after rinsing and ultrasonication. Statistical analysis was achieved using nonparametric Mann-Whitney tests. Results showed that allografts not treated with antibiotics were highly susceptible to bacterial infection. Antibiotic treatment decreased infection. Application of antibiotic after thawing cryopreserved allografts led to a significant decrease. None of the biomaterials tested provided sufficient protection against bacteria resistant to the antibiotics used.

[Transplantation of cryopreserved carotids in the rabbit: effect of cryoprotective agents]. / Transplantation de carotides cryopréservées chez le lapin: effet des agents cryoprotecteurs.

The cryopreservation of blood vessels has been carried out for some decades with variable results. In order to study the behaviour of cryopreserved allografts by using new technique of cryopreservation a study on the ultrastructure arterial tissue consequences by microscopic techniques has been carried. The graft has been harvested from carotid artery of donor rabbit, implanted to a carotid artery of a recipient rabbit and extracted at 1, 3 and 5 months after the operation. An intimal thickening and a cellular loss in the media have been observed. However, good patency has been observed in all cryopreserved allografts. Manifestations of rejection are delayed in groups with polyethylene glycol.

Cryopreserved aortic allograft replacement of infected prosthetic grafts in man: processing and clinical results.

Aortic allografts preserved at 4 degrees C have been used successfully for the replacement of infected prosthetic grafts, but have a limited storage duration and this does not allow for rigourous security of the allograft. Original cryopreservation protocol has been developed, characterized by the use of polyethylene glycol 20,000 30 g/l associated with 12.5% DMSO, high concentration of antibiotics (lincomycin 300 mg/l, vancomycin 125 mg/l), controlled freezing rate, and storage in the vapour phase of liquid nitrogen (-150 degrees C). Cryopreserved arterial allografts were used for the replacement of infected prostheses in 22 patients. In 2 patients, allograft-related dysfunction was observed, 3 patients died in the early postoperative period from non-allograft-related causes, and, 17 patients were cured of infection without any dysfunction of the allograft. These results are comparable to replacement by fresh allograft, but cryopreservation allows for better microbiological security, long-term storage, and, thus, better management of the available allografts.

Treatment of vascular graft infection by in situ replacement with cryopreserved aortic allografts: an experimental study.

PURPOSE: The purposes of this study were to prove the efficacy of cryopreserved aortic allografts to treat an established vascular graft infection by in situ replacement in an animal model and to evaluate the role of the antibiotics normally used to decontaminate the allografts. METHODS: Twenty-three dogs underwent infrarenal aortic replacement with a gelatin-sealed knitted polyester graft contaminated in vitro by Staphylococcus epidermidis RP-62. One week later, the 18 surviving animals underwent reoperation for graft removal and were randomized into three groups for in situ replacement: group I (control, n = 6) received a new gelatin-sealed graft; group II (n = 6) received a non-antibiotic-treated cryopreserved allograft; and group III (n = 6) received an antibiotic-treated cryopreserved allograft. Control grafts and allografts were removed 4 weeks after the initial intervention for quantitative bacteriologic analysis and histologic analysis. Bacteriologic results were expressed as colony-forming units per square centimeter of graft material. Qualitative bacteriologic analysis was also obtained from perigraft fluid and tissue. RESULTS: All of the initially implanted grafts and all of the control grafts (group I) were infected at the time of removal. In group II, three out of six allografts were not totally incorporated, whereas in group III incorporation was always complete, with a significantly decreased inflammatory reaction. All of the antibiotic-treated allografts were sterile, whereas three untreated allografts grew bacteria. CONCLUSIONS: In this model, cryopreserved aortic allografts were more resistant to reinfection than synthetic grafts after in situ replacement of an infected prosthetic graft. However, the antibiotic loading of the cryopreserved aortic allograft appears to be essential to obtain optimal therapeutic effects.

[Valvular homografts]. / Les homogreffes valvulaires.

Renewed interest in heart valve homografts is related to recent advances in viability. Increased viability is achieved by collecting explanted hearts from multi-organ donors and cryopreservation. Right access is usually used in case of hereditary cardiopathy to resect or repair the aortic, mitral and tricuspid valves. Life-long anticoagulant treatment can thus be avoided. Current mid-term and long-term results are very promising.

Homograft replacement of the mitral valve. Graft selection, technique of implantation, and results in forty-three patients.

UNLABELLED: Because of experience gained in reconstructive mitral valve surgery, we have reevaluated the implantation of cryopreserved homografts in the mitral position. Forty-three patients, aged 11 to 69 years (mean 34 years), underwent mitral valve replacement with cryopreserved mitral homografts. The indications for the procedure were acute endocarditis (n = 14), rheumatic stenosis (n = 26), systemic lupus endocarditis (n = 2), and marasmic endocarditis (n = 1). All homografts were obtained from hearts explanted in the course of transplantation and were cryopreserved at -160 degrees C in 10% dimethyl sulfoxide solution without antibiotics. Appropriate sizing was based on morphologic study of the homografts and preoperative echocardiographic assessment of the recipient valve. In 82 homografts analyzed, the height of the anterior leaflet was 25 +/- 3 mm and the distance from the anulus to the apex of the anterior papillary muscle was 21 +/- 3 mm. The morphologic features of the papillary muscles were classified according to four types of increasing complexity. Nine valves with complex (type IV) papillary muscle abnormalities were discarded. Echocardiographic measurements of the valve were matched with those of the homograft identification cards and a slightly larger homograft was selected (measurements + 3 mm). Partial homograft replacement was done in case of a localized lesion (abscess or calcification) (n = 21). Total homograft replacement was undertaken in the presence of diffuse lesions (n = 22). Two hospital deaths occurred as a result of poor cardiac output. One patient required reoperation on the tenth postoperative day after a dehiscence on the valvular suture line. After a mean follow-up of 14 months, there has been one late death caused by a bronchial neoplasm and one reoperation for residual stenosis (partial replacement). The remaining patients were in either New York Heart Association class I (n = 25) or II (n = 13). Thirty-three patients were in sinus rhythm. Follow-up echocardiography has revealed no mitral regurgitation (n = 20), minimal mitral regurgitation (n = 13), and mild mitral regurgitation (n = 5). Surface valve area has been calculated at 2.5 +/- 0.4 cm2 in partial homograft reconstruction and 2.7 +/- 0.3 cm2 in total homograft replacement, with a transvalvular gradient of 3 +/- 4 mm Hg. CONCLUSION: In a selected group of patients, the use of mitral homografts significantly extended the present limitations of reparative surgery of the mitral valve.

Effect of cold anoxia and cryopreservation on metabolic and contractile functions of human mammary artery.

The ability of human internal mammary artery smooth muscle cells to maintain histoenzymatic activity and contractile response after various times of cold anoxia prior to and following cryostorage was evaluated. The results showed that the enzyme histochemical status of human mammary arteries was largely unchanged after both cold anoxia and cryopreservation. Neither in fresh nor in cryopreserved mammary arteries did cold anoxia for up to 24 h change maximal contractile responses to potassium depolarization and norepinephrine. However, compared to unfrozen controls, the contractile responses were significantly reduced in cryopreserved mammary arteries. In conclusion, after cryopreservation of human mammary arteries, the enzyme activities were globally maintained, whereas the contractile responses were reduced. For up to 24 h after harvesting cold anoxia at 4 degrees C is well tolerated and allows preservation of metabolic and functional properties of these arteries.

Evaluation of cryopreserved arteries as alternative small vessel prostheses.

Biologic or synthetic grafts have had limited success in small vessel applications. Studies were initiated to assess the potential use of cryopreserved (CP) arteries as coronary artery bypass conduits. Sheep carotid arteries (internal diameter: 4 mm; length: 10 cm) were cryopreserved in a nutrient media containing 10% DMSO and were stored in a nitrogen vapor at -150 degrees C. After thawing, histological, enzyme-histochemical and functional studies showed slight histological alterations, preservation of enzymal activities and an abolition of the contractile response. In a sheep model, arterial substitution of a 10 cm segment of carotid artery was realised by implantation of fresh autografts ( n = 4); fresh allografts (n = 9) and CP allografts (n = 9). After 3 months, all autografts were patent with slight histological alterations. Fresh and CP allografts showed similar modifications: patency rate was 7/9 in both groups. Intimal thickening with cell proliferation was seen in fresh (3/7) and CP (4/8) arteries; loss of smooth muscle medial cells was constant. Adventitia was always involved by a marked inflammatory reaction. One characteristic of CP allografts was the frequent presence of large dystrophic calcifications. In conclusion, morphologic and functional arterial changes occurred after freezing and thawing. In spite of vascular rejection, the patency rate of allografts after 3 months of implantation in arterial circulation remained high and does not seem influenced by cryopreservation.

High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults.

BACKGROUND: A Phase I-II trial to assess the toxicity and efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ cell tumors and metastatic trophoblastic disease was performed. METHODS: Thirty-nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic disease, received tandem high dose therapy combining ifosfamide (7500-12,500 mg/m2), carboplatin (875-1225 mg/m2), and etoposide (1000-1250 mg/m2), followed by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin- or carboplatin-based regimen and the response of 37 could be evaluated; 69 cycles of this tandem high dose therapy were administered. RESULTS: The overall response rate was 46%, including a complete response (CR) rate of 35%. Of 21 patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR. No CRs were obtained in patients with refractory extragonadal germ cell tumors. Nine partial responders after the first cycle became complete responders after the second. Nine (23%) of the patients were long term survivors (> 18 months), 7 of them in continuous CR. Side effects primarily were renal toxicity and enterocolitis. Seven patients (18%) died of therapy-related be explored and the maximum tolerated doses of this three-drug regimen remain to be determined. CONCLUSION: This tandem therapeutic regimen is able to overcome resistance to a platinum-based regimen in highly refractory germ cell tumors and gestational trophoblastic disease and to cure a number of patients.

Mitral valve replacement using a cryopreserved mitral homograft.

Mitral valve replacement, using a cryopreserved mitral homograft, was performed in a 49-year-old patient with calcified mitral stenosis. Postoperative course was uneventful. Transesophageal echocardiography performed 6 months later showed normal function of the mitral homograft.

[Mitral valve replacement with cryopreserved mitral homograft]. / Remplacement valvulaire mitral par homogreffe mitrale cryopréservée.

Mitral valve replacement using a cryopreserved mitral homograft was performed in a 49 year old patient with calcified mitral stenosis. The surgical technique is described. The postoperative course was uneventful. Transoesophageal echo performed 4 months later showed a normal function of the mitral homograft.

The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma.

During the last few years, high-dose therapy with hemopoietic stem cell support has become a well-admitted therapeutic option for young patients with MM. The role of allogeneic or autologous graft and of blood rather than bone marrow as the source of hemopoietic stem cells must be further investigated. Autologous PBSC transplantation has, however, both practical and theoretic advantages over allogeneic and autologous BMT: (1) It can be applied to most patients, especially if blood stem cells are collected early in the course of therapy. (2) It usually induces relatively rapid hematologic reconstitution. (3) In comparison with autologous BMT, it appears to minimize the hazard of the reinfusion of malignant cells.

Phase I-II study of two consecutive courses of high-dose epipodophyllotoxin, ifosfamide, and carboplatin with autologous bone marrow transplantation for treatment of adult patients with solid tumors.

We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.

Separation of living red blood cells by gravitational field-flow fractionation.

The field-flow fractionation technique, using the earth's gravitational field, has been applied to peripheral blood cell populations. A more or less symmetrical, gaussian-like, elution peak is generally observed for the red cell population. The bimodal cell population obtained after a massive transfusion is shown to result in a shoulder on the red blood cell elution profile. In one case where a similar shouldering peak was obtained from a non-transfused donor, the existence of an immunological double population has been demonstrated. This suggests that field-flow fractionation has some potential for complementary biomedical diagnosis.