High-dose gamma irradiation for soft tissue allografts: High margin of safety with biomechanical integrity.

Screening and processing methods currently in place have made the risk of bacterial and viral infections from allograft tissues extremely low. However, the development of a terminal sterilization method that does not adversely affect tissue function would provide an added safety to tissues for transplantation. We assessed whether high-dose gamma irradiation could be used as an effective terminal sterilization method for allografts without impairing the preimplantation mechanical integrity of the tissues. Semitendinosus tendons were pretreated with a radioprotectant solution and then irradiated to 50 kGy under well-defined conditions that included a tight dose range and maintained low temperatures. Maximum force, strain, stress, modulus, and strain energy density for tendons irradiated to 50 kGy were compared to nonirradiated control tendons and tendons irradiated to 18 kGy by a commercial tissue bank using their existing method. The preimplantation biomechanical properties of the 50-kGy group compared favorably to the nonirradiated and 18 kGy groups. A study to evaluate the postimplantation mechanical and biological performance of grafts irradiated to 50 kGy is ongoing. Pathogen inactivation was also quantified following 50 kGy of irradiation, with > or =4.5 logs of Sindbis virus and 4.9 logs of parvovirus kill achieved. Analysis of Clostridium sordellii inactivation kinetics indicated that a 16 log10 reduction is predicted with 50 kGy of irradiation. A high dose of gamma irradiation using the described conditions can reduce infectious risks associated with soft tissue allografts while maintaining the preimplantation biomechanical performance of the tissues.     

BONE ALLOGRAFT BANKING IN SOUTH AUSTRALIA

The South Australian Bone Bank has expanded to meet an increased demand for allograft bone. During a 5 year period from 1988 to 1992, 2361 allografts were harvested from 2146 living donors and 30 cadaveric donors. The allografts were screened by contemporary banking techniques which include a social history, donor serum tests for HIV-1, HIV-2, hepatitis B and C, syphilis serology, graft microbiology and histology. Grafts were irradiated with 25 kGy. The majority of grafts were used for arthroplasty or spinal surgery and 99 were used for tumour reconstruction. Of the donated grafts 336 were rejected by the bank. One donor was HIV-positive and two had false positive screens. There were seven donors with positive serology for hepatitis B, eight for hepatitis C and nine for syphilis. Twenty-seven grafts had positive cultures. Bone transplantation is the most frequent non-haematogenous allograft in South Australia and probably nationally. The low incidence of infectious viral disease in the donor population combined with an aggressive discard policy has ensured relative safety of the grafts. The frequency of graft rejection was similar to other bone banks but the incidence of HIV was lower.     

Development of heating method by microwave for sterilization of bone allografts

The purpose of this study was to develop a disinfection method using a microwave apparatus to treat large bone allografts. Heating of a bone allograft is an effective method for the disinfection of bacteria or inactivation of viruses. However, the size of the bone we can treat is limited, and following the popular method of using a bathtub is a lengthy process. The experimental system described here was designed using a microwave oven, an optical-fiber thermometer, and a power regulator. Large and small specimens, a femoral head, and a metatarsal were harvested from a bovine femur. The influence of size and the electrical or thermal characteristics of the specimens were assessed regarding temperature distribution after microwave irradiation. The effects of humidity or hot-air supply were also assessed. The average temperature of the bovine femoral head became 80°C throughout the 15min of microwave irradiation, although the temperature in the metatarsal did not attain uniformity. Microwave irradiation with a hot-air supply realized a uniform distribution of temperature at 83.0° ± 0.4°C in the metatarsal within 15min. Use of microwave irradiation enables quick heating for disinfection of large allograft bones when a hot-air supply was used as well.     

Allograft safety: viral inactivation with bone demineralization

A study was performed to validate the effectiveness of a bone demineralization process with respect to its inactivation of viruses. The viruses selected for study included human immunodeficiency virus (HIV), duck hepatitis B virus (a model for human hepatitis B), bovine viral diarrheal virus (a model for human hepatitis C), human cytomegalovirus, and human poliovirus (a model for small nonenveloped viruses, e.g., hepatitis A). This study was performed in compliance with Good Laboratory Practice regulations using validation methodology similar to that used to ensure the safety of blood derivatives and other products. Use of the bone demineralization process described in this report resulted in a reduction in infectivity of greater than one million (10(6)) for all viruses and as much as one trillion (10(12)) for the poliovirus.     

Tendon allograft sterilized by peracetic acid/ethanol combined with gamma irradiation

Background

Research and clinical applications have demonstrated that the effects of tendon allografts are comparable to those of autografts when reconstructing injured tendons or ligaments, but allograft safety remains problematic. Sterilisation could eliminate or decrease the possibility of disease transmission, but current methods seldom achieve satisfactory sterilisation without affecting the mechanical properties of the tendon.

Hypothesis

Peracetic acid-ethanol in combination with low-dose gamma irradiation (PE-R) would inactivate potential deleterious microorganisms without affecting mechanical and biocompatible properties of tendon allograft.

Study design

Controlled laboratory design.

Methods

HIV, PPV, PRV and BVDV inactivation was evaluated. After verifying viral inactivation, the treated tendon allografts were characterised by optical microscopy, scanning electron microscopy and tensile testing, and the cytocompatibility was assessed with an MTT assay and by subcutaneous implantation.

Results

Effective and efficient inactivation of HIV, PPV, PRV and BVDV was observed. Histological structure and ultrastructure were unchanged in the treated tendon allograft, which also exhibited comparable biomechanical properties and good biocompatibility.

Conclusion

The preliminary results confirmed our hypothesis and demonstrated that the PE-R tendon allograft has significant potential as an alternative to ligament/tendon reconstruction.

Clinical relevance

Tendon allografts have been extensively used in ligament reconstruction and tendon repair. However, current sterilisation methods have various shortcomings, so PE-R has been proposed. This study suggests that PE-R tendon allograft has great potential as an alternative for ligament/tendon reconstruction.

What is known about this subject

Sterilisation has been a great concern for tendon allografts. However, most sterilisation methods cannot inactivate viruses and bacteria without impairing the mechanical properties of the tendon allograft.

What this study adds to existing knowledge

Peracetic acid/ethanol with gamma irradiation can effectively inactivate viruses and bacteria. Meanwhile, tendon allografts sterilised by this method maintain their physiological tendon structure, biomechanical integrity and good compatibility.     

Etiology of DNA Virus Infections in Liver Transplant Recipients With Neonatal Hepatitis

Neonatal hepatitis is a syndrome of symptoms associated with a history that includes any type of infectious, genetic, toxic, or metabolic causation. Various infectious agents have been implicated in hepatic inflammation in neonates including bacterial and viral pathogens, especially DNA viruses. We used molecular and antigenic methods to evaluate the role of DNA viruses, such as hepatitis type B viruses (HBV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and adenovirus, in neonatal hepatitis complications. Twenty-six paraffin-embedded biopsy and autopsy tissues obtained between 1996 and 2007 from 22 infants with neonatal hepatitis were studied retrospectively. The genome prevalence of HBV, HCMV, HSV, and adenovirus were analysed using qualitative polymerase chain reaction (PCR) protocols. The antigenic presentation of HSV-1, HSV-2, HBV, HCMV, and adenovirus were evaluated using immunohistochemistry (IHC) methods. The HCMV genome was detected separately in 1 of 22 (4.5%) paraffin-embedded autopsy and biopsy tissues. Also 3/22 (13.6%) samples were infected with HBV and HSV genomes. HBV and HSV-1 antigens were present in 1/26 (4.5%) neonatal samples and HSV-2 antigens in 5/26 (22.7%) by IHC protocols, but adenovirus and HCMV antigens were not detected among samples from infants with neonatal hepatitis. Detection of separate co-infections of HSV, HCMV, and HBV genomes in autopsy and biopsy tissues of HBV and HSV-1 or HSV-2 antigens in these patients, showed the importance of these viral infections in clinical neonatal hepatitis.     

Hepatitis B core antibody positive donors as a safe and effective therapeutic option to increase available organs for lung transplantation

BACKGROUND: The use of hepatitis B core antibody (HBcAb+) and hepatitis C antibody (HCV Ab+) positive donors represents one strategy to increase available donor organs, but this remains controversial because of concern for viral transmission to recipients. We hypothesized that isolated HBcAb+ donors represent minimal risk of viral transmission in vaccinated lung transplant (LTx) recipients. METHODS: A retrospective study was performed of LTx recipients who received HBcAb+ or HCV Ab+ pulmonary allografts. We analyzed liver function studies, viral hepatitis screening tests, quantitative polymerase chain reaction for hepatitis B viral DNA (HBV DNA) and hepatitis C viral RNA (HCV RNA), freedom from bronchiolitis obliterans syndrome, acute rejection, and survival. RESULTS: Between April 1992 and August 2003, 456 LTx operations were performed. Twenty-nine patients (HB group) received HBcAb+ allograft transplants with a median posttransplant follow-up of 24.5 months. Three critically ill patients (HC group) received HCV Ab+ allografts with a median follow-up of 21.5 months. One-year survival for the HB group is 83% versus 82% for all patients who received non-HB organs (P=0.36). No patient in the HB group developed clinical liver disease because of viral hepatitis, and all patients alive (n=21) at follow-up are, to date, HBV DNA and/or HBcAb negative. All patients in the HC group tested HCV RNA positive; one patient died of liver failure at 22 months. CONCLUSIONS: Risk of viral transmission with HCV Ab+ allografts seems high after LTx. However, the use of HBcAb+ pulmonary allografts in recipients with prior hepatitis B vaccination seems to be a safe and effective strategy to increase organ availability.     

Musculoskeletal tissue banking in Singapore: 15 years of experience (1988-2003)

PURPOSE: To report 15 years' experience of musculoskeletal tissue banking by the National University Hospital Tissue Bank. METHODS: This study describes the development of Singapore's national bone bank since its establishment in 1988. The bone bank's protocol follows guidelines recommended by the American Association of Tissue Banks and the European Association of Tissue Banks using strict donor selection criteria. Informed consent is obtained from all potential donors for tissue procurement and laboratory tests. Detailed medical history, thorough clinical examination, and chart review is performed for consenting donors. Suitable donors are subjected to tests for hepatitis B, hepatitis C, syphilis, and culture/sensitivity test of tissue for aerobic and anaerobic organisms. For living donors, repeat testing for AIDS and hepatitis C is performed at least 180 days after procurement. Tissue procurement is performed under sterile conditions. Small tissues are procured using the 'sterile double jar technique' and long bones using the 'sterile triple wrap technique', both developed by the author. Deep-frozen bones are gamma irradiated at 25 kilograys. Morsellised bones are lyophilised and gamma irradiated. Meticulous preparation for grafts is performed during transplantation. Antibiotic prophylaxis is used for 2 weeks. RESULTS: The bank maintains a good quality control. In January 2003, it was accredited ISO 9001 status. Up to June 2003, it has procured 440 bones from 440 living donors and 1055 allografts from 63 deceased donors. 854 musculoskeletal transplantations have been performed using tissues processed by the bank. Complication rate encountered was only 2.2%. CONCLUSION: The tissue bank provides high-quality allografts for safe tissue transplantations.     

Factors affecting the ten-year outcome of human renal allografts. The effect of viral infections

Long-term (10-year) results of kidney transplantation have been analyzed from this center with respect to several variables. In this report the influence of viral disease was added in studying the effect of cadaver versus living-related donor, recipient race, and compliance. Over all, 10-year actuarial patient and graft survival were 68% and 48%, respectively. Cytomegalovirus, hepatitis B and C, and HIV-1 were studied for their effects, and survival curves analyzed statistically. Although cadaver and living-related donor, recipient race, and compliance were 3 main variables influencing graft survival, these 4 viruses were not selective in their effects on any of them. Hepatitis B surface antigen positivity and hepatitis C antibody positivity did not influence overall mortality or graft survival. Only cytomegalovirus seronegative status was important (as opposed to seropositive status, which was not). Of seronegative patients only those receiving a kidney from a seropositive donor were adversely affected. The presence of HIV-1 antibody had an adverse effect on graft survival, but the question remains as to whether overall mortality in HIV seropositive patients is any worse than those receiving dialysis therapy.     

Comparison of the risk of viral infection between the living and nonliving musculoskeletal tissue donors in Australia

Screening of musculoskeletal tissue donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) has been implemented in the United States and other developed nations. However, in contrast to the donor demographics in the United States, the majority of Australian musculoskeletal tissue donations are primarily from living surgical donors. The objective of our study was to determine and compare the risk of viral infection associated with musculoskeletal tissue donation from living and nonliving donors in Australia. We studied serum samples from 12 415 consecutive musculoskeletal tissue donors between 1993 and 2004. This included 10 937 surgical donations, and 1478 donations obtained from postmortem organ donation patients and cadaveric donors. Current mandatory retesting of surgical donors 6 months postdonation reduces the risk of viral infection by approximately 95% by eliminating almost all donors in the window period. The addition of nucleic acid amplification testing for nonliving donors would similarly reduce the window period, and consequently the residual risk by approximately 50% for hepatitis B virus, 55% for HIV, and 90% for HCV. NAT, using appropriately validated assays for nonliving donors, would reduce the residual risk to levels comparable to that in living donors (where the 95% reduction for quarantining pending the 180‐day re‐test is included).     

Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication

Kumar M, Bandi S, Cheng K, Gupta S. Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication. Xenotransplantation 2011; 18: 380–389. © 2011 John Wiley & Sons A/S. Abstract: Background: Studies of natural hepatitis B virus infection must be restricted to humans or primates due to viral species‐specificity. Alternative hepadnavirus animal models, e.g., woodchuck hepatitis virus in captive woodchucks, are not convenient, while in transgenic mice hepatitis B virus or viral proteins are expressed permanently through integrated genomes. Availability of small animal models that are easily produced and permit rapid assays will be quite helpful. Aims: We examined whether transplantation of human cells in the peritoneal cavity of mice will generate an appropriate mass of cells with hepatitis B virus replication. Methods: HepG2 2.2.15 cells were transplanted intraperitoneally into NOD/SCID mice. Replication of hepatitis B virus and viral gene expression was determined by analysis of blood and transplanted tissues with viral DNA and hepatitis B core antigen expression. Interruption of viral replication was examined. Results: After intraperitoneal transplantation with microcarrier scaffolds, 2.2.15 cells engrafted and proliferated in the peritoneal cavity of NOD/SCID mice. Hepatitis B virus replicated in transplanted 2.2.15 cells as shown by hepatitis B core antigen expression. Moreover, viral particles were secreted into the blood. Hepatitis B virus replication was susceptible to conventional antiviral drug therapy, such as lamivudine, as well as experimental antiviral gene therapy with a synthetic mimic of an antiviral cellular microRNA. Conclusions: Intraperitoneal transplantation of human cells rapidly provided reservoirs of hepatitis B virus in mice. This simple xenotransplantation approach will be effective and convenient for studies of hepatitis B and other human viruses in vivo.     

Klinik und Therapie der Virushepatitiden

Acute hepatitis can be caused by the enterically spread hepatitis A and E viruses and the parenterally spread hepatitis B, C or D viruses. The clinical features of acute viral hepatitis are similar among the five viruses and include non-specific symptoms and icterus. In general, a specific therapy is not necessary, but patients with fulminant hepatitis may require liver transplantation. For acute hepatitis C, the effect of interferon-alpha on the risk of chronicity is evaluated in clinical trials. Chronic hepatitis is defined as inflammatory reaction in the liver that continues without improvement for at least 6 months after infection with hepatitis B, C or D viruses. Hepatitis B resolves in more than 90% of the patients, but chronic infection can lead to liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is an insidious disease, because early diagnosis is missed easily due to asymptomatic presentation and about 70% of infected patients develop chronic hepatitis. The benefits of interferon-alpha and/or nucleoside analogues have been proven in recent clinical trials that show sustained responses in more than a third of all patients with chronic viral hepatitis. The future treatment of chronic viral hepatitis will likely include immunomodulation and gene therapy.     

Chronic viral hepatitis in renal transplant recipients with allografts functioning for more than 20 years

BACKGROUND: The impact of infection with hepatotropic viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]) on morbidity and mortality, and allograft function in renal transplant recipients with allografts functioning for >20 years is not known. METHODS AND RESULTS: Seventy-nine of 511 renal transplants performed at the Cleveland Clinic Foundation from January 1963 to January 1978 are known to have functioned for at least 20 years (level 5A). Fifty-four of these patients had hepatitis testing updated after their 19th year of transplantation. Fifteen patients had evidence of ongoing viral infection: persistent hepatitis B surface antigen in three (6%), HCV antibody (enzyme-linked immunosorbent assay II supplemented by recombinant immunoblot assay) in 11 (20%), and both viruses in one (2%). Of the 10 surviving patients, 8 were tested further for viral replication. HCV RNA (polymerase chain reaction; Amplicore) was positive in 6/7 (86%), and HBV DNA (hybridization) was positive in 1/2 (50%). An elevated alanine aminotransferase (>35 U/L) was present in all hepatitis patients, alpha-fetoprotein >10 ng/ml in 2/8 (25%), and cryoglobulins >50 microg/ml in 3/6 (50%) infected with HCV. No hepatocellular carcinoma was detected by hepatic ultrasound. In patients with chronic viral hepatitis, probable cirrhosis developed in 20% (3/15) compared to one patient in the group without hepatitis, but there was no mortality from liver failure in either group. Diabetes mellitus was significantly more common in those with than without hepatitis (11/15 vs. 10/39; P=0.002), but severe infection was not (9/15 vs. 15/39). Five hepatitis patients (33%) have died of non-hepatic causes (one from meningitis, one from unknown cause, and three from coronary heart disease [CHD] vs. only two individuals without hepatitis [5%]; P= 0.014). Although the more frequent occurrence of CHD among those with hepatitis was not significant (7/15 vs. 8/39; P=0.09), CHD as a cause of death in those with HCV was significantly increased (P=0.03). CONCLUSIONS: Twenty-year renal transplant recipients infected with hepatotropic viruses (HBV and HCV) have a high rate of active viral replication (88%), a greater frequency of diabetes (P=0.01), and a higher overall mortality (P=0.014).     

Coimbra University Hospitals' bone and tissue bank: twenty-two years of experience

We report the microbiological contamination rate of sterilely procured 3953 tissue allografts obtained during 22 years of activity for musculoskeletal reconstruction from 1982 to 2003. From 1987 to 2000, allograft retrievals were performed in 191 cadaveric donors and in 323 living donors. In the former group 30 retrievals (15.7%) were excluded based on laboratory criteria. Among living donors 108 femoral heads (33.4%) were also excluded by the same criteria. The microbiological contamination rate of sterilely procured allografts in the operating room was 8.3% for cadaveric donors and 18.2% for living donors. A questionable positive serology for HIV antigen was registered in two non-heart-beating donors. Hepatitis C virus antibodies were positive in two other non-heart-beating donors. Hepatitis B virus serological markers were positive or questionable in more than 11 non-heart-beating donors. In living donors 20 femoral heads were excluded (6.1%) due a positive or questionable hepatitis B virus serology. One femoral head donor showed a positive HTLV-I antibody and another one a positive syphilis serology. No positive serology cases for the HIV antibodies were found. No cases were registered of transmission of viral diseases from the donor to the recipient. Our extremely rigorous criteria led to the exclusion of a considerable number of both donors and allografts.     

Injuries from biologic material of suicide bombers

BACKGROUND: The management of penetrating wounds caused by suicide bomber bone fragments, contaminated by infectious viruses such as hepatitis or human immunodeficiency virus, is a new medical challenge. The aim of this study was to review the literature and add our experience in the treatment of such wounds. PATIENTS AND METHODS: The files of 94 patients with multiple penetrating fragment injuries of the musculoskeletal system were reviewed. Following any necessary life-saving procedures, the patients underwent wound debridement with delayed wound closure. Broad-spectrum antibiotic treatment was started immediately on admission, and all patients were inoculated with antitetanus toxin and hepatitis B vaccine. RESULTS: The most common injuries were multiple lacerations caused by penetration of small metal fragments. Those that were not removed on initial debridement and continued to cause pain were removed during follow-up. Twenty-three patients presented with 49 open fractures caused by the penetrating nails or impact against other objects. Three cases were complicated by chronic osteomyelitis. Three patients presented with injuries caused by bone fragments from the suicide bomber. Samples of bone from one suicide bomber tested positive for hepatitis B virus. None of the patients developed clinical signs of hepatitis B, human immunodeficiency virus or other severe infections during follow-up. CONCLUSIONS: The penetration of biologic material may transmit severe incurable infectious disease.     

Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation

HYPOTHESIS: Hepatic allografts from donors positive for antibody to hepatitis B core antigen (anti-HBc) frequently transmit hepatitis B virus (HBV) infection to recipients. Therefore, most transplantation centers will not use these organs for orthotopic liver transplantation (OLT). Although it is expensive and not always efficacious, hepatitis B immune globulin (HBIG) has been used routinely for indefinite periods to prevent HBV infection in liver allograft recipients. We assessed the effectiveness of long-term use of a nucleoside analog, lamivudine, in preventing HBV transmission by anti-HBc-positive allografts. DESIGN: Retrospective study. SETTING: A tertiary care center. PATIENTS: Twelve patients received hepatic allografts from anti-HBc-positive donors at Loyola University Medical Center, Chicago, between February 23, 1998, and March 13, 2001. INTERVENTION: All patients received 10 000 U/d of intravenous HBIG for 7 days. In addition, they received 300 mg/d of lamivudine in divided doses. Their liver biopsy specimens were tested for HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAb). Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody (HBsAb). MAIN OUTCOME MEASURE: The incidence of HBV infection in recipients who received HBcAb-positive donor livers and lamivudine prophylaxis. RESULTS: All recipients were anti-HBc negative before OLT. Five of the recipients had HBsAb titers greater than 150 U at the time of OLT. Three of the donor livers were HBV DNA positive and 2 were hepatitis B core antigen positive at the time of OLT. Donor serum was HBcAb positive in all 12 donors. None of the recipients have become infected with HBV with a follow-up of 2 to 38 months. CONCLUSION: Perioperative use of HBIG combined with long-term use of lamivudine can prevent HBV infection in recipients who receive hepatic allografts from HBcAb-positive donors.     

Is it possible to resterilize disposable laparoscopy trocars in a hospital setting?

Nosocomial infections associated with interventional procedures have been attributed to improper decontamination of instruments. Disinfection of solid laparoscopic instruments, such as telescopes, by 2% glutaraldehyde and ethylene oxide was shown to be effective in preventing infection transmission. However, instrument design in more complex surgical instruments may hamper the quality of disinfection. The aim of this study is to investigate the safety of hospital disinfection of disposable laparoscopic instruments with a relatively more complex design. A total of 40 laparoscopic trocars were divided into two equal groups: group 1 was contaminated with bacteria and yeast, and group 2 was contaminated with the hepatitis B virus. Each group was then divided to two equal subgroups. After disinfecting subgroup A with 2% glutaraldehyde and B with ethylene oxide, samples were obtained for bacterial cultures and for virus detection using polymerase chain reaction (PCR). Bacterial and yeast cultures were positive in three instruments in group 1A and in two instruments in group 1B. Tests results for the hepatitis B virus were negative in group 2A, but positive in group 2B. Results of this study indicate that disinfection for multiple use of disposable laparoscopic instruments with a relatively complex structure is not effective and may result in nosocomial disease transmission by bacteria, fungi, and viruses.     

In vitro study of the role of various preservation methods on mechanical properties of allografts of the patellar tendon]

Tendon allografts are presently used for surgical reconstruction of the anterior cruciate ligament. The aim of this study was the in vitro evaluation of the modification of the mechanical properties of conserved human patellar tendons, deep-frozen or freeze-dried and sterilized with gamma rays. Thirty pairs of patellar tendons (central third) with their bony attachments were removed from fresh corpses, frozen in liquid nitrogen, then conserved at -80 degrees C. Out of each pair, one tendon was submitted to an additional treatment and the other was used as a control. Three types of treatment were studied: 2.5 Mrad irradiation (groupe I), freeze-drying with 1% residual humidity (groupe II), consecutive freeze-drying and irradiation (group III). After warming up (controls and group I treated tendons), the specimens were submitted to mechanical tests on the pulling machine with a suitable arrangement. Two types of tests were performed: a creep test (80 cycles at 1 Hz between 0 and 50 N) then an ultimate tensile strength test (0.25 mm/s). Freeze-drying causes macroscopic morphological alterations, which are even more marked if irradiation is applied in addition. The three types of treatment induce an increase in creep and a decrease in the ultimate, tensile strength and in Young's module, all being statistically significant. The three types of treatment alter the mechanical properties of the allograft. Freeze-drying maintains a better resistance of the graft. The combination of freeze-drying and irradiation is the most damaging method, and freeze-drying even seems to potentialize the harmful effects of irradiation resistance (group II freeze-dried grafts), the treated allografts present with changes in their viscoelastic properties that are incompatible with their clinical use. This study has also shown that some parameters influence the extent of the damaging effects of these three treatments, and experiments are being continued to optimize the conservation and sterilization procedure.     

Recurring fibro-obliterative venopathy in liver allografts.

Recurrent diseases in liver allografts are not uncommon. These occur most frequently in those transplanted for viral hepatitis B and C. We report an unusual case of recurrent process in two consecutive liver allografts received by a 37-year-old woman, who previously had an unremarkable past medical history but developed a rapidly progressive cholestatic liver failure. Histopathologic examination of the native liver showed fibroocclusive lesions of both terminal hepatic venules and portal vein branches. The exuberant fibroobliterative process created dense fibrosis with whorled appearance, and broad fibrous septa connecting adjacent central areas, and sometimes bridging portal to central areas. Dense portal fibrosis resulted in compression atrophy and loss of bile ducts. The first allograft, which failed within 3 months, showed histopathologic findings similar to that of the native liver. A liver biopsy that was performed 20 months after the second liver transplant again showed similar histopathology. The histopathologic features and clinical presentation of this patient suggest an unusual form of recurring progressive fibroobliterative venopathy causing liver failure.