ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Fungal infections constitute some of the most difficult clinical management problems encountered after solid organ transplantation. Although the predominant pathogens continue to beCandidaspecies followed byAspergillusspecies, emerging fungal pathogens including azole-resistant yeast,Fusarium, and dematiaceous fungi are becoming more significant. Identification of novel risk factors has expanded traditional concepts of the epidemiology of these infections. Optimal prophylaxis of fungal infections constitutes an area of active research. Diagnosis continues to be a challenge, but newer methods including antigen assays and panfungal or specific fungal polymerase chain reaction methodology are promising. Advances in therapy include lipid amphotericin formulations, newer azoles such as voriconazole, ravuconazole, and posaconazole, and echinocandins such as the recently approved drug caspofungin, as well as immunomodulatory therapy.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Infections with the polyomavirus, BK have been documented in renal transplant recipients for at least three decades. It is only over the past 5 to 6 years that BK virus (BKV) has been recognized as a cause of nephropathy resulting in renal allograft dysfunction and loss. Intense investigative efforts focused on developing practical methods for sensitive and specific diagnosis, as well as surveillance and monitoring, have led to a number of polymerase chain reaction–based methods for qualitative and quantitative assay of BKV in various tissues and fluids. The pathophysiologic mechanisms by which BKV causes disease have not as yet been unraveled but recent studies suggest that viral mutations may enhance pathogenicity. The finding that JC virus may also be implicated in causing renal nephropathy in renal allograft recipients further complicates the picture. BKV infection and rejection usually evolve concomitantly and cannot be distinguished from each other. There is no known efficacious therapy for this disease, thus management requires careful titration of immunosuppressive agents to allow for viral clearance without precipitating irreversible rejection. For renal allograft recipients, BKV infection is indeed a major challenge of the new century.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Increasingly, hepatotropic viruses, in particular hepatitis B virus (HBV) and hepatitis C virus (HCV), have had a significant impact on the overall outcome of recipients of solid organ allografts. The viruses can become active either as recurrence of preexisting infection or asde novoinfection in the posttransplant setting. Depending on the virus and the type of allograft, antiviral therapy, immunoprophylaxis, and modification of immunosuppression are important considerations in the management of these infections after transplantation. These issues are discussed for renal and liver transplant recipients.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

For more than 15 years, patients have been placed on selective bowel decontamination (SBD) regimens at some centers in an effort to reduce the incidence of bacterial and fungal infections after liver transplantation. Despite this substantial experience, the efficacy of SBD has not been shown. Most reports of outcomes are descriptive or make use of historical controls. There have been only three randomized controlled trials of SBD, and two of the three did not show a significant reduction in infection rates. Further evaluation of SBD is warranted, and multiple studies will be needed to evaluate the different regimens and schedules of initiation.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Acute and chronic rejection constitutes serious limitations to survival of all solid organ allografts, and considerable evidence suggests that both pathologies are likely driven by human cytomegalovirus (CMV)–mediated vascular injury. This hypothesis is supported by the observation that human CMV infection is associated with transplant arteriosclerosis (TA) and acute rejection. The common pathologic feature of chronic rejection seen in all allografts is TA, an obliterative and fibrotic process involving the vasculature and other hollow structures. These changes are most apparent in cardiothoracic organ transplants, where most grafts are lost owing to TA affecting the coronary arteries and obliterative bronchiolitis (OB) after lung transplant. Epidemiologic and observational data, experimental models, and therapeutic trials provide evidence supporting a role for human CMV in the progression to TA. Human CMV infection has been reported to be a risk factor for TA and OB. Endomyocardial biopsies from patients during CMV viremia demonstrate endothelial and vascular smooth muscle cell proliferation and endothelialitis. These changes, which are consistent with vascular injury induced by CMV, have been shown to be predictors of subsequent diffuse TA. Human CMV immediate early proteins (IE-1 and IE-2) have recently been shown to rapidly increase the constitutive expression of intercellular adhesion molecule– in vascular endothelial cells through the regulation of the intercellular adhesion molecule–1 gene promoter by a direct effect, independent of other intracellular cytokines. Viral chemokines such as US28 are now being implicated in the pathophysi-ology of vascular disease because of their ability to induce smooth muscle cell migration, a key event in the initiation of arteriosclerosis after vascular injury. This research direction has been fueled by observations suggesting that antiviral agents such as ganciclovir inhibit both acute and chronic rejection in rodent models and in humans. Acute rejection in renal transplant patients was significantly reduced by valacyclovir, in parallel with the drug's effect in preventing acute CMV disease. Similarly, patients treated prophylactically with ganciclovir during the initial 28 days after heart transplantation had a lower incidence of both acute CMV disease and TA compared with placebo. However, this benefit was not seen in seronegative patients receiving hearts from seropositive donors, consistent with the high-risk nature of this group (D+/R−) for developing acute CMV disease. Recent studies suggest that a combined regimen of ganciclovir plus cytomegalovirus immunoglobulin (CMVIG) reduces the incidence of acute CMV disease, TA, OB, and death from OB in this high-risk group. These observations emphasize the need for randomized controlled clinical trials to confirm a causal role for CMV (and other pathogens) in the disease process of acute rejection and TA.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Although corticosteroids have been a mainstay of immunosuppressive regimens for decades, their use has been associated with significant morbidity in transplant recipients. Several studies in liver transplant recipients suggest that steroid-sparing regimens are well tolerated immunologically and may reduce cardiovascular complications associated with their use. The safety and efficacy of steroid withdrawal in kidney, pancreas, and heart transplants are less clear. With the introduction of newer, potent immunosuppressive agents such as tacrolimus, mycophenolate mofetil, and sirolimus, steroid withdrawal is being tested more frequently in these organs. Recent data in clinical pancreatic islet transplantation even suggest that corticosteroids may be contraindicated in this type of transplant. This review covers the recent progress made in steroid-sparing regimens and some of the current controversies in islet and solid organ transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Polyclonal antibodies such as antithymocyte globulin and monoclonal antibodies such as OKT3 are widely used in clinical transplantation to improve long-term allograft survival by delaying the first episodes of acute rejection, to circumvent cyclosporine and tacrolimus-induced nephrotoxicity, and to treat acute rejection. In some centers, treatment with antithymocyte globulin or OKT3 is started at the time of grafting as induction therapy. In other centers, their use is limited to patients with preformed cytotoxic antibodies, second grafts, delayed graft function, prolonged cold ischemia time, or steroid-resistant rejection episodes. Newer polyclonal antibodies such as rabbit antithymocyte globulin (ATG) and monoclonal antibodies against interleukin-2&agr; receptors such as Daclizumab (Roche, Inc., Nutley, NJ) and basiliximab were also approved to prevent acute rejection and improve graft function. The effect of monoclonal antibodies against adhesion molecules such as anti–intercellular adhesion molecule 1, and antileukocyte function-associated antigen 1 in the clinical transplantation is not clear and needs further investigation.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Recurrent hepatitis C is a major source of morbidity and mortality after liver transplant. Immunosuppression is known to play a major role in the rate of recurrence. As treatment options remain limited and are of unclear effectiveness, efforts must be made to modulate the immunosuppressive regimen to minimize risk of recurrence. High cumulative doses of steroids and treatment of rejection with steroid boluses appear to have the greatest impact on both rate of recurrence and severity of recurrence. Treatment of rejection with OKT3 has also been associated with severe recurrence. There have been no randomized studies showing any differences between cyclosporine-based immunosuppression or tacrolimus-based immunosuppression in risk of recurrent hepatitis C. It is still unclear whether newer immunosuppressive agents such as Daclizumab, mycophenolate mofetil, or basiliximab will have any impact on hepatitis C recurrence. Steroid avoidance using induction with Daclizumab or Thymoglobulin may be helpful and may be the immunosuppressive regimen of choice if long-term follow-up shows a benefit in patients transplanted for hepatitis C.

ISSN:1087-2418    

出版商:OVID    

年代:2001

数据来源: OVID