Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.

This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.

ObjectiveTo determine the effects of surgical portal decompression in Budd-Chiari syndrome (BCS) on survival, quality of life, shunt patency, liver function, portal hemodynamics, and hepatic morphology during periods ranging from 3.5 to 27 years. Summary Background DataExperiments in the authors' laboratory showed that surgical portal decompression reversed the deleterious effects of BCS on the liver. This study was aimed at determining whether similar benefit could be obtained in patients with BCS. MethodsFrom 1972 to 1999, the authors conducted prospective studies of the treatment of 60 patients with BCS who were divided into three groups: the first had occlusion confined to the hepatic veins treated by direct side-to-side portacaval shunt (SSPCS); the second had occlusion involving the inferior vena cava (IVC) treated by a portal decompressive procedure that bypassed the obstructed IVC; and the third group, who had advanced cirrhosis and hepatic decompensation and were referred too late for treatment by portal decompression, required orthotopic liver transplantation.

Infection with the pathogens human cytomegalovirus (HCMV) or Chlamydia pneumonia (CP) is linked to the development of vascular disease, including atherosclerosis. The role of pathogens in vasculopathies has been controversial. However, animal models have demonstrated a direct link between infection with CP and herpesviruses and the development of vascular disease. Clinical studies have shown a direct association of HCMV and CP with the acceleration of vascular disease. This article will review the evidence supporting the role for CP and HCMV in the development of vascular disease and will suggest a potential mechanism for HCMV acceleration of the disease process. Vascular diseases are the result of either mechanical or immune-related injury followed by inflammation and subsequent smooth muscle cell (SMC) proliferation and/or migration from the vessel media to the intima, which culminates in vessel narrowing. A number of in vitro and in vivo models have provided potential mechanisms involved in pathogen-mediated vascular disease. Recently, we have demonstrated that HCMV infection of arterial but not venous SMC results in significant cellular migration in vitro. Migration was dependent on expression of the HCMV-encoded chemokine receptors, US28, and the presence of the chemokines, RANTES or MCP-1. Migration involved chemotaxis and provided the first evidence that viruses may induce migration of SMC toward sites of chemokine production through the expression of a virally encoded chemokine receptor in infected SMC. Because SMC migration into the neointimal space is the hallmark of vascular disease, these observations provide a molecular link between HCMV and the development of vascular disease.

Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.With the escalation in the number of immunosuppressed patients undergoing immunosuppressive therapy following solid organ or bone marrow transplantation, human cytomegalovirus (HCMV) disease has now become a major clinical problem. While the majority of HCMV infections result in subclinical disease in healthy individuals, HCMV is a significant pathogen in immunocompromised patients (1,3,4,9,26,33,34,50,51,56). Primary HCMV infection is followed by lifelong persistence of the virus in a latent state, and reactivation of the latent virus is considered to be the major source of virus in these immunocompromised individuals. HCMV has been linked to the development of atherosclerosis, arterial restenosis following angioplasty, and solid organ transplant vascular sclerosis (TVS) (26)(27)(28)47). HCMV infection doubles the 5-and 3-year rates of graft failure due to accelerated TVS in cardiac and liver transplant patients, respectively (15; L. W. Miller, Editorial, J. Heart Lung Transplant. 11:S1-S4, 1992). The observation that HCMV infects many of the cell types involved in vascular disease, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells (SMC), suggests that HCMV may play a role in these disease processes. Because of the similarities between the CMV-speciesspecific viruses, animal models provide an ideal tool to study the association between CMV and TVS.The most compelling evidence that herpesviruses play a role in vascular disease comes from studies in animal models. Using a rat CMV (RCMV) solid organ transplant model, researchers have demonstrated, in light of the RCMV-associated acceleration of TVS, an association of herpesvirus ...