Outcomes of renal transplantation in older high risk recipients: is there an age effect?

BACKGROUND: The purpose of this study was to evaluate long-term outcomes in high risk renal transplant recipients over 60 years of age compared with those younger than 60 years of age. MATERIALS AND METHODS: We analyzed outcomes in 131 consecutive renal transplant recipients at our institution between November 2001 and December 2007. Primary outcomes included incidence of delayed graft function (DGF), acute rejection, graft survival, patient survival, and incidence of infections and neoplasms. RESULTS: Older recipients (Over 60 group, n = 45) received more organs from extended criteria donors (ECD) or donation after cardiac death donors (DCD) compared with younger recipients (Under 60 group, n = 86), 42% versus 17% respectively, P = 0.001. Multivariate analyses revealed that African American ethnicity and DCD donation had the greatest impact on the incidence of DGF in both groups; P < 0.05. Patient survival and graft survival beyond 1 y were similar between the two groups. CONCLUSION: Our data suggest that long-term transplant outcomes in older, high risk renal transplant recipients are similar to those of younger, high risk recipients. Older recipients' age and high-risk characteristics, such as African American ethnicity and increased sensitization, should not be a contraindication to renal transplantation in the elderly.

Risk of thrombogenicity among nonionic radiocontrast agents.

Several contrast agents have been approved in the United States for radiographic imaging purposes. Most of the older ionic, high-osmolar contrast agents are no longer used because of their side effect profile. Therefore, newer nonionic, low or iso-osmolar contrast agents have been widely accepted as an alternative due to their improved tolerability and safety. We investigated the thrombogenicity of the 6 different nonionic radiocontrast media in terms of their platelet reactivity and noted some minor differences among them. In the 50% contrast concentration group, all of the nonionic contrast agents inhibited aggregation, whereas in the 10% contrast concentration group, all agents showed similar aggregation curves in comparison to the normal control. At 50% contrast concentration, the inhibitory effect of aggregation appeared to be related to the inhibition of calcium mobilization, which may be one of the mechanistic effects.

p53, Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis in Egypt.

BACKGROUND AND AIMS: Oncogenes and tumor suppressor genes expression are well described in bladder cancer associated with schistosomiasis especially in Egypt. Scarce studies were directed to colorectal cancer (CRC) associated with Schistosoma mansoni (S. mansoni). Apoptosis (programmed cell death) and the genes regulating this process (e.g., Bcl-2) have recently become a focus of interest in the study of cancer development and progression. In the present study, we aimed to investigate the expression pattern of p53, Bcl-2 and C-Myc in CRC tissues obtained from Egyptian colorectal cancer patients divided in two different groups, one associated with Schistosoma mansoni (CRC-Sm) and the other without Schistosoma mansoni (CRC-NSm). METHODS: Seventy-five CRC tumors containing 36 draining lymph node metastatic tumors were immunohistochemically stained using specific monoclonal antibodies for p53, Bcl-2 and C-Myc, in addition the apoptotic activity of these tumors were analyzed. RESULTS AND CONCLUSIONS: Regardless of the S. mansoni infection, the obtained results showed that the apoptotic activity was more evident in p53 diffuse positive tumors (P = 0.021). There was a significant correlation between p53 diffuse positive staining and Bcl-2 positive immunostaining (P = 0.011). Signet ring cell carcinoma and mucinous adenocarcinoma exhibited both intense C-Myc expression than non-mucinous carcinoma (P = 0.001). When adjusting for S. mansoni infection, 58.3% of CRC-Sm cases were Bcl-2 positive compared to only (33.3%) of CRC-NSm (P = 0.046). Apoptotic activity was more evident in the latter group than of CRC-Sm tumors (P = 0.009). p53 and C-Myc expressions were found insignificantly different in CRC-Sm compared with CRC-NSm (P > 0.05). These observations suggest that the genotoxic agents produced endogenously through the course of schistosomiasis mansoni may play a role in CRC-Sm pathogenesis through the dysregulation of apoptosis by alteration the expression pattern of Bcl-2 protein differently from CRC-NSm suggesting a different biological behavior.

Cardiac transplantation across a positive prospective lymphocyte cross-match in sensitized recipients.

BACKGROUND: Although there is an increasing body of evidence for a deleterious effect of mismatched donor HLA antigens on the outcome of human cardiac transplantation, the role of anti-HLA lymphocytotoxic antibodies remains controversial. Thus, their appearance after cardiac transplantation has been associated with poor outcome by some groups; whereas others have reported them to be of no clinical significance. Furthermore, their presence prior to cardiac transplantation has also been the subject of similarly conflicting reports. The deleterious effect of such pre-existing antibodies has been predicted by a positive lymphocyte cross-match (LCM), which, for most patients awaiting renal transplantation and in many requiring a cardiac allograft, leads to cancellation of the operation. The reason for undertaking the current study was to test the hypothesis that the constraints which a positive LCM result impose in preventing renal transplantation may not apply to orthotopic heart transplantation (OHT). PATIENTS AND METHODS: Four sensitized patients underwent OHT across a positive prospective LCM. Three were females, and one of those females also underwent cadaveric renal transplantation at the time of OHT. All four patients received aggressive early post-transplant immunosuppressive therapy, which included plasmapheresis, intravenous immunoglobulin (IVIg), antiproliferative agents (cyclophosphamide, basiliximab) and cytokine down-regulators (calcineurin inhibitors, muromonab-CD3) and anticell antibodies (OKT3, ATG). They also received standard immunosuppressive therapy which included corticosteroids. Complement-dependent cytotoxicity (CDC) was used for the identification of anti-HLA lymphocytotoxic antibodies. Reactivity of the latter against more than 10% of a panel of well-characterized T cells was considered sensitization, and required LCM to be performed prospectively, which test was also performed using the CDC technique. RESULTS: Three of the patients exhibited evidence suggestive of acute or hyperacute rejection in endomyocardial biopsy specimens by postoperative day (POD) 7. Two of the three patients with rejection also exhibited haemodynamic instability (elevated filling pressures and reduced cardiac index) on POD 1, which improved with inotropic support. One patient sustained a cardiac arrest on POD 7, and was successfully resuscitated without sequelae. All patients are now doing well, postoperatively (follow-up: 17-57 months) post-transplant. Two patients have normal left ventricular function and one patient has mild left ventricular dysfunction. Two have no further evidence of sensitization (PRA < 10%). CONCLUSIONS: Although the number of patients in this study is small, the long-term successful outcome of OHT following positive prospective cross-matches suggests that such a test result, in contrast to the restraints it imposes on renal transplantation, may not be a contra-indication to transplantation of the human heart. If OHT proceeds after the LCM is reported positive, aggressive immunotherapy should not only be initiated early, but should also be targeted at humoral-vascular rejection in particular.

p53 expression and DNA ploidy pattern in Egyptian colorectal carcinoma.

BACKGROUND/AIMS: p53 gene mutation occurs in about 50-60% of colorectal carcinoma cases. This mostly occurs as a late event in the adenoma-carcinoma sequence. These late stages are associated with more aneuploidy compared to adenomas and early carcinomas. However there is a controversy regarding the relation between p53 overexpression and DNA index. This study was designed to investigate the relationship between p53 status and DNA ploidy pattern. METHODOLOGY: Nuclear DNA content of paraffin-embedded material from 83 colectomy specimens for colorectal carcinoma was measured by flow cytometry. Also, p53 was detected by immunohistochemistry in 73 out of the 83 tumor cases using a monoclonal antibody that detects both wild and mutant p53 proteins (Biogenex 1801). RESULTS: Aneuploidy was identified in 37 cases (46.25%). Tumors with rectal location were significantly more aneuploid in comparison to other sites (P = 0.009), p53 staining showed three patterns: diffuse staining (29 cases), focal (13 cases), and negative (31 cases). Diffuse p53 staining was associated with aneuploidy (P = 0.04). The majority of DNA indices fell within the range 1.1-2.2 (32 out of 37). Twenty-one of these had DNA index = 1.1-1.8 (aneuploidy short of tetraploidy) significantly associated with diffuse p53 staining compared with peritetraploid cases (DNA index 1.8-2.2) (P = 0.034). CONCLUSIONS: p53 immunohistochemistry demonstrates two distinct patterns in colorectal carcinoma. Diffuse p53 staining, which is associated with aneuploidy short of tetraploidy (DNA index 1.1-1.8), a finding which is different from previously published work. Focal p53 staining pattern, in contrast, is related to high G2M and more abnormal tetraploid peaks but less aneuploidy.