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Biomedical subjects

F Sanfilippo

Publications and source records attributed to F Sanfilippo.

At least 127 records · Page 7Linked to original sources
PubMed1987

Causes of death in renal transplant recipients. A review of autopsy findings from 1966 through 1985.

From 1966 through 1985, a total of 640 patients received 739 renal transplants at a single center transplantation program. Of 245 total deaths, a slide and chart review of all 116 autopsied cases (47%) identified the major causes of death as pneumonia (n = 43), sepsis (n = 32), hemorrhage (n = 15), peritonitis (n = 11), meningitis (n = 7), and pulmonary embolism (n = 5). Eighty-five (73.3%) of these patients died of complications directly associated with immunosuppression, almost all (n = 82) as a result of infection. Organisms most frequently identified at death were gram-negative bacilli (n = 72), Candida species (n = 23), cytomegalovirus (n = 17), enterococcus (n = 14), Staphylococcus aureus (n = 11), Aspergillus species (n = 10), Pneumocystis carinii (n = 5), and mycobacteria (n = 5). Significant associations were found between bolus steroid antirejection therapy and infection with Aspergillus cytomegalovirus. Diabetics had a higher incidence of fungal infections and bowel perforation than nondiabetics. During this 20-year period, overall one-year actual patient survival rates for the four respective five-year intervals increased dramatically (69.9%, 68.2%, 83.3%, and 91.8%), but the normalized death rate showed a smaller decrease for infectious vs noninfectious causes.

Adolescent↗
PubMed1987

Hemolytic anemia is not a frequent complication of ABO unmatched renal allografts from living related donors.

In summary, we could not document an increased incidence of HA nor a detrimental effect of CyA use in our recipients of ABO-unmatched LRD kidneys. Thus, it would appear that the incidence of HA in this situation is low enough that no special pretreatment of the kidney transplant or recipient is warranted. Since the long-term survival of ABO-unmatched LRD kidneys was equivalent to that of ABO-matched recipients there is no reason to select against them, or avoid the use of CyA. Rather a severe pretransplant anemia may predispose to a delayed recovery from anemia after transplantation.

ABO Blood-Group System↗
PubMed1987

Effect of class I HLA matching on graft survival in sensitized patients.

First, the proportion of highly sensitized transplant candidates grows in the absence of organ sharing. The unsensitized patient is transplanted readily; the sensitized patient has restricted access because of the need for a well-matched kidney to permit a negative cross-match. Second, well-matched grafts are equally successful in sensitized and unsensitized recipients. Finally, emphasis on organ sharing would reverse the trend of accumulation of sensitized candidates without decreasing graft survival.

Follow-Up Studies↗
PubMed1986

Reduced graft rejection with good HLA-A and B matching in high-risk corneal transplantation.

We examined the effect of matching for HLA-A and B antigens on the success of corneal transplantation in a single-center, prospective, masked study that began in March 1979. The study involved 97 consecutive recipients at high risk because of prior corneal graft rejection or serious vascularization of the native cornea. Donor corneas were selected on the basis of ABO-blood-group compatibility, a negative lymphocyte crossmatch, and optimal HLA-A and B matching; all clinical personnel were "masked" to the degree of HLA matching during the study. Among 38 patients receiving corneas with a good HLA match (two or more antigens), only 8 (21 percent) had graft rejection, as compared with 29 of 59 (49 percent) with a poor match (no or one antigen) (P less than 0.010). The mean (+/- SE) difference in rejection-free graft survival increased with time: 88.4 +/- 5.5 percent versus 73.5 +/- 5.9 percent at six months, and 80.1 +/- 7.5 percent versus 38.5 +/- 7.9 percent at two years. Cox multiple regression analysis, which included the HLA-A and B match and nine other potential confounding variables and risk factors also identified a significant (P less than 0.009) relative risk (4.6) of rejection reactions as well as irreversible graft rejection (P less than 0.016; relative risk, 11.2) with poor HLA-A and B matching. Our findings indicate that good HLA-A and B matching yields a significant long-term benefit in reducing the number of episodes of graft rejection and subsequent failure in high-risk recipients of corneal transplants.

ABO Blood-Group System↗
PubMed1986

The relative immunogenicity of corneal epithelium, stroma, and endothelium. The role of major histocompatibility complex antigens.

Corneal allografts have been shown to give rise to immune responses, but the role and relative importance of individual corneal cell populations in evoking such responses remain unclear. We dissected ACI (RT1a) rat corneas into separate epithelial, stromal, and endothelial components by a method that yields pure cell populations in tissue culture, and grafted these components separately to groups of fully allogeneic PVG (RT1c) recipients). Grafts of corneal stroma elicited strong cellular cytotoxic immune responses in a cell-mediated lymphocytotoxic assay, but corneal epithelium failed to generate any detectable response. Grafts of corneal endothelium alone, however, evoked a potent cellular cytotoxic response. Using congenic rats, it was found that grafts from PVG.1A (RT1a) donors to PVG (RT1c) recipients (which differ at both the RT1.A and B loci) yielded identical results. However, no corneal component graft from PVG.R1 (RT1rl) donors to PVG recipients (which differ only at RT1.A) generated a detectable immune response. Use of target lymphoblasts from congenic strains established that at least part of all responses detected were directed against class I (RT1.A) major histocompatibility complex antigens. These findings indicate that there is differential immunogenicity of specific corneal tissue components in the rat that may be further influenced by the degree of MHC disparity between donor and recipient.

Animals↗
PubMed1986

The expression of major histocompatibility complex and leukocyte antigens by cells in the rat cornea.

The well-characterized immunogenetic constitution of the rat has made it a valuable resource for the study of corneal transplantation. However, little is known about the expression of histocompatibility antigens in the rat cornea or about the populations of passenger leukocytes rat corneal grafts may contain. Thus the relevance of rat corneal transplantation to the human situation is unclear. We examined the expression of antigens of the histocompatibility complex (MHC) of the rat (RT1) and of antigens identifying rat leukocyte populations in corneas of selected rat strains using a sensitive immunoperoxidase technique. Class I MHC antigens were found in fairly uniform association with most cells of the rat corneal epithelium, endothelium, and stroma. In contrast, class II MHC antigens were not associated with most corneal parenchymal cells, but were clearly present on multiple isolated dendritic cells throughout the corneal stroma, especially near the limbus, and on very rare isolated cells in the limbal epithelium; these antigens were not detectable on the corneal endothelium. Cells expressing an antigen common to all rat leukocytes were present in a distribution similar to that of class II MHC antigen-bearing cells. There was no consistent expression of antigens associated with T lymphocytes, macrophages, neutrophils, or NK cells. It thus appears that the expression of MHC and leukocyte antigens by cells in the rat cornea is similar to that reported in the human, indicating that the rat may indeed provide a good model of human corneal transplantation.

Animals↗
PubMed1986

Relative contribution of major histocompatibility complex antigens to the immunogenicity of corneal allografts.

The relative contributions made by the major class I (RT1.A) and class II (RT1.B) antigens of the rat major histocompatibility complex (MHC) to the immunogenicity of corneal and skin allografts were investigated using congenic animals. PVG (RT1c) recipients were given skin or heterotopic cornea grafts from congenic PVG.1A (RT1a) or PVG.R1 (RT1r1) donors, which respectively share the entire RT1 complex or only the RT1.A (major class I MHC antigen) region with fully allogeneic ACI (RT1a) rats. Recipient splenocytes were tested at ten days posttransplant for their ability to lyse ACI, PVG.1A, PVG.R1, and PVG target cells in a secondary CML following 6 days in vitro stimulation with irradiated ACI spleen cells. Effector cells from PVG recipients of both RT1.A and B disparate (PVG.1A donor) and RT1.A disparate (PVG.R1) skin or cornea grafts lysed ACI, PVG.1A, and PVG.R1 (but not PVG) targets at levels significantly above controls given syngeneic grafts. However, the level of cytotoxicity against PVG.R1 as well as ACI and PVG.1A allogeneic targets was always significantly higher following PVG.1A grafts than following PVG.R1 grafts, indicating that the addition of a class II MHC antigen difference markedly augmented the immunogenicity of class I MHC antigen disparate cornea and skin grafts. Taken together with other recent evidence confirming the presence of Langerhans cells in the normal rat (and human) cornea, these results suggest that class II MHC-bearing cells make an important contribution to the immunogenicity of corneal allografts.

Animals↗
PubMed1986

Multivariate analysis of risk factors in cadaver donor kidney transplantation.

Data collected prospectively on 3811 kidney transplants performed between June 1977 and July 1982 with follow-up to July 1984 by the 42 member institutions of the South-Eastern Organ Procurement foundation were analyzed to identify factors associated with graft and patient outcome in patients not receiving cyclosporine. Multivariate Cox regression analysis was used to examine the association and relative risk of 24 variables with three actuarial outcomes: overall graft failure, irreversible rejection, and patient death. Factors having no suggested association with any outcome included: recipient sex, history of pregnancy, blood group, and time on dialysis; organ preservation method, time and source; donor race; crossmatch test sensitivity; and annual center transplant rate. In decreasing order of relative risk, the factors most significantly associated with irreversible rejection were: loss of two or more prior grafts, low HLA-A,B match, lack of pretransplant blood transfusion, high (greater than 60%) pretransplant sensitization to leukocyte (HLA) antigens, and delayed graft function. Splenectomy, insulin-dependent diabetes, and antilymphocyte serum therapy provided the greatest risk of patient death. Factors such as recipient age, race, and native nephrectomy had suggested associations with outcome. By adding each center as a separate covariate in the analysis, other center-dependent factors were quantitated and found in some cases to have a highly significant association with graft and patient outcome. These results provide a basis for evaluating the potential risk of graft loss or patient death for those prospective cadaver kidney transplant recipients not being considered for cyclosporine therapy.

Cadaver↗
PubMed1986

HLA matching for cadaver renal transplantation in SEOPF: the impact of cyclosporine. Southeastern Organ Procurement Foundation.

Since the introduction of CsA in 1983, several changes in SEOPF activity have been observed: 1. Organ recovery has increased at a rate slower than candidate registration, whereas the utilization rate has increased substantially. 2. Overall organ sharing has decreased for both CsA and non-CsA-treated patients. 3. The percentage of poor HLA-A,B matched recipients has increased for both CsA- and non-CsA-treated patients. 4. The use of cold storage preservation has increased for both CsA- and non-CsA-treated patients. 5. The use of ALS has decreased, predominantly in CsA-treated patients. 6. A majority of diabetics are being treated with CsA. 7. There is substantial individual variation in SEOPF center preferences for CsA use, HLA matching, and use of shared kidneys. In terms of graft outcome, the following associations have been observed: 1. The incidence of delayed graft function has increased with shared kidneys only, suggesting sharing of poorer quality as well as fewer kidneys. 2. First transplant recipients receiving CsA tend to have lower delayed graft function rates, possibly as a result of treatment selection. However, the risk of graft failure associated with delayed function is greater in patients receiving CsA. 3. By univariate analysis, there is an additive benefit of HLA-A,B matching and CsA use in patients receiving local kidneys with immediate function. 4. By multivariate analysis, there is a significant relative risk of graft rejection associated with poor HLA-A,B matching in patients receiving CsA. 5. By multivariate analysis, there is an apparent risk of graft loss associated with shared organs, but only in patients receiving CsA. One possible explanation is that poorer quality kidneys are being accepted for patients treated with CsA. 6. By multivariate subset analysis, there is a significant benefit of CsA use in patients whose HLA is poorly matched, but no observed benefit in well-matched patients. 7. Definitive evaluation of the relative effects of CsA and HLA matching on cadaver renal allograft survival must await long-term follow-up data on survival and function, and the ability to control for center bias in sharing, HLA matching, and CsA use.

Cyclosporins↗
PubMed1986

Acute cellular rejection and cyclosporine nephrotoxicity monitored by biopsy in a renal allograft recipient. The differentiation of drug nephrotoxicity from rejection by phenotyping of cellular infiltrates.

Serial allograft biopsies were performed on a renal transplant patient who experienced recurrent episodes of acute cellular rejection as well as cyclosporine nephrotoxicity. Five biopsies were performed after acute elevations of the serum creatinine level (15, 46, 155, 244, and 324 days after transplant). Each specimen was evaluated by routine histologic techniques as well as by immunofluorescence analysis and by monoclonal antibody labeling for determination of the cell phenotype of the mononuclear cell infiltrates within each specimen. The first and third specimens disclosed significant T-cell infiltrates with an equal number of T-cytotoxic-suppressor (Leu 2a) and T-helper-inducer (Leu 3a) cells in a diffuse cortical pattern, while the second biopsy showed a slightly milder infiltrate with a marked elevation (7:1) in the Leu 3a:Leu 2a ratio in the cortical-diffuse pattern. Clinically, the patient responded dramatically to cyclosporine dosage reduction following the second biopsy, and bolus steroid antirejection therapy following the first and third biopsies. These findings suggest that phenotypic cell marker analysis within the context of histologic pattern is a useful adjunct to the routine histologic evaluation of renal allograft biopsy specimens and may provide a means of differentiating rejection from cyclosporine nephrotoxicity.

Child, Preschool↗
PubMed1985

Widely disseminated Cunninghamella mucormycosis in an adult renal transplant patient: case report and review of the literature.

A case of widely disseminated mucormycosis involving Cunninghamella bertholletiae is reported. This represents the first report of Cunninghamella infection in a transplant patient and, to our knowledge, only the eighth reported case of human infection by this saprophytic fungus. The clinical course was similar to most of the previously reported cases in that the patient was immunocompromised prior to the infection and the diagnosis was made too late for appropriate therapeutic intervention. The current case is unique in that it involved a renal allograft recipient; that the major clinical signs and symptoms mimicked myocardial infarction; and that there was more widespread dissemination than in earlier cases. The histologic and laboratory identification of the fungus are presented and correlated with the clinical parameters (signs, symptoms, and therapy) of this case as well as the cases previously reported in the literature.

Adult↗
PubMed1985

Lack of influence of donor-recipient differences in subtypic HLA-A,B antigens (splits) on the outcome of cadaver renal transplantation.

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient differences in sub-typic HLA-A,B specialties (splits) influenced outcome. The number of HLA-A,B antigens matched and mismatched between each donor and recipient was calculated in three ways: (1) considering all antigens and splits as distinct (not matched); (2) considering all splits as only matched with their corresponding typic antigen (but not with each other); and (3) considering all splits as matched with both their corresponding typic antigen as well as each other. Overall graft survival, graft loss from irreversible rejection, and patient survival stratified by the level of HLA match were the same using all three methods. In addition, using multivariate Cox regression analysis, the strong association between good HLA matching and increased graft survival was the same using all three methods of matching. Patients with a given number of mismatched antigens had no significant decrease in survival when additional splits were considered mismatched with each other or their corresponding typic antigen. These results suggest that matching of typic HLA-A,B antigens plays a highly significant role in reducing graft rejection but that donor-recipient differences in splits have a negligible effect on graft outcome.

Graft Survival↗