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Biomedical subjects

G G Persijn

Publications and source records attributed to G G Persijn.

At least 55 records · Page 3Linked to original sources
PubMed1997

Changing patterns in organ donation in Eurotransplant, 1990-1994.

Organ transplantation has become the treatment of choice for patients with end-stage organ failure and has led to progressive increases in the size of waiting lists over the past decade. Unfortunately, from 1990 to 1994, the number of organ donors remained stable while the number of organs transplanted from these donors increased by only 10%. In view of the severity of the current organ shortage, elderly individuals are increasingly being accepted as organ donors. The graft survival rate with kidneys from donors older than 55 years is 5% lower than that with kidneys from younger donors at 1 years and 9% lower at 3 years post-transplantation. Graft survival is also significantly lower with organs from donors who die from cerebrovascular accidents than it is with organs from donors whose cause of death is cerebral trauma. The number of patients waiting for a nonrenal donor organ has increased rapidly in the past 5 years, and an increasing number of donor kidneys are now being provided by multiorgan donors. The favorable graft survival rate with multiorgan donor kidneys, which is significantly better than that obtained with single organ donor kidneys, confirms their suitability for renal transplantation.

Adult↗
PubMed1997

Demand, supply and allocation in Eurotransplant.

The main problem in organ transplantation is the continuing shortage of organ donors. Despite all efforts no major significant increases in organ availability are observed during the year 1996 in the participating Eurotransplant counties, while the demand i.e. the waiting lists are still increasing. Shortage of organs will also have its effects and constraints on the distribution i.e. the allocation of scarce organs. To meet the demand of the renal transplantation programs a special kidney allocation system was designed based upon many simulation studies. Already a few months after implementation of the new system very promising results were observed i.e. the discrepancies between the different countries in terms of kidney procurement and transplantation frequencies disappeared. Furthermore, twice as much long waiting kidney patients have been transplanted as previously and the percentage of well matched HLA donor-recipient combinations remained surprisingly high, nearly 24%.

Europe↗
PubMed1996

Association between specific HLA combinations and probability of kidney allograft loss: the taboo concept.

BACKGROUND: HLA matching improves the outcome of cadaveric renal transplantation. However, many allografts function well even in the presence of one or more HLA mismatches, which raises the question of whether some mismatches are better recognised by the recipient's immune system than others. We aimed to identify mismatched HLA donor-recipient combinations that were associated with increased graft loss. METHODS: We selected 2877 first, unrelated renal transplants with a single HLA A, B, or DR mismatch, undertaken between 1982 and 1992, from the Eurotransplant database. To enhance statistical power the analysis was restricted to mismatches of an HLA antigen that occurred in 100 or more donors. 1342 transplants met this criterion and were grouped into a definition set (n = 873) and a validation set (n = 469). In the definition set, we studied further only those recipient HLA antigens that occurred in at least 30 cases within each donor antigen mismatch subset. By a Cox proportional hazards model, donor-recipient combinations that led to significantly higher graft loss than in the whole group were defined. Such combinations were classified as taboo; the remaining combinations were classified as indifferent. FINDINGS: 106 individual recipient antigens were found at least 30 times with a corresponding donor mismatch in the definition set; 11 of the 106 had a significant effect on graft survival. Seven combinations were classified as taboo. Taboo combinations, confirmed as such in the validation set, were associated with graft survival of 81% at one year and 50% at 5 years, significantly lower than the rates in the group with indifferent combinations (89% and 69%; p = 0.04) or among 1190 recipients with no mismatches (89% and 72%; p = 0.03). The findings were substantiated by a multivariate analysis that included the effect of patient immunisation, cold ischaemia time, age, and sex. INTERPRETATION: Mismatched donor antigens are differentially recognised depending on the HLA phenotype of the recipient. The findings may have important clinical consequences for graft survival after transplantation.

Cadaver↗
PubMed1996

The outcome of kidney grafts from multiorgan donors and kidney only donors.

From 1988 to 1994, 15356 renal cadaveric transplantations have been performed within the Eurotransplant area (Austria, Belgium, Germany, Luxembourg and The Netherlands); 8746 kidneys were obtained from multiorgan donors and 6610 from kidney only donors. To evaluate the impact of the procurement policy, multiorgan donor (MOD) versus kidney only donor (KOD), on renal graft survival, an observational study has been performed. Multivariate analysis using Cox's proportional hazards model served to quantify the role of the procurement policy on renal graft survival after adjustment for other prognostic factors. The kidneys obtained from MODs had a significantly better graft survival at 1, 3, and 5 years after transplantation than the kidneys obtained from KODs (85%, 75%, and 58% versus 78%, 68%, and 46% (P=0.0001). In the Cox model, patients transplanted with a KOD kidney had a 1.28 times higher risk of losing their graft than patients transplanted with a MOD kidney. This benefit in graft survival for MOD kidneys could not be explained by the fact that the MODs were younger and male, and that UW was used as preservation solution. A plausible explanation is that MODs, on average, because of the nonrenal transplants, are better supervised. We expect that optimal donor management will contribute to a better outcome of all renal grafts.

Adenosine↗
PubMed1996

The impact of HLA-A matching on long-term survival of renal allografts.

An important contribution of HLA-A antigen matching in renal transplantation was reported initially, hut later publications showed a minor or absent role. We analyzed the contribution of HLA-A locus matching to graft survival in 17,672 first renal transplants from unrelated, nonliving donors. We show that an independent HLA-A matching effect still exists. Due to its relative weakness and late appearance, large numbers and longer follow-up periods are required. The HLA-A matching effect is a significant factor in first renal allograft survival up to 6 years after transplantation, with an increasing effect over time. This is in contrast to the strong, short-lived, effects of HLA-DR and -B matching, which can only be detected up to 6 months and 2 years after transplantation, respectively. A clear additive beneficial effect of HLA-A matching is shown in the group without B and DR mismatches. Therefore, prospective matching for the HLA-A antigens remains important for renal allograft survival.

Graft Survival↗
PubMed1996

Multiorgan donation in The Netherlands: limited by consent and policy.

The percentage of multiorgan donors (MOD) versus single organ donors of kidneys only (SOD-K) has remained markedly low in the Netherlands compared to the other countries in the Eurotransplant region. This suggests a possible loss of donor organs. We investigated the causes of this persisting low percentage of MOD by studying the reasons for kidney donation only. All kidney donors in the Eurotransplant region in 1992 were studied retrospectively. In order to be able to make a comparison between all countries investigated, non heart-beating donors and donors older than 55 years were excluded. Medical reasons were the most frequent cause for kidney donation only in the Netherlands, but this was not significantly different from the other countries in the Eurotransplant region. Multiorgan donation in the Netherlands was restricted by upper age limits for heart and liver transplantation and by the consent system.

Adult↗
PubMed1996

Long-term results of solid organ transplantation. Report from the Eurotransplant International Foundation.

Graft survival of cadaveric kidney-only, liver-only and heart-only transplants, performed in the Eurotransplant area between 1987-1990, was analysed, up to 5 years after transplantation. 1. HLA-A,-B,-DR mismatches had a statistically significant adverse influence on renal graft survival. 2. Kidney retransplantation was not found to be associated with a higher risk of graft loss, in contrast to liver and heart retransplantation. 3. The use of non-ideal donors (aged under 16 or over 55, non-head trauma donors) in renal transplantation should be re-evaluated, while elderly donors as well as elderly recipients jeopardized liver and heart transplant success rates. 4. A learning phase in liver and heart transplantation was evident from 1987-1990. 5. Time-effect studies can be used to adopt individual monitoring schemes. A persistent risk of graft loss in renal transplantation was observed for transplants from older donors and transplants in older recipients; these grafts constituted a very vulnerable group. For liver and heart retransplants it was noted that once patients had survived the first postoperative month, their relative risk of graft failure was no longer significantly different from patients with a first transplant. A well-considered long-term monitoring scheme for heart allograft recipients who are over age 55 is justified, as these patients had a higher risk of failure compared with younger patients. The same would be advantageous for liver transplants that are performed because of underlying liver malignancies.

Adolescent↗
PubMed1995

[5-year experience with a central bone bank].

Since December 1988 the Leiden Bone Bank Foundation, in cooperation with the BIS Foundation, makes allogeneic bone and related soft tissue available for transplantation. Bone banking has become a scientifically high level medical activity in which international standards are established in order to provide safe and effective allografts. Careful donor selection and extensive laboratory testing are the cornerstones for the prevention of disease transmission. In the first 5 years of the existence of the Leiden Bone Bank 450 deep frozen massive bone allografts, of which 221 osteoarticular and intercalary allografts, were shipped to different clinics inside and outside the Netherlands. Furthermore, 322 deep frozen soft tissues, 1877 units of freeze dried bone grafts and 5629 units of demineralized grafts were distributed. The number of transplants with allogeneic bone and related soft tissue from the Leiden Bone Bank increased each year by at least 30% Bone and related soft tissue allografts were used in orthopaedic surgery, neurosurgery and maxillofacial surgery. There are no known cases of transmission of infectious diseases by grafts distributed by the Leiden Bone Bank.

Bone Transplantation↗
PubMed1995

Irregular polymerase chain reaction-sequence-specific oligonucleotide hybridization patterns reveal seven new HLA-DRB1 alleles related to DR2, DR3, DR6, DR8, and DR11. Implications for sequence-specific priming.

In the past 3 years we have typed over 7000 individuals for HLA-DRB using a nonradioactive PCR-SSO method. The use of locally developed computer programs simplified data input and the interpretation of the DRB PCR-SSO readings. In this way we detected a number of samples with unexpected hybridization patterns. DRB1 exon 2 segments of these samples were amplified, cloned, and sequenced and appeared to identify seven new DRB alleles: DRB1*0304, a DRB1*0301 variant, was observed in three unrelated Caucasoid individuals; DRB1*1606, which is very similar to *1603; DRB1*1113 is a *1101 variant with some *1401 sequences; DRB1*1310 is *1301-like; DRB1*1311 is similar to *1305 and *1307; DRB1*1416 is a *1401 sequence with a HV3 derived from *1301; DRB1*0808 was found in an Ethiopian individual. Next, we studied the effectiveness of PCR-SSP typing of the newly defined DRB1 alleles. Only two variants were distinguished as odd by PCR-SSP and two were typed as regular specificities. Three alleles were not amplified by the primer sets used. As compared to PCR-SSO, the PCR-SSP typing method using currently available typing kits clearly has limitations as far as the recognition of new and variant alleles is concerned. The products of some of these new alleles may be distinguished using conventional serology.

Alleles↗
PubMed1994

[Potential cornea, heart valve, bone and skin donors in 5 Dutch hospitals far outnumber actual donors].

OBJECTIVE: To determine the number of potential cornea, heart valve, bone and skin donors among patients who died in Dutch hospitals, in comparison with the number of actual donors. DESIGN: Descriptive. SETTING: Five hospitals in the western part of the Netherlands. MATERIAL AND METHODS: The medical records of patients who died in 1989 were reviewed. Children younger than 4 weeks were excluded from the study. On the basis of criteria used by the Eurotransplant and Bio Implant Services Foundations and those of the skin bank of the Dutch Burns Foundation, it was determined if the deceased were medically suitable as cornea, heart valve, bone or skin donor. RESULTS: Data were collected on 2150 of 2369 deceased (90.8%), mean age 69.5 (17.0) (SD) years. Medical criteria for cornea donation were met in 72% of the cases, 6.8% of these became actual donors. The figures for heart value donors were 4.3% and 9.7% respectively, and for bone donors 2.7% and 0%. The percentage of potential skin donors could not be determined, because essential data were missing from the medical records. After extrapolation the number of donors among all patients who died in Dutch hospitals in 1989 amounted to 35,046 potential cornea donors, 2,093 potential heart valve donors and 1,314 potential bone donors. CONCLUSION: Only a very small proportion of the potential tissue donors were referred to Eurotransplant and Bio Implant Services. Therefore, waiting lists for tissue transplantation are not necessary.

Adolescent↗
PubMed1993

Relation between skin cancer, humoral responses to human papillomaviruses, and HLA class II molecules in renal transplant recipients.

Human papillomaviruses (HPV), especially the epidermodysplasia verruciformis (EV)-associated HPV 5, 8, 14, 17, 20, and 47, are thought to play a role in the pathogenesis of some skin cancers in recipients of renal allografts. MHC class I and class II genes are involved in the cellular immune response to viral and tumor Ag. Little is known about humoral responses to HPV in recipients with and without skin cancer. We investigated the prevalence of antibodies to the early (E) protein E7 and the major capsid late (L) protein L1 of HPV 8. In addition, we studied the association of HLA class II molecules with these antibody responses. The E7 and L1 open reading frames of HPV 8 were bacterially expressed as beta-galactosidase fusion proteins, which were purified by preparative gel electrophoresis. Serum samples from 36 renal transplant recipients with and 91 recipients without skin cancer were screened for the presence of IgG and IgM antibodies to HPV 8 E7 and L1, by Western blot analysis. The detection of anti-HPV 8 L1 antibodies represents the immune response to HPV 8 and possibly other EV-associated HPV, because cross-reactivity between the representatives of this HPV subgenus can occur. The antibody responses to HLA Ag were used as controls. Recipients who had IgM antibodies but no IgG antibodies to L1 of HPV 8 (patients with no apparent class switch from IgM to IgG) had skin cancer in 50% of cases, whereas recipients who produced IgG antibodies (patients with an apparently good humoral response to L1 of HPV 8) had skin cancer in only 18% of cases. The estimated relative risk of skin cancer in recipients with no class switch, compared with the risk in those with a good humoral response, was 4.5 (95% confidence interval, 1.1 to 18.1). We found no association between the antibody response to HLA Ag and the occurrence of skin cancer. A strong linkage between the absent class switch of antibody production in response to L1 of HPV 8 and HLA-DR7 was observed (relative risk, 26.2). Renal transplant recipients who have no apparent class switch from IgM to IgG production in response to Ag encoded by L1 of HPV 8 or possibly other EV-associated HPV are at an increased risk of skin cancer. The association with HLA-DR7 indicates a genetic control of skin cancer development or regression, involving genes in the class II region of the MHC.

Amino Acid Sequence↗
PubMed1993

Biotinylated DRB sequence-specific oligonucleotides. Comparison to serologic HLA-DR typing of organ donors in eurotransplant.

A novel HLA-DR typing method was applied using PCR-amplified fragments and biotin-labeled oligonucleotides (PCR-biotin-SSO). The PCR-biotin-SSO method can be used efficiently to perform HLA-DR typing for a large number of individuals when time is not the limiting factor. The reliability of HLA typing of cadaveric organ donors is of vital importance for organ exchange organizations such as ET. Due to lack of time, these typings are usually performed by the complement-dependent cytotoxicity. The individual donor center typings are immediately reported to ET, where the recipient selection procedure is started. DNA isolated from donor spleen material, sent to the ETRL for retyping purposes, was subjected to PCR-biotin-SSO typing. The results were compared with the serological HLA-DR typings as reported to ET. The analysis of 1052 donor samples for the broad DR1-DR10 antigens revealed a concordance rate of over 90% between the donor center and the ETRL. The majority of the discrepancies involved specificities of the HLA-DR5, DR6, and DR8 cross-reacting group, with DR6 as the predominant discordant specificity. The results indicate (a) that PCR-biotin-SSO is a reliable technique for DNA-based HLA-DR typing and (b) that HLA-DR serology is still a useful technique when time is limited, such as for cadaveric donor typing.

Base Sequence↗