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Biomedical subjects

M Cecka

Publications and source records attributed to M Cecka.

16 recordsLinked to original sources

UCLA liver transplantation: analysis of immunological factors affecting outcome.

From 1988 to 1993, UCLA completed 938 first and 1,146 total orthotopic liver transplants (OLT). Race analysis demonstrated a 1-year patient survival of 89% in Blacks (n = 45) versus 80% in Whites (n = 492, p < 0.02), with no significant difference shown between Hispanics (n = 278) and Whites. The 1-year patient survival in Asians was 50% (n = 58, p < 0.02 vs. Whites) even when hepatitis B was excluded (59%, n = 43). The 1-year patient survival of hepatitis B surface antigen positive Asians (n = 15) was only 21% (p < 0.02 vs. all others). OLT patients whose panel reactive antibody (PRA) was < 10% (n = 339) demonstrated no graft or patient survival advantage versus recipients whose PRA was > 10% (n = 71). A positive antidonor flow cytometry crossmatch (> 30 mean channel shifts, n = 76) was associated with a decreased 1-year graft survival (56% vs. 73%, p < 0.05) when compared to flow negative recipients (n = 185). Graft survival for 0 DR mismatches was 74% at 1 year compared with 57% for 1 DR mismatches (p < 0.02) and 59% for 2 DR mismatches (p < 0.02).

Adult

Twenty-year follow-up on the effect of HLA matching on kidney transplant survival and prediction of future twenty-year survival.

The difficulty in achieving long-term survival is demonstrated by the fact that an improvement of 30 percentage points in 1-year cadaver donor survival resulted in only a 10-percentage point improvement over 20 years. In early transplants from 1965 to 1974, the 20-year survival rate of HLA identical siblings was 46%, of parental donors 27%, and of cadaver donors 12%. More recent grafts, performed since 1987, had a projected survival of 57% for identical donors, 30% for parental donors, and 18% for cadaver donors. With respect to HLA matching for cadaver donor kidney transplants, a 0 AB-antigen mismatch produced higher graft survival than did mismatched transplants during the 20-year period from 1965 to 1984. After the introduction of HLA Class II typing in 1980 and general improvements in typing for transplants performed after 1987, the 0 ABDR-mismatched grafts have a projected 20-year survival of 40%. The projected survival rates for transplants with one or more mismatches fall progressively to 13% for transplants that have 6 ABDR mismatches. Thus, the success due to HLA matching has improved ever since the introduction of cyclosporine because of the concurrent improvements in tissue typing for Class I and Class II specificities.

ABO Blood-Group System

Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors.

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion-associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one-way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA-GVHD.

Aged

Clinical kidney transplants, 1988.

1. The one-year graft survival rate of cadaver donor transplants has increased from about 40% in 1965 to almost 80% in 1988. Much of the improvement lies in the reduction of the one-month failure rates, which went down from one quarter in 1965 to 10% in 1988. 2. Kidneys that failed to function in the first month occurred in 5% of first graft patients without cytotoxins and increased to 9% if cytotoxins to more than 50% of the random panel were present. The non-function rate was 9% in regrafted patients without antibodies and double (18%) in those with a PRA of less than 50%. 3. Some indication that the harmful antibodies can be detected by flow cytometry is provided by the fact that low graft survival rates resulted when transplants were done across a positive flow cytometry crossmatch in sensitized patients and in second graft recipients. In non-sensitized patients and in first graft patients, flow cytometry crossmatches against T cells were of no value. 4. The difference between first grafts, second grafts and transplants into sensitized patients disappeared when the grafts that did not function at one month were removed. 5. Cold ischemia time up to 36 hours had no effect on 1-3-year survival rates. Cold ischemia had relatively little effect even on delayed function in first transplants. However, in regrafts and in grafts into patients with preformed cytotoxins, increasing cold ischemia resulted in an increased incidence of delayed function.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Survival

The benefit and underutilization of sharing kidneys for better histocompatibility.

The data of the UCLA Kidney Transplant Registry were reviewed with regard to sharing. The percentage of first-cadaver cyclosporine-treated transplants since 1984 with long cold ischemia time increased with sharing distance: 25% of unshared grafts, 40% of locally shared, and 61% of distantly shared ones had cold ischemia times over 24 hr; for cold ischemia times over 36 hr the numbers were 6%, 12%, and 24%, respectively. The immediate function rate did not parallel sharing distance the way cold ischemia time did: 85.7% without sharing, 74.4% with local sharing, and 83.5% with distant sharing. The percentage of well-matched (0 HLA-B,DR mismatches) transplants was low (3-5%) regardless of sharing status. Well-matched shared grafts with cyclosporine immunosuppression had a 9% survival advantage at one year compared with poorly matched unshared ones (85% vs. 76%). Long-term, well-matched shared grafts had a half-life of 11.9 years compared with 7.5 years for poorly matched unshared ones (reflecting graft loss from 3 to 10 years posttransplant). We conclude that sharing for histocompatibility has an overall beneficial effect.

Graft Survival

The transfusion effect.

1. Many transplant centers have apparently abandoned their deliberate transfusion protocols believing that the beneficial effect of transfusions no longer outweighs the risks. 2. Pretransplant blood transfusions have consistently improved graft survival among recipients of first cadaver donor transplants. One-year graft survival rates were 5-8% higher for transfused patients transplanted each year between 1982 and 1987. Transplants performed in 1988 and 1989 showed a 3% improvement with transfusions. 3. Whereas large numbers of transfusions resulted in higher 1-year graft survival rates in the precyclosporine era, 2 or 3 transfusions provided the maximum effect in more recent transplants. 4. A disturbing decrease in the long-term survival of transplants to nontransfused patients and patients given 1-4 transfusions has been noted. Nontransfused recipients transplanted since 1985 had a higher loss rate after the first year than those transplanted prior to 1982. If this trend can be verified as more follow-up becomes available, it suggests that the transfusion effect has become a factor in long-term survival rather than one that affects only the immediate posttransplant period. 5. Transfusions decreased the risk and apparent severity of early rejection episodes. Twenty-six percent of transfused patients had early rejection and 1-year graft survival was 67%. Among nontransfused patients, rejections occurred in 42% and survival was 56%. Patients with no early graft dysfunction had 89% 1-year graft survival when transfused and 83% when not transfused. 6. Transfusions improved 1-year graft survival by 7% for Asian recipients, 6% for Blacks, and 4% for Whites. The improvement within each racial group was significant. 7. Kidneys that were mismatched for HLA-DR antigens and kidneys from donors younger than age 16 had significantly poorer survival when transplanted to nontransfused patients. Transfusions mitigated the effects of mismatching and donor age on 1-year graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Long-term survival of kidney grafts.

1. In the long-term period, the half-life effectively measured loss rate. For HLA-identical sib donors the half-life was 25 years; for parental donors, 13 years; and for cadaver donors, 8 years (now possibly 11 years). 2. HLA-A,B,DR matching exerted the greatest effect on half-life, for a half-life of 17 years was achieved for cadaver donors. This rate was not quite as high as that for A,B,DR matched siblings but was higher than the one haplotype mismatched parental donor transplants. 3. Caucasian recipients had a half-life of 8 years compared to 5 years for black recipients. 4. Excellent centers had a 10-year half-life compared to 5 years for fair centers. 5. Cold ischemia time over 24 hours, recipient age over 55, and donor age of 50-60 had a small effect on the half-life in the order of 1 to 3 years. 6. Among the short-term factors that affect the 1-year graft survival, there was a 12% difference between excellent and fair centers. An 11% difference between A,B,DR matched transplants and 6 A,B,DR mismatched grafts was noted. First-cadaver donor grafts had a 10% higher graft survival at 1-year than second grafts. Other factors together with the difference in 1-year graft survival between the extremes were as follows: sensitization 9%, race 8%, transfusion 6%, donor age 6%, diabetic 3%, recipient age 3% and cold ischemia 1%. Thus more factors affect short-term survival than long-term survival.

Cohort Studies

The center effect.

1. Transplant centers were grouped according to one-year graft survival rates of first cadaver transplant recipients treated with CsA. Not surprisingly, the major differences among center groups were associated with the success achieved with CsA in both patient and graft survival. Centers with the poorest survival rates were those with the least improvement over azathioprine and prednisone immunosuppression. 2. There was a definite "learning curve" associated with improvements using CsA immunosuppression for excellent and good centers. Fair centers have yet to see a significant improvement in graft survival overall with CsA. 3. Survival rates for living-related transplants varied little among the center groups, suggesting that most centers do equally well with low-risk transplants. 4. Pretransplant risk factors such as HLA matching, sensitization status, age, sex, and race of the recipients, and ischemia times varied little among the center groups. The center effect cannot be explained by recipient demographic risk factors.

Adolescent

Kidney preservation.

1. Machine preservation yielded better early graft function than simple cold storage of cadaver donor kidneys with more than 24 hours of CIT. However, there was no difference in one-year graft survival rates comparing machine and cold storage preservation regardless of CIT. 2. The percentage of kidneys that functioned immediately posttransplant progressively decreased from 65% with up to 5 minutes WIT to 45% with more than 20 minutes WIT. One-year graft survival rates fell from 80% with zero WIT to 72% with more than 20 minutes WIT. There was no clear effect of WIT in regrafted patients. 3. Although CIT had no apparent effect on one-year graft survival, the rate of graft loss after the first year was nearly double for kidneys with more than 48 hours CIT. This long-term effect of CIT was evident whether all patients transplanted since 1976 were considered or only CsA-treated patients. The increase in late graft loss was evident in kidneys stored more than 36 hours if the recipient received CsA.

Cold Temperature

T-cell hybridomas producing hapten-specific suppressor factors.

We have made several T-T hybridomas which secrete soluble factors capable of suppressing an in vitro antibody response to nitrophenol (NP), but not other unrelated antigens. These factors bind specifically to NP, and express determinants coded for in the I-J region of the mouse major histocompatibility complex. No determinants that cross-react with the constant regions of mouse immunoglobulins are present on the factors. Three sub-clones originating from the same initial culture well of hybridoma cells secrete factors which carry I-J determinants of different haplotypes. One clone expresses I-J determinants derived from the suppressor cell parent, another expresses I-J determinants derived from the tumour cell parent, and a third expresses both. This correlates exactly with I-J determinants expressed on the cell membrane, and suggests the participation of at least two genes in the determination of suppressor-factor structure.

Animals

The effect of individual HLA antigens on graft survival rates in kidney transplant patients.

We have used information available in the UCLA International Transplant Registry to study the effect of HLA antigens on graft survival outcome. All results showed that of all antigens tested, the presence of DRl in the recipient was associated with the highest graft survival rate. There was a positive matching effect for most DR antigens that were either presumed homozygous or heterozygous in the recipient. A regression analysis not only confirmed the association of DR1 and low immune response, but also suggested a greater importance of the DR rather than A or B locus to graft survival rates. Recipients with DR1.5 had the highest survival rates when DR1 was compared with other DR antigens and the heterozygous combinations of the two groups. This suggests that presence of heterozygous DR antigens may have combined effects on graft survival.

Follow-Up Studies