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Biomedical subjects

M R Mickey

Publications and source records attributed to M R Mickey.

At least 37 records · Page 2Linked to original sources
PubMed1988

Kidney transplant mortality relationships.

1. Patient mortality for adults was described by the sum of 3 components of risk: age-dependent risk; transplant-dependent risk, depending on time after first transplant; and failure-dependent risk, depending on time after failure. 2. The age-dependent risk increased exponentially at a rate about two-thirds the rate of increase in the general population. This risk was about twice as large for recipients of cadaver kidneys as for those who received grafts from HLA-identical siblings; the risk for recipients of parent donor grafts was intermediate. The risk for transplant recipients was much larger than that for the general population over most of the age range. 3. The transplant-dependent component decreased exponentially with the time after transplant and was reduced by half after about 2.25 years. The component was about 4 times as large for recipients of cadaveric kidneys as from HLA-identical sibling donors. Since patients studied were limited to those who survived at least 3 months after transplant, the transplant-dependent component of risk, as defined, does not represent the larger and more rapidly decreasing loss that occurs within a month or two after transplant. 4. The failure-dependent component was large and decreased exponentially with time after graft failure; the risk was reduced by half in about 7.5 months. For recipients of cadaveric organs, "excess" of death in the first year after failure was about 10%--slightly more than percent excess death as in the first year after transplant. In the case of diabetics, the excess deaths in the year after failure was about 25%. 5. Life expectancy at various ages at transplant was calculated from the estimates of risk of death. The maximum loss for males transplanted from HLA-identical siblings was about 10 years. The maximum occurred at age-at-transplant 20 years; life expectancy for patients transplanted at that age was about 42 years. Perhaps 5% to 10% of patients transplanted at age 20 from cadaveric donors might expect to survive into their 80's. 6. Survival analysis with allocation to graft failure of patient-death-with-functioning-graft fractionally (according to probability that the death was transplant related) provided a method of adjusting for patient age in studying graft survival. In younger patients, death was most likely attributable to the transplant, whereas in older patients, death was likely not attributable to the transplant. 7. Appropriate attribution of patient death to graft failure is important to the study of long-term graft survival, particularly among older patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Clinical transplants 1988. Overview.

1. The 3-month actual graft survival of 6-antigen matched transplants in the UNOS program was 96% compared to 85% in control kidneys which were not shipped (p = 0.004). Actuarial graft survival at 1 year was 89% for the 6-antigen matched kidneys and 78% for the controls (p = 0.02). 2. Several individual centers reported 1-year graft survival rates of 85-95% (in the first half of this volume). Various immunosuppressive protocols and attention to patient care resulted in high 10-year survival of 53% in 1 instance (Leuven). 3. The 1-year graft survival peaked at about 77% for transplants performed in 1985, 1986, and 1987. 4. Among transplants performed since 1984, HLA matching of cadaver donor transplants showed a 13% difference at 1 year between the best and worst A,B,DR matches, which expanded in 3 years to an 18% difference. 5. The center effect, which produces about a 13% difference in 1-year graft survival for cadaver donors, decreased to 0 in HLA-identical transplants. Thus, when the donor and recipient were histocompatible, all centers were able to achieve superior results. The results of the 6-antigen Match Study appear to validate this conclusion. 6. Preformed antibody is associated with a 9% decrease in graft survival for greater than 50% PRA in first grafts and 4% in second grafts. For peak antibodies, the difference was 7% for first grafts and 11% for second grafts. 7. Platelet flow cytometry in 23 patients with a positive flow cytometry crossmatch to T cells furnished a further refinement in grouping the patients. All 11 patients with a negative platelet crossmatch had functioning grafts at 1 month whereas only 5 of 12 patients with a positive platelet crossmatch had a functional graft at 1 month (p = 0.003). 8. The duration of first graft effect on the second graft has diminished considerably as immunosuppression improved. Patients whose first graft survived more than a year and who had a high 1-year graft survival of the second graft lost their second graft at an accelerated rate after the first year. At the end of 4 years, their survival was the same as that of the responder patients who had rejected their first grafts within 3 months. 9. False positive crossmatches, especially in "highly" sensitized patients were identified by the use of DTT. Transplants into 69 patients who were positive by the standard test but negative after DTT had a 94% 1-month function rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadaver↗
PubMed1988

Calculation of probability of paternity using DNA sequences.

This paper formally incorporates allele measurement error into the Essen-Möller version of the probability of paternity. For highly polymorphic genetic systems, an approximate solution to the problem is developed resulting in simple formulas. The DNA sequence of the D14S1 region provided a practical example for testing this approximation. For these sequences, allelic uncertainty arises from determining length of DNA fragments from mobility in gel electrophoresis. D14S1 and standard test results from 35 paternity cases establish the validity of our computational method.

Blotting, Southern↗
PubMed1988

Blood transfusions and HLA matching--an either/or situation in cadaveric renal transplantation.

Cyclosporine-treated recipients of primary cadaver donor renal transplants had a one-year graft survival rate of 79% if they received pretransplant blood transfusions (n = 5308). The one-year survival rate for nontransfused recipients (n = 709) was significantly lower at 69% (P less than 0.001). The transfusion effect was larger in black recipients (a 17% difference) than in white recipients (5%). The effect was also larger in recipients of grafts poorly matched for HLA-A, B, -B, DR, or -DR antigens than in recipients of well-matched grafts. Transfusions did not significantly improve graft survival in recipients with zero or one HLA-A, B or -B, DR, or zero -DR-mismatched grafts. However, transfusions accounted for increases of 10%, 14%, and 17% in patients receiving grafts mismatched at 2, 3, or 4 HLA-B, DR antigens, respectively. Several factors including cyclosporine and HLA matching have contributed to improving graft survival rates in nontransfused recipients. Sensitization was noted in 20% of transfused patients awaiting primary renal transplants in Southern California, as compared with 10% in transplanted patients, suggesting a tendency to transplant nonsensitized patients. Of the sensitized patients, 75% were female. Based on these data, we suggest that high survival of primary kidney allografts in the cyclosporine era can best be maintained by the continued use of pretransplant transfusions for the majority of recipients--or, alternatively, by HLA matching for patients who are at higher risk of becoming sensitized.

Blood Transfusion↗
PubMed1988

The second histocompatibility locus in humans.

Even when HLA is completely matched in sibling donor transplants, as many as one third of the transplants are lost in 10 years. This means that a second or third histocompatibility locus plays some role in rejection of kidney grafts. We postulate that the second locus is Lewis. First, because among 18 second cadaver donor transplant patients having Lewis antibodies, the 1-year graft survival rate was 32% compared to 61% in 37 patients without Lewis antibodies (P = .02). The Lewis antibodies presumably were produced in the course of rejection of the first graft and had an effect on the success of the second graft. As indirect evidence, Lewis mismatching would be expected to occur more frequently in black patients than white, and correspondingly, a lower graft survival rate was noted in black patients receiving sibling, parent, and cadaver donor grafts.

Graft Survival↗
PubMed1988

Clinical experience with azathioprine: the pros.

We performed a randomized, placebo-controlled, double-blind, comparative clinical trial of 36 weeks of methylprednisolone and 3 years of azathioprine in 98 patients in the chronic progression phase of multiple sclerosis (MS). We demonstrated a trend in favor of the combination therapy for limiting progression. The relapse rate in the azathioprine recipients was half that of the control group, and visual evoked potential latencies were stabilized in those who received the combination. We think that a therapeutic trial of continuous use of the combination of adrenal steroids with azathioprine would be worthwhile if administered early in the course of the disease.

Azathioprine↗
PubMed1988

Alternatives to randomized clinical trials.

Data bases describing the natural history of patients with multiple sclerosis or the clinical course of patients treated with placebos might serve as "historical controls" in future clinical therapeutic trials. The results of clinical trials with such controls can be misleading. There is a strong tendency for the new treatment to appear efficacious when historical controls are the comparison group. Therefore, claims of efficacy deduced from trials using such controls should be closely questioned. Thus, such comparison groups probably would be useful for preliminary and early phase II (pilot) trials rather than in more definitive phase III (full) trials.

Clinical Trials as Topic↗
PubMed1987

Correlation of clinical and immunologic states in multiple sclerosis.

Cyclophosphamide was administered to 14 patients with chronic progressive multiple sclerosis on an intermittent escalating dosage schedule adjusted to maintain numbers of peripheral blood B lymphocytes and helper/inducer (CD4) T cells below the fifth percentile of the normal population. Peripheral blood B cells, T cells, suppressor/cytotoxic (CD8) T cells, CD4 cells, and FcR+-bearing cell numbers and percentages were monitored at one-week to two-week intervals. Clinical status was assessed by neurologic examinations at approximately four-week intervals. Regression analysis revealed a statistically significant correlation between changes in immunologic status and changes in clinical state. The immunologic changes preceded the neurologic changes. Increases in percent of CD8 cells and decreases in percent of CD4 cells forecast improved clinical course. These findings, coupled with other studies, strongly suggest a pathogenetic role for helper and suppressor T cells in the production of clinical signs of multiple sclerosis.

B-Lymphocytes↗
PubMed1987

Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial.

To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.

Adult↗
PubMed1987

The current role of pre-transplant blood transfusions and tissue typing in cadaveric renal transplantation.

In a retrospective analysis of 74 consecutive cadaveric renal transplants performed at our center during a 38-month period we assessed the influence of random blood transfusions and tissue matching on graft and patient survival. All patients received cyclosporine and low dose prednisone with or without azathioprine as immunosuppressive therapy. Actual patient survival was 100 per cent at 1 year and actuarial 1-year graft survival was 82 per cent. Random blood transfusions and histocompatibility matching at the HLA-DR locus did not influence graft survival. Matching at 2 or more HLA-A and B loci was associated with a significant detrimental influence (p less than 0.05) on graft survival. We conclude that the use of cyclosporine-based immunosuppression overcomes much of the adverse effect of poor tissue matching and may obviate the need for random blood transfusions in cadaveric renal transplantation during the first year of engraftment.

Azathioprine↗
PubMed1987

Empirical paternity exclusion rates.

We have developed an empirical method of estimating paternity exclusion rates for any genetic system by counting exclusions among fictitious "nonfather" paternity cases generated from true paternity disputes. Especially for multiallele multiloci systems, this technique has advantages over traditional formulae methods in that it replaces tedious (and, in some cases, impossible) computations with simple data file manipulations, and it avoids introducing quantities such as gametic disequilibrium and recombination fraction that are difficult to measure. Exclusion rates for standard and one-parent paternity cases are given for three racial groups (Caucasians, blacks, and Hispanics) in four genetic systems (HLA, ABO, MNSs, and Rh). Beside the method, of interest are our findings of higher HLA exclusion rates (93.25% for Caucasians, 94.62% for blacks, and 95.82% for Hispanics) compared with rates previously reported and high combined exclusion rates (89.59% for Caucasians, 91.65% for blacks, and 92.54% for Hispanics) in one-parent paternity cases.

ABO Blood-Group System↗
PubMed1987

The effect of zero HLA class I and II mismatching in cyclosporine-treated kidney transplant patients.

The effect of HLA matching on one-year first cadaver donor graft survival rates between best and worst matches was 6% (P less than 0.001) for A, B; 7% (P less than 0.001) for DR; 9% (P less than 0.001) for A, DR; 15% (P less than 0.001) for B, DR; and 17% (P less than 0.001) for A, B, DR. For second cadaver donor grafts, the differences were comparable. Analysis of the cyclosporine-treated patients separately yielded similar results: 5% (NS) for A, B; 7% (P less than 0.001) for DR; 13% (P less than 0.001) for A, DR; 16% (P less than 0.001) for B, DR; and 18% (P less than 0.001) for A, B, DR. The most significant effect of matching was achieved by zero mismatching B and DR antigens. The one-year graft survival for patients with zero A, B, DR mismatch was 88% with cyclosporine. Without cyclosporine, zero mismatched A, B, DR grafts survive at 84%; this difference is not statistically significant. Zero mismatching for class I and II antigens (that is, A, DR or B, DR with cyclosporine) gives one-year graft survivals of 84% and 87%, respectively. The zero mismatching HLA class I and II antigen effect is lost when even one antigen is mismatched. Transfusions improved the one-year graft survival 10% in cyclosporine-treated patients, but not in those who were not treated with cyclosporine. Seventy-one patients transfused with more than 4 units of blood, zero B, DR mismatched, and treated with cyclosporine had a 91% one-year graft survival. Recipient pool sizes for obtaining zero A, B, DR or B, DR mismatched donors are calculated. Zero A, B, DR mismatched patients can be transplanted at a 19% frequency with a 10,000 recipient pool. The success rate for zero mismatching of class I and class II antigens indicates that kidney sharing and large recipient pool sizes are a reasonable policy.

Azathioprine↗
PubMed1987

Low kidney graft survival in Lewis negative patients after regrafting and newer matching schemes for Lewis.

Le-cadaver donor kidney transplant recipients regrafted had a 1-year graft survival rate of 0%. This was statistically significantly lower than survival rates in Lea or Leb patients of 60% and 64%, respectively, at 1 year (P = .01 and P = .009). We conclude that if Le- patients had rejected an Le+ graft, a repeated incompatibility should be avoided since the recipients had already demonstrated immunoreactivity against this epitope. Recipients being confronted with an Le group mismatch in the first graft often have successful grafts and the difference in 1-year graft survival of Lea (75%), Leb (76%), and Le- (68%) patients was not statistically significant different. We suggest that the matching scheme for the Le groups be reevaluated. The older method of matching on the basis of Le+ and Le- is probably no longer justified. According to chemical structure, it would appear that Leb should be a universal recipient and Lec a universal donor. This scheme, however, has failed to correspond to interracial transplants between whites and blacks. A matching scheme that requires identity between donor and recipient showed a remarkable correlation with the results between black-to-black, black-to-white, white-to-black and white-to-white transplants.

Blood Group Incompatibility↗
PubMed1987

HLA matching effects.

1. Transplants without A,B mismatches that had good early function (grade A at 3 months) had a strikingly lower long-term failure rate (equivalently, longer half-life) than transplants that had poor early function. This was found in HLA-identical sibling donor transplants as well as in cadaver donor grafts. The same superiority was observed in parent donor grafts although the number of zero mismatch grafts in this group was too small to permit a sensitive analysis. In cadaver donor grafts, zero A,B mismatch transplants had a longer half-life than mismatched grafts in both early function groups in first transplants but only in the poorer early function group in regrafts. These results were based on transplants done from 1970 to 1979; there was not enough experience with DR-typed grafts for their inclusion into a similar analysis. This finding does not at present have consequences for recipient selection. The finding would have consequences if an association of early function with matching at another system (e.g., Lewis) or with some assessable non-responsiveness were to be shown. 2. The Excess Match Index (EMI), defined as number of matches less number of mismatches, was shown to be associated with graft survival. It was shown that within groups defined by number of mismatches, survival tended to be greater if the number of matches were more; likewise, within groups defined by number of matches, survival tended to be greater if the number of mismatches was less. The within-match group and within-mismatch group comparisons were based on small numbers of transplants and the corresponding findings are not firmly established. The potential significance of the index, which follows from the finer gradation of the extent of matching, is that it may supply a useful basis for priority schemes for selection of recipients, particularly in donor sharing programs. 3. A recipient selection scheme based on the EMI applied to DR matching was evaluated in a simulation study with the result that most of the gains from DR matching could be obtained with relatively small recipient pools. Nearly all of the gain was achieved by a pool size of 400 (pool size for ABO-identical recipients) and most of the gain could be achieved with smaller pools. The result is encouraging since it indicates that much of the gain from HLA matching can probably be achieved with practically attainable size recipient pools. It was important that the priority scheme not lead to a distribution of phenotypes in the pool that differs substantially from the population.(ABSTRACT TRUNCATED AT 250 WORDS)

Graft Survival↗
PubMed1987

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↗