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Biomedical subjects

M R Mickey

Publications and source records attributed to M R Mickey.

At least 19 recordsLinked to original sources
PubMed1992

Survival of children with chronic myeloid leukemia.

We analyzed survival in 203 children with Philadelphia-chromosome-positive chronic myeloid leukemia (CML). Median survival was 4.1 years; average annual risk of death was 20%. These survival data are similar to those reported in adults. Because there is no possibility of long-term disease-free survival in children with CML with conventional therapies, the findings of this study suggest that bone marrow transplantation should be considered in these patients.

Adolescent↗
PubMed1991

National allocation of cadaveric kidneys by HLA matching. Projected effect on outcome and costs.

BACKGROUND: Although receiving a cadaveric kidney matched at the HLA-A, B, and DR loci enhances graft survival in cyclosporine-treated patients, the value of a national system of kidney allocation based on HLA matching, with the attendant increased likelihood of better matching, is still questioned. Some fear that the costs of a national system are unjustified when only a small fraction of donors would exactly match any of the 16,000 potential recipients anyway. We estimated the effect on graft survival of the use of HLA matching for all allocations of cadaveric kidneys in the United States. METHODS: The graft-survival rates in five mutually exclusive groups of transplants with increasing numbers of HLA mismatches were estimated by partitioning the data for 22,190 first-time recipients of cadaveric kidneys. Overall graft survival was projected as a weighted average with use of the percentages of transplants in the hierarchical groups in recipient waiting pools of various sizes. We compared the benefits and costs of HLA matching in a national system with those of introducing cyclosporine, which was projected to enhance graft survival by 7 percentage points at 10 years. RESULTS: Sharing kidneys nationally on the basis of hierarchical HLA matching was estimated to enhance graft survival by an additional 5 percentage points at 10 years. The anticipated five-year cost of national allocation of kidneys by HLA matching for 7000 recipients, including consideration of the costs of graft removal and dialysis after transplant rejection, would be +4F6.5 million less than the cost of using cyclosporine alone. CONCLUSIONS: The use of an HLA allocation system will not add to the cost of renal transplantation, but it will improve the long-term results to the same extent as cyclosporine. We propose the initiation of a national kidney-sharing system based on hierarchical levels of HLA matches.

Cadaver↗
PubMed1991

A report from the UNOS Scientific Renal Transplant Registry.

The UNOS Kidney Transplant Registry is now fully operational. Aside from scientific reports from UCLA, analysis of the same data base from investigators who initiate projects through UNOS central in Richmond, as well as from HICFA and USRDS, can be anticipated. Plans are underway to simplify the reporting process. With the large number of accumulated cases, it should be possible to analyze many factors in the future. Presently, histocompatibility differences in living related vs cadaver donors and degrees of HLA mismatching among recipients of cadaveric kidneys are major factors. Immunization by transplant rejection is the second most important factor.

Graft Survival↗
PubMed1990

Dietary restriction alone and in combination with oral ethoxyquin/2-mercaptoethylamine in mice.

To investigate effects of dietary caloric restriction (DR) combined with antioxidant feeding, long-lived hybrid mice were divided into four dietary groups at weaning, and followed until natural death. Groups "C" and "R" received control (97 kcal/wk) and restricted (56 kcal/wk) diets respectively. Groups "C+ alpha ox" and "R+ alpha ox" received C or R diets supplemented with an antioxidant mixture (2-mercaptoethylamine plus ethoxyquin). R mice (mean life span 41 months) significantly outlived the other three groups (mean life span 30-34 months). Hepatic degeneration and increased hepatoma in the R+ alpha ox group suggested unusual hepatotoxicity of this regimen. Antioxidants had little effect on splenic cell mitogen response in similarly fed mice sacrificed at 12-15 months. Gompertz analysis suggests that the beneficial effect of DR may be due to reductions in initial vulnerability or rate-of-aging parameters, or both, and that the relative influence of each factor may vary with animal strain and DR protocol used.

Animals↗
PubMed1989

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↗
PubMed1989

DNA damage and repair in female C57BL/10 mice of different ages injected with the carcinogen benzo[a]pyrene-trans-7,8-diol.

Female C57BL/10 mice 2 and 14 months of age were killed 3, 6, 9, 12, 18 and 24 h after injection with 0.4 mg of benzo[a]pyrene-trans-7,8-dihydrodiol. The amount of carcinogen bound to DNA isolated from liver and kidney of each mouse was determined as benzo[a]pyrene-7,8,9,10-tetrol liberated upon acid hydrolysis of the DNA and measured by synchronous scanning fluorometry. Considerable variability was observed and a subset of animals in the middle-aged group failed to sustain appreciable damage upon injection of the carcinogen. Nevertheless, repair of DNA-bound carcinogen from both the liver and kidney of 2-month-old animals was clearly evident. In the subset of 14-month-old animals who sustained damage, evidence for removal of DNA-bound carcinogen was marginal.

Aging↗
PubMed1989

A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.

Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.

Adolescent↗
PubMed1989

The UNOS Scientific Renal Transplant Registry.

1. After 2 years of data collection and compiling, the UNOS Scientific Renal Transplant Registry was analyzed for the first time. One-year graft survival rates were 89% for first parent donor transplants (257), 76% for first cadaver (7,049), 65% for second cadaver (1,072), and 57% for multiple retransplant recipients (221). 2. The side-by-side comparison of the UNOS and UCLA registries revealed a remarkable similarity between results from the 2 databases. The concordance between the registries makes us confident in the validity of the UNOS data and also suggests that centers submitting data to the voluntary UCLA Registry are representative of the national experience. 3. Eighty-nine recipients of 6-antigen matched first cadaver transplants were identified in the UNOS Registry with 88% graft survival at 1 year. This result is comparable to that obtained from surveys that identified 224 recipients with 90% graft survival at 1 year. These results underscore the importance of sharing cadaver kidneys to achieve perfectly matched transplants. 4. Blood transfusions improved graft survival by 5% at 1 year. More than one-quarter of the first cadaver transplant recipients were nontransfused. 5. The first follow-up report after discharge of the transplant recipient was requested at 6 months by UNOS. This delay in reporting transplant outcome resulted in a serious lag between the time a transplant was performed and its availability for analysis. The UCLA Registry collects a report at 3 months and had more recent transplants available for analysis.

Databases, Bibliographic↗
PubMed1989

Center variability.

1. Variation among centers accounted for about one-third of the assignable variation in kidney transplant graft survival. 2. Centers varied systematically in their use of CsA and of pretransplant transfusions and in transplant cold ischemia times--factors strongly related to graft outcome. About 90% of patients received CsA. 3. At some centers, graft survival rates in the low 90% range were attained for first transplants from cadaver donors. 4. Variation among centers was less noticeable at high survival rates. Nearly all centers had good results using HLA-identical sibling donors. 5. Centers with better survival rates tended to treat fewer transplants with CsA. There was a modest, but potentially interesting, negative correlation.

Analysis of Variance↗
PubMed1989

The natural history and response to therapy of chronic urticaria and angioedema.

Previous reports have suggested that the etiology of chronic urticaria/angioedema (greater than 6 weeks) can be identified 10% to 30% of the time while few reports have addressed the natural history of chronic urticaria/angioedema. An analysis of all patients referred to the authors' practice between 1983-1985 with a diagnosis of urticaria/angioedema was performed. Patients with hereditary angioedema were excluded. Eighty-six of the 214 patients had chronic urticaria/angioedema. In the remaining 128 cases of acute urticaria there were four exercise induced, nine contact, six cold induced, six drug induced, 11 food induced, one viral hepatitis associated, 29 with dermographism, and 62 undetermined. An etiology could not be determined in any of the patients with chronic urticaria/angioedema. Laboratory tests, including CBC, chemistry panel, urinalysis, ANA, rheumatoid factor, complement studies, sedimentation rate, and skin tests were all noninformative. Chronic angioedema without urticaria occurred in only nine cases, 31 cases had chronic urticaria alone, and 46 cases had both chronic urticaria and angioedema. Of the patients followed over the 3-year period, 27 resolved while 48 continued to have urticaria/angioedema. Response to medications was variable and will be discussed. Our study suggests that an etiology is determined in much less than 10% of patients with chronic urticaria; fortunately, 32% of our cases resolved over a 3-year period.

Adrenal Cortex Hormones↗
PubMed1989

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↗
PubMed1988

Dominant effect of histocompatibility on ten-year kidney transplant survival.

Using actuarial methods, factors influencing long-term graft survival were examined in 33,594 recent (since 1974) kidney transplants reported to the University of California, Los Angeles, Transplant Registry. One- and 10-year graft-survival rates as well as late (from 3 through 10 years) graft-loss rates (half-lives) were determined. The donor-recipient relationship had the greatest influence on long-term graft survival. Transplants between HLA-identical siblings had graft-survival rates of 89% at 1 year and 68% at 10 years, compared with 76% and 43% for parental donors, and 58% and 26% for cadaver donor transplants, respectively. These differences were also evident from the graft half-lives, which were 22 years for HLA-identical sibling, 12 years for parental, and 8 years for cadaver donor allografts. In cadaver donor transplants, matching for HLA-A,B antigens had the greatest influence on long-term graft survival, with a 15% 10-year graft survival (39% vs. 24%) and 7-year half-life (14 vs. 7 years) advantage seen with the best (zero HLA-A,B mismatches) compared with the worst (4 HLA-A,B) cases, respectively. Some of the factors studied, such as transplant number and pretransplant transfusions, tended to influence the short- rather than long-term graft-survival rates. Others, including HLA-A,B matching, early graft function and the recipient's original disease, influenced both early and late graft survival. Over all, histocompatibility between donor and recipient had by far the greatest influence on the long-term success of renal allografts.

Actuarial Analysis↗
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↗