M. Ray Mickey

Estimation of Error Rates in Discriminant Analysis

Several methods of estimating error rates in Discriminant Analysis are evaluated by sampling methods. Multivariate normal samples are generated on a computer which have various true probabilities of misclassification for different combinations of sample sizes and different numbers of parameters. The two methods in most common use are found to be significantly poorer than some new methods that are proposed.

Sinus disease in children with respiratory allergy.

Sinus disease has been assumed to exist in children with respiratory tract allergy, although a systematic evaluation of the relationship of these two processes has never been reported. We have been impressed that sinus involvement often adds significantly to the morbidity rate of allergic disease; when controlled or eliminated, the allergic respiratory process appears easier to control. This study was ‘undertaken to: (1) better define the prevalence of sinus disease in allergic children, and (2) establish clinical and laboratory diagnostic criteria.

Bone Marrow Transplantation after the Chernobyl Nuclear Accident

On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed.

Effect of theophylline on gastroesophageal reflux in normal adults

In a randomized, double-blind manner, 15 normal adults were given a single oral loading dose of anhydrous theophylline (6.5 +/- 0.9 mg/kg) and nine normal adults were given placebo. All subjects were tested for serum theophylline levels, acid reflux (using intraesophageal pH probe), and lower esophageal sphincter pressure (LESP) at 1.5, 4, and 8 hr after treatment. Of subjects with negative baseline acid reflux tests, eight of 13 (61.5%) given theophylline developed positive acid reflux tests compared with none of eight subjects given placebo. One of nine (11%) placebo subjects reported heartburn compared with 11 of 15 (73%) subjects given theophylline. The maximum mean percent change in LESP from baseline was +5.62 +/- 28.8% in the placebo group and -25.01 +/- 23.7% in the theophylline group (p = 0.01) at 4 hr after treatment. While only two of nine (22%) adults given placebo had at least a 14% reduction in LESP following treatment, all of the 15 subjects sustained a minimum of 14% relaxation in LESP. This study confirms that oral theophylline at therapeutic serum levels inhibits LESP and induces gastroesophageal reflux (GER) measured by acid reflux tests in most normal adults.

Ameliorating the Effects of Child Sexual Abuse An Exploratory Study of Support by Parents and Others

This study examines the support of nonabusing parents and others as it affects subsequent adjustment to childhood victimization and womens attitudes toward men. A form of log linear analyses on the data from 61 women 18 to 36 years of age in Los Angeles County revealed that as a result of child sexual abuse, negative attitudes toward men tended not to be related to the severity of the experience(s), if nonabusing parents and others supported victims upon the disclosure of the incident(s). The importance of support to the disclosure process is discussed in helping victims to regain control of their lives and in lessening the lasting effects of child sexual abuse.

Intact humoral and cell-mediated immunity in chronic marijuana smoking

The immune system of 12 healthy chronic marijuana-smoking adults was evaluated while they smoked marijuana daily for 64 consecutive days under controlled hospitalized conditions. Studies included enumeration of B and T cell subpopulations, lymphocyte proliferative responses to PHA and to allogeneic cells, and serum immunoglobulin levels. Percent B cells, initially low in 2 patients, became normal. Baseline total B cells, determined either by surface immunoglobulins (338 cells/mm3 +/- 60 SEM) or complement receptors (162 cells/mms +/- 27) were significantly (p less than 0.05) less than control but increased to normal (485 +/- 97 and 239 +/- 47) over time. Percent T cells, initially low (less than 40%) in 4 patients, became normal. Baseline T cells (951 cells/mm3 +/- 70 SEM), significantly lower than controls (2,010 +/- 210, p less than 0.05), increased to normal by day 63 (1,875 +/- 281). In vitro lymphocyte response to graded doses of PHA and to allogeneic cells was normal initially and did not change over time. Serum IgG (1,064 +/- 33), IgA (166 +/- 13), and IgM (96 +/- 6) were normal. Serum IgE levels increased in 4 subjects without evidence of allergy. Short-term chronic marijuana use does not have a substantial adverse effect on B or T cells of young healthy adults.

HLA matching and cadaver kidney transplant survival in North America: influence of center variation and presensitization.

SUMMARY In an analysis of 4,851 first cadaver kidney transplants, we found a statistically highly significant correlation between the number of HLA antigens mismatched and graft survival (P < 0.0005 at 1 year). The difference in the survival rates of grafts with no HLA mismatch compared with grafts with four mismatches was 11 to 12%, similar to results of previous analyses. HLA-A locus antigens had a slightly stronger effect than B locus antigens. The correlation of HLA matching with graft survival was most significant at centers with poor overall transplant outcome, and there was no correlation at centers with very good overall results. Presensitization also had the strongest effect at centers with poor overall graft survival.

Population correlation matrices for sampling experiments

A procedure is given for generating correlation matrices which can be used as population correlation matrices for sampling experiments. The algorithm specifies the eigenvalues and randomly selects a correlation matrix from the class of all correlation matrices which possess these same eigenvalues. It is possible to obtain a set of correlation matrices which are indexed by the degree of interdependence among the variables by parameterizing the eigenvalues with a single parameter. An example is the case in which the eigenvalues form a geometric progression. Examples are given and an application to the problem of stopping rules in stepwise regression is discussed. Other applications are also briefly discussed.

Antibody responses following rubella immunization analyzed by HLA and ABO types

HLA typing was performed on 232 rubella seronegative (HAI antibody titer <8) children immunized with RA 27/3 vaccine. High convalescentphase geometric mean antibody titers were noted in children one to five years of age, in girls one to 12 years of age, in subjects with AB blood type and in vaccinees with HLA types B14 and BW22. Of nine children with rubella titers≧512, 44 percent had HLA type A28; in contrast, only eight percent of the total group had A28 HLA type. HLA-A2 was present in four, and HLA types B12 and BW17 were present in three of the six children in whom seroconversion did not occur. Fifteen of 37 sibling pairs had identical antibody responses; in contrast, only 18 percent of randomly paired children had titers identical to each other. Vaccine-related symptomatology could not be associated with any HLA type. The results of this study suggest that infection with and antibody response to RA 27/3 rubella vaccine is influenced by genetic factors, which include cellular membrane determinants.

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 < 0.001) for A, B; 7% (P < 0.001) for DR; 9% (P < 0.001) for A, DR; 15% (P < 0.001) for B, DR; and 17% (P < 0.001) for A, B, DE. 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 < 0.001) for DR; 13% (P < 0.001) for A, DR; 16% (P < 0.001) for B, DR; and 18% (P < 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.