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Biomedical subjects

M R Mickey

Publications and source records attributed to M R Mickey.

At least 55 records · Page 3Linked to original sources

Sustained-release theophylline preparations in asthmatic children. A short-term comparison of two products and the relationship of serum theophylline levels and pulmonary function changes.

In a four-week study, 20 children with chronic asthma were treated in a randomized, double-blind, crossover manner with two sustained-release theophylline preparations (Theo-Dur and Uniphyl) to compare their drug concentrations and clinical efficacy. In addition, the effects of serum theophylline concentration on results of pulmonary function tests (PFTs) were evaluated. Twelve-hour doses (to achieve serum concentrations between 10 and 20 mg/L) of each drug were given for two weeks. Diaries of asthma symptoms and peak flows were kept daily. After 14 days of each treatment, children returned for measurement of theophylline levels and PFTs over a 12-hour period. The two drugs were equally effective in clinically controlling asthma over the two weeks of treatment. Serum theophylline levels obtained over the 12-hour dosing periods were not significantly different. Uniphyl provided less (but not significantly) deviation between peak and trough levels. Analysis of individual patient data did not reveal a predictable relationship between serum theophylline concentrations and results of PFTs.

Adolescent↗

Use of a tube spacer to improve the efficacy of a metered-dose inhaler in asthmatic children.

Many children with asthma do not use the standard metered-dose inhaler (MDI) skillfully. To improve drug delivery, correct problems of hand-lung incoordination, and reduce local side effects, a number of spacer devices have been developed. We evaluated one such device, a tube spacer (Aerochamber), in 16 asthmatic children (5 to 12 years). On four separate days and in a randomized, double-blind, placebo-controlled manner, they received either metaproterenol sulfate by MDI aerosol (130 micrograms) or placebo with and without the tube spacer. To maximize techniques, at each visit the children had proper instructions, including viewing a videotape. Spirometry was performed at baseline and 5, 15, and 30 minutes, and hourly for six hours, and the patient was monitored. Analysis of the entire group (forced expiratory volume at 1 s and midmaximal expiratory volume) revealed no difference between metaproterenol administered with or without the tube spacer, and both were significantly different than placebo through two hours. Six children had longer and three had better bronchodilatation with the MDI plus tube spacer than with the MDI alone. Side effects and vital signs did not differ between treatments. Under the circumstances of our study, the tube spacer device might enhance the use of the MDI in children who are not properly taught and/or who forget or cannot perform proper technique.

Asthma↗

Quantitation of myelination and demyelination by the measurement of myelin basic protein by ELISA.

Utilizing a competitive inhibition enzyme-linked immunosorbent assay (ELISA) we measured the amount of myelin basic protein (MBP) in brain, liver, and kidney of newborn mouse and compared these values with myelinated cerebellar explant cultures under various conditions. Explant cultures demyelinated with anti-myelin serum showed a 90% decrease in MBP when compared with controls. These results correlated with myelination and demyelination as observed by light microscopy. Newborn tissues including brain showed only negligible activity for MBP. This technique provides a sensitive and objective method for quantitating in-vitro demyelination.

Animals↗

Public determinants of HLA indicated by pregnancy antibodies.

A tentative table of public specificities in the HLA-A and -B loci is provided. It is based on an all-inclusive survey of placenta extracts from 50,000 pregnancies. We postulate that most of the specificities found are directed against public epitopes. In support of this postulate are the facts that certain combinations occur very frequently, monoclonal antibodies have been made to some of the epitopes, and some have already been established by absorption experiments as being a single specificity. The immunogenicity score for each private and public specificity was computed by taking into account the chance of immunization. It was shown that immunogenicity can vary by factors of more than ten between different specificities. Significantly, immunogenicity of the public epitopes was just as high as against the private ones. This indicates that the public epitopes should be considered as independent, separate antigens in transplantation. Establishment of a table of public specificities and the recognition of each by international nomenclature would be the first step in evaluating public epitopes for transplantation matching.

Antilymphocyte Serum↗

Factors important in 10-year kidney transplant survival.

We reviewed 14,005 renal grafts with the temporal opportunity for 10-year survival (transplanted 1975 and earlier) and analyzed 10-year actuarial graft survival and the rate of late (3- through 10-year) graft loss as reflected by half-life. The 10-year graft survival for first transplants in HLA-identical siblings was 67% versus 38% for parental donors and 20% for cadaver donors. Factors with substantial influence on 10-year graft survival include transplant number, transfusions (0, 17%; greater than or equal to 1,33%), HLA-A,B mismatches (0, 29%; 1-2, 20%, 3-4, 17%), cold ischemia time (0-3 hours, 32%; 4-6 hours, 27%; 7-12 hours, 21%; greater than 12 hours, 16%), preservation method if CIT is no more than 24 hours (cold storage, 22%; machine, 17%), recipient race (Caucasian, 23%; black, 11%), original disease, recipient age, recipient sex, donor race, and the quality of early graft function (less than or equal to one month). Factors not significantly influencing 10-year graft survival were panel-reactive antibodies, warm ischemia time, preservation method if CIT was more than 24 hours, and donor sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Center effect.

1. The center effect persists through the period studied--transplants performed in 1983 and 1984. Consistent differences remain in outcome as measured by one-year graft survival. After discounting statistical variation, the extreme difference is approximately 40-50% for first grafts from cadaver donors. 2. The magnitude of the differences remains when cyclosporine is used. 3. Centers differ with respect to factors generally considered related to graft outcome, but the differences account at most for a small fraction of the differences between success rates. 4. Results were ambiguous as to whether the center effect applied to grafts from HLA-identical siblings. 5. The center effect is not entirely confined to the pre- and early posttransplant periods, since differences remain among grafts functioning three months posttransplant. Differences diminished, however, particularly among the centers with higher graft survival rates. 6. Factors not considered in the study are those relating to care after transplant and general medical risk assessments prior to transplant.

Female↗

Univariate and multivariate analyses of cadaver kidney graft survival data.

1. Clinical data on 6632 first cadaver transplants performed since January 1983 were analyzed by multivariate (Cox regression) and univariate (life-table) methods. 2. Cox regression analysis showed blood transfusion, recipient's race, HLA mismatch, highest antibody, warm ischemia time, and cyclosporine treatment as significant factors affecting graft survival. 3. A comparison of survival curves predicted by Cox regression analysis and that by the life-table method showed close agreement between the two methods. 4. Cyclosporine was one of the most significant variables affecting graft survival. There was a 13% overall increase in one-year graft survival due to cyclosporine treatment. However, other factors were still significant; they have not become obsolete in the cyclosporine era.

Cyclosporins↗

Empirical validation of the Essen-Möller probability of paternity.

The validity of the Essen-Möller formulation probability of paternity is supported by demonstrating its correctness in a model genetic system--the ABO system. An analysis was made of 1,393 paternity cases typed uniformly for HLA-A and -B, ABO, Rh, and MNSs, in which the mother named one man only as the child's father and in which both mother and putative father identified themselves as Caucasian. For purposes of analysis, putative fathers not excluded from paternity by the four systems tested were regarded as actual fathers. The joint distribution of observed triplets of ABO phenotypes is shown to be statistically consistent with expected values, and the fractions of "true" fathers for a given triplet closely approximated the probability of paternity calculated using a realistic prior probability. Recent allegations of fallaciousness of the method by Li and Chakravarty and Aickin are discussed in terms of the results presented.

ABO Blood-Group System↗

Behavior abnormalities and poor school performance due to oral theophylline use.

Studies evaluating adverse effects of oral theophylline on learning and behavior have been performed on children with asthma receiving long-term theophylline therapy. To further differentiate the effects of asthma itself from the drugs used, we evaluated 20 asthmatic children (6 to 12 years of age) who had not received oral bronchodilators for at least 6 months. A double blind, placebo-controlled, parallel format was used with a 4-week theophylline or placebo period preceded by a 2-week baseline. Theophylline serum levels were maintained between 10 to 20 micrograms/mL. During baseline and treatment periods, the child's home and school behavior/performance were monitored independently by their parents and teachers using standardized report forms. A battery of psychologic tests was administered at the end of baseline and treatment periods. Seven children receiving theophylline were noted to have a change in school behavior and/or performance during their 4 weeks on drug compared to baseline, whereas none of the children receiving placebo were noted to be different (P = .004). Thus, the short-term administration of theophylline to asymptomatic asthmatic children not receiving oral bronchodilators can adversely affect school performance and behavior. Because this population represents the majority of asthmatic children, one needs to use theophylline cautiously in this age group, monitor school performance closely, or seek other treatment modalities.

Achievement↗

Preferential effectiveness of cyclosporin in patients receiving kidney transplants after glomerulonephritis.

Glomerulonephritis patients transplanted with cadaver kidneys had a significantly higher one-year graft survival when immunosuppressed with cyclosporin rather than standard therapy (80% versus 59%, p less than 10(-5]. For nephrosclerosis patients the corresponding rates were 70% and 59% (p greater than 0.05); and in those with antecedent diabetes mellitus, polycystic kidney, and pyelonephritis the differences were negligible. In glomerulonephritis patients, but not in the other groups, cyclosporin was additive to the effect of transfusions and of HLA-A, B and HLA-Dr matching.

Cyclosporins↗

Increased vulnerability of the donor organ in related kidney transplants for certain diseases.

The one-year kidney transplant survival rates from parental donors into recipients with pyelonephritis (PN) was 79% as compared with the low rate of 62% for polycystic disease (PC) and diabetes mellitus (DM). Even more striking was the 42% one-year graft survival in systemic lupus erythematosus (SLE) patients receiving parental donor grafts. HLA-identical sibling donor transplants into patients with DM had a low survival rate of 75% as compared with 90% in PN patients. These results were analyzed for interactions of donor type and disease by comparing the relative survival rates among types of donors within each recipient disease. After taking into account higher overall risks attributable to medical complications inherent in the different disease categories, related donor grafts into patients with PC, SLE, and DM have lower graft survival rates than would be expected from differences in cadaver donor rates by disease. In practical terms, for related donor transplants into patients with SLE, DM, and PC, it may be necessary to consider the vulnerability of the donor organ as another factor.

Cadaver↗

An illness severity score for multiple sclerosis.

A single score is desirable for evaluating progression in clinical trials of MS therapy. Our objective was to develop a more sensitive scoring that would reflect clinical assessment of relative severity of disability. An Illness Severity Score (ISS) was developed as a sum of weights corresponding to ratings of Kurtzke Disability Status Scale and Functional Systems Scales and phase of illness. Weights were computed from clinical comparison of pairs of patients. The score was standardized to have mean 50 and standard deviation 10 in a single clinic population. Score reproducibility (correlation = 0.93) was evaluated by two independent scorings of several patients. The ISS was satisfactory as the primary assessment in a small-scale clinical trial.

Humans↗

Improving success rates of kidney transplantation.

One-year patient survival rates have improved remarkably, from 84% in 1968 to 97% in 1980 for parental donor grafts, and from 65% to 90% for cadaver donor grafts. In contrast, graft survival rates showed a steady decline from 1968 to 1975 but subsequently improved at a rate of 2.4% per year for parent donor transplants and 2.7% per year for cadaver donor transplants. During this period of improving survival rates, the pretransplant transfusion exposure rate increased from 52% in 1977 to 91% by 1981. We conclude that transplantation has now reached a new level of acceptability as a clinical treatment modality and that blood transfusion has produced its effect on graft survival when results are disseminated over a large number of transplant centers.

Blood Transfusion↗