Biomedical subjects
Publications and source records attributed to D Zelterman.
We propose a statistical method to test the homogeneity of relative risk in cohort studies. We illustrate its application to an original data set from a low-risk group of end-stage renal disease patients on haemodialysis. The use of the method is as a global test against the omnibus alternative.
The concentrations of four arachidonic acid metabolites, prostaglandin E2, 6-keto-prostaglandin F1 alpha, leukotriene B4, and leukotriene C4, were measured in middle ear fluid of chinchillas 6 to 72 hours after middle ear inoculation of log-phase, heat-killed encapsulated Streptococcus pneumoniae organisms. Compared with saline-inoculated ears, significant increases in the mean concentrations of all four metabolites were observed in the pneumococcus-inoculated ears 24 hours after inoculation, but not after 6, 48, or 72 hours. Since pneumococcus inoculation caused an influx of inflammatory cells as early as 6 hours after inoculation, before the increase in arachidonate metabolites, the initial stimulus for inflammatory cell chemotaxis is probably not metabolic products of arachidonic acid such as leukotriene B4. These metabolites may, however, amplify the subsequent inflammatory response.
Middle ear infection with Streptococcus pneumoniae is important in the pathogenesis of acute and chronic otitis media, and lysozyme in middle ear fluid (MEF) is an important inflammatory mediator in this disease. To determine the source of lysozyme during the early period of acute pneumococcal otitis media, chinchillas were irradiated to induce neutropenia, and their middle ears were inoculated with heat-killed, encapsulated pneumococci. The number of inflammatory cells and concentration of lysozyme were measured in MEF between 6 and 72 hours after inoculation. In pneumococcus-inoculated ears, the mean number of inflammatory cells but not lysozyme was significantly lower in MEF from irradiated animals than that from nonirradiated animals at 6 hours. Since lysozyme accumulated in MEF before the influx of inflammatory cells in irradiated animals, the initial release of this inflammatory mediator is most likely not from inflammatory cells; and mucosal epithelial cells, the only other known source of lysozyme in the middle ear environment, were the probable source induced by the direct stimulation of pneumococci. Inflammatory cells may contribute lysozyme later in the inflammatory response, since cellular and lysozyme concentrations in irradiated and nonirradiated animals were similar between 24 and 72 hours. These results suggest that future therapeutic interventions to limit middle ear inflammation in acute otitis media may need to recognize the direct action of pneumococcal cells or their envelope components on middle ear epithelium.
We examine several tests of homogeneity of the odds ratio in the analysis of 2 x 2 tables arising from epidemiologic 1:R matched case-control studies. The T4 and T5 statistics proposed by Liang and Self (1985, Biometrika 72, 353-358) are unable to detect obvious inhomogeneity in two numerical examples and in simulation studies. The null hypothesis is rejected by the chi-square statistic of Ejigou and McHugh (1984, Biometrika 71, 408-411) and by a new proposed method whose significance level must be simulated.
The results of medical tests update the probability of diagnosis (diagnosability) of a patient from the population prevalence of a disease. This paper demonstrates a method of combining several mutually dependent tests as the sum of log odds ratios, and of separating the log odd ratios of the test results and those of prevalences. Extending Kullback's discriminant function between two states to m states (m greater than or equal to 2), it is shown that the information of a test can be measured by discrimination and divergence, which are well-defined measures in information theory and test theory. The performance of diagnostic cytology can then be compared to the results of histopathologic diagnoses or to a peer-reviewed consensus without the use of arbitrarily given scores or without unfounded assumptions about underlying continuous variables. They can also provide a way to optimize the categorization (classification) of Papanicolaou smears and a means of quality control for morphologic tests. These methods can be used to evaluate the performances of cytology laboratories that use two classifications consisting of different numbers of categories (classes) and states.
I discuss alternatives to the one compartment model, delta Yt = alpha + beta exp(- gamma t). Instead of comparing the one and two compartment models, I derive statistics for testing mixtures of the parameters (beta, gamma) in the one compartment model. I apply the proposed methods to the problem of hydrogen clearance in blood flow measurement and to vanadium depuration data.
Various measures of biological activity were studied in batches of lyophilized Tice Bacillus Calmette-Guérin (BCG) that have been used intrapleurally as adjuvant therapy in surgically resected Stage I lung cancer patients by our own group, the North American Lung Cancer Study Group, and the Ludwig Lung Cancer Study Group. The biological activities of BCG that were studied were: (a) inhibition of solid tumor growth in mice following s.c. inoculation of BCG admixed with methylcholanthrene-induced fibrosarcoma cells (MC 43); (b) protection against tumor colonization of lungs and prolongation of survival in mice pretreated intrapleurally with BCG and later inoculated i.v. with a lethal dose of MC 43 tumor cells; and (c) growth properties in vitro, including a determination of the relative amounts of growing and nongrowing material and the sensitivity of growing material to inhibition by isoniazid. Significant differences in biological activity among batches of BCG were found. Some batches of BCG protected mice against circulating tumor cells, while others did not. Batches of BCG which protected mice against circulating tumor cells were found to have greater sensitivity to isoniazid and higher viability than batches which did not elicit this antitumor activity. There were also trends of some batches of BCG outperforming others in the clinic. Cumulative disease-free interval of patients was longer with batches which protected mice against circulating tumor cells than with batches which did not protect mice against circulating tumor cells. The results of this study suggest that preclinical testing of BCG for antitumor activity may improve the efficacy of this agent in future clinical trials.
ACT/DB is a client-server database application for storing clinical trials and outcomes data, which is currently undergoing initial pilot use. It stores most of its data in entity-attribute-value form. Such data are segregated according to data type to allow indexing by value when possible, and binary large object data are managed in the same way as other data. ACT/DB lets an investigator design a study rapidly by defining the parameters (or attributes) that are to be gathered, as well as their logical grouping for purposes of display and data entry. ACT/DB generates customizable data entry. The data can be viewed through several standard reports as well as exported as text to external analysis programs. ACT/DB is designed to encourage reuse of parameters across multiple studies and has facilities for dictionary search and maintenance. It uses a Microsoft Access client running on Windows 95 machines, which communicates with an Oracle server running on a UNIX platform. ACT/DB is being used to manage the data for seven studies in its initial deployment.
PURPOSE: Treatment with hematopoietic growth factors increases the percentage of hematopoietic progenitor cells in cell cycle. Following withdrawal of certain growth factors, preclinical data suggest that there is a transient fall in the percentage of progenitor cells in cycle below the baseline, thus providing a window to administer chemotherapy with reduced risk of myelotoxicity. PATIENTS AND METHODS: Patients with histologically confirmed, previously untreated neoplasia, were treated with pIXY321 by subcutaneous injection at a dose of 375 microg/m2 twice daily (total dose 750 microg/m2/day) for seven days (days -8 to -2), followed by a two-day rest (days -1 to 0). Patients received ICE (ifosfamide, carboplatin and etoposide) on days 1 to 3. On day 4, pIXY321 was resumed until hematologic recovery. Peripheral blood was collected on days -8, -2, -1, 1, and cell cycle distribution was determined using flow cytometry. RESULTS: Twenty patients were treated in this study and received a total of 54 cycles. Partial responses were observed in three of 13 patients with non-small cell lung cancer (23 percent) and two of five patients with small cell lung cancer (40 percent). Six of 15 patients had an increased number of cells in S+G2/M on day 1 of ICE following seven days of pIXY321 and two days off (days -1 to 0). The average increase was 63 percent (range 6-253). Seven patients had a decreased number of cells in S+G2/M. The average decrease was 55 percent (range 6.3-78). There were no significant differences among the fifteen patients with regards to the observed toxicity of the chemotherapy. DISCUSSION: pIXY321 in this schedule did not consistently decrease the percentage of cycling progenitor cells in the peripheral blood. Future studies should define whether other growth factors and/or schedules can synchronize progenitor cell cycling and protect the marrow compartment from cycle specific chemotherapy.
Federal regulations for use of neuroleptic drugs in Medicare- and Medicaid-certified nursing homes throughout the United States were implemented October 1, 1990. These regulations constitute the first time that prescription drugs are required, by law, to be justified by indications documented in the medical chart. This study used extant data to estimate ineligible neuroleptic use at the individual and nursing home levels had these regulations been in effect in 1976 through 1985. Subjects, randomly sampled admissions (N = 5752) and residents (N = 3191), were followed up for up to 24 months in 60 nursing homes. One half of neuroleptic use in each cohort could be considered ineligible under the regulations; all but one of the nursing homes had one or more individuals who were treated with the ineligible use of neuroleptics. Improvements in documentation and/or prescription of neuroleptic drugs for nursing home elderly will be needed to ensure compliance with these new regulations.
Discrimination is the expectation of log odds ratios. Performance in diagnostic cytology, as compared to the results of histopathology or to a peer-reviewed consensus, can be measured by the total discrimination, which is a well-defined measure of information in information theory and test theory. The total discrimination, as a measure of performance, was calculated for the Gynecologic Cytology Laboratory of the University of Minnesota for the years 1985 through 1987, based on 3,545 sets of single-slide Papanicolaou smears and colposcope-directed biopsies. Similar calculations were made for the performances of physicians and technicians on peer-reviewed "clear-cut" Papanicolaou smears, as reported in a study from the Centers for Disease Control (CDC). For fair comparison of the two different sets of observations, the cytologic categories and corresponding histologic states were merged into five categories and states. The cytologic performance of our laboratory, tested against the histologic diagnoses, and the performances of the physicians and technologists tested against peer-reviewed check samples by the CDC were 0.53, 0.45 and 1.17 decits, respectively. These values generally agree with the conclusions derived by more conventional methods used by the CDC. When sampling errors of cytology specimens are taken into account, the performance of our laboratory, measured by the total discrimination of the cytology-histology confusion matrix, was approximately equal to the performance of the group of technologists studied by the CDC, which was in turn significantly better than that of the group of physicians studied by the CDC. This study demonstrates the value of using the total discrimination for quantifying the performance of a cytology laboratory, a cytopathologist or a cytotechnologist, without the arbitrary means usually used to evaluate such performances.
The performance of a cytology laboratory can be objectively quantitated as the total discrimination, a defined quantity of information. The total discrimination is dependent on the number of categories used in gynecologic cytology and on the corresponding histologic states; over-classification results in a higher rate of misinformation and reduced total discrimination. Total divergence is another measure of the association between cytologic categories and histologic states; in contrast to the total discrimination, the total divergence does not require a one-to-one correspondence between the cytologic categories and the histologic states. Using data from the Gynecologic Cytology Laboratory of the University of Minnesota, the total discrimination was maximized when gynecologic cytology used three categories of diagnosis, consisting of (1) normal, atypical benign or reactive atypia, (2) cervical intraepithelial neoplasia (CIN) and (3) all malignancies. The use of four categories, (1) normal, atypical benign or reactive atypia, (2) mild or moderate dysplasia, (3) severe dysplasia or squamous carcinoma in situ and (4) all malignancies, was almost equally informative. Observations on the total divergences resulted in similar conclusions. These findings generally support the recommendation of the consensus workshop sponsored by the National Cancer Institute (the Bethesda System nomenclature) to group all degrees of CIN into two large categories.
The performance of diagnostic cytology on Papanicolaou smears can be periodically monitored by calculating the total discrimination or the total divergence of the cytologic diagnoses against the histologic diagnoses on samples obtained by colposcope-directed biopsies. Using these measures, the annual performances of the Gynecologic Cytology Laboratory of the University of Minnesota between 1980 and 1988 were retrospectively analyzed. For those years, the total discrimination and total divergence behaved similarly and were sensitive to the performance of the total system, including specimen sampling errors and laboratory precision. The lowest limits of the permissible range of the total discrimination and total divergence were 0.15 and -1.21 decits, respectively, for a single-slide Papanicolaou test if an 80% "hit" rate was accepted as the lowest threshold for each category. The optimal numbers of category-states were not a sensitive indicator of the quality of a laboratory; i.e., the optimal number of diagnostic categories remained at three throughout the period studied.
School-based clinics in St. Paul have provided comprehensive health services, including reproductive health care, for almost two decades. This study examines the effects of those clinics on the birthrates in their respective schools, using a newly developed methodology with numerous advantages over previous methods for estimating student birthrates. Confidentially matching the names of female students from school records with the names of mothers on birth records at the Department of Health provided birthrates for each of the St. Paul public high schools with clinics for each year between 1971 and 1986. The results show that birthrates fluctuated dramatically from one year to the next, but school-wide birthrates were not significantly lower in the years immediately following the opening of a clinic than in the years preceding it.