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Biomedical subjects

D B Holiday

Publications and source records attributed to D B Holiday.

10 recordsLinked to original sources

Asbestos in extrapulmonary sites: omentum and mesentery.

STUDY OBJECTIVES: Asbestos fibers have not been reported in tissues from the peritoneal cavity. Therefore, omentum, mesentery, and lung tissues from 20 individuals in whom mesothelioma was diagnosed were analyzed for asbestos bodies and asbestos fibers. DESIGN: Tissue was digested and prepared filters were analyzed by light microscopy and analytical transmission electron microscopy. RESULTS: Asbestos bodies were found in the lungs of 18 individuals, mesentery samples from 5, and omentum samples from 2. Uncoated asbestos fibers were found in lungs of 19 patients, 17 of whom had fibers in at least one extrapulmonary site. The most common asbestos in the omentum and mesentery was amosite. Several features of asbestos found in lung influenced the likelihood of amphibole fibers being found in the omentum or mesentery. Lung features included total amphibole fiber burden, length, aspect ratio, and ferruginous body burden. An increased total ferruginous body burden was strongly associated with increased likelihood of detecting amphiboles in the omentum (p < 0. 05). CONCLUSION: Asbestos fibers reach areas in the peritoneal cavity where some mesotheliomas develop. This study suggests their presence can be predicted based on concentrations and characteristics of fiber burdens in lung tissue.

Aged↗

Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study.

A randomized, placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects. The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia. The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days resulted significant increases in serum concentrations of both agents with no clinically significant toxicity. Skin yellowing was observed in approximately 35% of patients and may have contributed adversely to protocol adherence. Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene, even after dietary carotene intake was adjusted for (P < 0.0001). Baseline concentrations of retinol were apparently lowered by smoking (P < 0.002) and increased by drinking (P < 0.0001). Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation (P < 0.001). No significant reduction in sputum atypia was observed after treatment.

Adult↗

A beta-linked mannan inhibits adherence of Pseudomonas aeruginosa to human lung epithelial cells.

Adherence through carbohydrate-binding adhesins is an early step in colonization of the lung by gram-negative organisms, and because published data indicate that binding involves mannose groups, we tested the ability of a beta-linked acetyl-mannan (acemannan) to inhibit adherence of Pseudomonas aeruginosa to cultures of human lung epithelial cells. Adherence of radiolabelled P.aeruginosa to A549 cells (a type II-like pneumocyte line) increased linearly with the duration of the incubation. Acemannan inhibited adherence of bacteria, and the extent of inhibition was related to the concentration of the mannan. Inhibition required continued contact between acemannan and the target epithelial cells; cells washed free of acemannan no longer discouraged bacterial binding. Comparison of binding between seven different strains of P.aeruginosa indicated that fewer mucoid than non-mucoid bacteria adhered, but binding of either phenotype was inhibited by acemannan. Mannose, methyl alpha-D-mannopyranoside, methyl beta-D-mannopyranoside and dextran did not affect adherence of any of the non-mucoid strains. Mannose inhibited adherence by one mucoid strain, but not the other, indicating differences between strains of the same phenotype. Since prior treatment of epithelial cells with concanavalin A did not affect acemannan-induced inhibition of bacterial adherence, we concluded that the inhibitory effect of acemannan probably does not involve mannose-containing receptors.

Analysis of Variance↗

Two biochemical markers effectively used to separate smokeless tobacco users from smokers and nonusers.

Data from asbestos workers were used to devise a cutpoint classifier to identify subjects as Nonuser (non-tobacco user), Smokeless (exclusive smokeless tobacco user), and Smoker (ignited tobacco user). In some clinical trials and smoking cessation programs, Smokeless should be separated from Smoker. One therefore needs a marker for smoke exposure, such as thiocyanate, since nicotine levels, as measured by cotinine, could be similar in both groups. Levels of cotinine (ng/mL) and thiocyanate (mumol/L) levels (mean +/- SD) were, respectively: 320.9 +/- 201.1 and 145.9 +/- 63.7 for the Smoker group; 339.1 +/- 327.5 and 32.0 +/- 16.9 for the Smokeless group; and 0.6 +/- 2.6 and 58.2 +/- 33.2 for the Nonuser group. For Nonuser, Smokeless, and Smoker, respectively, the self-reported status was 45.1%, 10.8%, and 44.1%, which was adjusted to 42.2%, 11.6%, and 46.2%; the classifier yielded sensitivities of 100%, 76.1%, and 92.2%; specificities of 96.1%, 97.6%, and 96.4%; and predictive values of 94.9%, 80.6%, and 95.6%. The classifier successfully identified Nonusers, separated Smokeless from Smoker, and determined the prevalence of false reports in our cohort.

Adult↗

PRESS-related statistics: regression tools for cross-validation and case diagnostics.

In the health science literature, a common approach of validating a regression equation is data-splitting, where a portion of the data fits the model (fitting sample) and the remainder (validation sample) estimates future performance. The R2 and SEE obtained by predicting the validation sample with the fitting sample equation is a proper estimate of future performance, tending to correct for the natural upward bias of the R2 and SEE obtained from fitting sample alone. Data-splitting has several disadvantages, however. These include: 1) difficulty, arbitrariness, and inconvenience of matching samples; 2) the need to report two sets of statistics to determine homogeneity; and 3) the lack of equation stability due to diluted sample size. The PRESS statistic and associated residuals do not require the data to be split, yield alternative unbiased estimates of R2 and SEE, and provide useful case diagnostics. This procedure is easy to use, is widely available in modern statistical packages, but is rarely utilized. The two methods are contrasted here using a simulation from original data for predicting body density from anthropometric measurements of a group of 117 women. The PRESS approach is particularly appropriate for smaller datasets; methods of reporting these statistics are recommended.

Adult↗

Selection of skin test antigens to evaluate PPD anergy.

BACKGROUND: A purified protein derivative (PPD) tuberculin skin test may be nonreactive because of cutaneous anergy, technical problems with the test, or absence of tuberculosis infection. This study investigated the sensitivity and specificity of five test agents in measuring cutaneous anergy when the PPD test is nonreactive. Agents evaluated include antigens for Candida, mumps, histoplasmin, tetanus, and Trichophyton. METHODS: Delayed-type hypersensitivity skin test records were analyzed in 1113 patients admitted to the University of Texas Health Center at Tyler from December 1988 through June 1993. These patients were admitted with initial diagnoses of diseases other than active tuberculosis or human immunodeficiency virus infection. RESULTS: Patients with a negative PPD test reacted most often to the control skin test Candida (63.5%), followed by mumps (52.2%), histoplasmosis (37.2%), tetanus (35.7%), and Trichophyton (6.1%). Analysis of these data indicates that the use of more than three of the four most commonly reactive control tests (Candida, mumps, and histoplasmin or tetanus) yielded minimal additional precision in the determination of skin test anergy compared with using all five control skin tests. This finding remained constant whether the PPD was considered negative at < 5 mm, < 10 mm, or < 15 mm of induration. CONCLUSIONS: In controlling for false-negative PPD tests, the use of three skin test antigens, Candida, mumps, and tetanus, should provide reliable control for delayed-type hypersensitivity anergy.

Animals↗

Growth factors for human pleural mesothelial cells in soluble products from formed clots.

Fibrin deposition within the pleural space may influence repair following pleural injury. Although the mesothelial surface can organize fibrin, the contribution of pleural mesothelial cells to pleural repair is unknown. During coagulation thrombin cleaves Fibrinopeptide A (FPA, A alpha 1-16) and fibrinopeptide B (FPB) from the A alpha and B beta chains of fibrinogen to generate fibrin monomer. Since these peptides are mitogenic for human fibroblasts, we considered that they might stimulate replication of human pleural mesothelial cells (HPMC). Application of fluid expressed from fibrin clots significantly increased cell number and stimulated uptake of 3H-thymidine by HPMC compared with untreated cells. The mitogenic response of subconfluent HPMC to dilutions of clot fluid (30-150 micrograms/ml protein) was comparable to that of 0.1 nM TGF-beta. Fibrinopeptide A (7.5-30 microM) stimulated 3H-thymidine uptake in HPMC, but FPB had only a slight effect at 30 microM. Antibody to FPA antibody significantly attenuated the mitogenic effect of clot fluid, indicating that a major component is FPA. Our study suggests that fibrinopeptides released during fibrin formation in vivo may stimulate local mesothelial regeneration following pleural injury.

Catalysis↗

Identifying disagreement in ordinal ratings within a fixed panel of cytotechnologists.

In many clinical settings, a fixed number of raters screen specimens with more than two ordinal outcomes (for example, mild, moderate, severe). A design is proposed that facilitates the measurement of both interrater and intrarater agreement and associated trends. Design deficiencies are discussed, as are the propriety and interpretation of some common indices of reliability and reproducibility. The concepts are illustrated with data from cytopathologic ratings for sputum light microscopy.

Animals↗

Comparison of three tracers for detecting lung epithelial injury in anesthetized sheep.

We compared the ability of three aerosolized tracers to discriminate among control, lung inflation with a positive end expired pressure of 10 cmH2O, lung vascular hypertension and edema without lung injury, and lung edema with lung injury due to intravenous oleic acid. The tracers were 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt 492), 99mTc-human serum albumin (99mTc-ALB, mol wt 69,000), and 99mTc-aggregated albumin (99mTc-AGG ALB, mol wt 383,000). 99mTc-DTPA clearance measurements were not able to discriminate lung injury from lung inflation. The 99mTc-AGG ALB clearance rate was unchanged by lung inflation and increased slightly with lung injury. The 99mTc-ALB clearance rate (0.06 +/- 0.02%/min) was unchanged by lung inflation (0.09 +/- 0.02%/min, P greater than 0.05) or 4 h of hypertension without injury (0.09 +/- 0.04%/min, P greater than 0.05). Deposition of 99mTc-ALB within 15 min of the administration of the oleic acid increased the clearance rate to 0.19 +/- 0.06%/min, which correlated well with the postmortem lung water volume (r = 0.92, P less than 0.01). This did not occur when there was a 60-min delay in the deposition of 99mTc-ALB. We conclude that 99mTc-ALB is the best indicator for studying the effects of lung epithelial injury on protein and fluid transport into and out of the air spaces of the lungs in a minimally invasive manner.

Animals↗

Sputum cytology within and across laboratories. A reliability study.

A total of 11 cytotechnologists at sites in Texas (TX1, TX2), California (CA) and Arkansas (AR) were assessed for agreement of six-category diagnoses of sputum cytology slides prepared by the method of Saccomanno. For three observers at TX1 there was more agreement within observers (27-60%) than across observers (13-50%). Within-1 category intraobserver agreement underwent a twofold to threefold increase, to 77-93%; within-2 category agreement was 90-100%. Interobserver within-1 category agreement was 47-92%; within-2 category agreement was 83-100%. Agreement was significantly greater than chance (using kappa) in 69% of all intraobserver and interobserver pairings. Intralaboratory agreement was 40% for CA and 40-57% for TX2. Among pairings of the four sites, the range of interlaboratory agreement was 13-60% over several occasions. The overall range of agreement with the TX1 standard was 17-50% over observers/occasions. Within certain categories, outside agreement with the TX1 standard was 53-90% for normal, 39-80% for squamous metaplasia, 68-84% for mild atypia, 80-100% for moderate atypia and 93-100% for severe atypia or carcinoma. We conclude that agreement is acceptable for extreme atypia, but more training or refinement of the guidelines may be needed, if justified, to better differentiate the lowest categories. Good agreement appears to be as likely for observers with many years of overall experience as for those with high exposure to the Saccomanno method. For potential statistical analyses, the scale should probably be condensed into three to four categories to reduce extraneous variability.

Cytodiagnosis↗