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Biomedical subjects

J W McLarty

Publications and source records attributed to J W McLarty.

At least 19 recordsLinked to original sources

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

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

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

Changing utilization of cytopathology versus histopathology in the diagnosis of lung cancer.

We studied the utilization rates of 1) cytopathology procedures [sputum, fine-needle aspirates (FNA), bronchial washings and brushings] versus 2) histopathology procedures (bronchial biopsies, lymph node biopsies, lobectomies, pneumonectomies) in the diagnosis of lung cancer, over two time periods (1967/1987). Comparisons were made in the utilization rates of these two diagnostic procedures in two groups of 100 patients each. Statistically significant changes included 1) an increase of cytopathology procedures, as the sole means of diagnosis; 2) an increase in FNAs; 3) an increased percentage of positive cytopathologic diagnosis; and 4) a decrease of major surgical procedures (lobectomy, pneumonectomy), as means of initial pathologic diagnosis. This study provides data supporting the trend of decreasing surgical procedures for initial diagnosis of lung cancer, with greater, more effective utilization of cytopathologic (particularly FNA) procedures.

Cytodiagnosis

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

Usefulness of combined light and electron microscopy: evaluation of sputum samples for asbestos to determine past occupational exposure.

Ferruginous bodies (FB) in sputa are recognized as an indicator of past exposure to asbestos. However, a great variability exists in FB production, even in individuals with a history of occupational exposure. A further complication in interpreting the presence of FBs in sputa is that all individuals in modern society are exposed to asbestos and, in lung tissue studies, have been shown to harbor appreciable numbers of asbestos fibers. Thus, some of these individuals should occasionally produce FBs in their sputa. The present study was undertaken to determine if uncoated asbestos fiber content could be used to better discriminate occupationally exposed individuals from the general population. Randomly selected sputum samples from 12 former workers in an amosite asbestos plant and 12 controls were studied. The samples were prepared for the study by digesting the sputa in sodium hypochlorite. The digests were filtered through 0.2-microns polycarbonate filters for collection of particulates. The filters were screened for FBs by light microscopy at 200 X, and the presence or absence of uncoated asbestos fibers was determined at 5000 X in an AMRAY 1000A scanning electron microscope. The use of electron microscopy revealed the presence of commercial amphiboles in the sputa of the occupationally exposed individuals and enabled a differentiation of these samples from those of the general population.

Adult

Effects of lung volume on clearance of solutes from the air spaces of lungs.

Several investigators have shown that the clearance rate of aerosolized 99mTc-labeled diethylenetriamine pentaacetate (DTPA, mol wt = 492, radius = 0.6 nm) from the air spaces of the lungs of humans and experimental animals increases with lung volume. To further investigate this phenomenon we performed a compartmental analysis of the 2-h clearance of DTPA from the lungs of anesthetized sheep using a new method to more accurately correct for the effects of DTPA recirculation. This analysis showed that the DTPA clearance in eight sheep ventilated with zero end-expired pressure was best described by a one-compartment model with a clearance rate of 0.42 +/- 0.15%/min. Ventilating eight sheep with an end-expired pressure of 10 cmH2O throughout the study increased the end-expired volume 0.4 +/- 0.1 liter BTPS and created a clearance curve that was best described by a two-compartment model. In these sheep 56 +/- 16% of the DTPA cleared from the lungs at a rate of 7.9 +/- 2.9%/min. The remainder cleared at a rate similar to that measured in the sheep ventilated with zero end-expired pressure (0.35 +/- 0.18%/min). Additional control and lung inflation experiments were performed using 99mTc-labeled human serum albumin (mol wt = 66,000, radius = 3.6 nm). In six control sheep ventilated with zero end-expired pressure the albumin clearance was best described by a one-compartment model with a clearance rate of 0.06 +/- 0.02%/min. The clearance rate in six sheep with increased lung volume was slightly larger (0.09 +/- 0.02, P less than 0.05) but was well described by a one-compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols

Amoxicillin-clavulanic acid in the treatment of lower respiratory tract infections caused by beta-lactamase-positive Haemophilus influenzae and Branhamella catarrhalis.

Twenty-one adult patients hospitalized with lower respiratory tract infections due to Branhamella catarrhalis or Haemophilus influenzae or both were treated with the combination of oral amoxicillin and potassium clavulanate (Augmentin) in an open, noncomparative clinical trial. Diseases included pneumonia, empyema, and exacerbations of bronchiectasis and chronic lung disease. Thirteen of 16 B. catarrhalis and six of nine H. influenzae isolates were beta-lactamase positive. The patients with B. catarrhalis were treated for a mean of 5.3 days, and those with H. influenzae were treated for a mean of 7.0 days. The overall response to therapy was excellent, with 18 of 19 beta-lactamase-producing strains eradicated on therapy. One patient secondarily infected with Pseudomonas aeruginosa was a clinical failure, and two patients with H. influenzae who became culture positive again after therapy were considered microbiologic failures. Gastrointestinal side effects (especially nausea) were common, although all patients completed a course of therapy. Sputum levels of amoxicillin were surprisingly low (less than 0.05 to 0.54 micrograms/ml), a finding which may explain the high relapse rate (22%) seen with H. influenzae, as these are below the usual MICs of amoxicillin for this organism. The combination of amoxicillin plus potassium clavulanate appears to be an excellent drug for treatment of beta-lactamase-producing strains of these two species, although mild gastrointestinal side effects are common.

Aged

Lupus lung.

The morphologic findings from 18 autopsy lungs of systemic lupus erythematosus were studied. Each case revealed varying degrees of pleuropulmonary disease. A universal feature was visceral pleural thickening, while findings present in more than one half of the cases included pulmonary congestion (17/18) and edema (15/18), pleural adhesions (11/18) and pleural effusions (10/18) and intraalveolar hemorrhage (10/18). Also seen were bronchopneumonia (9/18), interstitial fibrosis (6/18), cytomegalovirus infection (3/18), interstitial pneumonitis (2/18), hyaline membranes (2/18), and acute vasculitis (1/18) and pleuritis (1/18). These results, together with those of previously reported studies of lupus lung, establish that although certain characteristic pleuropulmonary disease processes are frequently found at autopsy, none is a highly specific marker for the disease.

Adolescent

Diagnostic criteria for pulmonary disease caused by Mycobacterium kansasii and Mycobacterium intracellulare.

A study of 271 patients infected with Mycobacterium kansasii and 226 patients with Mycobacterium avium-intracellulare complex has led to the proposal of new diagnostic criteria. These criteria, based on the presence or absence of cavitation and on the duration of sputum positivity after initiation of therapy, are proposed to more accurately distinguish colonizations from active invasion of tissue than the current diagnostic criteria.

Humans

Regression analysis of cytopathological data.

Epithelial cells from the human body are frequently labelled according to one of several ordered levels of abnormality, ranging from normal to malignant. The label of the most abnormal cell in a specimen determines the score for the specimen. This paper presents a model for the regression of specimen scores against continuous and discrete variables, as in host exposure to carcinogens. Application to data and tests for adequacy of model fit are illustrated using sputum specimens obtained from a cohort of former asbestos workers.

Adult

Serum protein concentrations and respiratory tract abnormalities following short-term exposure to amosite: a comparison between former asbestos workers and unexposed controls.

A group of 176 former asbestos workers and 76 unexposed controls of similar age were evaluated and compared for concentrations of serum immunoglobulins, alpha 1-antitrypsin, carcinoembryonic antigen (CEA), pulmonary function, radiographic appearance of the lungs, rales, cellular atypia and ferruginous bodies in sputum, and smoking habits. Test subjects were evaluated as a single group and also according to years of exposure to asbestos. Both test and control populations were independently subjects to parametric and nonparametric correlation analyses. Partial correlations were also determined for both groups after controlling for age, race, sex and smoking habits. Analysis of variance was used to compare test and control groups. Smoking, particularly heavy smoking, was an important variable influencing abnormalities of the respiratory tract and CEA in former asbestos workers but not in controls. Except for immunoglobulin A (IgA), serum proteins, CEA, and alpha 1-antitrypsin were not significantly different between test and control subjects. Analysis of variance revealed significant increases between test and control groups for cellular atypia, X-ray abnormalities, rales, and pulmonary restriction. Partial correlation analysis of the asbestos-exposed group revealed important correlations between ferruginous bodies in sputum, rales, and radiographic appearance of the lungs.

Adult

The clinical significance of ferruginous bodies in sputa.

The clinical significance of ferruginous bodies in sputa was examined in a study of 674 former asbestos workers. Data from occupational histories and smoking behavior questionnaires, chest radiographs, spirometric measurements and counts of ferruginous bodies were obtained as part of a five-year surveillance program. Statistical analysis demonstrated that ferruginous bodies found in the sputa were significantly related to radiographic findings of interstitial pulmonary disease and pleural fibrosis and to spirometric findings of restrictive lung disease. Age and cigarette smoking were also found to be related to the presence of ferruginous bodies.

Adult

Comparison of sputum and lung asbestos body counts in former asbestos workers.

The asbestos (ferruginous) body content of lung tissues was compared to the number of asbestos bodies (AB) in sputum from 6 former amosite asbestos workers. Lung tissue was obtained at autopsy (5 subjects) and lobectomy (1 subject), and AB content was determined by a digestion-concentration technique. The sputum obtained was collected by both spontaneous cough (a pooled, 3-day specimen) and aerosolized hypertonic saline induction. Four slides treated with Papanicolaou's stain were prepared from each cytologic specimen and scored from 0 to 3 + on the basis of the total number of AB counted on the 4 slides. A significant correlation (P < 0.02) was found between the number of AB per gram of lung tissue and the percentage of sputum specimens from each worker than were positive for AB. Asbestos bodies were identified in 46% of sputum specimens from the 4 workers whose lungs contained 900 or more AB/g of lung tissue.

Aged

Pretreatment, prediagnosis immunoglobulin, and alpha 1-antitrypsin levels in patients with bronchial carcinoma.

Sera from 148 patients suspected of having bronchial carcinoma were evaluated for concentrations of IgA, IgM, IgG, and alpha 1-antitrypsin (alpha 1-AT). Histologically, 137 tumor specimens obtained by bronchoscopy or surgical biopsy were diagnosed as squamous cell carcinoma (55%), adenocarcinoma (18%), undifferentiated small cell carcinoma (20%), or undifferentiated large cell carcinoma (7%). The tumor types of the remaining 11 patients were not identifiable from the records but were included as a separate group. Serum protein values were compared with those of a control group of 60 healthy adult volunteers. Regression analysis of age, race, and sex effects on the results of comparisons between test and control groups indicated that, with the possible exception of age and IgM, these three independent variables did not significantly influence the observations. Both serum IgA and alpha 1-AT were significantly elevated in all tumor groups when compared to the control levels. This was not the situation for serum IgG. Results for serum IgM were equivocal and depended on the statistical methods used. Although the serum immunoglobulin concentrations for the small cell carcinoma group were consistently lower than those for the other tumor cell types, no statistically significant difference existed between the five tumor groups in this regard.

Age Factors