Creation of a CT Image Library for the Lung Screening Study of the National Lung Screening Trial.

The CT Image Library (CTIL) of the Lung Screening Study (LSS) network of the National Lung Screening Trial (NLST) consists of up to three annual screens using CT imaging from each of 17,308 participants with a significant history of smoking but no evidence of cancer at trial enrollment (Fall 2002-Spring 2004). Screens performed at numerous medical centers associated with 10 LSS-NLST screening centers are deidentified of protected health information and delivered to the CTIL via DVD, external hard disk, or Internet/Virtual Private Network transmission. The collection will be completed in late 2006. The CTIL is of potential interest to clinical researchers and software developers of nodule detection algorithms. Its attractiveness lies in its very specific, well-defined patient population, scanned via a common CT protocol, and in its collection of evenly spaced serial screens. In this work, we describe the technical details of the CTIL collection process from screening center retrieval through library storage.

The craniofacial anomalies archive at St. Louis Children's Hospital: 20 years of craniofacial imaging experience.

This article describes how the Craniofacial Imaging Laboratory at the Cleft Palate and Craniofacial Deformities Institute, St. Louis Children's Hospital, Washington University Medical Center, has developed an electronic archive for the storage of computed tomography image digital data that is independent of scanner hardware and independent of units of storage media (i.e., floppy disks and optical disks). The archive represents one of the largest repositories of high-quality computed tomography data of children with craniofacial deformities in the world. Archiving reconstructed image data is essential for comparative imaging, surgical simulation, quantitative analysis, and use with solid model fabrication (e.g., stereolithography). One tertiary craniofacial center's experience in the establishment and maintenance of such an archive through three generations of storage technology is reported. The current archive is housed on an external 35-GB hard drive attached to a Windows-based desktop server. Data in the archive were categorized by specific demographics into groups of patients, number of scans, and diagnoses. The Craniofacial Imaging Laboratory archive currently contains computed tomography image digital data for 1827 individual scans. The earliest scan was done in 1980; the most recently stored scan for the purposes of this report occurred in May of 2000. The average number of scans archived per complete year was 94, with a range of 59 to 138. Of the 1827 total scans, 74 percent could be classified into specific diagnostic categories. The majority of the archive (55 percent) is composed of the following five diagnoses: sagittal synostosis (17 percent), unilateral coronal synostosis (11 percent), hemifacial microsomia (10 percent), plagiocephaly without synostosis (10 percent), and metopic synostosis (7 percent). Storage of computed tomography image data in a digital archive currently allows for continuous upgrading of image display and analysis and facilitates longitudinal and cross-sectional studies, both intramural and extramural. Internet access for clinical and research purposes is feasible, but contingent on protection of patient confidentiality. The future of digital imaging regarding craniofacial computed tomography scan storage and processing is also discussed.

JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathy.

Most immunosuppressed individuals who develop progressive multifocal leukoencephalopathy (PML) have a rapid fatal outcome, whereas some become long-term survivors. We explored the impact of the cellular immune response against JC virus (JCV) on the clinical outcome of 7 HIV+ and 3 HIV- individuals with PML. Of the 4 HIV+/PML survivors, all had detectable cytotoxic T lymphocytes (CTL) specific for JCV T or VP 1 proteins compared to none of the 3 HIV+/PML progressors tested. Of the 3 HIV-/PML patients, 1 was recently diagnosed with PML and showed evidence of neurologic improvement without any treatment. This patient had CTL specific for the VP1 protein of JCV. The other 2 HIV-/PML survivors were stable 3-8 years after the diagnosis of PML. They did not have any detectable CTL against JCV. These findings suggest that JCV-specific immune response is associated with favorable outcome in HIV+ individuals with PML. The lack of detectable JCV-specific CTL in 2 HIV-/PML survivors might indicate a burnt-out disease without sufficient antigenic stimulation to maintain the cellular immune response. The detection of JCV-specific CTL in an HIV- patient recently diagnosed with PML, who was showing evidence of neurological improvement without any treatment, indicates that this finding may be used as a favorable prognostic marker of disease evolution in the clinical management of patients with PML. As the quest for an effective treatment of PML continues, JCV-specific cellular immune response deserves further attention because it appears to play a crucial role in the prevention of disease progression.

Anti-inflammatory and lung function effects of montelukast in asthmatic volunteers exposed to sulfur dioxide.

BACKGROUND: Sulfur dioxide (SO(2)) gas may induce acute asthmatic responses when inhaled by individuals in the setting of community or occupational air pollution during exercise. Some asthma medications mitigate the SO(2) response, which is not fully understood but appears to involve multiple mechanisms. OBJECTIVE: We tested the hypothesis that pretreatment with the cysteinyl-leukotriene inhibitor montelukast sodium protects against the inflammatory and bronchoconstrictive effects of SO(2) in the airways of asthmatic subjects. METHODS: Asthmatic volunteers (enrolled, 12 subjects; completed study, 11 subjects) were exposed to 0.75 ppm SO(2) for 10-min periods during exercise (mean ventilation, 35 L/min) and were exposed similarly to filtered air (control condition) after double-blinded pretreatments with montelukast (10 mg/d for 3 days) and placebo. RESULTS: After montelukast pretreatment, specific airways resistance, FEV(1), symptoms, and eosinophil counts in induced sputum showed statistically and clinically significant improvements in preexposure measurements and/or decreased responses to SO(2) exposure or exercise. The mean FEV(1) immediately after exposure was 95% of baseline FEV(1) with montelukast pretreatment vs 82% with placebo. CONCLUSION: Montelukast significantly protects against airways eosinophilic inflammation and bronchoconstriction from SO(2) exposure during exercise. This implies a role for leukotrienes in SO(2)-induced lung effects.

Day-to-day particulate exposures and health changes in Los Angeles area residents with severe lung disease.

We measured particulate matter (PM2.5 and PM10) exposures, home temperature, arterial blood oxygen saturation, blood pressure, and lung function in 30 volunteer Los Angeles area residents during four-day intervals. Continuous Holter electrocardiograms were recorded in a subgroup on the first two days. Subjects recorded symptoms and time-activity patterns in diaries during monitoring, and during a reference period one week earlier/later. All subjects had severe chronic obstructive pulmonary disease. PM10 (24-hr mean) at monitoring stations near subjects' homes averaged 33 micrograms/m3, and ranged from 9 to 84 micrograms/m3. In longitudinal analyses, day-to-day changes in PM2.5 and PM10 outside subjects' homes significantly tracked concurrent station PM10 (r2 = 0.22 and 0.44, respectively). Indoor and personal concentrations were less related to station readings (r2 < or = 0.1), but tracked each other (r2 > or = 0.4). In-home temperatures tracked outdoor temperatures more for lows (r2 = 0.27) than for highs (r2 = 0.10). These longitudinal relationships of subject-oriented and station PM measurements were generally similar to cross-sectional relationships observed previously in similar subjects. Among health measurements, only blood pressure showed reasonably consistent unfavorable longitudinal associations with particulates, more with station or outdoor PM than with indoor or personal PM.

Effect of inhaled salmeterol on sulfur dioxide-induced bronchoconstriction in asthmatic subjects.

UNLABELLED: This study tested the capability of a single 42-microgram dose of inhaled salmeterol xinafoate, a long-acting beta 2-agonist, to protect against bronchoconstrictive effects of exposure to 0.75 ppm sulfur dioxide (SO2) during exercise, for up to 24 h. Ten SO2-responsive adult volunteers with stable asthma were studied under 4 conditions of drug pretreatment/exposure, administered in random order, double-blind: salmeterol/SO2, placebo/SO2, salmeterol/clean air, and placebo/clean air. Each subject underwent 10-min exposure/exercise challenges in a chamber 1, 12, 18, and 24 h after pretreatment. Exercise ventilation rates averaged 29 L/min. Response was measured as the decrement in FEV1 between preexposure and postexposure (lowest value within 30 min). After salmeterol, mean decrement post-SO2 was 7% at 1 h and 12% at 12 h. At 18 and 24 h after salmeterol, and at all times after placebo, mean decrements were 25 to 30%. After 18 and 24 h, salmeterol still improved base-line FEV1 relative to placebo, although improvement was not statistically significant at 24 h. Acute symptom increases accompanied FEV1 decrements. CONCLUSION: In our asthmatic subjects, pretreatment with salmeterol imparted clinically and statistically significant (p < 0.01) protection against bronchoconstriction induced by SO2/exercise for at least 12 h, and maintained an improvement in lung function for as much as 18 h.

Exposures of health-care workers to ribavirin aerosol: a pharmacokinetic study.

We assessed health risks to nurses and therapists exposed occupationally to ribavirin aerosol, a known rodent teratogen, by measuring uptake as a function of exposure concentration. During a 4-d period, healthy, nonsmoking, young adult volunteers (N = 14) were exposed 4 h/d respirable ribavirin aerosol at concentrations that exceeded occupational levels. Intermittent exercise occurred during exposure, and all activities occurred in a simulated hospital room. Ribavirin was assayed in plasma, red cells, and urine; lung function and symptoms were also measured. In 7 volunteers who were exposed to 30 mg/m3 (i.e., received approximately 10% of therapeutic dose), postexposure ribavirin concentrations in plasma and urine were similar on all 4 d, averaging (0.89 mumol/l and 131 mumol/l, respectively. These concentrations decreased after exposure, with half-times of 37-39 h. Red-cell concentrations averaged 31 mumol/l on d 4, accounting for < 5% of inhaled ribavirin mass, and they remained stable for 4 d afterward. In 7 volunteers exposed to 3 mg/m3 (i.e., approximately 1% of therapeutic dose), plasma averaged 0.075 mumol/l and red cells averaged 3 mumol/l on d 4 (i.e., near detection limits). Small variations occurred in lung function, reported symptoms, and hematologic values for exposures to both 3 and 30 microgram/m3; therefore, these effects were most likely not caused by ribavirin. Typical occupational exposures to ribavirin, without recommended protective measures, should result in undetectable or barely detectable body burdens, i.e., approximately 0.1%-1% of levels reported to be toxic to laboratory animals.

A graphical user interface for quantitative imaging and analysis of electrophoretic gels and autoradiograms.

DNA/GUI (DNA Graphical User Interface) is an interactive software system for rapid and efficient analysis of images of the types used in genome mapping, such as autoradiograms and electrophoretic gels. Images are digitized using a commercially available charge-coupled-device (CCD) camera system and analyzed on a graphics workstation using a menu-driven user interface. DNA/GUI features automatic lane and band detection, simultaneous display of multiple images and a unique spatial-normalization algorithm. Images and their associated data are archived and easily available for later recall. Preliminary results indicate that DNA/GUI is a useful tool in the analysis and comparison of images used in a variety of applications such as genetic-linkage analysis and DNA restriction mapping. The interactive display software is based on the X Window System and is therefore readily portable to a variety of graphics workstations.

Responses to sulfur dioxide and exercise by medication-dependent asthmatics: effect of varying medication levels.

Twenty-one volunteers with moderate to severe asthma were exposed to sulfur dioxide (SO2) at concentrations of 0 (control), 0.3, and 0.6 ppm in each of three medication states: (1) low (much of their usual asthma medication withheld), (2) normal (each subject on his own usual medication schedule), and (3) high (usual medication supplemented by inhaled metaproterenol before exposure). Theophylline, the medication usually taken by subjects, was often supplemented by beta-adrenergics. Exposures were for 10 min and were accompanied by continuous heavy exercise (ventilation approximately 50 l/min). Lung function and symptoms were measured before and after exposure. With normal medication, symptomatic bronchoconstriction occurred with exercise and was exacerbated by 0.6 ppm SO2, as reported for mildly unmedicated asthmatics studied previously. Both baseline and post-exposure lung function were noticeably worse in the low-medication state. High medication improved baseline lung function and prevented most bronchoconstrictive effects of SO2/exercise. High medication also increased heart rate and apparently induced tremor or nervousness in some individuals.

Color contrast perimetry.

A method for color perimetry is proposed in which colored test objects are presented in a white surround, so that the luminance of the object and its surround are identical. The color of the test object then may be varied in its degree of saturation, while maintaining a constant luminance. A color video instrument controlled by a microcomputer is used as a tangent screen. Foveally viewed, colored test objects are adjusted initially in luminance by heterochromatic flicker photometry to match the luminance of a white background at 100 apostilb. The relative foveal scotoma for blue light requires that test objects large enough to include the perifoveal retina be used for flicker photometry of blue test objects. Due to the progressively increasing threshold for luminance contrast detection in extrafoveal retina, differences in luminance between the colored objects and the white surrounding, as the test objects are moved into the extrafoveal visual field, appear to remain subthreshold. Test object detection can thus be expected to be a perimetric measure of color contrast detection, relatively unaffected by luminance contrast detection. This strategy should simplify the use of colored objects for clinical perimetric testing and should provide a specific test of color vision in the extrafoveal visual field.

The effectiveness of antiarrhythmic agents on early-cycle premature ventricular complexes.

Twelve patients completed a double-blind, crossover antiarrhythmic drug trial in which 300 mg of quinidine, 500 mg of procainamide, 100 mg of phenytoin, or placebo was given four times daily on subsequent weeks. Analysis of 24-hour Holter tapes with a computerized analysis system (Argus/H) permitted accurate counting of premature ventricular complexes (PVCs) subclassified according to coupling interval. No antiarrhythmic agent demonstrated a significant overall reduction in the number of PVCs, but both quinidine and procainamide showed a statistically significant (p less than 0.05) reduction of PVCs with coupling intervals less than 400 msec. This effect was noted both in isolated PVCs (quinidine only) and in PVCs that were part of a couplet or run (both drugs). These findings demonstrate that clinically important effects of procainamide and quinidine can occur in the absence of an overall reduction in the number of PVCs.

Exposures of human volunteers to a controlled atmospheric mixture of ozone, sulfur dioxide and sulfuric acid.

Nineteen human volunteers with normal pulmonary function and no history of asthma were exposed on two separate days to clean air and to an atmospheric mixture containing ozone (O3), 0.37 ppm, sulfur dioxide (SO2), 0.37 ppm, and sulfuric acid aerosol (B2SO4), 100 micrograms/m3. Subjects were exposed under carefully controlled conditions for two hours. During this period, the subjects alternately exercised for 15 minutes, at a level calculated to double minute ventilation, and rested for 15 minutes. The experimental goal was to determine whether the presence of the copollutants, H2SO4 and SO2, would significantly enhance the irritant potential of ozone, or cause decrements in pulmonary function on the order of 10 - 20 percent. Statistical analysis of the group averaged data suggested that the mixture may have been slightly more irritating to the subjects than was O3 alone. A large percentage of the subjects exhibited small decrements in pulmonary function. The group averaged FEV1.0 (forced expiratory volume in one second) on the exposure day was depressed 3.7 percent from the control value. One might expect O3 alone to depress FEV1.0 by about 2.8 percent under similar exposure conditions.

Human biochemical response to ozone and vitamin E.

To determine whether vitamin E (dl-alpha-tocopherol) supplementation of the diet provides protection from inhaled oxidants such as ozone (O3) in community air pollution, its effects were studied in healthy adult volunteers, Experimental groups received 800 or 1600 IU of vitamin E for 9 wk or more; control groups received placebos. Double-blind conditions were maintained throughout the study. Biochemical parameters studied included red blood cell fragility; hematocrit and hemoglobin values; red cell glutathione concentration; and the enzymes acetylcholinesterase, glucose-6-phosphate dehydrogenase, and lactic acid dehydrogenase. No significant differences between the responses of the supplemented and placebo groups to a controlled O3 exposure (0.5 ppm for 2 h) were found for any of these parameters. The results indicate that vitamin E supplementation in humans, at the levels employed in this experiment, gives no added protection against blood biochemical effects of O3 in intermittently exercising subjects under exposure conditoins simulating summer ambient air pollution episodes.

Effect of low-level exposure to ozone on arterial oxygenation in humans.

We investigated the effect on arterial blood oxygenation of exposure to 0.2 ppm of ozone in purified air for 2 hours with intermittent light exercise and heat stress. Similar exposures to purified air alone provided control data. In 12 healthy volunteers, blood gases were measured before and during exposure via an indwelling brachial cannula. Six of these subjects and 6 other subjects underwent separate similar studies in which "arterialized" earlobe capillary blood was sampled. Arterial Po2 and alveolar-arterial Po2 differences varied significantly among different experimental conditions, but the variability was similar in the presence or absence of ozone. Small significant variations in body temperature were observed; these did not appear to be sufficient to affect blood gas measurements substantially. Over-all, we found no evidence for an adverse effect of the exposure to ozone on arterial oxygenation.

A detection algorithm for multiform premature ventricular contractions.

This paper reports an algorithm developed to identify and quantify multiform PVCs. The algorithm clusters PVCs of similar morphology using a combination of time-domain and frequency-domain analysis. Initially, PVCs are grouped together on the basis of four time-domain-based morphological feature measurements. However, these time-domain-based clusters many times are nonunique because commonly encountered signal changes can cause substantial variations in the feature measurements of clinically similar beats. These redundant clusters are consolidated using two frequency-domain parameters: The First Spectral Moment (FSM) (center of gravity) of the amplitude spectrum, and the 5-Hz phase angle.

Biochemical response of squirrel monkeys to ozone.

Biochemical studies were performed on blood and lung tissue of squirrel monkeys (Saimiri sciureus) following acute exposure to 0.75 ppm ozone (O3) for 4 h/d for 4 consecutive days. One group of animals was sacrificed at the end of the last exposure day and another group was sacrificed 4 d later after the last exposure. Evidence was sought for oxidation-induced changes known to occur in rodents when high levels of O3 are inhaled. A significant increase in red blood cell membrane fragility was observed, as well as significant decreases in red blood cell glutathione and erythrocyte acetylcholinesterase; however, the red blood cell enzymes, lactic acid dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G6PDH) were not changed significantly. Lung tissue analysis showed that lipid peroxidation was markedly increased and tissue vitamin E levels were significantly decreased. The tissue enzymes G6PDH, glutathione reductase, and LDH significantly increased in activity. No significant changes were seen in either superoxide dismutase or malic acid dehydrogenase. The results of this experiment indicate that O3, or reaction products resulting from O3-tissue interaction in the lung, pass the air-blood barrier and are capable of producing biochemical changes in blood as well as in lung tissue.