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Computational modeling offers versatility, scalability, and cost advantages to researchers in the trauma and injury biomechanics communities. The Global Human Body Models Consortium (GHBMC) is a group of government, industry, and academic researchers developing human body models (HBMs) that aim to become the standard tool to meet this growing research need. The objective of this study is to present the methods used to develop the average seated male occupant model (M50, weight = 78 kg, height = 175 cm) from five separately validated body region models (BRMs). BRMs include the head, neck, thorax, abdomen, and a combined pelvis and lower extremity model. Modeling domains were split at the atlanto-occipital joint, C7-T1 boundary, diaphragm, abdominal cavity (peritoneum/retroperitoneum), and the acetabulum respectively. BRM meshes are based on a custom CAD model of the seated male built from a multi-modality imaging protocol of a volunteer subject found in literature.[1] Various meshing techniques were used to integrate the full body model (FBM) including 1-D beam and discrete element connections (e.g. ligamentous structures), 2D shell nodal connections (e.g. inferior vena cava to right atrium), 3D hexahedral nodal connections (e.g. soft tissue envelope connections between regions), and contact definitions varying from tied (muscle insertions) to sliding (liver and diaphragm contact). The model was developed in a general-purpose finite element code, LS-Dyna (LTSC, Livermore, CA) R4.2.1., and consists of 1.95 million elements and 1.3 million nodes. The element breakdown by type is 41% hexahedral, 33.7% tetrahedral, 19.5% quad shells and 5% tria shell. The integration methodology presented highlights the viability of using a collaborative development paradigm for the construction of HBMs, and will be used as template for expanding the suite of GHBMC models.

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A novel image reconstruction algorithm has been developed and demonstrated for fluorescence-enhanced frequency-domain photon migration (FDPM) tomography from measurements of area illumination with modulated excitation light and area collection of emitted fluorescence light using a gain modulated image-intensified charge-coupled device (ICCD) camera. The image reconstruction problem was formulated as a nonlinear least-squares-type simple bounds constrained optimization problem based upon the penalty/modified barrier function (PMBF) method and the coupled diffusion equations. The simple bounds constraints are included in the objective function of the PMBF method and the gradient-based truncated Newton method with trust region is used to minimize the function for the large-scale problem (39919 unknowns, 2973 measurements). Three-dimensional (3-D) images of fluorescence absorption coefficients were reconstructed using the algorithm from experimental reflectance measurements under conditions of perfect and imperfect distribution of fluorophore within a single target. To our knowledge, this is the first time that targets have been reconstructed in three-dimensions from reflectance measurements with a clinically relevant phantom.

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Molecular targeting with exogenous near-infrared excitable fluorescent agents using time-dependent imaging techniques may enable diagnostic imaging of breast cancer and prognostic imaging of sentinel lymph nodes within the breast. However, prior to the administration of unproven contrast agents, phantom studies on clinically relevant volumes are essential to assess the benefits of fluorescence-enhanced optical imaging in humans. Diagnostic 3-D fluorescence-enhanced optical tomography is demonstrated using 0.5 to 1 cm(3) single and multiple targets differentiated from their surroundings by indocyanine green (micromolar) in a breast-shaped phantom (10-cm diameter). Fluorescence measurements of referenced ac intensity and phase shift were acquired in response to point illumination measurement geometry using a homodyned intensified charge-coupled device system modulated at 100 MHz. Bayesian reconstructions show artifact-free 3-D images (3857 unknowns) from 3-D boundary surface measurements (126 to 439). In a reflectance geometry appropriate for prognostic imaging of lymph node involvement, fluorescence measurements were likewise acquired from the surface of a semi-infinite phantom (8x8x8 cm(3)) in response to area illumination (12 cm(2)) by excitation light. Tomographic 3-D reconstructions (24,123 unknowns) were recovered from 2-D boundary surface measurements (3194) using the modified truncated Newton's method. These studies represent the first 3-D tomographic images from physiologically relevant geometries for breast imaging.

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We present in vivo fluorescent, near-infrared (NIR), reflectance images of indocyanine green (ICG) and carotene-conjugated 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH-car) to discriminate spontaneous canine adenocarcinoma from normal mammary tissue. Following intravenous administration of 1.0 mg kg-1 ICG or 0.3 mg kg-1 HPPH-car into the canine, a 25 mW, 778 nm or 70 mW, 660 nm laser diode beam, expanded by a diverging lens to approximately 4 cm in diameter, illuminated the surface of the mammary tissue. Successfully propagating to the tissue surface, ICG or HPPH-car fluorescence generated from within the tissue was collected by an image-intensified, charge-coupled device camera fitted with an 830 or 710 nm bandpass interference filter. Upon collecting time-dependent fluorescence images at the tissue surface overlying both normal and diseased tissue volumes, and fitting these images to a pharmacokinetic model describing the uptake (wash-in) and release (wash-out) of fluorescent dye, the pharmacokinetics of fluorescent dye was spatially determined. Mapping the fluorescence intensity owing to ICG indicates that the dye acts as a blood pool or blood persistent agent, for the model parameters show no difference in the ICG uptake rates between normal and diseased tissue regions. The wash-out of ICG was delayed for up to 72 h after intravenous injection in tissue volumes associated with disease, because ICG fluorescence was still detected in the diseased tissue 72 h after injection. In contrast, HPPH-car pharmacokinetics illustrated active uptake into diseased tissues, perhaps owing to the overexpression of LDL receptors associated with the malignant cells. HPPH-car fluorescence was not discernable after 24 h. This work illustrates the ability to monitor the pharmacokinetic delivery of NIR fluorescent dyes within tissue volumes as great as 0.5-1 cm from the tissue surface in order to differentiate normal from diseased tissue volumes on the basis of parameters obtained from the pharmacokinetic models.

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BACKGROUND: Empyema remains a cause of morbidity and mortality. Thoracoscopy has proved its versatility in the management of pleural space disorders. The suitability of video-assisted thoracic surgery (VATS) for decortication in the management of the fibrotic stage of empyema is unclear. METHODS: VATS evacuation of empyema and decortication was performed on seventeen patients presenting with pleural space infections. A retrospective review was performed and constitutes the basis of this report. RESULTS: VATS evacuation of empyema and decortication was successfully performed in 13 of 17 patients. Blood loss was 325 +/- 331 cc. Mean hospital stay was 18 +/- 10 days. Postoperative hospitalization was 11 +/- 7 days. Chest tubes remained in place for 7 +/- 3 days. There were no operative mortalities. CONCLUSIONS: Video-assisted evacuation of empyema and decortication is an effective modality in the management of the exudative and fibrinopurulent stages of empyema. An organized empyema should be approached thoracoscopically, but may require open decortication.

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Lung volume reduction surgery (LVRS) has emerged as a surgical therapeutic intervention for advanced emphysema. Designed for the relief of dyspnoea, LVRS has been demonstrated to be efficacious in a subset of carefully selected patients. Short-term improvements in dyspnoea are accompanied by improvements in forced expiratory volume in one second ranging 13-96%. Lung volumes likewise improve, with lessening of trapped gas, residual volume, and total lung capacity. Improvements in functional status and quality-of-life measures parallel the improvements in dyspnoea and lung function. One preliminary study suggests that life expectancy after 3 yrs may be improved following LVRS. Many questions regarding lung volume reduction surgery in terms of operative technique, selection of patients, and outcome remain to be answered. Data are available which begin to address some of these issues. Bilateral procedures have greater short-term improvements than unilateral procedures, but the rate of loss of function following the surgery may also be greater. Stapled resection of lung tissue has been demonstrated to be superior to laser ablation. In a majority of reports, outcome is superior in patients with heterogeneous distribution of their emphysema, and patients with alpha1-proteinase inhibitor deficiency emphysema do less well than patients with smoker's emphysema.

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We present near-infrared frequency-domain photon migration imaging for the lifetime sensitive detection and localization of exogenous fluorescent contrast agents within tissue-simulating phantoms and actual tissues. We employ intensity-modulated excitation light that is expanded and delivered to the surface of a tissue or tissue-simulating phantom. The intensity-modulated fluorescence generated from within the volume propagates to the surface and is collected using a gain-modulated image-intensified charge-coupled device camera. From the spatial values of modulation amplitude and phase of the detected fluorescent light, micromolar volumes of diethylthiatricarbocyanine iodide (tau = 1.17 ns) and indocyanine green (ICG) (tau = 0.58 ns) embedded 1.0 cm deep in a tissue phantom are localized and discriminated on the basis of their lifetime differences. To demonstrate the utility of frequency-domain fluorescent measurements for imaging disease, we image the fluorescence emitted from the surface of in vivo and ex vivo canine mammary gland tissues containing lesions with preferential uptake of ICG. Pathology confirms the ability to detect spontaneous mammary tumors and regional lymph nodes amidst normal mammary tissue and fat as deep as 1.5 cm from the tissue surface.

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BACKGROUND: Although the eradication of Helicobacter pylori is of primary importance when initiating treatment, it is also important to have a strategy for patients who are H pylori-negative, fail to demonstrate eradication or have a tendency to become re-infected or relapse. PATIENTS AND METHODS: In a double-blind, parallel-group clinical trial of 928 patients (from 70 centres in 16 countries) with duodenal ulcers who after a short term study had relief of symptoms and healed ulcers proved endoscopically, 308 were randomly assigned to receive omeprazole 10 mg in the morning, 308 to receive omeprazole 20 mg in the morning and 312 to receive ranitidine 150 mg at bedtime for up to 12 months. Symptoms were assessed every three months and endoscopy repeated at three, six and 12 months, or more often if indicated by recurrence of symptoms. The safety screening included basal serum gastrin concentrations and gastric mucosal histopathology. RESULTS: The remission rates up to 12 months were 87% for the omeprazole 20 mg group, 71% for the omeprazole 10 mg group and 63% for the ranitidine group. Omeprazole 20 mg differed significantly from both omeprazole 10 mg (P=0.0001, 95% CI 9 to 23) and ranitidine (P=0.0001, 95% CI 17 to 31). There was no statistically significant difference between omeprazole 10 mg and ranitidine over the 12-month period, but the 95% confidence interval allowed differences between 0% and 16% in favour of omeprazole at 12 months. A Cox regression analysis revealed that longer treatment courses to heal, smoking, a long ulcer history and young age negatively contributed to the odds of staying in remission. The treatments were well tolerated. There was a slight increase in basal serum gastrin concentrations, reflecting the different degrees of acid inhibition induced by the three treatments. No dysplastic or neoplastic lesions were found in any biopsies. CONCLUSIONS: More duodenal ulcer patients are maintained in remission with omeprazole 20 mg daily than with omeprazole 10 mg daily or with ranitidine 150 mg at bedtime.

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Symptomatic gastroesophageal reflux is a common complication of pregnancy and lactation. However, the safety of many effective medical therapies, including oral proton pump inhibitors, has not been well defined. The administration of oral omeprazole to a 41-year-old female during the third trimester of pregnancy, after ranitidine and cisapride failed to control her refractory gastroesophageal reflux, is reported. No adverse fetal effects were apparent, and the patient elected to continue omeprazole therapy (20 mg/day) while breastfeeding. Peak omeprazole concentrations in breast milk (58 nM, 3 h after ingestion) were less than 7% of the peak serum concentration (950 nM at 4 h), indicating minimal secretion. Although omeprazole is a potentially useful therapy for refractory gastroesophageal reflux during pregnancy and lactation, further data are needed to define better its safety and efficacy.

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Cigarette smoking causes the development of chronic bronchitis and chronic obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke might initiate release of inflammatory mediators by bronchial epithelial cells. To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release from cultured human bronchial epithelial cells was examined. CSE augmented IL-8 release from bronchial epithelial cells in a concentration- and time-dependent manner. Most of the augmenting activity of CSE on IL-8 release from bronchial epithelial cells was lost after volatilization or lyophilization treatment. Two major volatile factors in cigarette smoke, acrolein and acetaldehyde, augmented IL-8 release. Four cell strains were tested and showed increased IL-8 release in response to CSE. In addition, bronchoalveolar lavage was performed on 11 nonsmokers and 12 smokers. IL-8 concentration was greater in the proximal, bronchial samples than in distal, alveolar samples, and IL-8 in BAL from smokers was higher than in BAL from nonsmokers. There was a significant correlation between IL-8 concentration and neutrophil count in bronchial samples of BAL fluid. These data support the hypothesis that exposure to cigarette smoke may induce bronchial epithelial cells to release IL-8 and that this may contribute to airway inflammation in smokers.

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This study tested the effectiveness of the AutoSet self-titrating nasal continuous positive airway pressure (nCPAP) system in treating obstructive sleep apnea (OSA), and choosing a suitable pressure for subsequent conventional fixed-pressure nCPAP therapy. Twenty-one adult men with untreated OSA were studied with full polysomnography on each of four nights: diagnostic, manual and AutoSet nCPAP titration (in random order), and conventional fixed-pressure nCPAP at the pressure recommended by the AutoSet titration. Titration was satisfactorily performed in 20 of 21 subjects. Severe mask leak prevented automated titration in one subject and caused transient unnecessary increases in pressure in three subjects. In the 20 subjects, respiratory disturbance index (RDI) was 60.3 +/- 5.7 events/h (mean +/- SEM) on the diagnostic night. RDI was lower with manual titration (10.1 +/- 3.0, p < 0.001), and lower still with Autoset (2.8 +/- 0.9, p < 0.01) and fixed pressure (2.5 +/- 0.7, p = ns versus AutoSet) nCPAP. There were similar changes in the arousal index, which was 52.7 +/- 4.6 events/h on the diagnostic night, 14.2 +/- 2.4 with manual titration and 8.9 +/- 0.9 with AutoSet titration, and 9.5 +/- 1.0 on the night of conventional fixed-pressure CPAP (p < 0.001 versus diagnostic). We conclude that the AutoSet system is suitable for automated nCPAP pressure titration.

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Congenital cystic adenomatoid malformation is an uncommon cause of respiratory distress in infants and is a rare entity in adults. Presentation in older patients is that of recurrent pulmonary infections. Usually a single lobe is involved. This report describes congenital cystic adenomatoid malformation involving the entire right lung in a 22-year-old woman presenting with gastrointestinal bleeding due to cavernous transformation of the portal and splenic veins.

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The presence of asbestos bodies (ABs) in sputum specimens of individuals with occupational asbestos exposure has been well-documented. The aim of this study was to determine their clinical relevance in comparison to the concentration of AB in bronchoalveolar lavage (BAL) and lung tissue. Subjects were included following a well-documented exposure of asbestos history (n = 93) or BAL fluid analysis positive for ABs (n = 42). The subjects with a well documented history of AB exposure were divided into three groups: heavy (Group 1, n = 29); moderate (Group 2, n = 31); or occasional exposure (Group 3, n = 33). BAL fluid was available from all subjects, and lung tissue from 21 subjects. To assess the variability, 10 sputum positive subjects collected subsequent sputum on days 2, 7, 14, 30 and 90. ABs were determined by light microscopy after membrane filtration of specimen digests. The mean sputum AB content was highest in Group 1 (2.4 +/- 5.5 AB.mL-1), lower in Group 2 (0.2 +/- 0.3 AB.mL-1) and lowest in Group 3 (0.1 +/- 0.1 AB.mL-1) suggesting a correlation with cumulative exposure. However, many negative sputum samples were noted, when BAL specimens were positive. The AB content of sputum and BAL specimens did not correlate. ABs were found in sputum of all subjects with a tissue content of > 1,000 AB-cm-3, but in none with contents of < 1,000 AB-cm-3. Substantial variability of ABs was found in the five sequentially collected sputa of 10 initially positive patients (coefficient of variation 28-93%), but only two false negatives were found in these 50 samples. Thus, sputum analysis for asbestos bodies is an insensitive method for assessing the lung asbestos burden, much less sensitive than bronchoalveolar lavage fluid analysis. However, a sputum sample positive for asbestos bodies is suggestive of a high lung asbestos burden.

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The method of preparation of bronchoalveolar lavage fluid (BALF) for cytological examination can significantly affect the results of cellular quantitation. Investigations have shown that cytocentrifugation leads to an underestimation of the number of lymphocytes and membrane filter preparation to an underestimation of the number of neutrophils. As a simple alternative to these two techniques, BALF cells could be prepared by the microscope slide smear technique, which is familiar as the means for preparing peripheral blood for differential counts. In order to compare cell differentials determined by microscope slide technique with differentials resulting from cytocentrifugation, cells were isolated from 35 BALF samples using standard methods, and counted using a haematocytometer. Forty thousand cells in 200 microL were prepared by cytocentrifugation (3 min, 57 x g; Cytospin 2) and 5 x 10(5) cells in 5 microL by microscope slide smear. Both samples were air-dried, stained using May-Grünwald Giemsa stain, and 600 cells were counted to obtain differentials. To test the adequacy of sampling by the microscope slide smear technique, known quantities of lymphocytes or neutrophils were added to fixed numbers of BALF cells, microscope slide smears prepared, and differentials determined on 600 cells. The resulting differentials were compared to the calculated differentials. Preparation of BALF cells with the microscope slide smear technique yielded well-preserved cell morphology. Compared to cytocentrifugation, microscope slide smear preparations had significantly higher percentages of lymphocytes. The microscope slide smears for the samples with predetermined numbers of cells yielded lymphocyte and neutrophil percentages which did not differ from the calculated differentials (59.6 +/- 1.5 vs 59.6 +/- 5.2% and 54.6 +/- 6.0 vs 53.1 +/- 6.0%, respectively). Varying the number of cells counted from 100 to 800 confirmed the reproducibility of the counts for counting 600 cells. Using 5 x 10(5), 2.5 x 10(5), or 1 x 10(5) cells per preparation demonstrated that adequate specimens could be obtained from as few as 1 x 10(5) cells. Thus, microscope slide smear preparation is a simple and accurate method for the quantitation of bronchoalveolar lavage fluid cytology.

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The mature pulmonary epithelium forms a continuous lining to the airspace. Recent data suggest that this specialized epithelium may also contribute to host defence via interactions with inflammatory cells. Pulmonary epithelial cells can serve as part of the local immune system, providing structures and functions crucial for the maintenance of normal pulmonary function. This article will briefly review the morphology and development of the pulmonary epithelial cells, their function with regard to host defence, alterations of the pulmonary epithelium associated with airway diseases, and potential therapeutic implications for the treatment of respiratory diseases.

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Cigarette smoking is the foremost cause of death in the United States and is a major health problem worldwide. Clearly, the best way to eliminate the risk of smoking-related diseases, is to quit smoking. Smoking cessation has immediate and long-term benefits and substantially reduces the risk of many smoking-related diseases. Unfortunately, quitting smoking is rarely easy. For those smokers who cannot or do not wish to quit, reduction in their total smoking may represent a potential health benefit. Reduction in total smoking can, theoretically, be achieved by: 1) reducing the number of cigarettes smoked daily; and/or 2) switching to a low tar/low nicotine cigarette. Smokers, however, tend to self-adjust nicotine to maintain relatively constant levels. Reduction in tar/nicotine content or number of cigarettes, therefore, may not produce health benefits. Smoking reduction with alternative nicotine delivery, however, may represent an alternative option for smokers who cannot, or do not, wish to quit.

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Chronic obstructive pulmonary disease (COPD) and asthma are chronic inflammatory diseases which cause considerable morbidity and mortality. A number of in vivo methods have been developed to assess airway inflammation both to study mechanistic factors leading to airway inflammation as well as to assess disease activity. These have included non-invasive tests such as pulmonary function testing, bronchial provacation testing and nuclear medicine scans. Bronchoalveolar lavage and bronchoscopic derived biopsies of the airways have provided information regarding cell populations and inflammatory mediators involved in the pathogenesis of chronic airway and lung inflammation. Induced sputum may become a less invasive means to sample the lower respiratory tract in patients with these disorders.

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Bronchoalveolar lavage (BAL) provides a simple method of sampling inhaled particles deposited in the lower respiratory tract. We hypothesized that BAL could be used to measure the quantity and quality of lung asbestos burden. This would be true if BAL fluid asbestos fiber content reflected the total content as well as the size distribution of both uncoated and coated asbestos fibers in lung parenchyma. Therefore, we analyzed the asbestos fiber counts of 23 individual sample pairs in both BAL fluid and lung tissue samples obtained from 20 patients with occupational asbestos exposure using transmission electron microscopy (TEM). In addition, fiber type, fiber size, and aspect ratio were compared. Coated asbestos fibers were found in 10 of 23 BAL samples and 16 of 23 biopsies. The mean concentrations of coated asbestos fibers (i.e., asbestos bodies) in BAL and lung parenchyma showed a positive correlation (r = 0.75, p < 0.001). Likewise, the mean amphibole fiber concentrations correlated positively (r = 0.55, p < 0.01). However, there was no relationship between the mean chrysotile fiber counts in BAL and lung parenchyma (r = 0.18, p = 0.40). Asbestos fibers in lung tissue were significantly longer (8.2 +/- 0.5 versus 4.8 +/- 0.6 microns; p < 0.001) but had the same width (0.12 +/- 0.27 versus 0.11 +/- 0.15 microns; p = 0.24) when compared with those retrieved by BAL from the airspace compartment. The aspect ratio (dividing fiber length by width) was much higher in lung tissue than in BAL fluid (66.4 +/- 0.4 versus 42.9 +/- 0.5; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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PURPOSE: A prospective study to determine the usefulness of quantitative bacterial cultures of fluid obtained via fiberoptic bronchoscopy and bronchoalveolar lavage as an aid in the diagnosis of bacterial pneumonia. PATIENTS AND METHODS: All patients undergoing fiberoptic bronchoscopy with bronchoalveolar lavage during a 6 1/2-month period. Presence of pneumonia was determined using clinical, radiographic, laboratory, and histologic data. Quantitative bacterial cultures of bronchoalveolar lavage fluid were determined using a 1-microL culture loop. RESULTS: Quantitative bacterial cultures of bronchoalveolar lavage (BAL) fluid were sensitive and specific predictors of bacterial pneumonia. Using 10(3) colony-forming units (cfu)/mL as the threshold value for a positive culture, we determined the sensitivity and specificity to be 90% and 97%, respectively. The data were also analyzed for the subgroups of patients who were intubated or were receiving antibiotics. The sensitivity and specificity were 78% and 96% for the group of patients receiving antibiotics and 100% and 82% for the group of patients intubated for more than 24 hours at the time of BAL. Values for the area under the receiver operating characteristic curve for the 3 groups were 0.94, 0.88, and 0.96, respectively. CONCLUSIONS: Quantitative bacterial cultures of BAL fluid are sensitive and specific in the diagnosis of bacterial pneumonia. The use of antibiotics at the time of BAL reduces the sensitivity of the test, and prolonged intubation reduces the specificity of the test.

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