Solvent system effects on the physical and mechanical properties of electrospun Poly(ε-caprolactone) scaffolds for in vitro lung models.

Mechanical properties are among the key considerations for the design and fabrication of complex tissue models and implants. In addition to the choice of material and the processing technique, the solvent system can significantly influence the mechanical properties of scaffolds. Poly(ε-caprolactone) (PCL) has been abundantly used to develop constructs, fibrous in particular, for pharmaceutical and biomedical research due to the flexibility offered by PCL-based fibrous matrices. The effect of solvent type on the morphological features of electrospun fibres has been extensively studied. Nevertheless, comprehensive studies on the impact of the solvent system on the mechanical properties of electrospun PCL fibres are lacking. This study elucidates the relationship between topographical, physical and mechanical properties of electrospun PCL fibrous meshes upon using various solvent systems. The results of the mechanical investigation highlight the significance of inter-fibre bonds on the mechanical properties of the bulk membranes and that the option of altering the solvent system composition could be considered for tuning the mechanical properties of the PCL scaffolds to serve specific biomedical application requirements. The applicability of the developed membranes as artificial ECM (Extracellular matrix) in the lung will then be investigated and compared to the commercial Polycarbonate (PC) membranes that are often used for in vitro lung models.

Mechanical properties and in vitro characterization of polyvinyl alcohol-nano-silver hydrogel wound dressings.

Polyvinyl alcohol (PVA) hydrogels are materials for potential use in burn healing. Silver nanoparticles can be synthesized within PVA hydrogels giving antimicrobial hydrogels. Hydrogels have to be swollen prior to their application, and the common medium available for that in hospitals is saline solution, but the hydrogel could also take up some of the wound's fluid. This work developed gamma-irradiated PVA/nano-Ag hydrogels for potential use in burn dressing applications. Silver nitrate (AgNO3) was used as nano-Ag precursor agent. Saline solution, phosphate-buffered solution (PBS) pH 7.4 and solution pH 4.0 were used as swelling media. Microstructural evaluation revealed an effect of the nanoparticles on PVA crystallization. The swelling of the PVA-Ag samples in solution pH 4.0 was low, as was their silver delivery, compared with the equivalent samples swollen in the other media. The highest swelling and silver delivery were related to samples prepared with 0.50% AgNO3, and they also presented lower strength in PBS pH 7.4 and solution pH 4.0. Both PVA-Ag samples were also non-toxic and presented antimicrobial activity, confirming that 0.25% AgNO3 concentration is sufficient to establish an antimicrobial effect. Both PVA-Ag samples presented suitable mechanical and swelling properties in all media, representative of potential burn site conditions.

Ablation of chronic total occlusions using kilohertz-frequency mechanical vibrations in minimally invasive angioplasty procedures.

Certain minimally invasive cardiology procedures, such as balloon angioplasty and stent implantation, critically require that the site of an arterial blockage be crossed by an intraluminal guidewire. Plaques resulting in near or totally occluded arteries are known as chronic total occlusions, and crossing them with conventional guidewires is a significant challenge. Among the most promising proposed solutions is the delivery of high-power, low-frequency ultrasonic vibrations to the occlusion site via an intraluminal wire waveguide. The vibrating distal tip of the ultrasound wire waveguide is used to transmit energy to the surrounding plaques, tissues, and fluids to ablate or weaken atherosclerotic plaque. Potential mechanisms of interaction with the plaque and adjacent fluids identified in the literature include: (i) direct contact with the waveguide distal tip, (ii) subcavitational acoustic fluid pressure fluctuations, (iii) cavitation, and (iv) acoustic streaming. We summarize developments in this area over more than two decades, describing experimental methods for device performance characterization, preclinical tests, early clinical investigations, and, later, full clinical trials. The article also reviews theoretical foundations and numerical models suitable for device design and analysis. Finally, important issues for future research and for the development of this technology will be considered.

Cell encapsulation within PVA-based hydrogels via freeze-thawing: a one-step scaffold formation and cell storage technique.

Cryogelation is a physical hydrogel formation method for certain polymers, notably polyvinyl alcohol (PVA). The hypothesis of this study is that a PVA-based solution with the necessary intracellular cryoprotectant and nutrient supply can be used, first for storage of vascular smooth muscle cells, and subsequently to form a suitable tissue-engineering scaffold during the thawing process. Bovine arterial smooth muscle cells were encapsulated within PVA-gelatin hydrogels over a wide range of serum, DMSO and cell culture medium concentrations. Several parameters expected to affect gelation and cell viability (PVA viscosity, DMSO concentration, serum presence) were assessed with experimental designs and the optimal conditions for cell survival were determined. Cell viability can be improved by increasing concentration of DMSO and serum without compromising the gelation process. An additional crosslinking step using a coagulation bath was beneficial for hydrogel stability but caused peripheral accumulation of cells. In conclusion, a freeze-thaw process can be utilized to prepare and store cell-laden hydrogels with adjustable mechanical properties.

Physically crosslinked composite hydrogels of PVA with natural macromolecules: structure, mechanical properties, and endothelial cell compatibility.

Polyvinyl alcohol (PVA) hydrogels have been considered potentially suitable for applications as engineered blood vessels because of their structure and mechanical properties. However, PVA's hydrophilicity hinders its capacity to act as a substrate for cell attachment. As a remedy, PVA was blended with chitosan, gelatin, or starch, and hydrogels were formed by subjecting the solutions to freeze-thaw cycles followed by coagulation bath immersion. The structure-property relationships for these hydrogels were examined by measurement of their swelling, rehydration, degradation, and mechanical properties. For the case of pure PVA hydrogels, the equilibrium swelling ratio was used to predict the effect of freeze thaw cycles and coagulation bath on average molecular weights between crosslinks and on mesh size. For all hydrogels, trends for the reswelling ratio, which is indicative of the crosslinked polymer fraction, were consistent with relative tensile properties. The coagulation bath treatment increased the degradation resistance of the hydrogels significantly. The suitability of each hydrogel for cell attachment and proliferation was examined by protein adsorption and bovine vascular endothelial cell culture experiments. Protein adsorption and cell proliferation was highest on the PVA/gelatin hydrogels. This study demonstrates that the potential of PVA hydrogels for artificial blood vessel applications can be improved by the addition of natural polymers, and that freeze-thawing and coagulation bath treatment can be utilized for fine adjustment of the physical characteristics.

Effect of curing characteristics on residual stress generation in polymethyl methacrylate bone cements.

Residual stresses resulting from the shrinkage of polymethyl methacrylate (PMMA) bone cement have been implicated in the formation of cracks in cement mantles following total hip arthroplasty. This study investigates whether two such cements, with differentiated solidification characteristics (i.e. working and setting times), display significant differences in their residual stress characteristics in an experiment designed to replicate the physical conditions of total hip arthroplasty. Experiments were performed using a representative femoral construct to measure and compare the temperatures and residual strains developed for standard PMMA cement mantles (CMW 1 Gentamicin) and slow curing cement mantles (SmartSet HV Gentamicin) during and following polymerization. These experimental results revealed no statistically significant difference (t-test, p > 0.05) for peak exotherm temperature and residual strain levels between the cements (measured after 3 h). The tailored polymerization characteristics of the slow-curing cement do not significantly affect residual stress generation, compared with the standard cement. It is often considered that residual stresses significantly relax following polymerization and before biomechanical loads are first applied during rehabilitation (up to 3 days later). This was examined for durations of 18 h to 3 days. Axial strains in the model femur and stem reduced by averages of 5.5 and 7.9 per cent respectively, while hoop strains in the stem exhibited larger reductions. An axisymmetric transient thermoelastic finite element model of the experiment was developed, allowing residual stresses to be predicted based on differential scanning calorimetry (DSC) measurements of the heat released throughout the exothermic curing reaction. The model predictions closely replicated the experimental measurements of both temperature and residual strain at 3 h, suggesting that residual strains can be fully accounted for by the thermal contraction mechanism associated with cooling after solidification.

Vascular cell viability on polyvinyl alcohol hydrogels modified with water-soluble and -insoluble chitosan.

Polyvinyl alcohol (PVA) hydrogels blended with chitosan or other biological macromolecules have shown promise for cell culture and tissue engineering. This study investigates the attachment and growth of bovine aortic endothelial (BAEC) and smooth muscle cells (BASMC) on the PVA hydrogels modified with water soluble and water insoluble chitosan. Cell adhesion on the surface of the membranes was examined by phase contrast microscopy while cell morphologies were studied using immunocytochemistry staining with EC and SMC specific biomarkers (F-actin and alpha actin respectively). Cells cultured on 6% PVA, 0.4% chitosan (water soluble and insoluble) hydrogel membranes displayed excellent adhesion and spreading characteristics, in addition to negligible cell structural morphological changes in comparison to a polystyrene control. Similar vascular cell adhesion features were apparent on PVA membranes blended with water-soluble and -insoluble chitosan. Fluorescent activated cell sorter (FACS) analysis was used to determine BAEC and BASMC proliferation and cell viability. Apoptotic levels in BAEC after 7 days were 12.8% +/- 2.5% on the PVA- chitosan WS-1 membrane and 10.1% +/- 1.5% on the control well (n = 3) while comparable results were also noted for BASMC. Equivalent proliferative activity was apparent for BAEC on the control and PVA-chitosan membrane after 7 days, while BASMC showed increased proliferative activity on the membranes. These results indicate that the PVA-chitosan blended hydrogel membranes show promise for cell culture and tissue engineering applications.

Mechanisms of colchicine effect in the treatment of asbestosis and idiopathic pulmonary fibrosis.

The objective of this study was to evaluate the mechanisms of colchicine action in pulmonary fibrosis. The study included 10 patients with pulmonary fibrosis (idiopathic pulmonary fibrosis 5, asbestosis 4, and scleroderma 1) who had been admitted to Bellevue Hospital Center, a tertiary care public hospital in New York City. We administered colchicine 0.6 mg orally for 12 weeks to patients with pulmonary fibrosis. Symptoms, high resolution CT scans, pulmonary function tests, and bronchoalveolar lavage parameters were compared prior to and after treatment. Results showed declines in dyspnea index, selective improvement in several CT scans, but no statistically significant change in BAL cells, cytokines, fibronectin, or hydroxyproline. However, there was a decline in hydroxyproline in the BAL fluid in 8/10 patients. We concluded that colchicine has a mild antifibrotic effect which may be in inhibiting collagen formation since there was no effect on the inflammation that accompanies fibrosis.

Respiratory symptoms at age 8 years in a cohort of very low birth weight children.

The childhood respiratory consequences of very low birth weight (birth weight < or =1,500 g) are incompletely understood, especially since the introduction of recent changes in neonatal care. To assess prevalence, trends, and risk factors for respiratory symptoms, the authors followed to age 8 years a cohort of 384 very low birth weight children from six regional neonatal intensive care units in Wisconsin and Iowa who were born between August 1, 1988, and June 30, 1991. A control group of 154 Wisconsin schoolchildren was also assembled. Respiratory symptoms in the past 12 months and history of asthma ("asthma ever") were reported by parents on a questionnaire used in the International Study of Asthma and Allergies in Childhood (ISAAC). Control group prevalence resembled ISAAC prevalence worldwide and in Canada, but respiratory symptoms were twice as common among very low birth weight children. With advent of the availability of pulmonary surfactants, the prevalence of wheezing at age 8 decreased from 50% to 16% (p = 0.002) among children with bronchopulmonary dysplasia, but it increased from 14% to 38% among those with milder neonatal respiratory disease. Bronchopulmonary dysplasia, family history of asthma, smoking in the household, and patent ductus arteriosus were predictive of wheezing in the previous 12 months. Antenatal steroid therapy had a borderline-significant protective association with wheezing (odds ratio = 0.56, 95% confidence interval: 0.29, 1.1). There were interaction effects between several of the predictors.

Early lung cancer action project: initial findings on repeat screenings.

BACKGROUND: The Early Lung Cancer Action Project (ELCAP) was designed to evaluate the usefulness of annual computed tomography (CT) screening for lung carcinoma. With the baseline results having been reported previously, the focus of the current study was on the early results of the repeat screenings. METHODS: A cohort of 1000 high-risk individuals was recruited for baseline and annual repeat CT screening. At last follow-up, a total of 1184 annual repeat screenings had been performed. A positive result from the screening test was defined as newly detected, one to six noncalcified pulmonary nodules with interim growth. The diagnostic workup of the individuals was guided by recommendations supplied by the ELCAP investigators to the collaborating clinicians. RESULTS: Of the 1184 repeat CT screenings, the test result was positive in 30 (2.5%). In 2 of these 30 cases, the individual died (of an unrelated cause) before diagnostic workup and the nodule(s) resolved in another 12 individuals. In the remaining 16 individuals, the absence of further growth was documented by repeat CT in 8 individuals and further growth was documented in the remaining 8 individuals. All eight individuals with further nodular growth underwent biopsy and malignancy was diagnosed in seven. Six of these seven malignancies were nonsmall cell carcinomas (five of which were Stage IA and one of which was Stage IIIA) and the one small cell carcinoma was found to be of limited stage. The median size dimension of these malignancies was 8 mm. In another two subjects, symptoms prompted the interim diagnosis of lung carcinoma. Neither of these malignancies was nodule-associated but rather were endobronchial; one was a Stage IIB nonsmall cell carcinoma and the other was a small cell carcinoma of limited stage. CONCLUSIONS: False-positive screening test results are uncommon and usually manageable without biopsy; compared with no screening, such screenings permit diagnosis at substantially earlier and thus more curable stages. Annual repetition of CT screening is sufficient to minimize symptom-prompted interim diagnoses of nodule-associated malignancies.

Early lung cancer action project: a summary of the findings on baseline screening.

PURPOSE: The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low radiation dose computed tomography (low-dose CT) in persons at high-risk for lung cancer. METHODS: Since starting in 1993, the ELCAP has enrolled 1,000 asymptomatic persons, 60 years of age or older, with at least 10 pack-years (1 pack per day for 10 years, or 2 packs per day for 5 years) of cigarette smoking, no prior cancer, and medically fit to undergo thoracic surgery. After a structured interview and informed consent, baseline chest radiographs and low-dose CT were obtained on each subject. The diagnostic work-up of screen-detected noncalcified pulmonary nodules (NCN) was guided by ELCAP recommendations which included short-term high-resolution CT follow-up for the smallest nodules. Baseline RESULTS: On low-dose CT at baseline compared to chest radiography, NCN were detected three times as commonly (23% versus 7%), malignancies four times as commonly (2.7% versus 0.7%), and stage I malignancies six times as commonly (2.3% versus 0.4%). Of the 27 CT-detected cancers, 96% (26/27) were resectable; 85% (23/27) were stage I, and 83% (19 of the 23 stage I) were not seen on chest radiography. Following the ELCAP recommendations, biopsies were performed on 28 of the 233 subjects with NCN; 27 had a malignant and one a benign NCN. Another three individuals underwent biopsy outside of the ELCAP recommendations; all had benign NCNS: No one had thoracotomy for a benign nodule. CONCLUSION: Baseline CT screening for lung cancer provides for detecting the disease at earlier and presumably more commonly curable stages in a cost-effective manner.

The normal CT appearances of the second carina and bronchial stump after left upper lobectomy.

We retrospectively evaluated the computed tomography (CT) appearance of the bronchial stump and second carina (left upper lobe spur) after left upper lobectomy. There were 69 CT examinations in 38 patients; all were free of recurrent or metastatic disease. The spur was graded as a) sharp (wedge-shaped tip configuration with <90 degrees angulation), b) lobulated (bulbous tip with <90 degrees angulation), or c) widened (>90 degrees angulation regardless of tip configuration). The bronchial stump was evaluated for the presence or absence of soft tissue in proximity to the surgical staples. The spur had a sharp appearance in 33 of 38 patients (87%) and was lobulated in 5 of 38 (13%). No patient had soft tissue at the bronchial stump. Serial examinations showed no change in the appearance of either structure. The spur remains sharp after left upper lobectomy in most patients; lobulation occurs in 13%. No changes occur over time. Interval change, widening of the spur, or soft tissue at the bronchial stump may suggest abnormality. Knowledge of normal and potentially abnormal appearances is essential to proper CT interpretation, particularly in the setting of postoperative surveillance for recurrent or metastatic disease.

Early Lung Cancer Action Project: overall design and findings from baseline screening.

BACKGROUND: The Early Lung Cancer Action Project (ELCAP) is designed to evaluate baseline and annual repeat screening by low-radiation-dose computed tomography (low-dose CT) in people at high risk of lung cancer. We report the baseline experience. METHODS: ELCAP has enrolled 1000 symptom-free volunteers, aged 60 years or older, with at least 10 pack-years of cigarette smoking and no previous cancer, who were medically fit to undergo thoracic surgery. After a structured interview and informed consent, chest radiographs and low-dose CT were done for each participant. The diagnostic investigation of screen-detected non-calcified pulmonary nodules was guided by ELCAP recommendations, which included short-term high-resolution CT follow-up for the smallest non-calcified nodules. FINDINGS: Non-calcified nodules were detected in 233 (23% [95% CI 21-26]) participants by low-dose CT at baseline, compared with 68 (7% [5-9]) by chest radiography. Malignant disease was detected in 27 (2.7% [1.8-3.8]) by CT and seven (0.7% [0.3-1.3]) by chest radiography, and stage I malignant disease in 23 (2.3% [1.5-3.3]) and four (0.4% [0.1-0.9]), respectively. Of the 27 CT-detected cancers, 26 were resectable. Biopsies were done on 28 of the 233 participants with non-calcified nodules; 27 had malignant non-calcified nodules and one had a benign nodule. Another three individuals underwent biopsy against the ELCAP recommendations; all had benign non-calcified nodules. No participant had thoracotomy for a benign nodule. INTERPRETATION: Low-dose CT can greatly improve the likelihood of detection of small non-calcified nodules, and thus of lung cancer at an earlier and potentially more curable stage. Although false-positive CT results are common, they can be managed with little use of invasive diagnostic procedures.

Multinodular disease: anatomic localization at thin-section CT--multireader evaluation of a simple algorithm.

PURPOSE: To evaluate the interobserver variability and accuracy of an algorithm for anatomic localization of small nodules evident on thin-section computed tomographic (CT) images of the lungs. MATERIALS AND METHODS: Four experienced chest radiologists independently evaluated thin-section CT images in 58 patients by using an algorithm and a standard score sheet. Nodules were placed into four possible anatomic locations or categories: perilymphatic, random, associated with small airways disease, or centrilobular. Algorithm accuracy was assessed by comparing the localization by the observers to that expected for each specific disease in the study group on the basis of reports in the literature. Interobserver variability was assessed by placing cases into one of three groups: (a) complete concordance, (b) triple concordance, and (c) discordant. RESULTS: All observers agreed in 79% (46 of 58) of the cases with regard to nodule localization; three of the four concurred in an additional 17% (10 of 58). The observers were correct in 218 (94%) of 232 localizations in the 58 cases. There were no apparent differences in the number of either discordant or incorrect localizations between the observers. The most noteworthy source of error and of disagreement between observers was the confusion of perilymphatic and small airways disease-associated nodules in a small number of cases. CONCLUSION: The proposed algorithm is reproducible and accurate in the majority of cases and facilitates nodule localization at thin-section CT.

Viral and Pneumocystis carinii infections of the lung in the immunocompromised host.

Viruses and Pneumocystis carinii are significant causes of pneumonia in immunocompromised patients, particularly patients with impaired cell-mediated immunity. They are often simultaneously considered in the differential diagnosis of diffuse pneumonitis in these patients and, because radiographic appearances and the periods of vulnerability to these infections may overlap, may be difficult to differentiate. This article will correlate radiographic findings to evolving histopathologic changes in select specific infections, as they affect three different immune impaired populations: (a) acquired immunodeficiency syndrome, (b) immunosuppression secondary to therapy for underlying malignancy or with solid organ transplantation, and (c) immune impairment in the bone marrow transplant patient. Appreciation of the specific clinical setting in which to consider these infections will be emphasized.

Primary multifocal tuberculous osteomyelitis with involvement of the ribs.

Two cases of primary multifocal tuberculous osteomyelitis with involvement of the rib cage are presented. The lungs were normal and the appearance of the skeletal lesions did not suggest tuberculosis. These lesions were predominantly lytic, with minimal soft tissue involvement. Tuberculosis should be high in the differential diagnosis of multiple destructive bone lesions, especially in patients from regions where tuberculosis is endemic.

Pulmonary nodule detection: low-dose versus conventional CT.

PURPOSE: To quantitate the effectiveness of low-dose computed tomography (CT) in the identification of pulmonary nodules while controlling for anatomic nodule characteristics and to establish what factors lead to reduced diagnostic sensitivity at low-dose CT. MATERIALS AND METHODS: Each of six participating radiologist independently rated 200 image panels by using a four-point confidence scale. Conventional images were obtained at 200 mAs; low-dose images were obtained at 20 mAs. To fully control their characteristics, nodules were simulated with a given diameter, shape, and section thickness while preserving the resolution, noise level, and reconstruction artifacts of the original images. Panels were matched so that nodules on low-dose and conventional images had equivalent sizes, locations, and relationships to blood vessels. RESULTS: Among 864 positive panels, 259 (60%) of 432 low-dose panels and 272 (63%) of 432 conventional panels were correctly interpreted (P = .259). Lowering the x-ray dose significantly reduced the detectability of peripheral nodules (P = .019) and nodules separated from blood vessels (P = .044). Surprisingly, 3-mm nodules were detected with approximately equal sensitivity (P = .181) at conventional and low-dose CT. The specificity of low-dose images was 88% (148 of 168 panels) versus 91% (153 of 168 panels) for conventional images (P = .372). CONCLUSION: Low-dose CT is acceptable for pulmonary nodule identification, making it suitable for primary screening. These results confirm the strong effect of size, location, and angiocentricity on the sensitivity of nodule detection with conventional CT.

Epstein-Barr-virus-associated lymphoproliferative disease of the lung: CT and histologic findings.

PURPOSE: To assess the computed tomographic (CT) and histologic findings of intrathoracic lymphoproliferative disease (LPD) associated with the Epstein-Barr virus (EBV). MATERIALS AND METHODS: The authors retrospectively reviewed the CT scans of the chest and the pathologic specimens obtained in 24 patients with histologically proved intrathoracic LPD and with positive serologic findings or immunohistochemical staining for EBV. Five patients had acquired immunodeficiency syndrome (AIDS); one had common variable immune deficiency; and 18 were receiving immunosuppressive therapy for heart, lung, or heart-lung (n =15) or bone marrow (n = 2) transplantation and vasculitis (n = 1). RESULTS: Final diagnoses included malignant lymphoma (n = 15), polyclonal LPD (n = 8), and hyperplasia of bronchus-associated lymphoid tissue (n = 1). CT findings included multiple nodules (n = 21), lymphadenopathy (n = 9), areas of groundglass opacification (n = 8), septal thickening (n = 7), consolidation (n = 5), pleural effusion (n = 4), and solitary endobronchial lesion (n = 2). The nodules were 2-4 cm in diameter, involved mainly the middle and lower lung zones, and frequently had a predominantly peribronchovascular (n = 15) or subpleural (n = 14) distribution. CONCLUSION: EBV-associated LPD may range from benign lymphoid hyperplasia to high-grade lymphoma. The most common CT manifestation consists of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution.

Association of tocolytic therapy with antenatal steroid administration and infant outcomes. Newborn Lung Project.

The use of tocolytic agents to halt premature labor is controversial. We examine a database on very low-birth-weight infants born following the onset of premature labor (n = 540) for association between tocolytic and antenatal steroid therapy, and to assess neonatal and childhood outcomes following combined therapy. Data are from a multicenter regionally based study of all infants below 1501 g at seven neonatal intensive care units (NICUs) in Wisconsin and Iowa, born August 1, 1988 through June 30, 1991. Infant outcomes analyzed are death in the first 30 days, respiratory distress syndrome (RDS), and intraventricular hemorrhage (IVH). Fewer deliveries occurred within 12 hours of labor onset with tocolytics (61 vs. 75% without). A strong association between tocolytic therapy and antenatal steroid administration was found [adjusted odds ratio OR = 5.7, 95% confidence interval CI: (3.3, 10.0)]. Tocolytics were associated with lower mortality in the first 30 days [OR = 0.29, CI: (0.15, 0.56)]. Joint administration of tocolytics and antenatal steroids versus neither was associated with lower incidence of the combined outcome of respiratory distress syndrome (RDS) or death [OR = .30, CI: (0.15, 0.60)] and grade III-IV IVH or death [OR = 0.35, CI: (0.14, 0.98)]. Tocolytic therapy alone was not associated with IVH grade III-IV [OR = 1.0, CI: (0.57, 1.9)] among survivors.