A novel in-line high frequency interrupter for use with bubble CPAP: A feasibility study in a premature lamb model.

BACKGROUND: Recent in vitro testing of high frequency (HF) oscillation applied to bubble continuous positive airway pressure (BCPAP) using a novel flow interrupter device (HFI) demonstrated significantly improved CO2 washout while not altering delivered mean airway pressure (MAP) in a premature infant lung model. This study's aim was to evaluate the safety and efficacy of the HFI paired with BCPAP in an animal model of prematurity prior to clinical testing. DESIGN/METHODS: Twelve fetal lambs, 131-135 days gestation, weight 3.51±0.42 kg, were delivered by Cesarean section. The lambs were supported by mechanical ventilation and weaned to spontaneous breathing with BCPAP at 6 cmH2O. A combined CO2/airflow sensor measured end-tidal (EtCO2) and tidal volume (VT). Blood gases, heart rate (HR), arterial pressure (Part), minute ventilation (MV), MAP, ventilatory efficiency index (VEI), thoracoabdominal phase angle and labored breathing index (LBI) were recorded over a 10-minute baseline period followed by four randomized 10-minute intervals with HFI set to either 8, 10, 12 or 15 Hz. RESULTS: EtCO2 decreased from baseline by 11.1±2.2SE%, 16.6±4.3SE%, 13.5±4.9SE%, and 19.5±4.5SE% at 8, 10, 12, and 15 Hz respectively (p < 0.001). Blood gases, SpO2, HR, Part, MAP, VT, MV, esophageal pressure, phase angle, and LBI underwent no significant change with HF. Respiratory rate decreased, and VEI increased, by 14.9±4.5SD% (p = 0.037) and 83±22SD% (p < 0.011) respectively, averaged over all frequencies. CONCLUSIONS: We demonstrated the safety and efficacy of a novel BCPAP flow interrupter device. HF applied to the respiratory system resulted in significantly improved CO2 clearance and ventilation efficiency with no deleterious physiological effects in a pre-term lamb model.

Dexamethasone-induced intrauterine growth restriction modulates expression of placental vascular growth factors and fetal and placental growth.

Prenatal exposure to glucocorticoids (GC) is a central topic of interest in medicine since GCs are essential for the maturation of fetal organs and intrauterine growth. Synthetic glucocorticoids, which are used in obstetric practice, exert beneficial effects on the fetus, but have also been reported to lead to intrauterine growth retardation (IUGR). In this study, a model of growth restriction in mice was established through maternal administration of dexamethasone during late gestation. We hypothesised that GC overexposure may adversely affect placental angiogenesis and fetal and placental growth. Female BALB/c mice were randomly assigned to control or dexamethasone treatment, either left to give birth or euthanised on days 15, 16, 17 and 18 of gestation followed by collection of maternal and fetal tissue. The IUGR rate increased to 100% in the dexamethasone group (8 mg/kg body weight on gestational days 14 and 15) and pups had clinical features of symmetrical IUGR at birth. Dexamethasone administration significantly decreased maternal body weight gain and serum corticosterone levels. Moreover, prenatal dexamethasone treatment not only induced fetal growth retardation but also decreased placental weight. In IUGR placentas, VEGFA protein levels and mRNA expression of VEGF receptors were reduced and NOS activity was lower. Maternal dexamethasone administration also reduced placental expression of the GC receptor, αGR. We demonstrated that maternal dexamethasone administration causes fetal and placental growth restriction. Furthermore, we propose that the growth retardation induced by prenatal GC overexposure may be caused, at least partially, by an altered placental angiogenic profile.

Effects of xenon gas on human airway epithelial cells during hyperoxia and hypothermia.

BACKGROUND: Hypothermia with xenon gas has been used to reduce brain injury and disability rate after perinatal hypoxia-ischemia. We evaluated xenon gas therapy effects in an in vitro model with or without hypothermia on cultured human airway epithelial cells (Calu-3). METHODS: Calu-3 monolayers were grown at an air-liquid interface and exposed to one of the following conditions: 1) 21% FiO2 at 37°C (control); 2) 45% FiO2 and 50% xenon at 37°C; 3) 21% FiO2 and 50% xenon at 32°C; 4) 45% FiO2 and 50% xenon at 32°C for 24 hours. Transepithelial resistance (TER) measurements were performed and apical surface fluids were collected and assayed for total protein, IL-6, and IL-8. Three monolayers were used for immunofluorescence localization of zonula occludens-1 (ZO-1). The data were analyzed by one-way ANOVA. RESULTS: TER decreased at 24 hours in all treatment groups. Xenon with hyperoxia and hypothermia resulted in greatest decrease in TER compared with other groups. Immunofluorescence localization of ZO-1 (XY) showed reduced density of ZO-1 rings and incomplete ring-like staining in the 45% FiO2- 50% xenon group at 32°C compared with other groups. Secretion of total protein was not different among groups. Secretion of IL-6 in 21% FiO2 with xenon group at 32°C was less than that of the control group. The secretion of IL-8 in 45% FiO2 with xenon at 32°C was greater than that of other groups. CONCLUSION: Hyperoxia and hypothermia result in detrimental epithelial cell function and inflammation over 24-hour exposure. Xenon gas did not affect cell function or reduce inflammation.

Pulmonary mechanics measurements by respiratory inductive plethysmography and esophageal manometry: Methodology for infants on non-invasive respiratory support.

BACKGROUND: Infants are commonly supported with non-invasive ventilation (NIV) such as nasal CPAP and high flow nasal cannula (HFNC). These modes utilize a nasal/oral interface precluding use of a traditional airway flow sensor, such as a pneumotachometer (PNT), needed for pulmonary mechanics (PM) measurements. Respiratory Inductive Plethysmography (RIP), when properly calibrated, records tidal volume non-invasively from chest wall movements. Our aim was to integrate RIP into an existing neonatal pulmonary function testing system to measure PM in infants on NIV and to compare measurements of dynamic lung compliance (CL) and resistance (RL) using RIP with those obtained using a PNT. DESIGN/METHODS: RIP ribcage (RC) and abdominal (ABD) signals were recorded simultaneously with the flow signal from a PNT; transpulmonary pressure was estimated using an esophageal catheter. Two calibration algorithms were applied to obtain RC and ABD scaling factors. RESULTS: Forty PM measurements were performed on 25 infants (GA 31.5±2.9 weeks; birth weight 1598±510 g; median age 7 days). Correlation coefficients for RIP- vs. PNT-based PM were r2 = 0.987 for CL and r2 = 0.997 for RL. From Bland-Altman analysis, the mean bias (±95% CI) between RIP and PNT methods was -0.004±0.021 ml/cmH2O/kg for CL and 0.7±2.9 cmH2O/(L/sec) for RL. The upper, lower limits of agreement (±95% CI) were 0.128±0.037, -0.135±0.037 ml/cmH2O/kg for CL and 18.6±5.1, -17.2±5.1 cmH2O/(L/sec) for RL. CONCLUSION: Properly calibrated RIP may be a useful tool with sufficient diagnostic accuracy for PM measurements without need for a nasal/oral airflow sensor in infants receiving NIV.

Variability in the primary emissions and secondary gas and particle formation from vehicles using bioethanol mixtures.

Bioethanol for use in vehicles is becoming a substantial part of global energy infrastructure because it is renewable and some emissions are reduced. Carbon monoxide (CO) emissions and total hydrocarbons (THC) are reduced, but there is still controversy regarding emissions of nitrogen oxides (NOx), aldehydes, and ethanol; this may be a concern because all these compounds are precursors of ozone and secondary organic aerosol (SOA). The amount of emissions depends on the ethanol content, but it also may depend on the engine quality and ethanol origin. Thus, a photochemical chamber was used to study secondary gas and aerosol formation from two flex-fueled vehicles using different ethanol blends in gasoline. One vehicle and the fuel used were made in the United States, and the others were made in Brazil. Primary emissions of THC, CO, carbon dioxide (CO2), and nonmethane hydrocarbons (NMHC) from both vehicles decreased as the amount of ethanol in gasoline increased. NOx emissions in the U.S. and Brazilian cars decreased with ethanol content. However, emissions of THC, CO, and NOx from the Brazilian car were markedly higher than those from the U.S. car, showing high variability between vehicle technologies. In the Brazilian car, formation of secondary nitrogen dioxide (NO2) and ozone (O3) was lower for higher ethanol content in the fuel. In the U.S. car, NO2 and O3 had a small increase. Secondary particle (particulate matter [PM]) formation in the chamber decreased for both vehicles as the fraction of ethanol in fuel increased, consistent with previous studies. Secondary to primary PM ratios for pure gasoline is 11, also consistent with previous studies. In addition, the time required to form secondary PM is longer for higher ethanol blends. These results indicate that using higher ethanol blends may have a positive impact on air quality. IMPLICATIONS: The use of bioethanol can significantly reduce petroleum use and greenhouse gas emissions worldwide. Given the extent of its use, it is important to understand its effect on urban pollution. There is a controversy on whether there is a reduction or increase in PM emission when using ethanol blends. Primary emissions of THC, CO, CO2, NOx, and NMHC for both cars decreased as the fraction of ethanol in gasoline increased. Using a photochemical chamber, the authors have found a decrease in the formation of secondary particles and the time required to form secondary PM is longer when using higher ethanol blends.

The OncoSim model: development and use for better decision-making in Canadian cancer control.

The Canadian Partnership Against Cancer was created in 2007 by the federal government to accelerate cancer control across Canada. Its OncoSim microsimulation model platform, which consists of a suite of specific cancer models, was conceived as a tool to augment conventional resources for population-level policy- and decision-making. The Canadian Partnership Against Cancer manages the OncoSim program, with funding from Health Canada and model development by Statistics Canada. Microsimulation modelling allows for the detailed capture of population heterogeneity and health and demographic history over time. Extensive data from multiple Canadian sources were used as inputs or to validate the model. OncoSim has been validated through expert consultation; assessments of face validity, internal validity, and external validity; and model fit against observed data. The platform comprises three in-depth cancer models (lung, colorectal, cervical), with another in-depth model (breast) and a generalized model (25 cancers) being in development. Unique among models of its class, OncoSim is available online for public sector use free of charge. Users can customize input values and output display, and extensive user support is provided. OncoSim has been used to support decision-making at the national and jurisdictional levels. Although simulation studies are generally not included in hierarchies of evidence, they are integral to informing cancer control policy when clinical studies are not feasible. OncoSim can evaluate complex intervention scenarios for multiple cancers. Canadian decision-makers thus have a powerful tool to assess the costs, benefits, cost-effectiveness, and budgetary effects of cancer control interventions when faced with difficult choices for improvements in population health and resource allocation.

Implementing low-dose computed tomography screening for lung cancer in Canada: implications of alternative at-risk populations, screening frequency, and duration.

BACKGROUND: Low-dose computed tomography (ldct) screening has been shown to reduce mortality from lung cancer; however, the optimal screening duration and "at risk" population are not known. METHODS: The Cancer Risk Management Model developed by Statistics Canada for the Canadian Partnership Against Cancer includes a lung screening module based on data from the U.S. National Lung Screening Trial (nlst). The base-case scenario reproduces nlst outcomes with high fidelity. The impact in Canada of annual screening on the number of incident cases and life-years gained, with a wider range of age and smoking history eligibility criteria and varied participation rates, was modelled to show the magnitude of clinical benefit nationally and by province. Life-years gained, costs (discounted and undiscounted), and resource requirements were also estimated. RESULTS: In 2014, 1.4 million Canadians were eligible for screening according to nlst criteria. Over 10 years, screening would detect 12,500 more lung cancers than the expected 268,300 and would gain 9200 life-years. The computed tomography imaging requirement of 24,000-30,000 at program initiation would rise to between 87,000 and 113,000 by the 5th year of an annual nlst-like screening program. Costs would increase from approximately $75 million to $128 million at 10 years, and the cumulative cost nationally over 10 years would approach $1 billion, partially offset by a reduction in the costs of managing advanced lung cancer. CONCLUSIONS: Modelling various ways in which ldct might be implemented provides decision-makers with estimates of the effect on clinical benefit and on resource needs that clinical trial results are unable to provide.

Expression analysis of cannabinoid receptors 1 and 2 in B cells during pregnancy and their role on cytokine production.

The endocannabinoid system consists in a family of lipids that binds to and activates cannabinoid receptors. There are two receptors so far described, the cannabinoid receptor 1 (CB1) and 2 (CB2). In the context of pregnancy, the endocannabinoid system was shown participates in different key aspects of reproductive events. B-lymphocytes are pleiotropic cells belonging to the adaptive arm of the immune system. Besides immunoglobulin production, B-lymphocytes were recently shown to be actively involved in antigen presentation as well as cytokine production, thus playing a central role in immunity. In this study we first aimed to characterize the expression of CB1 and CB2 receptors in B cells during pregnancy and then analyze the impact of their activation in term of cytokine production by B cells from pregnant and non-pregnant mice. We observed that the expression of CB1 and CB2 receptors in B-lymphocytes is differentially regulated during pregnancy. While CB2 expression is down regulated CB1 is augmented in B-lymphocytes of pregnant mice. Additionally, the treatment of activated B-lymphocytes with specific CB1 and CB2 agonists, showed a different response in term of cytokine production. Particularly, CB1 against boosted the production of the anti-inflammatory cytokine IL-10 by activated B-lymphocytes from pregnant mice.

Using the Cancer Risk Management Model to evaluate the health and economic impacts of cytology compared with human papillomavirus DNA testing for primary cervical cancer screening in Canada.

BACKGROUND: In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. METHODS: We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. RESULTS: Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. CONCLUSIONS: Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes.

Using the Cancer Risk Management Model to evaluate colorectal cancer screening options for Canada.

BACKGROUND: Several screening methods for colorectal cancer (crc) are available, and some have been shown by randomized trials to be effective. In the present study, we used a well-developed population health simulation model to compare the risks and benefits of a variety of screening scenarios. Tests considered were the fecal occult blood test (fobt), the fecal immunochemical test (fit), flexible sigmoidoscopy, and colonoscopy. Outcomes considered included years of life gained, crc cases and deaths prevented, and direct health system costs. METHODS: A natural history model of crc was implemented and calibrated to specified targets within the framework of the Cancer Risk Management Model (crmm) from the Canadian Partnership Against Cancer. The crmm-crc permits users to enter their own parameter values or to use program-specified base values. For each of 23 screening scenarios, we used the crmm-crc to run 10 million replicate simulations. RESULTS: Using base parameter values and some user-specified values in the crmm-crc, and comparing our screening scenarios with no screening, all screening scenarios were found to reduce the incidence of and mortality from crc. The fobt was the least effective test; it was not associated with lower net cost. Colonoscopy screening was the most effective test; it had net costs comparable to those for several other strategies considered, but required more than 3 times the colonoscopy resources needed by other approaches. After colonoscopy, strategies based on the fit were predicted to be the most effective. In sensitivity analyses performed for the fobt and fit screening strategies, fobt parameter values associated with high-sensitivity formulations were associated with a substantial increase in test effectiveness. The fit was more cost-effective at the 50 ng/mL threshold than at the 100 ng/mL threshold. CONCLUSIONS: The crmm-crc provides a sophisticated and flexible environment in which to evaluate crc control options. All screening scenarios considered in this study effectively reduced crc mortality, although sensitivity analyses demonstrated some uncertainty in the magnitude of the improvements. Where possible, local data should be used to reduce uncertainty in the parameters.

High flow nasal heliox improves work of breathing and attenuates lung injury in a newborn porcine lung injury model.

BACKGROUND: High flow nasal cannula (HFNC) has been shown to improve ventilation and oxygenation and reduce work of breathing in newborns with respiratory distress. Heliox, decreases resistance to airflow, reduces the work of breathing, facilitates the distribution of inspired gas, and has been shown to attenuate lung inflammation during the treatment of acute lung injury. HYPOTHESIS: Heliox delivered by HFNC will decrease resistive load, decrease work of breathing, improve ventilation and attenuate lung inflammation during spontaneous breathing following acute lung injury in the newborn pig. METHODS: Spontaneously breathing neonatal pigs received Nitrox or Heliox by HFNC and studied over 4 hrs following oleic acid injury. Gas exchange, pulmonary mechanics and systemic inflammation were measured serially. Lung inflammation biomarkers were assessed at termination. RESULTS: Heliox breathing animals demonstrated lower work of breathing reflected by lower tracheal pressure, phase angle and phase relationship. Ventilation efficiency index was greater compared to Nitrox. Heliox group showed less lung inflammation reflected by lower tissue interleukin-6 and 8. CONCLUSION: High flow nasal Heliox decreased respiratory load, reduced resistive work of breathing indices and attenuated lung inflammatory profile while ventilation was supported at less pressure effort in the presence of acute lung injury.

Endocannabinoid system and nitric oxide are involved in the deleterious effects of lipopolysaccharide on murine decidua.

Endocannabinoids are an important family of lipid-signaling molecules that are widely distributed in mammalian tissues and anandamide (AEA) was the first member identified. The uterus contains the highest concentrations of AEA yet discovered in mammalian tissues and this suggests that it might play a role in reproduction. Previous results from our laboratory have shown that AEA modulated NO synthesis in rat placenta. The production of small amounts of nitric oxide regulates various physiological reproductive processes such as implantation, decidualization and myometrial relaxation. But in an inflammatory setting such as sepsis, NO is produced in big amounts and has toxic effects as it is a free radical. The results presented in this study indicate that LPS-induced NO synthesis and tissue damage were mediated by AEA. Decidual LPS-induced NO production was abrogated either by co-incubation with CB1 (AM251) or CB2 (SR144528) antagonists which suggests that both receptors could be mediating this effect. On the other hand, LPS-induced tissue damage and this deleterious effect was partially abrogated by incubating tissue explants with LPS plus CB1 receptor antagonist. Our findings suggest that AEA, probably by increasing NO synthesis, participates in the deleterious effect of LPS in implantation sites. These effects could be involved in pathological reproductive events such as septic abortion.

Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin.

Twenty-one-day-old Wistar rats were fed a diet containing 0.6% cuprizone for 2 weeks. Studies carried out after withdrawal of cuprizone showed histological evidences of marked demyelination in the corpus callosum. Biochemical studies of isolated myelin showed a marked decrease in myelin proteins, phospholipids, and galactocerebrosides as well as a marked decrease in myelin yield. Treatment of these animals with a single intracranial injection of 350 ng of apotransferrin at the time of withdrawal of cuprizone induced a marked increase in myelin deposition resulting in a significantly improved remyelination, evaluated by histological, immunocytochemical, and biochemical parameters, in comparison to what was observed in spontaneous recovery. Immunocytochemical studies of cryotome sections to analyze developmental parameters of the oligodendroglial cell population at the time of termination of cuprizone and at different times thereafter showed that in the untreated animals, there was a marked increase in the number of NG2-BrdU-positive precursor cells together with a marked decrease in MBP expression at the peak of cuprizone-induced demyelination. As expected, the amount of precursor cells decreased markedly during spontaneous remyelination and was accompanied by an increase in MBP reactivity. In the apotransferrin-treated animals, these phenomena occurred much faster, and remyelination was much more efficient than in the untreated controls. The results of this study suggest that apotransferrin is a very active promyelinating agent which could be important for the treatment of certain demyelinating conditions.

Growth-associated protein-43 is degraded via the ubiquitin-proteasome system.

Growth-associated protein-43 (GAP-43) is a phosphoprotein whose expression in neurons is related to the initial establishment and remodeling of neural connections. GAP-43 gene expression is known to be regulated at both the transcriptional and the postranscriptional levels. However, very little is known about the cellular mechanism involved in the degradation of this protein. Ubiquitin (Ub) is well known for its role in targeting cytoplasmic proteins for degradation by the 26S proteasome. The ubiquitin-proteasome system (UPS) consists of a conserved cascade of three enzymatic components that attach Ub covalently to various substrates and control the degradation of protein involved in several important cellular processes. In this study, we investigated the degradation of GAP-43 in transfected NIH 3T3 cells and neuronal cultures. We found that the proteasome inhibitors, lactacystin and MG132 increased the cellular GAP-43 level, leading to the accumulation of polyubiquitinated forms of this protein in transfected cells and that the Ub-proteasome pathway is also involved in the turnover of this protein in neurons. We conclude based on our findings that GAP-43 is a substrate of the UPS.

Cold perfluorochemical-induced hypothermia protects lung integrity in normal rabbits.

To test the hypothesis that intrapulmonary perfluorochemical (PFC) liquid may induce hypothermia, and to compare the effects of internal (IC), external (EC), and combined cooling techniques (EC + IC), 14 juvenile rabbits were randomized to EC by a cold blanket (4 degrees C, n = 5), IC by intrapulmonary cold PFC liquid lavage (4 degrees C, n = 5), or combined IC with PFC and EC (n = 4). Arterial blood gas, blood pressure, and lung mechanics were monitored, and lung histology was examined by light microscopy. The results showed that cooling rates and the time needed to be cooled down to 30 degrees C were significantly faster in EC and EC + IC than IC (p < 0.05). Blood gas analysis and cardiopulmonary function were within the normal range in all groups. Histological assessment revealed varied atelectasis in all lung regions in EC, whereas PFC-filled lungs (IC and EC + IC) demonstrated more homogenous expansion and no evidence of atelectasis. The results indicate that intrapulmonary PFC may be an effective technique to induce and/or augment hypothermia while supporting gas exchange, lung volume and pulmonary architecture.

Feasibility of lung cancer hyperthermia using breathable perfluorochemical (PFC) liquids. Part I: Convective hyperthermia.

Clinical studies have shown that hyperthermia in combination with radiotherapy and/or chemotherapy may be effective in the treatment of advanced cancer. No method of lung hyperthermia, however, has been accepted as standard or superior. This investigation sought to demonstrate in animals the thermal and physiologic feasibility of lung hyperthermia induced using heated breathable perfluorochemical (PFC) liquids, a method termed liquid-filled lung convective hyperthermia (LCHT). The ability to use LCHT is rooted in the development of both PFC liquid ventilation, now in clinical development with the PFC perflubron (LiquiVent), and a PFC blood substitute also in late Phase III trials (Oxygent). As LCHT background, the PFC technologies and biology are first reviewed. The physical properties of a variety of PFCs were evaluated for LCHT and it was concluded that more than one liquid is suitable based on such properties. Using total liquid ventilation type devices, LCHT was shown to deliver successfully localized (lobar) lung heating in sheep, and bilateral whole lung heating and whole-body hyperthermia in rabbits, cats and lambs. During LCHT, lung parenchymal temperatures were uniform (<1 degree C) across heated regions. In addition, based on patterns relating lung tissue temperatures to inspiratory and expiratory PFC liquid temperatures in the endotracheal tube, LCHT may minimize invasive thermometry requirements in the lung. Based on acute experiments, it was concluded that LCHT appears feasible and may simplify lung hyperthermia. It was recommended that potentially synergistic combinations of LCHT with other whole-body hyperthermia or local heating modalities, and with chemotherapeutic lung drug delivery, also be explored in the future.

Feasibility of lung cancer hyperthermia using breathable perfluorochemical (PFC) liquids. Part II: Ultrasound hyperthermia.

Enhanced local control of disease in lung cancer has been shown to improve survival, and controlled clinical trials of hyperthermia adjunctive to radiotherapy in other cancers have shown improved disease control and survival over radiotherapy alone. The challenge of lung hyperthermia, however, persists. This investigation sought to demonstrate the feasibility of localized lung hyperthermia at depth via therapeutic ultrasound. The method is based on using breathable perfluorochemical liquids as acoustic coupling media in the lung, liquids that have also been shown to enable controlled liquid-filled lung convective hyperthermia (LCHT). The ability to use both lung convective hyperthermia and liquid-filled lung ultrasound hyperthermia (LUHT) provides potential flexibility in heating patterns for the hyperthermic treatment of lung cancer with concurrent radiotherapy and/or chemotherapy. Using custom ultrasound transducers designed and built for these studies, the acoustic properties of three candidate perfluorochemicals were characterized over a range of temperatures, gas contents and ultrasound frequencies and acoustic intensities. Both sound speed and attenuation were measured in the neat liquids and in isolated lungs filled with the perfluorochemicals. Successful ultrasound hyperthermia at depth was demonstrated in vivo in sheep lung lobes in intraoperative conditions. In addition, the use of ultrasound diagnostic imaging was explored as a tool for use in conjunction with lung ultrasound hyperthermia.

Labour market income inequality and mortality in North American metropolitan areas.

OBJECTIVE: To investigate relations between labour market income inequality and mortality in North American metropolitan areas. METHODS: An ecological cross sectional study of relations between income inequality and working age (25-64 years) mortality in 53 Canadian (1991) and 282 US (1990) metropolitan areas using four measures of income inequality. Two labour market income concepts were used: labour market income for households with non-trivial attachment to the labour market and labour market income for all households, including those with zero and negative incomes. Relations were assessed with weighted and unweighted bivariate and multiple regression analyses. RESULTS: US metropolitan areas were more unequal than their Canadian counterparts, across inequality measures and income concepts. The association between labour market income inequality and working age mortality was robust in the US to both the inequality measure and income concept, but the association was inconsistent in Canada. Three of four inequality measures were significantly related to mortality in Canada when households with zero and negative incomes were included. In North American models, increases in earnings inequality were associated with hypothetical increases in working age mortality rates of between 23 and 33 deaths per 100 000, even after adjustment for median metropolitan incomes. CONCLUSIONS: This analysis of labour market inequality provides more evidence regarding the robust nature of the relation between income inequality and mortality in the US. It also provides a more refined understanding of the nature of the relation in Canada, pointing to the role of unemployment in generating Canadian metropolitan level health inequalities.

Positive end-expiratory pressure modulates perfluorochemical evaporation from the lungs.

To study the effects of positive end-expiratory pressure (PEEP) level on perfluorochemical (PFC) elimination profiles (E(L)), 6 ml/kg of perflubron were instilled into healthy anesthetized rabbits. The ventilation strategy was to maintain constant minute ventilation (300 ml/kg/min) and mean airway pressure (7-8 cm H(2)O) while randomly changing the PEEP levels from 5 to 0, 1, 3, and 10 cm H(2)O, each for a period of 15 min. The PFC content in the expired gas was measured and the E(L) was calculated. There was a significant reduction in the E(L) when decreasing the PEEP levels from 5 to 0 cm H(2)O, but no differences were seen when the PEEP was increased from 5 to 10 cm H(2)O. The results indicate that PEEP levels influence PFC elimination profiles; therefore, the measurement of the E(L) and PEEP levels should be considered when optimizing supplemental PFCs during partial liquid ventilation.