Effects of metformin on autoimmune immunoglobins and interferon-γ in patients with early diagnosed pemphigus vulgaris: a prospective clinical trial.

The management of pemphigus vulgaris (PV) is challenging. This study aimed to evaluate the immunomodulating effects of metformin on PV. The study was conducted in two phases: in the first phase, patients received routine first-line treatment (prednisolone plus azathioprine) for 2 months, then in the second phase, metformin was added to this regimen for another 2 months. After addition of metformin to the first-line medications, significant reductions were seen in serum IgG1 (reduced from 534.92 ± 134.83 mg/dL to 481.58 ± 130.46 mg/dL, P < 0.001), IgG4 (51.83 ± 27.26 mg/dL to 44.50 ± 26.05 mg/dL, P < 0.001) and interferon-γ (277.99 ± 108.71 pg/mL to 45.05 ± 17.080 pg/mL, P = 0.03) concentrations. The suppressant effect of metformin was greatest on IgG4 (coefficient of variation 1.28), the dominant subclass of IgG involved in PV. Metformin could have immunomodulating effects on PV with controlling effects on steroid complications.

Soft Tissue Characterization with Temporal Enhanced Ultrasound through Periodic Manipulation of Point Spread Function: A Feasibility Study.

Temporal enhanced ultrasound (TeUS) is a tissue characterization approach based on analysis of a temporal series of US data. Previously we demonstrated that intrinsic or external micro-motions of scatterers in the tissue contribute towards the tissue classification properties of TeUS. This property is beneficial to detect early stage cancer, for example, where changes in nuclei configuration (scatteres) dominate tissue properties. In this study, we propose an analytical derivation and experiments to acquire TeUS through manipulation of US imaging parameters, which may be simpler to translate to clinical applications. The feasibility of the proposed method is demonstrated on tissue-mimicking phantoms. Using an autoencoder classifier, we are able to classify phantoms of varying elasticities and scattering sizes.

Effect of nasal airway nonlinearities on oscillometric resistance measurements in infants.

Oscillometric measurements of respiratory system resistance (Rrs) in infants are usually made via the nasal pathways, which not only significantly contribute to overall Rrs but also introduce marked flow (V')-dependent changes. We employed intrabreath oscillometry in casts of the upper airways constructed from head CT images of 46 infants. We examined oscillometric nasal resistance (Rn) in upper airway casts with no respiratory flow (R0) and the effect of varying V' on Rn by simulating tidal breathing. A characteristic nonlinear relationship was found between Rn and V', exhibiting segmental linearity and a prominent breakpoint (V'bp) after log-log transformation. V'bp was linearly related to the preceding value of end-expiratory volume acceleration (V″eE; on average r2 = 0.96, P < 0.001). Rn depended on V', and R at end-expiration (ReE) showed a strong dependence on V″eE in every cast (r2 = 0.994, P < 001) with considerable interindividual variability. The intercept of the linear regression of ReE versus V″eE was found to be a close estimate of R0. These findings were utilized in reanalyzed Rrs data acquired in vivo in a small group of infants (n = 15). Using a graphical method to estimate R0 from ReE, we found a relative contribution of V'-dependent nonlinearity to total resistance of up to 33%. In conclusion, we propose a method for correcting the acceleration-dependent nonlinearity error in ReE. This correction can be adapted to estimate R0 from a single intrabreath oscillometric measurement, which would reduce the masking effects of the upper airways on the changes in the intrathoracic resistance.NEW & NOTEWORTHY Oscillometric measurements of respiratory system resistance (Rrs) in infants are usually made via the nasal pathways, which not only significantly contribute to overall Rrs but also introduce marked flow acceleration-dependent distortions. Here, we propose a method for correcting flow acceleration-dependent nonlinearity error based on in vitro measurements in 3D-printed upper airway casts of infants as well as in vivo measurements. This correction can be adapted to estimate Rrs from a single intrabreath oscillometric measurement.

Comparison of pleural and esophageal pressure in supine and prone positions in a porcine model of acute respiratory distress syndrome.

Patients with moderate to severe acute respiratory distress syndrome (ARDS) benefit from prone positioning. Although the accuracy of esophageal pressure (Pes) to estimate regional pleural pressure (Ppl) has previously been assessed in the supine position, such data are not available in the prone position in ARDS. In six anesthetized, paralyzed, and mechanically ventilated female pigs, we measured Pes and Ppl into dorsal and ventral parts of the right pleural cavity. Airway pressure (Paw) and flow were measured at the airway opening. Severe ARDS [arterial partial pressure of oxygen ([Formula: see text])/fraction of inspired oxygen ([Formula: see text]) < 100 mmHg at positive end-expiratory pressure (PEEP) of 5 cmH2O] was induced by surfactant depletion. In supine and prone positions assigned in a random order, PEEP was set to 20, 15, 10, and 5 cmH2O and static end-expiratory chest wall pressures were measured from Pes (PEEPtot,es) and dorsal (PEEPtot,PplD) and ventral (PEEPtot,PplV) Ppl. The magnitude of the difference between PEEPtot,es and PEEPtot,PplD was similar in each position [-3.6 cmH2O in supine vs. -3.8 cmH2O in prone at PEEP 20 cmH2O (PEEP 20)]. The difference between PEEPtot,es and PEEPtot,PplV became narrower in the prone position (-8.3 cmH2O supine vs. -3.0 cmH2O prone at PEEP 20). PEEPtot,PplV was overestimated by Pes in the prone position at higher pressures. The median (1st-3rd quartiles) dorsal-to-ventral Ppl gradient was 4.4 (2.4-6.8) cmH2O in the supine position and -1.5 (-3.5 to +1.1) cmH2O in the prone position (P < 0.0001) and marginally influenced by PEEP (P = 0.058). Prone position narrowed end-expiratory dorsal-to-ventral Ppl vertical gradient, likely because of a more even distribution of mechanical forces over the chest wall.NEW & NOTEWORTHY In a porcine model of acute respiratory distress syndrome, we found that static end-expiratory esophageal pressure did not change significantly in prone position compared with supine position at any positive end-expiratory pressure (PEEP) tested between 5 and 20 cmH2O. Prone position was associated with an increased ventral pleural pressure and reduced end-expiratory dorsal-to-ventral pleural pressure (Ppl) vertical gradient, likely due to a more even distribution of mechanical forces over the chest wall.

The ageing joint-standard age- and sex-related values of bone erosions and osteophytes in the hand joints of healthy individuals.

OBJECTIVE: To analyze the age-related changes of the physiological hand joint architecture. METHOD: To address this concept, healthy individuals (each 10 women and 10 men in six different age decades spanning from 21 to 80 years) were recruited through a field campaign, investigated for the absence of rheumatic diseases and other comorbidities and received high-resolution quantitative computed tomography (HR-pQCT) examination of the hand joints. Number and extent of erosions and osteophytes were quantified across the ages and different sexes. RESULTS: Bone erosions [median (Q1-Q3), 1 (0-2)] and osteophytes [2 (1-4)] were found in healthy women and men with no significant sex differences. Structural changes however accumulated with age: the overall incidence rate ratio (IRR) for the number of erosions and osteophytes per age were 1.04 (95% CI: erosions 1.03-1.06; osteophytes: 1.03-1.05). This means a 4% increase in the number of erosions and osteophytes per year. Using third decade as reference, healthy individuals in the age decades from 50 years had higher IRR for erosion numbers (sixth, seventh, eigth decade: 4.87 (2.20-11.75), 6.81 (3.08-16.46) and 6.92 (3.11-16.79)) compared to younger subjects (fourth, fifth decade: 1.80 (0.69-4.87), 1.53 (0.59-4.10)). The IRRs of osteophytes also indicate a gradual increase after the fifth decade, with IRRs of 2.32 (1.32-4.17), 4.17 (2.38-7.49) and 6.86 (3.97-12.20) for the sixth, seventh and eigth decades, respectively. CONCLUSIONS: Structural changes in the hand joints of healthy individuals are age dependent. While being rare under 50 years of age, erosions and osteophytes accumulate above the age of 50, suggesting that the threshold between "normal" and "pathological" is shifted with the increase of age.

Differential expression of S1P receptor subtypes in human bladder transitional cell carcinoma.

PURPOSE: Sphingosine 1 phosphate (S1P), S1P receptors (S1PRs) and their signaling pathways play an important role in the fate of cancer cells. The expression pattern of S1PR subtypes (S1PR1-S1PR5) may alter in cancer development stages, depending on the origin and the pathologic features of tumors. The present study aimed to examine the relationship between plasma S1P levels and the expression of S1PR subtypes in bladder tumors. METHODS/PATIENTS: These changes were evaluated in terms of the pathologic grades and stages of human bladder cancer samples. For this, tumor biopsies from 41 new bladder cancer patients as well as 26 normal-looking bladder tissues were collected and processed for immunohistochemistry (IHC) and quantitative real-time RT-PCR of S1PR subtypes. Plasma S1P level was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The results show that tissue S1PR1, S1PR2 and S1PR3 are over-expressed in all tumors regardless of their pathological grade (~ 3, ~ 6 and ~ 104 folds, respectively). These results were corroborated by IHC data showing accumulation of S1PR subtypes 1 and 2 in the tissues. Plasma S1P in the plasma samples from patients was in the range of control samples (Controls; 256 ± 47; patients, 270 ± 41). CONCLUSIONS: Overexpression of S1PR1, S1PR2 and S1PR3 in bladder tumor biopsies which were corroborated with the pathological grades and stages may suggest that S1PR profile in tumor biopsies is a promising marker in the diagnosis of bladder carcinoma.

Comparison between neurally-assisted, controlled, and physiologically variable ventilation in healthy rabbits.

BACKGROUND: Various ventilation strategies have been proposed to reduce ventilation-induced lung injury that occurs even in individuals with healthy lungs. We compared new modalities based on an individualised physiological variable ventilation model to a conventional pressure-controlled mode. METHODS: Rabbits were anaesthetised and ventilated for up to 7 h using pressure-controlled ventilation with (Group PCS, n=10), and without (Group PC, n=10) regular sighs. Variable ventilation in the other two groups was achieved via a pre-recorded spontaneous breathing pattern [Group physiologically variable ventilation (PVV), n=10] or triggered by the electrical activity of the diaphragm [Group neurally adjusted ventilation assist (NAVA), n=9]. Respiratory elastance, haemodynamic profile, and gas exchange were assessed throughout the ventilation period. Cellular profile, cytokine content of bronchoalveolar lavage fluid, and wet-to-dry lung weight ratio (W/D) were determined after protocol completion. Lung injury scores were obtained from histological analysis. RESULTS: Marked deteriorations in elastance were observed (median and 95% confidence interval) in Group PC [48.6 (22)% increase from baseline], while no changes were detected in Groups PCS [3.6 (8.1)%], PVV [18.7 (13.2)%], and NAVA [-1.4 (12.2)%]. In comparison with Group PC, Group PVV had a lower lung injury score [0.29 (0.02) compared with 0.36 (0.05), P<0.05] and W/D ratio [5.6 (0.1) compared with 6.2 (0.3), P<0.05]. There was no difference in blood gas, haemodynamic, or inflammatory parameters between the groups. CONCLUSIONS: Individualised PVV based on a pre-recorded spontaneous breathing pattern provides adequate gas exchange and promotes a level of lung protection. This ventilation modality could be of benefit during prolonged anaesthesia, in which assisted ventilation is not possible because of the absence of a respiratory drive.

Quantitative Imaging of Regional Aerosol Deposition, Lung Ventilation and Morphology by Synchrotron Radiation CT.

To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R2 = 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.

Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities.

BACKGROUND: It is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. METHODS: In a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV̇). Heterogeneity of ventilation was calculated as the coefficient of variation in sV̇ (CVsV̇ ). The coefficient of variation in lung densities (CVD ) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FI O2 0.21; ZEEP and FI O2 1.0; PEEP 12 cmH2 O and FI O2 1.0 (Open Lung-PEEP = OLP). RESULTS: The mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV̇ and poor aeration at ZEEP-0.21 than at OLP: 12.9 ± 9.0 vs. 0.6 ± 0.4% in the non-dependent level, and 17.5 ± 8.2 vs. 0.4 ± 0.1% in the dependent one (P = 0.041). The CVsV̇ of the total imaged lung at PEEP 12 cmH2 O was significantly lower than on ZEEP, regardless of FI O2 , indicating more heterogeneity of ventilation during ZEEP (0.23 ± 0.03 vs. 0.54 ± 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. CONCLUSION: ZEEP together with low FI O2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.

Individual and regional factors of access to the renal transplant waiting list in france in a cohort of dialyzed patients.

Several studies have investigated geographical variations in access to renal transplant waiting lists, but none has assessed the impact on these variations of factors at both the patient and geographic levels. The objective of our study was to identify medical and non-medical factors at both these levels associated with these geographical variations in waiting-list placement in France. We included all incident patients aged 18-80 years in 11 French regions who started dialysis between January 1, 2006, and December 31, 2008. Both a multilevel Cox model with shared frailty and a competing risks model were used for the analyses. At the patient level, old age, comorbidities, diabetic nephropathy, non-autonomous first dialysis, and female gender were the major determinants of a lower probability of being waitlisted. At the regional level, the only factor associated with this probability was an increase in the number of patients on the waiting list from 2005 to 2009. This finding supports a slight but significant impact of a regional organ shortage on waitlisting practices. Our findings demonstrate that patients' age has a major impact on waitlisting practices, even for patients with no comorbidity or disability, whose survival would likely be improved by transplantation compared with dialysis.

Radiation dose and image quality in K-edge subtraction computed tomography of lung in vivo.

K-edge subtraction computed tomography (KES-CT) allows simultaneous imaging of both structural features and regional distribution of contrast elements inside an organ. Using this technique, regional lung ventilation and blood volume distributions can be measured experimentally in vivo. In order for this imaging technology to be applicable in humans, it is crucial to minimize exposure to ionizing radiation with little compromise in image quality. The goal of this study was to assess the changes in signal-to-noise ratio (SNR) of KES-CT lung images as a function of radiation dose. The experiments were performed in anesthetized and ventilated rabbits using inhaled xenon gas in O2 at two concentrations: 20% and 70%. Radiation dose, defined as air kerma (Ka), was measured free-in-air and in a 16 cm polymethyl methacrylate phantom with a cylindrical ionization chamber. The dose free-in-air was varied from 2.7 mGy to 8.0 Gy. SNR in the images of xenon in air spaces was above the Rose criterion (SNR > 5) when Ka was over 400 mGy with 20% xenon, and over 40 mGy with 70% xenon. Although in human thorax attenuation is higher, based on these findings it is estimated that, by optimizing the imaging sequence and reconstruction algorithms, the radiation dose could be further reduced to clinically acceptable levels.

Quantitative functional imaging and kinetic studies with high-Z contrast agents using synchrotron radiation computed tomography.

1. There is an increasing demand in diagnostic radiology for extracting additional morphological and functional quantitative parameters from three-dimensional computed tomography (CT) images. Synchrotron radiation computed tomography (SRCT) is the state-of-the-art method in preclinical X-ray CT, because its performance is close to the theoretical limits in terms of accuracy and precision. 2. The SRCT method with monochromatic X-ray beams yields absolute high-Z element contrast agent concentrations, without errors arising from beam hardening or scatter artefacts, by using digital subtraction techniques of the sinograms. Each pixel of the reconstructed difference images provides a quantitative concentration versus time curve of inhaled or injected high-Z contrast agents (xenon or iodine) with a high sensitivity. This is the key point of two functional imaging techniques that were developed at the European Synchrotron Radiation Facility: brain perfusion and lung function (ventilation and perfusion). 3. These two imaging techniques provide parametric images expressed in absolute perfusion parameters (blood volume, blood flow, mean transit time and capillary permeability) or ventilation parameters (lung volume, regional lung ventilation, bronchial lumen size, regional airway and lung compliance) with a high accuracy and precision. 4. The aim of the present brief review is to give a snapshot of the status and perspectives of these two imaging techniques, with emphasis on the performances and interests for functional imaging. Two separate sections will then describe the results obtained so far using SRCT as an in vivo functional imaging tool for measuring changes in haemodynamics and ventilation, in the investigation of experimental pathophysiology and in the effects of therapeutic intervention.

Simultaneous in vivo synchrotron radiation computed tomography of regional ventilation and blood volume in rabbit lung using combined K-edge and temporal subtraction.

In K-edge subtraction (KES) imaging with synchrotron radiation computed tomography (SRCT), two images are taken simultaneously using energies above and below the K-absorption edge of a contrast agent. A logarithmic difference image reveals the contrast agent concentration with good accuracy. Similarly, in temporal subtraction imaging (TSI) the reference image is taken before the introduction of the contrast agent. Quantitative comparisons of in vivo images of rabbit lung indicated that similar results for concentrations of iodine in blood vessels and xenon in airways are obtained by KES and TSI, but the level of noise and artifacts was higher in the latter. A linear fit showed that in the lung parenchyma rho(TSI) = (0.97 +/- 0.03)rho(KES) + (0.00 +/- 0.05) for xenon and rho(TSI) = (1.21 +/- 0.15)rho(KES) + (0.0 +/- 0.1) for iodine. For xenon the calculation of time constant of ventilation gave compatible values for both of the methods. The two methods are combined for the simultaneous determination of the xenon concentration (by KES) and the iodine concentration (by TSI) in lung imaging, which will allow simultaneous in vivo determination of ventilation and perfusion.

Comparison of 99mTc-DTPA and urea for measuring cefepime concentrations in epithelial lining fluid.

The efficacy of antimicrobial agents against pulmonary infections depends on their local concentrations in the lung. The aims of the present study were to: 1) compare technetium-99m diethylenetriaminepenta-acetic acid (99mTc-DTPA) and urea as markers of epithelial lining fluid (ELF) dilution for measuring ELF concentrations of pharmaceuticals; 2) quantify ELF cefepime concentrations in normal and injured lung; and 3) measure the increase in permeability to cefepime following oleic acid-induced acute lung injury. A modified bronchoalveolar lavage technique, based on equilibration of infused 99mTc-DTPA, was used to measure ELF volume. Cefepime was administered intravenously at steady plasma levels. Six serial bronchoalveolar lavages were performed 5 h after the beginning of infusion. ELF to plasma cefepime concentration ratios were 95 +/- 17 and 100 +/- 14.5% in normal and injured lung respectively. When urea was used as marker, cefepime concentration ratios were underestimated at 16.4 +/- 2.7 and 73.9 +/- 8.4% respectively. Cefepime blood/ airspace clearance increased from 3.8 +/- 0.7 micro x min(-1) in controls to 39.8 +/- 4.9 microL x min(-1) in acute lung injury. It was concluded that: 1) cefepime concentrations in epithelial lining fluid were in equilibrium with those in plasma in both normal and injured lung after 5 h at steady plasma concentrations; 2) epithelial lining fluid cefepime concentration by the urea method was much less underestimated in injured versus normal lung; and 3) acute lung injury induces a 10-fold elevation of cefepime blood/airspace clearance.

Effect of tidal volume on distribution of ventilation assessed by synchrotron radiation CT in rabbit.

A respiration-gated synchrotron radiation computed tomography (SRCT) technique, which allows visualization and direct quantification of inhaled stable xenon gas, was used to study the effect of tidal volume (Vt) on regional lung ventilation. High-resolution maps (pixel size 0.35 x 0.35 mm) of local washin time constants (tau) and regional specific ventilation were obtained in five anesthetized, paralyzed, and mechanically ventilated rabbits in upright body position at the fourth, sixth, and eighth dorsal vertebral levels with a Vt from 4.9 +/- 0.3 to 7.9 +/- 0.4 ml/kg (means +/- SE). Increasing Vt without an increase in minute ventilation resulted in a proportional increase of mean specific ventilation up to 65% in all studied lung levels and reduced the scattering of washin tau values. The tau values had log-normal distributions. The results indicate that an increase in Vt decreases nonuniformity of intraregional ventilatory gas exchange. The findings suggest that (SRCT) provides a new quantitative tool with high spatial discrimination ability for assessment of changes in peripheral pulmonary gas distribution during mechanical ventilation.

[Mortality rates in rural and urban areas of Brittany]. / Mortalité urbaine et rurale en Bretagne.

Relative differences in environment, behaviour, social composition as well as access to health care tend to suggest that levels of health may vary between urban and rural areas. The aim of this study was to identify rural-urban variations in mortality risks in the region of Brittany for the period from 1988 to 1992. The definition of urban and rural areas used adhered to that of the zoning of urban areas established by the INSEE (the National Statistical Office). The amalgamation of all causes of standardised mortality ratios (SMR) show only a moderately increased risk in the rural areas compared with the overall regional level (+4% in men, +5-7% in women). The analysis of cause specific SMRs display higher rural mortality for cardiovascular diseases and external causes of death, road traffic accidents in particular (+24% in men). Among all specific causes investigated, only lung cancer mortality risk appears to be higher in urban areas.

Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent.

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.

In vivo measurement of lung capillary-alveolar macromolecule permeability by saturation bronchoalveolar lavage.

OBJECTIVE: Measurement of capillary-alveolar permeability to fluorescein isothiocyanate-dextran (FITC-D) (molecular mass, 71,300 daltons) by a sequential bronchoalveolar lavage (BAL) technique. DESIGN: Animal research. SETTING: The Department of Physiology at a scientific and medical university. SUBJECTS: Nine anesthetized and mechanically ventilated dogs. INTERVENTIONS: Two separate experiments were performed in each subject-an initial control experiment followed by an oleic acid-induced lung injury. The indicator was administered at constant blood concentration before serial BAL including eight fluid instillation-recovery cycles. MEASUREMENTS: Plasma to BAL solute clearance at saturation (capillary-alveolar clearance at saturation, mL/min) was calculated and normalized to lavage fluid volume (measured by 1251 serum albumin dilution) to obtain a transport rate (TR) constant. MAIN RESULTS: TR for FITC-D70 was 4.0+/-0.8 and 46.1+/-18.1 x 10(-5) x min(-1) in control and injured lung, respectively (p < .02). Capillary-alveolar clearance of FITC-D70 was not affected by the lavage procedure itself. TR reflected essentially epithelial permeability in normal lung and combined epithelial and endothelial permeability in injured lung. A significant correlation was found between cardiac output and TR in injured lung. CONCLUSIONS: Saturation BAL allowed us to estimate capillary-alveolar macromolecule permeability in vivo in dogs. Further study may allow bedside evaluation of lung injury by BAL in patients.

Time-dependent pressure distortion in a catheter-transducer system: correction by fast flush.

BACKGROUND: Distortion of the pressure wave by a liquid-filled catheter-transducer system leads most often to an overestimation in systolic arterial blood pressure in pulmonary and systemic circulations. The pressure distortion depends on the catheter-transducer frequency response. Many monitoring systems use either mechanical or electronic filters to reduce this distortion. Such filters assume, however, that the catheter-transducer frequency response does not change over time. The current study aimed to study the changes with time of the catheter-transducer frequency response and design a flush procedure to reverse these changes back to baseline. METHODS: An in vitro setup was devised to assess the catheter-transducer frequency response in conditions approximating some of those met in a clinical environment (slow flushing, 37 degrees C, 48-h test). Several flush protocols were assessed. RESULTS: Within 48 h, catheter-transducer natural frequency decreased from 17.89 +/- 0.36 (mean +/- SD) to 7.35 +/- 0.25 Hz, and the catheter-transducer damping coefficient increased from 0.234 +/- 0.004 to 0.356 +/- 0.010. Slow and rapid flushing by the flush device built into the pressure transducer did not correct these changes, which were reversed only by manual fast flush of the transducer and of the catheter. These changes and parallel changes in catheter-transducer compliance may be explained by bubbles inside the catheter-transducer. CONCLUSIONS: Catheter-transducer-induced blood pressure distortion changes with time. This change may be reversed by a manual fast flush or "rocket flush" procedure, allowing a con. stant correction by a filter.