Turning a conventional camera into a 3D camera with an add-on.

We propose to add an optical component in front of a conventional camera to improve depth estimation performance of depth from defocus (DFD), an approach based on the relation between defocus blur and depth. The add-on overcomes ambiguity and the dead zone, which are the fundamental limitations of DFD with a conventional camera, by adding an optical aberration to the whole system that makes the blur unambiguous and measurable for each depth. We look into two optical components: the first one adds astigmatism and the other one chromatic aberration. In both cases, we present the principle of the add-on and experimental validations on real prototypes.

Laser in situ keratomileusis and surface ablation in pregnancy.

PURPOSE: Although corneal refractive surgery is contraindicated during pregnancy, some patients are unaware that they are pregnant when they undergo surgery. Our objectives were to determine the functional outcomes of corneal refractive surgery during pregnancy and to compare the results with those of nonpregnant women. METHODS: We performed a multicenter, retrospective, interventional case series review of patients who were pregnant and who underwent laser in situ keratomileusis (LASIK) or surface ablation (photorefractive keratectomy, PRK) from September 11, 2002 to December 12, 2020 (group 1, n=82 eyes). Patients were included consecutively. Findings were compared with those of nonpregnant women (group 2, n=164 eyes). Functional (visual and refractive) outcomes are described. Follow-up was at least 550 days (control group, median [IQR], 990 days [715-1496]; study group, 895 days [709-1310]). The setting was Clínica Baviera, Spain, (AIER Eye Hospital Group). RESULTS: A statistically significant difference was found between the groups in terms of efficacy index (EI). No complications of pregnancy or labor were reported. Similarly, a search of medical records revealed no adverse effects in the infants. CONCLUSIONS: To the best of our knowledge, this is the first case series on pregnancy and refractive surgery. We do not recommend performing LASIK or surface ablation on pregnant women. Our objective in the present study was to present relevant scientific data obtained from women who underwent refractive surgery while unaware that they were pregnant.

Solid organ transplant training objectives for residents.

With the aim of analyzing the current state of the educational objectives in the training of medical residents in solid organ transplantation (SOT), we conducted a review of the status of the official programs of the specialities involved in SOT, focusing particularly on lung transplantation. A survey of medical residents was also conducted to allow reflexion about the topic. We obtained 44 surveys from 4 University Hospitals with active programs in SOT, mainly from intensive care medicine and anesthesiology residents. We detected an important number of courses oriented to organ donation but very limited in terms of basic training in the management of the immediate postoperative period, principles of immunosuppression and updates on immunosuppressive therapy and complications (particularly rejection and infection). We also identified that these educational aspects should be directed not only to medical residents from specialities with a close retation to SOT, but also to all who may at some time have a relation to such patients. The use of information and communication techniques (ICTs), on-line courses and also simulations should be instruments to take into account in the biomedical training of medical residents. We conclude that we need a specific training program in complications of SOT, as well as fundamental principles in immunology and immunosuppressor pharmacology.

Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: The TACROVID trial protocol.

INTRODUCTION: Some COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients. METHODS: and analysis: TACROVID is a randomized, open-label, single-center, phase II trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature ≤37.5 °C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate ≤24 rpm; for 48 consecutive hours. DISCUSSION: Methylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries. TRIAL REGISTRATION NUMBER: NCT04341038 / EudraCT: 2020-001445-39.

Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease.

Inhibition of airway epithelial sodium channel (ENaC) function enhances mucociliary clearance (MCC). ENaC is positively regulated by channel-activating proteases (CAPs), and CAP inhibitors are therefore predicted to be beneficial in diseases associated with impaired MCC. The aims of the present study were to 1) identify low-molecular-weight inhibitors of airway CAPs and 2) to establish whether such CAP inhibitors would translate into a negative regulation of ENaC function in vivo, with a consequent enhancement of MCC. To this end, camostat, a trypsin-like protease inhibitor, provided a potent (IC(50) approximately 50 nM) and prolonged attenuation of ENaC function in human airway epithelial cell models that was reversible upon the addition of excess trypsin. In primary human bronchial epithelial cells, a potency order of placental bikunin > camostat > 4-guanidinobenzoic acid 4-carboxymethyl-phenyl ester > aprotinin >> soybean trypsin inhibitor = alpha1-antitrypsin, was largely consistent with that observed for inhibition of prostasin, a molecular candidate for the airway CAP. In vivo, topical airway administration of camostat induced a potent and prolonged attenuation of ENaC activity in the guinea pig trachea (ED(50) = 3 microg/kg). When administered by aerosol inhalation in conscious sheep, camostat enhanced MCC out to at least 5 h after inhaled dosing. In summary, camostat attenuates ENaC function and enhances MCC, providing an opportunity for this approach toward the negative regulation of ENaC function to be tested therapeutically.

Correction to: Can We Accurately Predict Cost Effectiveness Without Access to Overall Survival Data? The Case Study of Nivolumab in Combination with Ipilimumab for the Treatment of Patients with Advanced Melanoma in England.

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Can We Accurately Predict Cost Effectiveness Without Access to Overall Survival Data? The Case Study of Nivolumab in Combination with Ipilimumab for the Treatment of Patients with Advanced Melanoma in England.

BACKGROUND: Nivolumab with ipilimumab (the Regimen) is the first immuno-oncology combination treatment to demonstrate long-term clinical benefit for advanced melanoma patients. We evaluated the cost effectiveness of the Regimen in this population, with and without the availability of overall survival (OS) data. METHODS: A partitioned survival model and a Markov state-transition model were developed to estimate the lifetime costs and benefits of the Regimen versus ipilimumab. These models were built with and without the availability of OS data, as only progression-free survival data were available from the head-to-head, phase III trial against ipilimumab at the time of the National Institute for Health and Care Excellence (NICE) submission. Patient utilities and resource use data were sourced from trial data or the literature. RESULTS: Incremental cost-effectiveness ratios (ICERs) and absolute costs were similar between the models with and without OS data, but the model with OS data generated more than 1 additional quality-adjusted life-year (QALY) across both treatment arms. In both models, based on list prices, the Regimen was the most cost-effective treatment. CONCLUSIONS: The analyses show that the Regimen is a cost-effective treatment for advanced melanoma patients in England, and methods to overcome the lack of OS can give reasonable estimates of QALYs gained and ICERs.

Visual outcomes, spectacle independence and satisfaction after diffractive trifocal intraocular lens implantation. / Resultados visuales, independencia de gafas e insatisfacción tras implante de una lente intraocular difractiva trifocal.

PURPOSE: To investigate visual outcomes, spectacle independence, and patient satisfaction after trifocal intraocular lens implantation. METHODS: A retrospective study conducted on 5,186 patients who underwent phacoemulsification and were implanted with a diffractive trifocal intraocular lens (FineVision Micro F, PhysIOL SA, Liège, Belgium). RESULTS: The mean pre-operative keratometry was 43.61±1.55 D, and mean keratometric cylinder was -0.86±0.66 D. At 3 months post-operatively, values changed to 43.59±1.56 and -0.71±0.46 D, respectively. Mean sphere varied from 2.04±2.60 to 0.14±0.38 D, and mean spherical equivalent from 1.64±2.61 to -0.05±0.36 D. More than 60% of the patients achieved better corrected distance visual acuity. The majority had a final residual refractive error (predictability) lower than 1 D (99.1%), with 14.3% needing optical adjustment (bioptics). Posterior capsulotomy was performed in 2.2%, and the lens was replaced in 5 patients. A high percentage of patients were satisfied in terms of vision and spectacle independence at all distances. Although 2% referred to worsening of night vision quality, only 2% were not very satisfied and 20 patients were dissatisfied. The causes were: blurred vision (7 cases), spectacle dependence (10), dysphotopsia (7), and dry eye (4). CONCLUSIONS: The implantation of this model provided good visual performance in all distances, as well as high levels of spectacle independence and satisfaction.

Mycophenolate mofetil levels in stable kidney transplant recipients.

The usefulness of mycophenolate mofetil (MMF) levels in stable kidney transplant patients is not well known. We measured MMF trough levels in 137 adult kidney recipients with more than 1 year of stable graft function. The MMF dose was adjusted according to hematological or gastrointestinal toxicity, it was 500 mg in 22 (16%) patients; 750 mg in 22 (16%); 1000 mg in 69 (50.5%); 1500 mg in 15 (11%); and 2000 mg in 9 (6.5%). We analyzed the total dose, virgule dose/kg, and MMF levels in relation to efficacy parameters (creatinine, proteinuria) and hematological toxicity (erythrocytes, leukocytes, and platelets) at the time of MMF level determinations and 3 months thereafter. Statistical analyses were performed with SSPS 12.0, including sensitivity and specificity analyses by ROC. Mean MMF levels were 3.68 mg/L (Pc25, 1.6-Pc75, 4.4 mg/L) with significant differences according to dose (P < .001). Trough MMF levels did not have discriminatory capacity in the area under the ROC for anemia, renal failure, or proteinuria at the time of determination or 3 months later. The percentage of patients without proteinuria was high among patients with MMF levels between 1.6 and 4.4 mg/L. The MMF levels were low in patients who had a major increase in creatinine (1.6 vs 3.8 mg/L, P < .05). In stable renal transplant patients the levels of MMF were related to the administered dose, and they are higher than those previously described in patients with less than a year follow-up with a functioning kidney. They did not have discriminatory value at the time of determination or 3 months later. Nevertheless, low MMF levels could help recognize patients at risk of developing chronic nephropathy.

[The Cockcroft-Gault equation is better than MDRD equation to estimate the glomerular filtration rate in patients with advanced chronic renal failure]. / La ecuación de Cockcroft-Gault es preferible a la ecuación MDRD para medir el filtrado glomerular en la insuficiencia renal crónica avanzada.

ABSTRACT The aim of this study was to compare the accuracy of three kidney function estimating equations: classic Cockcroft-Gault (classic CG), corrected Cockcroft-Gault (corrected CG) and simplified Modification of Diet in Renal Disease (MDRD), in patients with advanced chronic renal failure. The study was made in 84 nondialyzed patients with chronic renal disease in stage 4 or 5. The glomerular filtration rate was measured on a 24-hour urine collection as the arithmetic mean of the urea and creatinine clearances (CUrCr). In each patient, the difference between each estimating equation and the measured glomerular filtration rate was calculated. The absolute difference expressed as a percentage of the measured glomerular filtration rate indicates the intermethod variability. In the total group the glomerular filtration rate measured as the CUrCr was de 13,5+/-5,1 ml/min/1.73 m(2); and the results of the estimating equations were: classic CG 14,2+/-5 (p<0,05); corrected CG 12+/-4,2 (p<0,01) and MDRD : 12,1+/-4,8 ml/min/1.73 m(2) (p<0,01). The variability of the estimating equations was 15,2+/-12,2%, 17,1+/-13,4 % and 19,3+/-13,3% (p<0,05), for classic CG, corrected CG and MDRD respectively. The percent of estimates falling within 30% above o below the measured glomerular filtration rate was 90% for CG classic, 87% for corrected CG and 79% for MDRD. The intraclass correlation coefficients respect to CUrCr were 0,86 for classic CG, 0,81 for corrected CG and 0,77 for MDRD. The MDRD variability, but not classic CG variability or corrected CG variability, showed a positive correlation with the glomerular filtration rate (r=0,25, p<0,05). In patients with chronic renal disease in stage 5, the variability of the different estimating equations was similar. We conclude that in our population with advanced chronic renal failure the classic CG equation is more accurate than the MDRD equation. Corrected CG equation has not any advantage respect to classic CG equation.

Cell-cycle arrest biomarkers in urine to predict acute kidney injury in septic and non-septic critically ill patients.

PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1.73 m2 and hospitalisation 2 months prior to current admission. The [TIMP-2]·[IGFBP7] index was analysed twice, within the first 12 h of ICU admission. RESULTS: The sample included 98 patients. AKI incidence during ICU stay was 50%. Sepsis was diagnosed in 40.8%. Baseline renal variables were comparable between subgroups except for a higher baseline eGFR in non-septic patients. Patients were stratified based on the presence of AKI and their highest level of [TIMP-2]·[IGFBP7] within the first 12 h of stay. [TIMP-2]·[IGFBP7] index values were dependent on the incidence of AKI but not of sepsis. [TIMP-2]·[IGFBP7] values were significantly related to AKI severity according to AKIN criteria (p < 0.0001). The AUROC curve to predict AKI of the worst [TIMP-2]·[IGFBP7] index value was 0.798 (sensitivity 73.5%, specificity 71.4%, p < 0.0001). Index values below 0.8 ruled out any need for renal replacement (NPV 100%), whereas an index >0.8 predicted a rate of AKI of 71% and AKIN ≥ 2 of 62.9%. CONCLUSIONS: In our study, urinary [TIMP-2]·[IGFBP7] was an early predictor of AKI in ICU patients regardless of sepsis. Besides, index values <0.8(ng/mL)2/1000 ruled out the need for renal replacement.

Implantable collamer lens for correction of ametropia in eyes with corneal scarring. / Implantación de lente fáquica para corrección de miopía en pacientes con leucoma corneal.

CASES: Two cases are reported in which implantation of a collagen copolymer phakic intraocular lens (implantable collamer lens) corrected refractive errors in eyes with corneal scarring. A previous accident, in both cases, resulted in a central linear scar on the surface of the cornea of one eye. In the first patient, a corneal scar was visible in the left eye. The distance corrected visual acuity was 0.3 (-7.75 -4×160°). An uncorrected distance visual acuity of 0.25 was obtained by implanting an implantable collamer lens. In the second patient an oblique corneal scar was visible in the right eye. The distance corrected visual acuity was 0.25 (-8.75 -1.25×8°), and after implantation of the implantable collamer lens, uncorrected distance visual acuity was 0.25. DISCUSSION: The indications of the implantable collamer lens should be reviewed and possibly expanded.

LASIK and surface ablation in patients treated with amiodarone. / LASIK y ablación de superficie en pacientes tratados con amiodarona.

OBJECTIVE: To determine the anatomical and functional outcomes of corneal refractive surgery in patients on amiodarone, a drug listed as being contraindicated in patients undergoing this procedure. MATERIAL AND METHODS: A retrospective observational study was conducted on all consecutive patients who took amiodarone and who underwent LASIK or surface ablation from January 2003 to December 2014. Functional (visual and refractive) outcomes are described. RESULTS: A total of 20 patients (33 eyes) were included. No significant intraoperative or postoperative complications were found. CONCLUSIONS: In our experience, LASIK and surface ablation did not produce significant clinical complications in selected patients taking amiodarone. The absolute exclusion of certain systemic medications should be reconsidered.

Insulin inhibits liver expression of the CCAAT/enhancer-binding protein beta.

The CCAAT/enhancer-binding protein beta (C/EBP beta) is a transcription factor that is abundant in the liver. The concentration of C/EBP beta mRNA in the liver of mice and rats fed a high-carbohydrate diet, which causes a rise in blood insulin levels, was lower (80 and 65%, respectively) than that detected in animals fed a standard diet. Similarly, the expression of the human insulin gene in the liver of transgenic mice led to a decrease in the concentration of C/EBP beta mRNA. However, no change was detected in the mRNA levels of C/EBP alpha or cAMP regulatory element-binding protein transcription factors in the livers of these mice. Furthermore, the expression of the C/EBP beta gene increased in the liver of diabetic rats and decreased in the liver of diabetic animals treated with vanadate, an insulin mimetic agent. In addition, a decrease in C/EBP beta protein was observed in liver nuclei from mice after insulin injections, in mice fed a high-carbohydrate diet, and in transgenic mice expressing the insulin gene in the liver. These results suggest that insulin might control gene expression in vivo, at least in part, by a mechanism involving a decrease in the transcription factor C/EBP beta.

The Role of Omega-3 Polyunsaturated Fatty Acids in the Treatment of Patients with Acute Respiratory Distress Syndrome: A Clinical Review.

Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process. Recent report on the prognostic value of eicosanoids in patients with ARDS suggests that modulating the inflammatory response through the use of polyunsaturated fatty acids may be a useful strategy for ARDS treatment. The use of enteral diets enriched with eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) has reported promising results, showing an improvement in respiratory variables and haemodynamics. However, the interpretation of the studies is limited by their heterogeneity and methodology and the effect of ω-3 fatty acid-enriched lipid emulsion or enteral diets on patients with ARDS remains unclear. Therefore, the routine use of ω-3 fatty acid-enriched nutrition cannot be recommended and further large, homogeneous, and high-quality clinical trials need to be conducted to clarify the effectiveness of ω-3 polyunsaturated fatty acids.

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.

BACKGROUND AND PURPOSE: Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. EXPERIMENTAL APPROACH: The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). KEY RESULTS: In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. CONCLUSIONS AND IMPLICATIONS: NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds.

Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism.

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B(2) antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H(1)-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 microg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 microg dose of PPE increased RL by 132 +/- 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with diphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 +/- 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastase-kinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.

Budesonide affects allergic mucociliary dysfunction.

Airway inflammation characterized by neutrophils and free elastase contributes to allergic mucociliary dysfunction. Glucocorticosteroids are the most important anti-inflammatory agents used in the treatment of asthma, but their effect on allergic mucociliary dysfunction is not known. Therefore, we assessed both the prophylactic and therapeutic effects of the glucocorticosteroid budesonide on antigen-induced mucociliary dysfunction in sheep. Tracheal mucus velocity (TMV), a marker of mucociliary clearance, was measured by using a roentgenographic technique. When budesonide was administered either 30 min before or 1 h after airway challenge with Ascaris suum, the antigen-induced fall in TMV at 6 h was prevented. The effects on TMV at 8 and 24 h after challenge were also determined when budesonide and, for comparative purposes, alpha1-protease inhibitor were given 6 h after antigen challenge. Budesonide treatment improved TMV at 8 h, but TMV was not significantly different from antigen alone at 24 h. Treatment with alpha1-protease inhibitor, however, caused only a significant reversal of the antigen-induced fall in TMV at 24 h after challenge; this indicates a more prolonged effect than budesonide. Our results suggest that antiproteases may have a potential role as a therapeutic approach to mucociliary dysfunction in asthma and provide evidence for another means by which glucocorticosteroids contribute to the control of the disease.

Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways.

Pyocyanin (Pyo) and 1-hydroxyphenazine (1-HP) are extracellular products of Pseudomonas aeruginosa. To test whether these products were capable of producing an inflammatory response in the airways, combinations of Pyo and 1-HP at concentrations of 10(-4) and 10(-5) M were instilled into sheep airways, and indexes of inflammation were assessed by bronchoalveolar lavage (BAL) 24 h later. Challenge with the phenazines caused a significant dose-dependent increase in the number of cells and neutrophils recovered by BAL. Control challenges produced no such changes. The lung neutrophilia was accompanied by an increased concentration of albumin in BAL. The increases in BAL neutrophils and albumin could be blocked by treating the sheep with the 5-lipoxygenase inhibitor zileuton. Neither 1-HP nor Pyo was chemotactic to neutrophils when tested in vitro, but when alveolar macrophages (AM) were cultured in vitro in the presence of both Pyo and 1-HP (1 microM), the supernatants caused neutrophil chemotaxis. Analysis of AM culture supernatants incubated with the combination of pigments showed significant increases in leukotriene B4 and interleukin-8, and blocking these mediators separately or together reduced AM supernatant-induced neutrophil chemotaxis. We conclude that local instillation of Pyo and 1-HP can initiate an inflammatory response in the airways of sheep in vivo. This effect can be explained, in part, by the release of chemotactic factors produced by AM.