Bone Marrow Mononuclear Cell Therapy Led to Alveolar-Capillary Membrane Repair, Improving Lung Mechanics in Endotoxin-Induced Acute Lung Injury

The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups (n = 6 each). In the acute lung injur;y (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 mu g, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 x 10(7) cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance (E(st)), resistive (Delta P(1)), and viscoelastic (Delta P(2)) pressures] and histology (light and electron microscopy) were analyzed. Immunogold electron microscopy was used to evaluate if multinucleate cells were type II epithelial cells. BMDMC therapy prevented endotoxin-induced lung inflammation, alveolar collapse, and interstitial edema. In addition, BMDMC administration led to epithelial and endothelial repair with multinucleated type II pneumocytes. These histological changes yielded a reduction in lung E(st), Delta P(1), and Delta P(2) compared to ALI. In the present experimental ALI model, the administration of BMDMC yielded a reduction in the inflammatory process and a repair of epithelium and endothelium, reducing the amount of alveolar collapse, thus leading to an improvement in lung mechanics.

Pulmonary periarterial inflammation in fatal asthma

P>Background To date, little information has been available about pulmonary artery pathology in asthma. The pulmonary artery supplies the distal parts of the lungs and likely represents a site of immunological reaction in allergic inflammation. The objective of this study was to describe the inflammatory cell phenotype of pulmonary artery adventitial inflammation in lung tissue from patients who died of asthma. Methods We quantified the different inflammatory cell types in the periarterial region of small pulmonary arteries in lung tissue from 22 patients who died of asthma [fatal asthma (FA)] and 10 control subjects. Using immunohistochemistry and image analysis, we quantified the cell density for T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), eosinophils, mast cells (chymase and tryptase), and neutrophils in the adventitial layer of pulmonary arteries with a diameter smaller than 500 mu m. Results Our data (median/interquartile range) demonstrated increased cell density of mast cells [FA=271.8 (148.7) cells/mm<SU2</SU; controls=177.0 (130.3) cells/mm<SU2</SU, P=0.026], eosinophils [FA=23.1 (58.6) cells/mm<SU2</SU; controls=0.0 (2.3) cells/mm<SU2</SU, P=0.012], and neutrophils [FA=50.4 (85.5) cells/mm<SU2</SU; controls=2.9 (30.5) cells/mm<SU2</SU, P=0.009] in the periarterial space in FA. No significant differences were found for B and T lymphocytes or CD4<SU+</SU or CD8<SU+</SU subsets. Chymase/tryptase positive (MC(CT)) mast cells predominated over tryptase (MC(T)) mast cells in the perivascular arterial space in both asthma patients and controls [MC(CT)/(MC(CT)+MC(T))=0.91 (0-1) in FA and 0.75 (0-1) in controls, P=0.86]. Conclusions Our results show that the adventitial layer of the pulmonary artery participates in the inflammatory process in FA, demonstrating increased infiltration of mast cells, eosinophils, and neutrophils, but not of T and B lymphocytes.

Description of Nosocomial Infection Prevention Practices by Anesthesiologists in a University Hospital

Kishi D; Videira RLR Description of Nosocomial Infection Prevention Practices by Anesthesiologists in a University Hospital. Background and objectives: Anesthesiologists play an important role in the prevention of nosocomial infections. In anesthetic practice, physiologic barriers are routinely breached, allowing patient contamination with microorganisms and the consequent development of infection. The lack of adhesion to recommended practices can facilitate transmission of microorganisms. It is important to describe prophylactic practices of anesthesia-related nosocomial infections performed by anesthesiologists. Methods: Structured questionnaires were distributed to be answered voluntarily and anonymously by anesthesiologists. Results: Among 112 anesthesiologists, 75% answered the questionnaire. Surgical mask is used by 95.2% of anesthesiologists, 96.3% wear gloves frequently, 98.9% wear sterile gloves for neuraxial block, 91.3% use sterile technique for central venous puncture, 95.1% wash their hands between cases, 91.6% try to maintain the endotracheal tube sterile, 96.3% discard the prefilled propofol syringe at the end of each anesthesia, 30% clean the vials before using it in the neuraxial blocks, and 19.8% clean the vials before intravenous use. Conclusions: Respondents showed good adhesion to practices of nosocomial infection prophylaxis and to improve them educational multidisciplinary campaigns are necessary.

Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men.

Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. Results: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). Conclusions: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.) N Engl J Med 2010;363:2587-99.

A better understanding of urogenital tuberculosis pathophysiology based on radiological findings

Purpose: To assess the radiological findings of urogenital tuberculosis (UGT) in patients at different disease stages, for a better understanding of its pathophysiology. Patients and methods: We retrospectively reviewed the radiological exams of 20 men (median age 41 years; range: 28-65) with urogenital tuberculosis diagnosis. The patients were classified in the following groups: (1) bilateral renal tuberculosis with predominantly parenchymatous involvement; (2) unilateral renal tuberculosis; (3) unilateral renal tuberculosis with bladder tuberculosis and (4) bilateral renal tuberculosis with bladder tuberculosis. Results: One AIDS patient had multiple bilateral renal tuberculosis abscesses (group 1). Six patients had unilateral renal tuberculosis with hydronephrosis due to stenosis and thickening of the collecting system, without involvement of the bladder or contralateral kidney (group 2). Six patients had bladder tuberculosis with diffuse thickening of the bladder wall, with one very low or no function kidney while the other kidney was normal (group 3). Seven patients had bladder tuberculosis associated to a very low or no function kidney with the other kidney with high-grade vesicoureteral reflux-associated ureterohydronephrosis (group 4). In two patients, sequential exams showed evolution of tuberculosis from a unilateral renal and ureteral lesion to contracted bladder and dilatation of the contralateral kidney secondary to high-grade reflux. Conclusions: UGT may have variable radiological presentations. However, in two of our cases we have seen that tuberculosis involvement of the urinary tract may be sequential. Further evidences are necessary to confirm this hypothesis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Survival in Schistosomiasis-Associated Pulmonary Arterial Hypertension

Objectives The objective of this study was to evaluate the natural history of untreated schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) patients as compared to idiopathic pulmonary arterial hypertension (IPAH) with respect to hemodynamics recorded at presentation and 36 months survival. Background Schistossomiasis (Sch) is one of the most prevalent chronic infectious diseases in the world. Nevertheless data regarding one of its most severe clinical complications, pulmonary arterial hypertension (PAH), is scarce. Methods We retrospectively analyzed case notes of all consecutive patients diagnosed of Sch-PAH and IPAH referred to the Heart Institute in Sao Paulo, Brazil, between 2004 and 2008. None of the Sch-PAH received PAH specific treatment whereas all IPAH patients did. Results Sch-PH patients (n = 54) had less severe pulmonary hypertension as evidenced by lower levels of pulmonary vascular resistance (11.3 +/- 11.3 W vs. 16.7 +/- 10.6 W; p = 0.002) and mean pulmonary artery pressure (56.7 +/- 18.7 mm Hg vs. 64.6 +/- 17.4 mm Hg; p = 0.01) and higher cardiac output (4.62 +/- 1.5 l/min vs. 3.87 +/- 1.5 l/min; p = 0.009) at presentation than IPAH patients (n = 95). None of the Sch-PAH patients demonstrated a positive response to acute vasodilator testing, whereas 16.2% of IPAH patients did (p = 0.015). Survival rates at 1, 2, and 3 years were 95.1%, 95.1%, and 85.9% and 95%, 86%, and 82%, for Sch-PAH and IPAH, respectively (p = 0.49). Both groups had a higher survival rate when compared to IPAH survival as estimated by the NIH equation (71%, 61%, and 52%, respectively). Conclusions Sch-PAH has a more benign clinical course than IPAH despite a lack of demonstrable acute vasoreactivity at hemodynamic evaluation. (J Am Coll Cardiol 2010; 56: 715-20) (C) 2010 by the American College of Cardiology Foundation

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Salbutamol improves markers of epithelial function in mice with chronic allergic pulmonary inflammation

We investigated the effects of salbutamol on the markers of epithelial function in a murine model of chronic allergic pulmonary inflammation by recording the ciliary beat frequency (CBF) and the transepithelial potential difference (PD) in vivo. Mice were sensitized and received four challenges of ovalbumin (OVA group) or 0.9% saline (control group). Forty-eight hours after the 4th inhalation, we observed eosinophilia in the bronchoalveolar lavage and epithelium remodeling with stored acid mucus in the OVA group (P < 0.001). No difference in the baseline CBF was noticed between the groups; however, the OVA group had a significantly lower baseline PD (P = 0.013). Salbutamol increased the CBF in all groups studied, and the dose response curve to salbutamol increased the PD in the OVA group from 10(-4) M to 10(-2) M. We suggest that salbutamol affects the CBF and the depth of the periciliary layer, which, in great part, determines the ability of the cilia to propel the mucus layer. This effect may have a positive impact on airway mucociliary transport in asthma and may have clinical implications. (C) 2011 Elsevier B.V. All rights reserved.

Time course of haemodynamic, respiratory and inflammatory disturbances induced by experimental acute pulmonary polystyrene microembolism

Background and objective The time course of cardiopulmonary alterations after pulmonary embolism has not been clearly demonstrated and nor has the role of systemic inflammation on the pathogenesis of the disease. This study aimed to evaluate over 12 h the effects of pulmonary embolism caused by polystyrene microspheres on the haemodynamics, lung mechanics and gas exchange and on interleukin-6 production. Methods Ten large white pigs (weight 35-42 kg) had arterial and pulmonary catheters inserted and pulmonary embolism was induced in five pigs by injection of polystyrene microspheres (diameter similar to 300 mu mol l(-1)) until a value of pulmonary mean arterial pressure of twice the baseline was obtained. Five other animals received only saline. Haemodynamic and respiratory data and pressure-volume curves of the respiratory system were collected. A bronchoscopy was performed before and 12 h after embolism, when the animals were euthanized. Results The embolism group developed hypoxaemia that was not corrected with high oxygen fractions, as well as higher values of dead space, airway resistance and lower respiratory compliance levels. Acute haemodynamic alterations included pulmonary arterial hypertension with preserved systemic arterial pressure and cardiac index. These derangements persisted until the end of the experiments. The plasma interleukin-6 concentrations were similar in both groups; however, an increase in core temperature and a nonsignificant higher concentration of bronchoalveolar lavage proteins were found in the embolism group. Conclusion Acute pulmonary embolism induced by polystyrene microspheres in pigs produces a 12-h lasting hypoxaemia and a high dead space associated with high airway resistance and low compliance. There were no plasma systemic markers of inflammation, but a higher central temperature and a trend towards higher bronchoalveolar lavage proteins were found. Eur J Anaesthesiol 27:67-76 (C) 2010 European Society of Anaesthesiology.

Biopsy-Proven Pulmonary Determinants of Heart Disease

Heart disease (HD) can stress the alveolar blood-gas barrier, resulting in parenchymal inflammation and remodeling. Patients with HD may therefore display any of the symptoms commonly attributed to primary pulmonary disease, although tissue documentation of corresponding changes through surgical lung biopsy (SLB) is rarely done. Intent on exploring the basis of HD-related alveolar-capillary barrier dysfunction, a retrospective analysis of SLB histopathology was conducted in patients with clinically diagnosed HD, diffuse pulmonary infiltrates, and no evidence of primary pulmonary disease. Patients eligible for the study had a clinical diagnosis of heart disease, acute or chronic, and presented with diffuse infiltrates on chest X-ray. All qualified subjects (N = 23) who underwent diagnostic SLB between January 1982 and December 2005 were subsequently examined. Specific biopsy parameters investigated included demonstrable edema, siderophage influx, hemorrhage, venous and lymphatic ectasia, vascular sclerosis, capillary congestion, and fibroblast proliferation. Based on observed alveolar-capillary barrier (ACB) alterations, three main morphologic groups emerged: one group (6 patients) with alveolar edema; a second group (11 patients) characterized by pulmonary congestion; and a final group (6 patients) showing microscopic foci of acute ACB lung injury. Alveolar-capillary stress due to acute high-pressure or volume overload often manifests as diffuse pulmonary infiltrates with variable but generally predictable histopathology. In patients with biopsy-proven alveolar edema, pulmonary congestion, or acute microscopic lung injury, the clinician must be alert for the possibility of primary heart disease, particularly if the patient is elderly or when a history of myocardial, valvular, or coronary vascular disease exists.

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer

Background and objective: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. Methods: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). Results: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. Conclusions: The proposed models were effective in suggesting pleural tuberculosis or cancer.