Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT = 6 ml/kg and positive end-expiratory pressure (PEEP) = 5 cmH(2)O for 1 h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40 s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP = 40 cmH(2)O), with interposed periods of PIP = 10 cmH(2)O above a PEEP = 15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury. (C) 2009 Elsevier BLV. All rights reserved.

Gut ischemia/reperfusion induced acute lung injury is an alveolar macrophage dependent event

Background:. Although the role of the lung alveolar macrophage (AM) as a mediator of acute lung injury (ALI) after lung ischemia/reperfusion (I/R) has been suggested by animal experiments, it has not been determined whether AMs mediate ALI after intestinal I/R. The objective of this study was to determine the effect of AM elimination on ALI after intestinal I/R in rats. Mwthods: Male Wistar rats (n = 90) were randomly divided into three groups: the clodronate-liposomes (CLOD-LIP) group received intratracheal treatment with CLOD-LIP; the liposomes (LIP) group received intratracheal treatment with LIP; and the nontreated (UNTREAT) group received no treatment. Twenty-four hours later each group was randomly divided into three subgroups: the intestinal I/R subgroup was subjected to 45-minute intestinal ischemia and 2-hour reperfusion; the laparotomy (LAP) subgroup was subjected to LAP and sham procedures; the control (CTR) subgroup received no treatment. At the end of reperfusion, ALI was quantitated in all the animals by the Evans blue dye (EBD) method. Results: ALI values are expressed as EBD lung leakage (mu g EBD/g dry lung weight). EBD lung leakage values in the CLOD-LIP group were 32.59 +/- 12.74 for I/R, 27.74 +/- 7.99 for LAP, and 33.52 +/- 10.17 for CTR. In the LIP group, lung leakage values were 58.02 +/- 18.04 for I/R, 31.90 +/- 8.72 for LAP, and 27.17 +/- 11.48 for CTR. In the UNTREAT group, lung leakage values were 55.60 +/- 10.96 for I/R, 35.99 +/- 6.89 for LAP, and 30.83 +/- 8.41 for CTR. Within each group, LAP values did not differ from CTR values. However, in the LIP and UNTREAT groups, values for both the LAP and CTR subgroups were lower than values for the I/R subgroup (p < 0.001). The CLOD-LIP I/R subgroup value was less (p < 0.001) than the I/R subgroup values in the LIP and UNTREAT groups. These results indicated that I/R provokes ALI that can be prevented by CLOD-LIP treatment, and further suggested that AMs are essential for ALI occurrence induced by intestinal I/R in rats.

Is procalcitonin useful to differentiate rejection from bacterial infection in the early post-operative period of liver transplantation in children?

PCT is a protein that is recognized as an acute marker of inflammation. Previous studies performed in adults who underwent liver or heart transplantation indicated that PCT plasmatic levels help to differentiate between rejection and infection. The objective of this study was to evaluate whether PCT has the same role in liver-transplanted children. Thirty-six patients were studied between the first and the thirtieth post-operative days, and PCT determinations were prospectively performed according to the clinical status of the patient. In the non-complicated patients, PCT measurements performed on the first and second post-operative days revealed a median value of 1.60 ng/mL (mean 5.68 +/- 7.05; range 0.69-18.30). After the fourth day of transplantation, PCT plasma concentrations decreased to a median value of 0.21 ng/mL (mean 0.47 +/- 0.59; range 0.05-2.00; normal values are less than 0.5 ng/mL). In infected patients, PCT plasma levels demonstrated a significant increase, differing from the patients with acute liver rejection whose levels were similar to those of non-complicated patients. In conclusion, we could demonstrate that in the early post-operative period of liver transplantation in children, measuring PCT plasmatic levels might be a useful tool for differentiation between bacterial infection and acute liver rejection.

Evidence that two independent host genes influence the severity of tissue damage and susceptibility to acute pyelonephritis in murine systemic candidiasis

Tissue damage in the kidney and brain after systemic infection with Candida albicans was examined in recombinant inbred strains (AKXL) derived from AKR and C57/L progenitors. Nine of the 15 strains showed mild (C57/L-like) tissue damage. Of the remainder, two strains developed lesions comparable to the AKR parental strain, whereas four exhibited a much move severe pattern of tissue damage. This was characterized by pronounced mycelial growth in the brain, and gross oedema of the kidney, with extensive fungal colonization and marked tissue destruction. The presence of the null allele of the haemolytic complement gene (Hc) may be necessary but not sufficient, for the expression of the very severe lesions. The results were interpreted as reflecting the actions of two independent genes, which have been designated Carg1 and Carg2 (Candida albicans resistance genes 1 and 2). (C) 1997 Academic Press Limited.

Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia

Severe infections caused by Stenotrophomonas maltophilia are associated with high mortality, and strategies to improve the clinical outcome for infected patients are needed. A retrospective cohort study of patients with bloodstream infection (BSIs) and pneumonia caused by S. maltophilia was conducted. Multivariate analysis was performed to access factors associated with 14-day mortality. A total of 60 infections were identified. Among these, eight (13%) were pneumonias and 52 were BSIs; 33.3% were primary, 13% were central venous catheter (CVC)-related and 40% were secondary BSIs. Fifty-seven (85%) patients had received previous antimicrobial therapy; 88% had CVC, 57% mechanical ventilation and 75% were in the intensive care unit at the onset of infection. Malignancy (45%) was the most frequent underlying disease. The mean of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores was 17 and for the Sepsis-related Organ Failure Assessment (SOFA) score, it was 7 points. The overall and 14-day mortality were, respectively, 75% and 48%. Forty-seven (78%) patients were treated and, of these, 74% received trimethoprim-sulfamethoxazole. Independent risk factors associated with mortality were SOFA index > 6 points (0.005) and septic shock (0.03). The Kaplan-Meier estimations curves showed that patients with APACHE II score > 20 and SOFA score > 10 had a survival chance of, respectively, less than 8% and less than 10% (P <= 0.001) at 21 days after the first positive S. maltophilia culture. Our results suggest that the independent factors associated with outcome in patients with infection caused by S. maltophilia are septic shock and higher SOFA index.

Involvement of the central nervous system in patients with dengue virus infection

The findings of a neurological evaluation in 85 patients with confirmed, acute, dengue virus infection are described. Signs of central nervous system involvement were present in IS patients (21.2%). The most frequent neurological symptom was mental confusion. The frequency of neurological involvement did not differ between patients with primary and secondary dengue infection, and the prevalence of central nervous system involvement in dengue fever and dengue hemorrhagic fever also did not differ significantly. The presence of CNS involvement did not influence the prognosis of dengue infection. Dengue viral CSF RNA was found in 7 of 13 patients submitted to a spinal tap, the CSF viral load being less than 1000 copies/ml. PCR was negative in serum samples obtained from three patients on the same day as the CSF samples, suggesting that the dengue virus actively enters the CNS and that the presence of the virus in the CNS does not result from passive crossing of the blood-brain barrier. (C) 2007 Elsevier B.V. All rights reserved.

Vitamin D intoxication: a cause of hypocalcaemia and acute renal failure in a HIV patient

Hypercalcaemia in patients with HIV infection is usually associated with specific conditions such as lymphoma and granulomatous diseases. We described a case of severe hypercalcaemia consequent to vitamin D intoxication and secondary renal failure in a HIV patient under tenofovir using. Serum creatinine and calcium returned to near normal levels after vitamin D discontinuation, saline and furosemide administration. Some aspects of the drug-induced nephropathy are discussed.

Usefulness of qualitative polymerase chain reaction for Trypanosoma cruzi DNA in endomyocardial biopsy specimens of chagasic heart transplant patients

BACKGROUND: Chagas` disease reactivation (CDR) after heart transplantation is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. CDR affecting the myocardium induces lymphocytic myocarditis and should be distinguished from acute cellular rejection in endomyocardial biopsy (EMB) specimens. METHODS: We performed retrospectively qualitative polymerase chain reaction for T cruzi DNA using 2 sets of primers targeting nuclear DNA (nDNA) or kinetoplast DNA (kDNA) in 61 EMB specimens of 11 chagasic heart transplant recipients who presented with CDR. Thirty-five EMB specimens were obtained up to 6 months before (pre-CDR group) and 26 up to 2 years after the diagnosis of CDR. The control group consisted of 6 chagasic heart transplant recipients with 18 EMB specimens who never experienced CDR. RESULTS: Amplification of kDNA occurred in 8 of 35 (22.9%) EMB specimens of the pre-CDR group, in 5 of 18(27.8%) of the control group, and in 17 of 26(65.4%) EMB specimens obtained after the successful treatment of CDR. Amplification of nDNA occurred in 3 of 35 (8.6%) EMB specimens of the pre-CDR group, 0 of 18 (0%) of the control group, and 6 of 26 (23.1%) EMB specimens obtained after the successful treatment of CDR. CONCLUSIONS: Amplification of kDNA in EMB specimens is not specific for the diagnosis of CDR, occurring also in patients with no evidence of CDR (control group). However, amplification of nDNA occurred in a few EMB specimens obtained before CDR, but in none of the control group specimens. Qualitative PCR for T cruzi DNA in EMB specimens should not be used as a criterion for cure of CDR because it can persist positive despite favorable clinical evolution of the patients. J Heart Lung Transplant 2011;30:799-804 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.

CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION MIMICKING HENOCH-SCHONLEIN PURPURA

Introduction: Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent symptoms for at least 3 months, such as fever, hepatosplenomegaly and lymphadenopathy. The diagnosis is established due to the presence of anti-EBV antibodies or isolation of this infectious agent in affected tissues. Three cases of CAEBV infection mimicking Henoch-Schonlein purpura (HSP) were described. Case 1: Female 3-year old patient with cervical adenomegaly, anemia and fever developed palpable purpura, haematuria and arthritis. CAEBV infection was established by serology test. She received methylprednisolone and acyclovir. She had generalized lymphadenopathy, hepatomegaly, splenomegaly, disseminated intravascular coagulation and deceased. Case 2: Male 12-year old patient with persistent anemia, lymphadenopathy, hepatomegaly and splenomegaly had CAEBV infection diagnosis by serology test. He developed purpura and arthritis and received methylprednisolone. Case 3: Male 13-year old patient had purpura, abdominal pain, haematuria, hepatomegaly, splenomegaly, lymphadenopathy, anemia and elevated liver enzymes. The cervical lymph node biopsy was positive to EBV infection. He received methylprednisolone and acyclovir, developing acute fulminant hepatitis and death. Discussion: CAEBV infection mimicking HSP was rarely observed in our population

Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury

Prone position may delay the development of ventilator-induced lung injury (VILI), but the mechanisms require better elucidation. In experimental mild acute lung injury (ALI), arterial oxygen partial pressure (Pa(O2)), lung mechanics and histology, inflammatory markers [interleukin (IL)-6 and IL-1 beta], and type III procollagen (PCIII) mRNA expressions were analysed in supine and prone position. Wistar rats were randomly divided into two groups. In controls, saline was intraperitoneally injected while ALI was induced by paraquat. After 24-h, the animals were mechanically ventilated for 1-h in supine or prone positions. In ALI, prone position led to a better blood flow/tissue ratio both in ventral and dorsal regions and was associated with a more homogeneous distribution of alveolar aeration/tissue ratio reducing lung static elastance and viscoelastic pressure, and increasing end-expiratory lung volume and Pa(O2). PCIII expression was higher in the ventral than dorsal region in supine position, with no regional changes in inflammatory markers. In conclusion, prone position may protect the lungs against VILI, thus reducing pulmonary stress and strain. (C) 2009 Elsevier B.V. All rights reserved.

Effects of frequency and inspiratory plateau pressure during recruitment manoeuvres on lung and distal organs in acute lung injury

To evaluate the effects of frequency and inspiratory plateau pressure (Pplat) during recruitment manoeuvres (RMs) on lung and distal organs in acute lung injury (ALI). We studied paraquat-induced ALI rats. At 24 h, rats were anesthetized and RMs were applied using continuous positive airway pressure (CPAP, 40 cmH(2)O/40 s) or three-different sigh strategies: (a) 180 sighs/h and Pplat = 40 cmH(2)O (S180/40), (b) 10 sighs/h and Pplat = 40 cmH(2)O (S10/40), and (c) 10 sighs/h and Pplat = 20 cmH(2)O (S10/20). S180/40 yielded alveolar hyperinflation and increased lung and kidney epithelial cell apoptosis as well as type III procollagen (PCIII) mRNA expression. S10/40 resulted in a reduction in epithelial cell apoptosis and PCIII expression. Static elastance and alveolar collapse were higher in S10/20 than S10/40. The reduction in sigh frequency led to a protective effect on lung and distal organs, while the combination with reduced Pplat worsened lung mechanics and histology.

Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury

Objective: To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). Design: Prospective, randomized, and controlled experimental study. Setting: University research laboratory. Subjects: Wistar rats were randomly assigned to control (C) [saline (0.1 ml), intraperitoneally] and ALI [paraquat (15 mg/kg), intra peritoneally] groups. Measurements and Main Results: After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H(2)O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (Delta P2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and Delta P2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. Conclusions: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and Delta P2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful. (Crit Care Med 2009; 37:1011-1017)

Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury

The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI). In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 mu g i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg center dot kg(-1) i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured. In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design. Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.

Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice

Objective: Gorticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: One hundred twenty-eight BALB/c mice (20-25 g). Interventions: Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Gexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 mu g, ALIp) or intraperitoneally (125 mu g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALlexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively). Measurements and Main Results: At 24 hrs, lung state elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interieukin-6, and transforming growth factor (TGF)-beta levels in bronchoatveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta 1 and TGF-beta 2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFN gamma, and TGF-beta 2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups. Conclusions. Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.

Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice

Air pollution is associated with morbidity and mortality induced by respiratory diseases. However, the mechanisms therein involved are not yet fully clarified. Thus, we tested the hypothesis that a single acute exposure to low doses of fine particulate matter (PM2.5) may induce functional and histological lung changes and unchain inflammatory and oxidative stress processes. PM2.5 was collected from the urban area of Sao Paulo city during 24 h and underwent analysis for elements and polycyclic aromatic hydrocarbon contents. Forty-six male BALB/c mice received intranasal instillation of 30 mu L of saline (CTRL) or PM2.5 at 5 or 15 mu g in 30 mu L of saline (P5 and P15, respectively). Twenty-four hours later, lung mechanics were determined. Lungs were then prepared for histological and biochemical analysis. P15 group showed significantly increased lung impedance and alveolar collapse, as well as lung tissue inflammation, oxidative stress and damage. P5 presented values between CTRL and P15: higher mechanical impedance and inflammation than CTRL, but lower inflammation and oxidative stress than P15. In conclusion, acute exposure to low doses of fine PM induced lung inflammation, oxidative stress and worsened lung impedance and histology in a dose-dependent pattern in mice.