Expression profiling of extramedullary acute myeloid leukemia suggests involvement of epithelial-mesenchymal transition pathways.

Extramedullary (EM) colonization is a rare complication of acute myeloid leukemia (AML), occurring in about 10% of patients, but the processes underlying tissue invasion are not entirely characterized. Through the application of RNAseq technology, we examined the transcriptome profile of 13 AMLs, 9 of whom presented an EM localization. Our analysis revealed significant deregulation within the extracellular matrix (ECM)-receptor interaction and focal-adhesion pathways, specifically in the EM sites. The transcription factor TWIST1, which is known to impact on cancer invasion by dysregulating epithelial-mesenchymal-transition (EMT) processes, was significantly upregulated in EM-AML. To test the functional impact of TWIST1 overexpression, we treated OCI-AML3s with TWIST1-siRNA or metformin, a drug known to inhibit tumor progression in cancer models. After 48 h, we showed downregulation of TWIST1, and of the EMT-related genes FN1 and SNAI2. This was associated with significant impairment of migration and invasion processes by Boyden chamber assays. Our study shed light on the molecular mechanisms associated with EM tissue invasion in AML, and on the ability of metformin to interfere with key players of this process. TWIST1 may configure as candidate marker of EM-AML progression, and inhibition of EMT-pathways may represent an innovative therapeutic intervention to prevent or treat this complication.

Minimal residual disease negativity in elderly patients with acute myeloid leukemia may indicate different postremission strategies than in younger patients.

In the present analysis, we evaluated whether in elderly acute myeloid leukemia (AML) patients (>60 years), minimal residual disease (MRD) assessed by flow cytometry may have a role in guiding choice of postremission strategies. We analyzed 149 young and 61 elderly adults who achieved morphological CR after induction course of EORTC/GIMEMA protocols. Elderly patients reached a postconsolidation MRD negative status less frequently than younger ones (11 vs 28 %, p = 0.009). MRD negativity resulted in a longer 5-year disease-free survival (DFS) both in elderly (57 vs 13 %, p = 0.0197) and in younger patients (56 vs 31 %, p = 0.0017). Accordingly, 5-year cumulative incidence of relapse (CIR) of both elderly (83 vs 42 %, p = 0.045) and younger patients (59 vs 24 % p = NS) who were MRD positive doubled that of MRD negative ones. Nevertheless, CIR of MRD negative elderly patients was twofold higher than that of younger MRD negative ones (42 vs 24 %, p = NS). In conclusion, elderly patients in whom chemotherapy yields a MRD negative CR have duration of DFS and rate of CIR significantly better than those who remain MRD positive. Nonetheless, the high CIR rate observed in the elderly suggests that MRD negativity might have different therapeutic implications in this population than in the younger counterpart.

[Localized neuropathic pain--5% lidocaine medicated patch as a first-line treatment and as add-on therapy: literature review and personal experience]. / Dolore neuropatico localizzato: revisione della letteratura sull'utilizzo de Lidocaina cerotto 5% come first line treatment e nostra esperienza come add-on therapy.

Localized neuropathic pain (LNP) is a type of neuropathic pain characterized by consistent and circumscribed area(s) of maximum pain, which are associated with negative or positive sensory signs and/or spontaneous symptoms typical of neuropathic pain. This description outlines the clinical features of a group of pathologies, in which a LNP can be diagnosed and for whom topical targeted treatment with 5% Lidocaine medicated plaster can be suggested. Indeed both American as well as European guidelines already suggest 5% Lidocaine medicated plaster as a first line treatment in post herpetic neuralgia and in general in the treatment of conditions such as diabetic painful polyneuropathy and post surgical pain where a LNP can be ascertain. In a daily practice of a Pain Unit however the usual case mix encompasses also other causes of LNP, most of them with a scanty pain control in spite of a ongoing polytherapy. Aims of this paper were to focus on 5% Lidocaine medicated plaster as a first line treatment in LNP and to add new insight on its possible use as add-on therapy reporting our data on a consecutive series of 42 patients affected by LNP under unsatisfactory polytherapy in which 5% Lidocaine medicated plaster was able to achieve a satisfactory pain control.

A multicancer-like syndrome in a dog characterized by p53 and cell cycle-checkpoint kinase 2 (CHK2) mutations and sirtuin gene (SIRT1) down-regulation.

INTRODUCTION: We have investigated SIRT1, p53 and cell cycle-checkpoint kinase 2 (CHK2) gene dysfunction in a dog with a multicancer syndrome-like in order to evaluate their potential role in the determinism of the disease and to establish a possible correlation between SIRT1 transcript level and p53 expression status. MATERIAL AND METHODS: Blood sample and tumour samples from a pure breed English Setter dog with different tumours were used for this study. Nucleotide sequence analysis was performed with a DNA autosequencer in order to examine p53 and CHK2 mutations. In addition, the expression level of SIRT1 was quantified by Southern Blot analysis of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). RESULTS: Cytological examination revealed five different tumours: a cutaneous sebaceous epithelioma, a cutaneous mast cell tumour, a testicular Sertoli cell tumour, an oral malignant melanoma, and a cutaneous squamous cell carcinoma. Sequencing analysis revealed the presence of a nucleotide substitution, (CGG>CAG) exon 7 of the p53 gene in DNA from peripheral blood mononuclear cells (PBMCs) as well as in the melanoma; whereas the other four cancers showed the loss of the wild-type allele. Furthermore, CHK2 mutation at codon 311 has been identified in the melanoma and sebaceous epithelioma. In addition, SIRT1 cDNA expression decreased in all tumour samples compared to cDNA SIRT1expression level in peripheral blood mononuclear cells (PBMCs) in the same dog. CONCLUSIONS: These results suggest that the germ line mutation of the p53 gene at codon 248 might be, at least, one cause of the multicancer syndrome-like in our dog; furthermore, we show a possible correlation between SIRT1 transcript level and p53 mutations status. The regulatory role of SIRT1 in tumour suppressor pathways suggests that the net effect seen may represent both direct and indirect downstream regulation and it is likely to depend on the presence or absence of functional p53.

Antiapoptotic activity of bovine herpesvirus type-1 (BHV-1) UL14 protein.

Viruses have evolved different strategies to interfere with apoptotic pathways in order to halt cellular responses to infection. One previous study showed that transient transfection of bovine herpesvirus type-1 (BHV-1) UL14 protein is efficient in protecting Madin Darby kidney (MDBK) and human chronic myelogenous leukemia (K562) cells from sorbitol-induced apoptosis. This protein corresponds to a putative protein of BHV-1, which shares aminoacid sequence with a part of the peptide-binding domain conserved in human heat shock protein (HSP70) family. The pBK-CMV-UL14 plasmid transfected MDBK cells treated with sorbitol did not show caspase-3 and caspase-9 activation with respect to non-transfected MDBK cells (UL14 negative). Furthermore, we report that the expression of the full length sequence of BHV-1 UL14 is evident after 7 h of infection of BHV-1 on MDBK cells which were then treated with sorbitol. These results indicate that UL14 gene product has important implications to enhance cell survival in response to apoptotic stimuli.

The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia.

UNLABELLED: We assessed by multiparametric flow cytometry the levels of minimal residual disease (MRD) in 100 adult patients with acute myelogenous leukemia (AML) achieving complete remission after intensive chemotherapy. The aim of the study was to determine the optimal threshold, in terms of residual leukemic cells, and the time point of choice, that is, post-induction (post-Ind) or post-consolidation (post-Cons), able to better predict outcome. By applying the maximally selected log-rank statistics, the threshold discriminating MRD- from MRD+ cases was set at 3.5 x 10(-4) residual leukemic cells, a level that allowed the identification of distinct subgroups of patients, both at post-Ind and post-Cons time points. Post-Cons MRD- patients had a superior outcome in terms of relapse rate, overall survival (OS) and relapse-free survival (RFS) (P<0.001, for all comparisons), regardless of the MRD status after induction. In particular, patients entering MRD negativity only after consolidation showed the same outcome as those achieving early negativity after induction. Multivariate analysis, including karyotype, age, MDR1 phenotype, post-Ind and post-Cons MRD levels, indicated that the post-Cons MRD status independently affected relapse rate, OS and RFS (P<0.001, for all comparisons). IN CONCLUSION: (1) the threshold of 3.5 x 10(-4) is valid in discriminating risk categories in adult AML and (2) post-Cons MRD assessment is critical to predict disease outcome.

Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation.

A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of 3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all patients who were in the high-risk group relapsed at a median time of 7 months; in the low-risk group, five patients relapsed at a median time of 11 months and 14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC determinations post-ASCT showed increased MRD levels in three of the five patients who underwent subsequent relapse, while disease recurrence was unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor most strongly associated with relapse risk in the multivariate analysis (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen followed by ASCT has no impact on the unfavorable prognostic value of high pre-ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the prediction of impending relapse.

Relationship between function and perfusion early after acute myocardial infarction.

To assess the relationship between baseline left ventricle function, functional reserve and resting myocardial perfusion in patients with acute myocardial infarction (AMI). After AMI the presence of dysfunctioning but viable myocardium plays a determinant role in clinical outcome. Regional ventricular function was evaluated by echocardiography both in resting conditions and during dobutamine infusion (10 microg/kg/min). Perfusion was assessed by magnetic resonance imaging in a single slice approach where the first pass of an intravenously injected bolus of gadolinium-based contrast agent was followed through six regions of interest within the myocardium. In each patient a region with normal function was used as reference and the cross-correlation coefficient (CCC), which described the myocardial perfusion relatively to the reference region (CCC = 1 means equivalent perfusion), was obtained for the other five myocardial regions. Twenty-two patients were enrolled into the study. Sixty-one segments had normal function and normal perfusion (CCC = 0.92+/-0.23). The perfusion deficit was more marked in the 29 regions with resting akinesia-dyskinesia than in the 20 hypokinetic regions (CCC = 0.71+/-0.45 vs. 0.84+/-0.23; p < 0.05). Out of the 29 regions with resting akinesia-dyskinesia the 13 segments which showed functional improvement following dobutamine had a higher resting perfusion than the 16 segments which were unresponsive to dobutamine (CCC = 0.83+/-0.32 vs. 0.61+/-0.52, p < 0.05). Similarly, out of the 20 regions with resting hypokinesia the 11 segments having functional reserve showed an higher resting perfusion than the segments which did not (0.96+/-0.21 vs. 0.69+/-0.19; p < 0.05). Early after AMI, the perfusion deficit reflects the severity of the mechanical dysfunction. In regions with baseline dyssynergy resting perfusion is, in general, higher when contractile reserve can be elicited by stress-echo.

[Tumor samples as a tool for large-scale monitoring of antigen-specific lymphocytes in gastric and colorectal neoplasms]. / L'utilizzo di campioni di tessuto tumorale come mezzo per il monitoraggio su larga scala dei linfociti antigene specifici nelle neoplasie gastriche e colorettali.

The characterization of tumor-associated antigens has enabled to direct the host immune response towards the autologous tumor through appropriate loading and presentation of the antigen. In vivo conditions that generate large numbers of tumor antigens would be an important step in vaccine strategies. In this study we have therefore tested the ability of freshly isolated gastric and colorectal cancer cells to induce a specific anti-tumor response in autologous T lymphocytes. Because dendritic cells (DC) are critically involved in both initiating and boosting host immune responses, they have been used to present apoptotic bodies generated by irradiated tumor cells. Results show that these native antigens stimulate T cytotoxic response against tumor, but not peritumor normal tissues. Induction of IFN-gamma secreting cell activity, which is a standard readout in current cancer vaccine protocols, was also demonstrated by Elispot single-cells assay. These data show the antigenicity of gastric and colorectal tumor cells and open new perspectives in immunotherapy.

[Subdural effusion during bacterial meningitis]. / Versamento sottodurale in corso di meningite batterica.

Twelve children of age ranged from 4 to 34 months with Haemophilus influenzae type b meningitis treated at Meyer Hospital of Florence, were retrospectively reviewed. Eight patients had subdural effusion demonstrated with TC, RM and transfontanellar ultrasonography. All patients are cured without sequelae.

Ultrasound-guided alcoholization of celiac plexus for pain control in oncology.

BACKGROUND: Treatment of inoperable pancreatic cancer pain is of paramount importance. The ineffectiveness of pharmacological agents has led many investigators to recommend chemical neurolysis of the celiac ganglions for pain control. This procedure may be performed under either fluoroscopic or computed tomography (CT) guidance, or it may accompany laparotomy. The authors describe a modified sonographically (ultrasound-US)-guided technique for alcoholization of the celiac ganglions. METHODS: Twelve patients underwent the neurolytic procedure. Nine of 12 suffered from pancreatic cancer. The remaining three were affected by inoperable hepatic, gastric, or colon cancer, respectively, with multiple hepatic metastases. US-guided alcohol neurolysis was performed by an anterior approach. In the last four patients, PIA (percutaneous injection alcohol) needles, modified by the authors, replaced the spinal needles employed in the first eight patients to inject the alcohol. Pain and pain relief were rated according to a Simple Descriptive Scale (SDS), and treatment success was gauged by declining opiate doses and need for pharmacological therapy. Results after treatment performed using different needles were compared. RESULTS: Procedure-related mortality was zero. Complications of the neurolytic procedure included left pleural effusion in one patient and mild diarrhea in two other patients. Positive, negative, and indeterminant results were noted in nine (75%, p < 0.001), two, and one patient(s), respectively. CONCLUSIONS: The neurolytic technique, although far from being considered a routine procedure, appears to provide patients with safe and effective pain relief for pain unresponsive to conventional medical treatment.

[Magnetic resonance with an endorectal coil and a fast spin echo sequence in the staging of prostatic carcinoma. The correlation with histopathological data]. / Risonanza Magnetica con bobina endorettale e sequenza Fast Spin Echo nella stadiazione del carcinoma prostatico. Correlazione con i dati istopatologici.

INTRODUCTION: We investigated the accuracy of endorectal coil Magnetic Resonance Imaging (MRI) and Fast Spin Echo (FSE) technique in staging prostate cancer. MATERIAL AND METHODS: MRI was performed in 70 patients with biopsy proved prostatic cancer. A total of 33 patients subsequently underwent radical prostatectomy. T2-weighted FSE sequences (TR 3400-4100, TE 120, Echo train length 13) were acquired in all patients. Axial, sagittal and coronal 4-5 mm images were obtained with 13-14 cm field of view and 256 x 256 matrix. Additional T1-weighted spin echo images were acquired in 9 patients. Lesion staging on MR images was performed according to the American Urological System. MR data were compared with the pathologic findings of whole-mount sections of the surgical specimens. RESULTS: Overall accuracy for endorectal coil MR imaging was 60%; ten cases were underestimated and 3 cases were overestimated. The sensitivity and the specificity of endorectal coil MRI in diagnosing capsular penetration were 77% and 81%, respectively. Seminal vesicle invasion was detected with 87% sensitivity and 96% specificity. CONCLUSIONS: Endorectal coil MRI provides a more accurate preoperative local staging.

Molecular approaches to cancer immunotherapy.

The use of cytokines and costimulatory molecule gene-engineered tumor cells to enhance tumor immunogenicity and elicit curative responses against established tumors and tumor recurrences has become an attractive prospect. The immunotherapy data obtained in many experimental tumor systems using these engineered cells are reviewed here to provide a realistic assessment of the potential and limits of this technique.

Evolution of endotoxin induced acute lung injury in the rat.

To clarify the evolution of acute lung injury induced by endotoxin, the progression of lung damage in 26 rats submitted to intratracheal instillation of 5 mg/kg body weight endotoxin was examined by blood gas analysis, computerized tomography, light and electron microscopy. Hypoxaemia, hypercapnia, acidosis and inhomogeneous bilateral infiltrates developed gradually within 48 hours. Monocytes appeared within blood capillaries and the instertitium by 12 hours after treatment, then migrated into alveoli and underwent progressive differentiation into macrophages by 24 hours after treatment. Granulocytes were found within blood capillaries at an early stage, but outside capillaries only at 48 hours. Hyperplasia of type II pneumocytes and hypertrophy of interstitial fibroblasts also occurred at 48 hours. These data suggest that the pathogenesis of endotoxin induced pulmonary injury proceeds through an early phase of granulocyte migration inside capillaries and monocyte extravasation, an intermediate phase of monocyte differentiation into macrophages inside alveoli and a late phase of diffuse infiltration of alveoli by newly differentiated macrophages and late-extravasated neutrophils.

[Evaluation of total and inflated lung volumes by a quantitative study using computerized tomography in patients with acute noncardiogenic pulmonary edema (ARDS)]. / Valutazione dei volumi polmonari totali e aereati mediante lo studio quantitativo con tomografia computerizzata nei pazienti con edema polmonare acuto non cardiogeno (ARDS).

Our study was aimed at developing a method to assess lung volumes and relative percentages of well-inflated lung parenchyma in Adult Respiratory Distress Syndrome (ARDS) patients by processing conventional CT examinations of the lung and at investigating the prognostic value of CT findings. Fourteen patients (5 women and 9 men, age range: 35-79 years) admitted to the intensive care unit January, 1992, to June, 1994, because of severe ARDS, and with lung injury scores exceeding 2.5, were submitted to CT. A homologous group of 14 patients matched for sex and age and with normal lungs was examined as a control group to investigate the accuracy of our method. Two examinations were obtained in 7 of 14 ARDS patients; the trend of lung volumes and of the relative rates of well-inflated parenchyma could thus be calculated. During the examination, we maintained in all ARDS patients the same ventilatory pattern used in the intensive care unit. Consequently, in 18/21 examinations scans and respiratory phases were not correlated. In the control group no statistically significant differences were observed between the scans obtained with (inspiratory apnea) and without coordination with the respiratory phase. As for lung volumes, our results in normal subjects showed a good correlation with normal spirometric data. In ARDS patients lung volumes, although reduced, did not correlate with prognosis. As for the percentage of well-inflated parenchyma in ARDS patients, we observed a good correlation with prognosis in the patients submitted to two examinations and, in all patients, a good correlation with D(A-a)O2 index (p < 0.05), PaO2/FiO2 index (p < 0.005) and with the rate of arteriovenous shunt (p < 0.001). In conclusion, our results show that CT of the lung is a reliable and repeatable method for the functional assessment of the lung in ARDS patients.

Local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte and antibody-dependent immune memory.

The cDNA coding for mouse IL-10 (mIL-10) was transduced into the parental cells of a spontaneous adenocarcinoma of BALB/c mice (TSA-pc), and clones secreting small, medium, and large quantities of IL-10 were selected. In vivo, both low and high producer clones do not display an enhanced ability to grow in H-2 and non-H-2 incompatible mice. Instead, the intensity of their rejection increases in function of the amount of mIL-10 released. After an initial growth period in syngeneic mice, high producer clones undergo complete rejection due to the combined action of CD8+ lymphocytes, NK cells, and neutrophils. After this rejection, mice are immune to a subsequent challenge with TSA-pc. This memory rests on a strong lytic activity of CD8+ CTL and granulocytes. Following the rejection, mice also develop anti-TSA Ab that guide the granulocytes in TSA-pc memory reaction. A direct comparison shows that although TSA clones engineered to release IL-2 activate CTL and no anti-TSA Ab, those engineered to release IL-4 activate a strong Ab response but not CTL. The kind of cytokine released by the tumors appears to determine the type of response. However, IL-10 high producer cells do not deviate the immune memory, neither toward a Th1 nor a Th2. Both the CTL activity and the Ab responses induced by IL-10 high producer cells are the strongest so far observed in the TSA system.

5-Fluorocytosine-induced eradication of murine adenocarcinomas engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory.

The nonmammalian cytosine deaminase (CD) enzyme converts the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic metabolite 5-fluorouracil. Parental cells of a mammary adenocarcinoma (TSA-pc) of BALB/c mice were transfected with the CD gene (TSA-CD), and the ability of 5-FC to hamper their growth was evaluated. A quantity amounting to 0.5 mg of 5-FC/0.3 ml of medium inhibits the proliferation of TSA-CD cells, but not that of TSA-pc, nor that of TSA-pc transfected with neomycin-resistance gene only (TSA-neo). In BALB/c mice, 800 mg 5-FC/kg of body weight injected daily i.p. for 30 days causes total regression of incipient (1-day-old), and established (3- and 7-day-old) TSA-CD tumors, and of 3-day-old experimental lung metastases, but does not impair TSA-pc nor TSA-neo cell growth. Because in CD8+ T lymphocyte- and granulocyte-depleted mice 5-FC no longer impairs TSA-CD growth, immune mechanisms appear to play an important role in this regression. Following, regression, all mice are resistant to subsequent s.c. or i.v. lethal challenges with TSA-pc. The induction of this immune memory is dependent on CD4+ lymphocytes, whereas its effector phase depends on both CD4+ and CD8+ lymphocytes. The memory elicited in tumor-bearing mice by the 5-FC-dependent regression of TSA-CD tumors cures a significant number of mice with 4-day-old TSA-pc metastases, but does not impair the growth of 4-day-old solid s.c. tumors. The reliability of this regression and the subsequent establishment of an efficient immune memory against poorly immunogenic TSA-pc offer the prospect that CD-transduced tumor cells and 5-FC can be used as components of a live antitumor vaccine.

Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene or admixed with conventional adjuvants.

To evaluate the efficacy of vaccinations with cytokine-gene-transduced tumor cells, BALB/c mice were challenged with 1 x 10(5) parental cells of a syngeneic adenocarcinoma cell line (TSA-pc). No protection was observed in mice immunized 30 days earlier with 1 x 10(5) nonreplicating mitomycin-C-treated TSA-pc alone, or with Corynebacterium parvum or Complete Freund Adjuvant (CFA). Ten to 30% of mice immunized with nonreplicating cells engineered to produce interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene were protected. Fifty % of mice immunized with replicating TSA-pc admixed with C. parvum and 80-100% of mice immunized with replicating tumor cells transduced with IL-2, IL-4, IL-7, IL-10, or gamma-interferon gene were protected. No cure was afforded by TSA cells admixed with C. parvum or CFA, nor by TSA cells engineered with IL-6, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha gene injected starting 1 day after TSA-pc challenge. Complete tumor regression, however, was obtained in 10-20% of mice treated with TSA cells transduced with IL-2, IL-4, IL-7, or IL-10 and in 30% of those treated with TSA cells transduced with gamma-interferon gene.

[Expired ethane as a non-invasive marker of the course of experimental multiple organ dysfunction syndrome (MODS)]. / L'etano espirato come marker non invasivo della evoluzione della multiple organ dysfunction syndrome (MODS) sperimentale.

UNLABELLED: BACKGROUND AND WORK HYPOTHESIS: The mechanisms of organ damage in MODS are unclear. Given that lipid peroxidation induced by oxygen radicals may play a key role in organ damage, expired ethane, a marker of lipid peroxidation, could be correlated to the entity and evolution of experimental MODS. STUDY DESIGN AND METHODS: Forty wistar male rats (250 +/- 15 g body weight) were intraperitoneally injected with 10 ml of Zymosan mineral oil suspension (2.5%) to provoke MODS. Survival and symptoms were noted daily. On the 2nd, 7th and 14th day the animals underwent thorax CT scanning. CT images were processed to evaluate the relative density of lung parenchima. Expired ethane was measured using mass spectrometer and percentual changes were noted. Relative organ weight (liver and lung) were measured in 2nd, 7th and 14th day. STATISTICAL ANALYSIS: Pearson's linear correlation. RESULTS: The results show that maximal lung damage took place at the same moments as ethane concentrations peaked. A strict correlation (r = 0.93; p < 0.0001) was found between lung density and expired ethane. Strict correlation was found between organ weight, symptoms, survival and ethane production. CONCLUSIONS: Lipid peroxidation, as expressed by ethane production, might be an important cause of organ damage in MODS.