Comparative analysis of the pathological events involved in immune and non-immune TRALI models.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is characterized by leukocyte transmigration and alveolar capillary leakage shortly after transfusion. TRALI pathogenesis has not been fully elucidated. In some cases, the infusion of alloantibodies (immune model), whereas in others the combination of neutrophil priming by proinflammatory molecules with the subsequent infusion of biological response modifiers (BRMs) in the hemocomponent (non-immune model) have been implicated. Our aim was to compare the pathological events involved in TRALI induced by antibodies or BRMs using murine models. MATERIALS AND METHODS: In the immune model, human HNA-2(+) neutrophils were incubated in vitro with a monoclonal antibody (anti-CD177, clone 7D8) directed against the HNA-2 antigen and injected i.v. in NOD/SCID mice. In the non-immune model, BALB/c mice were treated with low doses of lipopolysaccharide (LPS) followed by platelet-activating factor (PAF) infusion 2 h later. Forty minutes after PAF administration, or 6 h after neutrophil injection, lungs were isolated and histological analysis, determination of a variety of cytokines and chemokines including keratinocyte-derived chemokine (KC), MIP-2, the interleukins IL-1ß, IL-6, IL-8 as well as TNFα, cell influx and alveolar capillary leakage were performed. RESULTS: In both models, characteristic histological findings of TRALI and an increase in KC and MIP-2 levels were detected. In contrast to the immune model, in the non-immune model, there was a dramatic increase in IL-1ß and TNFα. However, capillary leakage was only detected if PAF was administrated. CONCLUSIONS: Regardless of the triggering event(s), KC, MIP-2 and integrins participate in TRALI pathogenesis, whereas PAF is essential for capillary leakage when two events are involved.

Management of difficult airways in surgical patients at the Port Moresby General Hospital operating theatre and intensive care unit.

We report on the results of a retrospective audit of airway management in patients presenting to the Port Moresby General Hospital from 1998 to 2009. Safe and secure airway management can be challenging in the operating room during head and neck surgery. These challenges continue into the postoperative period and can present significant issues to intensive care staff. This series includes many patients with upper airway and upper gastrointestinal malignancy, head and neck trauma, head and neck infections, thyroid pathology and cleft palate. This series highlights the importance of anticipating the possibility of difficult airway preoperatively and modifying the airway management appropriately. We consider that all members of the operating team including surgeons, anaesthetists, intensive care physicians and nursing staff should cooperate and communicate effectively to optimize outcomes for these potentially difficult cases. A proposed airway management algorithm is presented to guide surgical teams performing head and neck surgery in Papua New Guinea and similar regions.

Metallothionein and p-Akt proteins in oral dysplasia and in oral squamous cell carcinoma: an immunohistochemical study.

BACKGROUND: Oral leukoplakia (OL) is the main potentially malignant lesion of the oral cavity, and oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of p-Akt and Metallothionein (MT) proteins in dysplasic and neoplasic oral lesions. METHODS: Immunohistochemical studies were carried out on 10 normal epithelium, 30 OL and 15 OSCC paraffin-embedded samples. Immunoperoxidase reaction for p-Akt and MT proteins was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. RESULTS: Using the ANOVA and the Tukey's post hoc statistical analyses, it was observed a significant difference in the immunoexpression for p-Akt and MT when the OSCC samples were compared with normal and dysplasic epithelial groups. In addition, the Pearson's correlation test showed a significant correlation between the proteins' expression. CONCLUSION: Based on the data obtained, p-Akt and MT activation may play an important role in the conversion of a potentially malignant oral lesion to a malignant carcinoma since its earlier stages.

Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin.

Statins are generally well tolerated, but can cause myopathy and have been associated with mitochondrial abnormalities. The aim of this study was to determine whether muscle mitochondrial DNA (mtDNA) levels are altered during statin therapy. We retrospectively quantified mtDNA in 86 skeletal muscle biopsy specimens collected as part of a previously published clinical trial of high-dose simvastatin or atorvastatin versus placebo.

Increased pulmonary toxicity with bleomycin and cisplatin chemotherapy combinations.

Combination chemotherapy that included bleomycin and cisplatin was administered to 45 evaluable patients (30 with cervix carcinoma and 15 with germ cell tumors). Bleomycin was given, following cisplatin infusion, either by intravenous continuous infusion over 72 h (germ cell tumor patients) or intramuscularly every 12 h for 4 days (cervix carcinoma patients). Total bleomycin doses ranged from 156 to 360 U. Nine patients with normal renal function and no previous pulmonary disease prior to chemotherapy developed serious pulmonary toxicity. Six patients died from irreversible respiratory failure. Postmortem lung studies were performed in all six patients and revealed findings compatible with bleomycin-induced lung toxicity. Renal tubular damage was found in four kidneys available for examination. Five (71.5%) of the seven patients whose serum creatinine increased after chemotherapy was initiated developed lung injury, whereas 10.5% of those without change in the serum creatinine level presented this complication (p = 0.001). Renal damage, following cisplatin administration, with subsequent accumulation of bleomycin was the likely cause of the high lung toxicity. Extreme caution is recommended in the administration of combined bleomycin-cisplatin chemotherapy. Whenever possible, bleomycin should precede cisplatin infusion to minimize the risk of lung toxicity.

FT-IR breath test in the diagnosis and control of treatment of methanol intoxications.

A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was tested for the diagnosis of methanol intoxications. Breath analysis with FT-IR was fast and easy, and no sample preparation was needed. The analyzer was adequately sensitive and accurate in detecting and quantitating clinically relevant amounts of ethanol and methanol in the breath of seriously ill patients. FT-IR spectrometry was also suitable for nearly on-line monitoring of the exhaled ethanol and methanol during hemodialysis. The breath analysis results correlated well with blood samples. The FT-IR method used also has a traceable calibration to physical properties of the analyte, and the measured spectra can be saved for later analysis.

[Centric registration relation in dentate patients using bilateral manipulation--comparative analysis of three techniques]. / Estudo do registro da relação cêntrica em pacientes dentados utilizando a manipulação bilateral--análise comparativa de três técnicas.

Three techniques of centric relation registration were compared using the "Jig" (LUCIA), the "Leaf-Gauge" (LONG JUNIOR) and an wax anterior guide. The casts were mounted and analysed in a Whip-Mix articulador. The results permitted to conclude that, from the statistical viewpoint, did not occurred significant differences among techniques and centric relation occurred in an area not in a point. Because of facility and quickness the technique advocated by LON JUNIOR is recommended.

Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine.

Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been suggested to be a novel independent risk factor for endothelial dysfunction and coronary heart disease. We investigated the association of ADMA concentration in serum with risk of acute coronary events. We did a prospective, nested, case-control study in middle-aged men from eastern Finland. In an analysis of men who did not smoke, those who were in the highest quartile for ADMA (>0.62 micromol/L) had a 3.9-fold (95% CI 1.25-12.3, p=0.02) increase in risk of acute coronary events compared with the other quartiles. Our findings suggest that ADMA is a predictor of acute coronary events.

Cellular infiltration in induced rat thyroiditis: phenotypic analysis and relationship to genetic restriction.

We have investigated the responsiveness to thyroglobulin (Tg) plus complete Freund's adjuvant (CFA) and B. pertussis in a variety of inbred and MHC congenic strains of rats in terms of both Tg-autoantibody titres and histological thyroiditis index. Severity of thyroiditis was strongly Tg-dependent and closely related to the RT.1-MHC haplotype. Phenotypic examination of the inflammatory thyroid infiltrate using single and double indirect immunofluorescence techniques revealed a high proportion of macrophages and T lymphocytes, mainly of the cytotoxic/suppressor subset, in the high responder strains. Thyroid epithelial class II MHC expression although not prominent was strain-restricted and related to the amount of Ia+ leukocyte infiltrate.

Interferon-mediated enhancement of thyroid major histocompatibility complex antigen expression. A flow cytometric analysis.

Epithelial expression of class II antigens encoded by the major histocompatibility complex (MHC) has been proposed as a means by which autoimmune thyroid disease may be initiated and maintained. We studied a rat thyroid epithelial cell line (FRTL-5), which constitutively expresses class I (OX18) but not class II (OX6 or OX17) determinants to quantify in vitro MHC antigen induction using flow cytometry. Recombinant rat gamma interferon (rIFN-gamma) induced dose-dependent expression of OX6 (I-A) antigen at greater than 48 h (maximum 80-90% of cells in culture at 100 U/ml), which was abrogated by DB-1, a monoclonal antibody to rat IFN-gamma. OX17 antigen (I-E) was also induced (86%) and OX18 (class I) markedly increased under these conditions. Other thyroid-active agents including the calcium ionophore A23187, dibutyryl cyclic AMP, thyroid-stimulating autoantibodies from Graves' disease patients (LATS), and TSH, caused no I-A induction. Supernatants from spleen cells stimulated with plant lectins (concanavalin A or phytohaemagglutinin), but not lectin alone, evoked substantial class II induction, which was inhibited by DB-1. These findings suggest that IFN-gamma is the central mediator of thyroid epithelial class II expression. FRTL-5 provides a powerful model for the analysis of thyroid MHC class II dynamics and a potential means of analysing the role of epithelial class II in autoimmune pathogenesis.

Epitope specificity of spontaneous and induced thyroglobulin autoantibodies in the rat.

We have investigated the epitope specificities of rat thyroglobulin (Tg) autoantibodies arising either spontaneously in BB hybrid and BB rats or following induction in normal rats with thyroglobulin and adjuvant. Using a panel of thyroglobulins from different animal species it was possible to identify three different patterns of reactivity. These were: 1) recognition of all species of thyroglobulin; (2) recognition restricted to rat and mouse thyroglobulins and 3) recognition biased towards dog, rat and mouse thyroglobulins. Furthermore, using human thyroglobulin manifesting different levels of iodination, it was possible to show that sera with recognition pattern 1 recognized the iodination site of thyroglobulin and that this was inhibitable by thyroxine. Taken together these data provide evidence of restricted epitope recognition by Tg autoantibodies in the rat.