[show abstract][hide abstract] ABSTRACT: Mediastinal tumors show a wide variability, and therefore, a standardized diagnostic and therapeutic workup is instrumental. We subdivided mediastinal tumors into nonlymphatic mediastinal tumors (NLMTs), most of which require surgical resection without need of preoperative histology, and mediastinal lymphadenopathy (MLA), requiring surgical biopsy for exact histologic classification. We investigated the accuracy of noninvasive diagnostic studies distinguishing between the two groups of MLA and NLMT.
A retrospective analysis was performed on patients who had previously undergone surgery on mediastinal tumors. Their data were statistically analyzed (chi2 test, logistic regression analysis), and the values of medical history, physical examination, laboratory tests, and computerized tomography scan discriminating between MLA and NLMT were assessed.
Out of 299 patients included in the study, 242 (80.9%) had MLA and 57 (19.1%) had NLMT. Sensitivity and specificity of noninvasive investigations for differentiation of MLA and NLMT were 98.2% and 86.0%, respectively. Whereas the prevalence of thoracic symptoms such as shortness of breath, cough, or chest pain was similar in both groups (MLA, 165 [69.3%]; NLMT, 41 [69.5%]; p = 0.98), systemic symptoms, including fever, night sweats, or weight loss (MLA, 110 [49.8%]; NLMT, 17 [29.3%]; p < 0.01), and signs of inflammation, such as c-reactive protein, erythrocyte sedimentation rate, and leukocytosis (MLA, 202 [85.6%]; NLMT, 34 [57.6%]; p < 0.001), were significantly more common in MLA.
Noninvasive diagnostic procedures, including medical history, physical examination, laboratory tests, and computerized tomographic scan, are highly sensitive in detecting MLAs that should undergo surgical biopsy. Our data suggest confirming all suspected NLMTs by fine needle aspiration (FNA) biopsy before surgery.
The Annals of Thoracic Surgery 05/2003; 75(4):1086-90. · 3.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Over the last few years immunonutrition has gained increasing importance. Among other compounds lipids, especially n-3 polyunsaturated fatty acids, were shown to influence the immune response. The anti-inflammatory effects they exert can be induced by free fatty acids, triglyceride fatty acids, after incorporation into the membrane phopspholipid bilayer or following metabolism to eicosanoids. n-3 Fatty acids influence inflammatory cell activation processes from signal transduction to protein expression even involving effects at the genomic level. n-3 Fatty acid-mediated mechanisms decreased cytokine-induced adhesion molecule expression, thereby reducing inflammatory leucocyte-endothelium interactions and modified lipid mediator synthesis, thus influencing the transendothelial migration of leucocytes and leucocyte trafficking in general. Even the metabolic repertoire of specific immunocompetent cells such as cytokine release or proliferation is modified by n-3 fatty acids. Beyond this they regulate lipid homeostasis shifting the metabolic pathways towards energy supply thus optimizing the function of immune cells. Due to the regulatory impact on different processes of inflammatory and immune cell activation n-3 fatty acids provide positive effects on various states of immune deficiencies and diseases with a hyperinflammatory character, among which selected examples are presented.
British Journal Of Nutrition 02/2002; 87 Suppl 1:S59-67. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dietary supplements of n-3 fatty acids have long been used to influence chronic inflammatory disorders. Recent studies with an immune-enhancing diet partly based on n-3 fatty acids report beneficial effects in patients with acute hyper-inflammatory diseases, such as the sepsis syndrome or adult respiratory distress syndrome (ARDS). The possible suppression of exaggerated leucocyte activity, the improvement of microcirculatory events, as well as the opportunity to administer intravenous lipids enriched in n-3 fatty acids signal the possibility of a combination of parenteral caloric support and pharmacological intervention. Using parenteral administration of fish oil-based lipids, a new rapid and highly effective anti-inflammatory agent may allow the option to alter the immune status in hyper-inflammatory diseases such as sepsis and ARDS.
British Journal Of Nutrition 02/2002; 87 Suppl 1:S69-75. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the efficacy and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.
British Journal Of Nutrition 02/2002; 87 Suppl 1:S77-82. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cell proliferation is a process that consumes large amounts of energy. A reduction in the nutrient supply can lead to cell death by ATP depletion, if cell proliferation is not limited. A key sensor for this regulation is the glycolytic enzyme pyruvate kinase, which determines whether glucose carbons are channelled to synthetic processes or used for glycolytic energy production. In unicellular organisms pyruvate kinase is regulated by ATP, ADP and AMP, by ribose 5-P, the precursor of the nucleic acid synthesis, and by the glycolytic intermediate fructose 1,6-P2 (FBP), thereby adapting cell proliferation to nutrient supply. The mammalian pyruvate kinase isoenzyme type M2 (M2-PK) displays the same kinetic properties as the pyruvate kinase enzyme from unicellular organisms. The mammalian M2-PK isoenzyme can switch between a less active dimeric form and a highly active tetrameric form which regulates the channeling of glucose carbons either to synthetic processes (dimeric form) or to glycolytic energy production (tetrameric form). Tumor cells are usually characterized by a high amount of the dimeric form leading to a strong accumulation of all glycolytic phosphometabolites above pyruvate kinase. The tetramer-dimer ratio is regulated by ATP, FBP and serine and by direct interactions with different oncoproteins (pp60v-src, HPV-16 E7). In solid tumors with sufficient oxygen supply pyruvate is supplied by glutaminolysis. Pyruvate produced in glycolysis and glutaminolysis is used for the synthesis of lactate, glutamate and fatty acids thereby releasing the hydrogen produced in the glycolytic glyceraldehyde 3-phosphate dehydrogenase reaction.
British Journal Of Nutrition 02/2002; 87 Suppl 1:S23-9. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Immunonutrition with omega-3 fatty acids and the "conditionally essential" amino acids arginine, glutamine, cysteine, and taurine can enhance the immune response in critically ill patients. This is due to the immunomodulating properties of these nutrients. Immunonutrition is especially important when a patient's immune response is compromised, as is the case post-operatively or after trauma. Immune deficiency is severely aggravated in sepsis and the systemic inflammatory response syndrome (SIRS). The resulting metabolic stress is characterized by glycolysis, lipolysis, and proteolysis, which may escalate to an hypercatabolic response or "autocannabilism." Catabolic metabolism results in insufficiency of both specific and unspecific immunocompetent cells. CONCLUSIONS: Immunonutrition should be started early in such patients for an optimal beneficial effect, preferably via the enteral route. It should include medium chain and long chain triglycerides, polyunsaturated omega-3 and omega-6 fatty acids (in the ratio 1:2), olive oil, and conventional amino acid preparations supplemented with the conditionally essential amino acids arginine, glutamine, cysteine, and taurine.
Langenbeck s Archives of Surgery 09/2001; 386(5):369-76. · 1.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lipoxygenase (LO) and cytochrome P450 monooxygenase products of arachidonic acid (AA) have been implicated in a large number of vasoregulatory processes. In intact, blood-free, perfused and ventilated human lungs (n = 8), isolated during surgery for bronchial carcinoma, we analyzed leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs), and epoxyeicosatrienoic acids (EETs) by sequential sampling of the recirculating buffer fluid. For the analysis we used multistep, solid-phase extraction, isocratic reversed-phase high-performance liquid chromatography, with elution of all metabolites within one run and photodiode array detection to obtain full UV spectra of eluting compounds. We detected no LT release in a 15-min baseline period, but the admixture of the calcium ionophore A23187 with the buffer fluid provoked the rapid appearance of all LTs. Some baseline release of 15-HETE was observed, and in response to A23187, maximum buffer concentrations were noted for 5-HETE, with 8-HETE, 9-HETE, 11-HETE, and 12-HETE being detected at lower levels. Marked baseline liberation of 11,12-EET and 8,9-EET was observed. In response to A23187, high oxirane buffer concentrations were registered, which far surpassed those of LTs and HETEs. The eicosanoid release was paralleled by a limited pulmonary artery pressor response and progressive vascular leakage. We conclude that ex-vivo-perfused human lungs release EETs > LTs > HETEs into the vascular compartment in response to inflammatory challenge. The marked oxirane synthesis in the lung vasculature may have major impact on lung vasoregulation when considering the possible function of these AA epoxides as endothelium-derived hyperpolarizing factors.
American Journal of Respiratory and Critical Care Medicine 06/2000; 161(6):1917-23. · 11.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Whereas the involvement of elicited xenoantibodies in delayed xenograft rejection is currently being substantiated, this study focuses on the role of the preformed fraction of xenoantibodies.
To check the influence of the latter, we combined pretransplant complement inactivation (cobra venom factor) and antibody reduction (plasmapheresis) in a guinea pig-to-rat heart transplant model.
Antibody reduction on plasmapheresis before xenografting did not prolong delayed xenorejection in decomplemented rats, although the immunohistologic pattern lacked the immunoglobulin deposits along endothelial walls found in xenografts of merely decomplemented recipients. Astonishingly, plasmapheresis, if carried out 2 days before transplantation, almost tripled xenograft survival, although preformed antibody levels were completely restored and even rebounding at the time of grafting. The pattern and number of infiltrating cells did not differ in dependence of the timing of plasmapheresis nor did the proliferative response of lymphocytes in the mixed lymphocyte reaction differ. However, plasmapheresis led to a retarded decrease of the mononuclear cell tumor necrosis factor alpha secretory potential, which correlated well with a diminished immunohistologic staining of tumor necrosis factor alpha secreted by graft-infiltrating mononuclear cells.
These findings argue against a pivotal role of preformed xenoantibodies in the pathomechanistic process of delayed xenograft rejection and challenge the therapeutic strategy to reduce preformed xenoantibody levels before xenotransplantation in complement-inactivated recipients.
Journal of Thoracic and Cardiovascular Surgery 04/2000; 119(3):477-87. · 3.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Quantification of lipoxygenase and cytochrome P450 products of both arachidonic acid (AA) and eicosapentaenoic acid (EPA) is of broad interest due to the multiple biological activities of these compounds. We developed a method combining (i) solid-phase extraction, (ii) isocratic reversed-phase high-performance liquid chromatographic separation, and (iii) online photodiode array detection with spectrum analysis for identification and measurement of all main 4- and 5-series eicosanoids (leukotrienes, hydroxyeicosatetraenoic acids/hydroxyeicosapentaenoic acids, epoxyeicosatrienoic acids) within one run. With these procedures, standard mixtures of AA- and EPA-derived lipid mediators were recovered from different biological liquids, like lung perfusate, human bronchoalveolar lavage fluid, and cell supernatant with linear characteristics for each compound. Recoveries of the different lipid mediators exceeded 80% showing excellent reproducibility. Application of the method to isolated, perfused, and ventilated human lungs challenged with the calcium ionophore A23187 and to human neutrophils stimulated in the presence of arachidonic acid and eicosapentaenoic acid with N-formyl-methionyl-leucyl-phenylalanine demonstrated the generation of a large array of lipoxygenase and cytochrome P450 products. Thus, convenient quantification of 4- and 5-series eicosanoids in fluids of biological interest is achieved by a technique comprising solid-phase extraction, isocratic reversed-phase high-performance liquid chromatography, and photodiode array-based online spectrum analysis of eluting compounds.
[show abstract][hide abstract] ABSTRACT: Extracellular AMP inhibits cell proliferation of MCF-7 and MDA-MB-453 whereas cell proliferation of the highly malignant Novikoff cell line is not affected. In medium with low glucose supply MDA-MB-453 cells grow well, Novikoff cells are slightly inhibited and MCF-7 cells are totally unable to grow. Isoelectric focusing revealed that a glyclytic enzyme complex exists in all three cell lines. In addition to the glycolytic enzymes, c-Raf-kinase, adenylate kinase, and nucleoside diphosphate kinase are also found within the complex. The differences in glucose in dependence of the three cell lines can be explained by the different constitutions of shuttle enzymes. MDA-MB-453 and Novikoff cells contain cytsolic glycerol 3-phosphate dehydrogenase which is associated with glyceraldehyde 3-phosphate dehydrogenase within the glycolytic enzyme complex and which is responsible for the transport of cytoslic hydrogen in the mitochondria. MCF-7 and Novikoff cells contain the pI 7.8 form of malate dehydrogenase which couples glycolysis with glutaminolysis.
Anticancer research 01/1998; 18(5A):3275-82. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: The immunosuppressive effect of intravenous fat emulsions with different n-3/n-6 fatty acid ratio was studied in the heterotopic rat heart allotransplant model. Twenty percent emulsions of safflower oil (n-3/n-6 = 1/370), fish oil (7.6/1), soybean oil (1/6.5) and a 1:1 mixture of safflower and fish oil (1/2, 1; oil control group) were continuously infused (9 g fat/Kg b.w./day; n = 10 each group) after transplantation until rejection. Graft survival time, subpopulations of infiltrating and circulating immunocompetent cells and Interleukin-6 release of circulating monocytes were analyzed. In the safflower oil, fish oil and soybean oil groups graft survival was prolonged to 13.3, 12.3 and 10.4 days vs. 6.7 days in the oil control group and 7.8 days in the saline control group (p < 0.01). In the two groups with the highest prolongation of graft survival the number of infiltrating cells was reduced by up to 50 percent and the peripheral blood monocyte interleukin-6 release by up to 45 percent. Beyond that, circulating T-cells were reduced in the fish oil group. Intravenous fat emulsions show a varying immunomodulatory effect in dependence of the n-3/n-6 fatty acid ratio. Both n-6 and n-3 fatty acids, if applied as main fatty acid source, exert immunosuppressive effects by a diminished infiltration, mobilisation and cytokine release of immunocompetent cells. Soybean oil with a more balanced n-3/n-6 fatty acid ratio than safflower is significantly less immunosuppressive than safflower oil and fat emulsions with a n-3/n-6 fatty acid ratio of 1/2 are immunologically neutral.
Archivos latinoamericanos de nutrición 12/1996; 46(4):269-74. · 0.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: omega-3 Fatty acids may have a major impact on immune responses involved in heart transplant rejection. We compared the effects of posttransplant intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions on graft survival, plasma fatty acid profiles, and levels of arachidonic acid versus eicosapentaenoic acid-derived lipid mediators.
Inbred PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a model of heterotopic heart transplantation. Animals received 9 g/kg body wt per day of either fish oil-derived (n = 8) or soybean oil-derived fat (n = 7) in the form of a continuously infused lipid emulsion; controls were sham-infused with saline (n = 8). Graft rejection was assessed by loss of activity of the transplant. The fish oil-derived preparation but not that originating from soybean oil caused an increase in total and free plasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of neutrophils with the Ca2+ ionophore A23187 demonstrated an increase in 5-series leukotriene (LT) generation in animals undergoing omega-3 lipid infusion (LTB5, omega-oxidation products of LTB5, LTA5 secretion), with 5-series/4-series LT ratios ranging between 0.08 and 0.36. Ratios of TX B3/B2 liberated from ex vivo stimulated platelets even approached 1:1 in omega-3 supplemented rats. Graft survival was 7.6 +/- 0.3 (mean +/- SEM) days in saline-infused, 10.4 +/- 0.7 in omega-6 lipid-infused, and 12.9 +/- 0.4 in omega-3 lipid-infused animals.
Posttransplant intravenous alimentation with fish oil-derived lipid emulsions prolongs heart transplant survival in excess to omega-6 lipids. Profound changes in fatty acid profiles and lipid mediator generation may underlie this finding.