Capillary Leak Syndrome: A condition characterized by recurring episodes of fluid leaking from capillaries into extra-vascular compartments causing hematocrit to rise precipitously. If not treated, generalized vascular leak can lead to generalized EDEMA; SHOCK; cardiovascular collapse; and MULTIPLE ORGAN FAILURE.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Hypoproteinemia: A condition in which total serum protein level is below the normal range. Hypoproteinemia can be caused by protein malabsorption in the gastrointestinal tract, EDEMA, or PROTEINURIA.Dictionaries, MedicalLymphoma, Large B-Cell, Diffuse: Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.

Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome. (1/91)

The dose-limiting toxicity of interleukin-2 (IL-2) and immunotoxin (IT) therapy in humans is vascular leak syndrome (VLS). VLS has a complex etiology involving damage to vascular endothelial cells (ECs), extravasation of fluids and proteins, interstitial edema, and organ failure. IL-2 and ITs prepared with the catalytic A chain of the plant toxin, ricin (RTA), and other toxins, damage human ECs in vitro and in vivo. Damage to ECs may initiate VLS; if this damage could be avoided without losing the efficacy of ITs or IL-2, larger doses could be administered. In this paper, we provide evidence that a three amino acid sequence motif, (x)D(y), in toxins and IL-2 damages ECs. Thus, when peptides from RTA or IL-2 containing this sequence motif are coupled to mouse IgG, they bind to and damage ECs both in vitro and, in the case of RTA, in vivo. In contrast, the same peptides with a deleted or mutated sequence do not. Furthermore, the peptide from RTA attached to mouse IgG can block the binding of intact RTA to ECs in vitro and vice versa. In addition, RTA, a fragment of Pseudomonas exotoxin A (PE38-lys), and fibronectin also block the binding of the mouse IgG-RTA peptide to ECs, suggesting that an (x)D(y) motif is exposed on all three molecules. Our results suggest that deletions or mutations in this sequence or the use of nondamaging blocking peptides may increase the therapeutic index of both IL-2, as well as ITs prepared with a variety of plant or bacterial toxins.  (+info)

Intrapulmonary protein leakage in immunocompromised children and adults with pneumonia. (2/91)

BACKGROUND: Pulmonary infections are associated with an increase in capillary permeability but information regarding age related differences in the local inflammatory response is lacking. To quantify the degree of capillary leakage during inflammation, the concentrations of the plasma proteins albumin, alpha1-antitrypsin, alpha2-macroglobulin and the locally produced proteins elastase, myeloperoxidase, lactoferrin and fibronectin were studied in the bronchoalveolar lavage (BAL) fluid of immunosuppressed children and adults with pneumonia. METHODS: Sixteen children aged 2-16 years and 15 adults who developed pneumonia while receiving immunosuppressive therapy for haematological malignancies were included in the study. Bronchoalveolar lavage was performed via a flexible bronchoscope with three aliquots of 1 ml/kg body weight in children and 200 ml in adults. Protein concentrations in BAL fluid were determined using highly sensitive immunoluminometric assays. RESULTS: Despite considerable variability, the median concentrations of all proteins in BAL fluid were significantly higher in both patient populations than in previously collected age adjusted reference values. The concentrations of serum derived proteins were significantly higher in children with pneumonia than in adult patients. In contrast, no differences were observed between the two groups for locally produced proteins. CONCLUSIONS: These data suggest that the degree of protein exudation is more pronounced in immunosuppressed children with pneumonia than in adults in a similar clinical situation. This is in agreement with our studies in healthy individuals and may reflect a greater permeability of the alveolar-capillary membrane in children, regardless of disease status.  (+info)

Evidence for the involvement of CD44 in endothelial cell injury and induction of vascular leak syndrome by IL-2. (3/91)

At sites of chronic inflammation seen during infections, autoimmunity, graft-vs-host response, and cytokine therapy, endothelial cell injury is known to occur, the exact mechanism of which is unknown. In the current study we used IL-2-induced vascular leak syndrome (VLS) as a model to investigate whether cytotoxic lymphocytes use CD44 in mediating endothelial cell injury. Administration of IL-2 to wild-type mice triggered significant VLS in the lungs and liver. In contrast, in CD44 knockout (KO) mice, IL-2-induced VLS was markedly reduced in the lungs and liver. IL-2-treated wild-type and CD44 KO mice had similar levels of perivascular infiltration with lymphocytes in the lungs and liver. This suggested that the decrease in VLS seen in CD44 KO mice was not due to the inability of lymphocytes to migrate to these organs. Ultrastructural studies demonstrated extensive endothelial cell damage in the lungs and liver of IL-2-treated wild-type, but not CD44 KO, mice. Moreover, CD44-KO mice exhibited a marked decrease in IL-2-induced lymphokine-activated killer cell activity. The induction of VLS was dependent on the expression of CD44 on immune cells rather than endothelial cells because adoptive transfer of CD44+, but not CD44- spleen cells along with IL-2 into CD44 KO mice triggered VLS. The IL-2-induced VLS was blocked by administration of F(ab')2 of Abs against CD44. The current study demonstrates that CD44 plays a key role in endothelial cell injury. Blocking CD44 in vivo may offer a novel therapeutic approach to prevent endothelial cell injury by cytotoxic lymphocytes in a variety of clinical disease models.  (+info)

Acute modulation of albumin microvascular leakage by advanced glycation end products in microcirculation of diabetic rats in vivo. (4/91)

Advanced glycation end products (AGEs) are nonenzymatic glycosylated adducts of proteins that accumulate in vascular tissue during diabetes and aging. The aim of this work was to study the role of AGEs and of the oxidative mechanisms in diabetes-induced changes in vascular permeability. Intravital videomicroscopy was used to study albumin microvascular leakage in cremaster muscle. The extravasation of a fluorescent macromolecular tracer (fluorescein isothiocyanate-albumin) was measured for 1 h and, after computer-aided image analysis, was expressed as variations of normalized gray levels (arbitrary units). Extravasation of the macromolecular tracer was much higher in diabetic rats than in control rats (slope of extravasation versus time increased by >100%, P < 10(-4)). This increase was significantly inhibited when we blocked AGEs binding to their endothelial receptor by intravenous bolus of soluble recombinant receptor to AGEs (rR-RAGE) (slope of extravasation versus time decreased by 19, 30, and 40%, for 0.5, 2.5, and 5.15 mg/kg rR-RAGE, respectively) or by a 6 mg/kg intravenous bolus of antibody against RAGE (slope decreased by 53%). Systemic injection of probucol (an antioxidant) also significantly inhibited the increase in the extravasation of the macromolecular tracer occurring in experimental diabetes (slope decreased by 51%, P < 10(-4)). These results strongly suggest that in experimental diabetes the interaction of circulating AGEs and endothelial RAGE mediates albumin micro-vascular leakage, possibly via AGE-RAGE-dependent enhanced oxidant stress.  (+info)

Adjuvant treatment of severe acute pancreatitis with C1 esterase inhibitor concentrate after haematopoietic stem cell transplantation. (5/91)

BACKGROUND: With an incidence of 4%, acute pancreatitis is a common complication of bone marrow or peripheral haematopoietic stem cell transplantation, which contributes significantly to morbidity and mortality in these patients. In most cases, the pathogenesis of acute pancreatitis cannot be attributed to a single pathogenetic factor, as treatment toxicity, acute graft versus host disease, infection, and cholestasis may all contribute. Acute pancreatitis is characterised by inflammation and activation of digestive proenzymes leading to autodigestive destruction of the pancreas and systemic activation of protease cascades including the complement system. AIM: To describe the effects of human C1 esterase inhibitor in two children, who developed severe acute pancreatitis with considerable complement activation after allogeneic haematopoietic stem cell transplantation. METHODS: Both children showed clinical features resembling those observed in capillary leakage syndrome. In both patients, treatment with C1 esterase inhibitor concentrate contributed to a rapid clinical stabilisation. CONCLUSIONS: These observations strongly support the proposed pathophysiological concept that early treatment with C1 esterase inhibitor interferes with the activation of the complement system in acute pancreatitis. Inhibition of complement activation prevents its adverse effects on vascular function and permeability, and thus stabilises intravascular fluid status and prevents multiorgan failure in acute pancreatitis.  (+info)

Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis. (6/91)

BACKGROUND: Capillary leakage with fluid loss into the third space contributes to many of the early systemic complications in severe acute pancreatitis. There has been increasing interest in endothelin as one of the factors affecting capillary permeability. AIM: To elucidate further the role of endothelin in the development of capillary leakage in acute pancreatitis by investigating the effect of exogenous endothelin administration and endothelin receptor blockade in sham operated animals and two models of acute pancreatitis. METHODS: Determination of capillary permeability in the pancreas and colonic mucosa by quantifying extravasation of fluorescein labelled dextran using a novel computer assisted video image analysis system. RESULTS: Pancreatic and colonic capillary permeability increased stepwise from mild to severe acute pancreatitis. Endothelin increased pancreatic and colonic capillary permeability in healthy animals and animals with mild acute pancreatitis but had no additional adverse effect in severe acute pancreatitis. Endothelin receptor blockade decreased pancreatic capillary permeability in sham operated rats but had no effect on the colon. In mild and severe acute pancreatitis, endothelin receptor blockade stabilised increased capillary permeability in both the pancreas and colon. CONCLUSIONS: Endothelin plays an important role in mediating capillary permeability in the pancreas. In severe pancreatitis, it increases capillary permeability even outside the pancreas, thereby contributing to capillary leakage. Endothelin receptor blockade significantly reduces capillary permeability in acute pancreatitis both in and outside the pancreas, suggesting a therapeutic approach to counteract capillary leakage in severe acute pancreatitis.  (+info)

Sensitive blood-retinal barrier breakdown quantitation using Evans blue. (7/91)

PURPOSE: This study investigated whether a nonradioactive dye, Evans blue, can be adapted as a safe alternative to the isotope-dilution method for quantitating blood-retinal barrier breakdown. METHODS: Blood-retinal barrier breakdown was induced in rats with vascular endothelial growth factor (VEGF) or through the induction of diabetes. After allowing Evans blue to circulate in the vasculature, the dye was cleared from the bloodstream with saline, citrate, or citrate-buffered paraformaldehyde, and the efficacies of the perfusion solutions were compared. Extravasated dye was detected at 620 nm and was normalized against the time-averaged Evans blue plasma concentration, the circulation time, and also against wet and dry retina weights. RESULTS: Evans blue leakage from retinas treated with VEGF was 4.0-fold higher than that of contralateral untreated eyes (n = 6 rats, P: < 0.05). Retinal Evans blue leakage of eyes from 1-week diabetic animals (n = 11 retinas) was 1.7-fold higher (P: < 0.05) than that of nondiabetic controls (n = 10 retinas). Intra-animal, inter-retina weights showed significantly less variability (P: < 0.05) with the use of dry weights (11.2%, n = 74 retina pairs) than with wet weights (20.5%, n = 93 retina pairs). CONCLUSIONS: The Evans blue dye technique can be modified to be as sensitive and quantitative as the isotope-dilution method for measuring blood-retinal barrier breakdown. The advantages of the Evans blue technique are its safety, relative simplicity, and economy.  (+info)

The toxicity of deglycosylated ricin A chain-containing immunotoxins in patients with non-Hodgkin's lymphoma is exacerbated by prior radiotherapy: a retrospective analysis of patients in five clinical trials. (8/91)

A retrospective analysis of 102 patients with relapsed, non-Hodgkin's lymphoma treated with two different ricin A chain-containing immunotoxins (ITs) in five Phase I clinical trials indicates that the dose-limiting toxicity, vascular leak syndrome, was more frequent and more severe in patients who had undergone prior radiotherapy (RT). Excluding patients with prior RT from the calculations of the maximum tolerated dose indicates that the maximum tolerated doses of these ITs had not been reached in any trial and are clearly higher than reported previously. Excluding patients with prior RT from future clinical trials may increase the dose of ITs that can be given in the absence of severe vascular leak syndrome.  (+info)

  • The abdomen, the central nervous system, and the organs (including the lungs) are typically spared, but the extravasation in the extremities is sufficiently massive to cause circulatory shock and compartment syndromes, with a dangerous hypotension (low blood pressure), hemoconcentration(thickening of the blood) and hypoalbuminemia (drop in albumin, a major protein) in the absence of other causes for such abnormalities. (wikipedia.org)
  • Pro-inflammatory cytokines acting on the vascular endothelium cause capillary leak that can ultimately result in hypotension with consequent multiorgan failure. (bmj.com)
  • Toxic shock syndrome (TSS) is a relatively rare but severe disease that is more common in children than adults and characterised by fever, erythematous rash and multiorgan failure. (bmj.com)
  • Capillary leak syndrome is characterized by the escape of blood plasma through capillary walls, from the blood circulatory system to surrounding tissues, muscle compartments, organs or body cavities. (wikipedia.org)
  • One study reports that it is caused by chemicals in the body that damage or temporarily separate the cells lining the capillary walls. (mayoclinic.org)
  • Health Canada s safety review concluded that there is a potential risk of capillary leak syndrome with the use of Yondelis. (canada.ca)
  • Health Canada carried out a safety review to look into the potential risk of capillary leak syndrome with the use of Yondelis. (canada.ca)
  • Health Canada is recommending updates to the Canadian product information to include the potential risk of capillary leak syndrome with the use of Yondelis. (canada.ca)
  • Risk of capillary leak syndrome (CLS) and hemolytic uremic syndrome (HUS). (oncologynurseadvisor.com)
  • Significant complications included 6 patients with acute respiratory distress syndrome, 28 patients with infectious complications, and 4 patients with anastomotic complications. (elsevier.com)
  • Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. (nih.gov)
  • Acute respiratory distress syndrome (ARDS) is a rare complication of generalized pustular psoriasis (GPP). (scielo.br)
  • Acute respiratory distress syndrome (ARDS) has been reported in patients receiving filgrastim products. (pfizerpro.com)
  • It is characterized by self-reversing episodes during which the endothelial cells which line the capillaries, usually of the extremities, separate for one to three days, causing a leakage of plasma mainly into the muscle compartments of the arms and legs. (wikipedia.org)
  • That's why the continuous capillaries in this area don't have any gaps between endothelial cells, and their surrounding basement membrane is also thicker. (healthline.com)
  • Loss of endothelial integrity promotes capillary leakage in numerous diseases, including sepsis, but there are no effective therapies for preserving endothelial barrier function. (pnas.org)
  • Scheinfeld N. Commentary on Degos disease: a C5b-9/interferon-α-mediated endotheliopathy syndrome by Magro et al: a reconsideration of Degos disease as hematologic or endothelial genetic disease. (medscape.com)
  • Hemolytic Uremic Syndrome (HUS) is a condition that affects your blood cells and kidney and can be life threatening. (medicineshoppe.com)
  • Capillary leak syndrome (CLS) and hemolytic uremic syndrome (HUS), including life-threatening cases of each, have been reported among patients treated with LUMOXITI. (astrazeneca-us.com)
  • Hemolytic Uremic Syndrome (HUS), including life-threatening cases, occurred in patients receiving Lumoxiti. (centerwatch.com)
  • ARDS can be caused by apulmonary capillary leak syndrome, an infection or by drugs hypersensivity reaction (methotrexate or acitretin) and it seems to be related to cytokines (interleukin 1, tumor necrosis factor α and interleukin 2). (scielo.br)
  • The appearance of interleukin-2 receptor-bearing cells may be symptomatic of some immunological disturbance which also results in the secretion of cytokines which subsequently affect the capillaries. (readabstracts.com)
  • Severe capillary leak syndrome with cardiac arrest triggered by influenza virus infection. (dbcls.jp)
  • Pregnancy was remarkable for severe twin-to-twin transfusion syndrome, of which she was the donor. (ispub.com)
  • It is a phenomenon most commonly witnessed in sepsis, and less frequently in autoimmune diseases, differentiation syndrome, engraftment syndrome, hemophagocytic lymphohistiocytosis, the ovarian hyperstimulation syndrome, viral hemorrhagic fevers, and snakebite and ricin poisoning. (wikipedia.org)
  • All clinical and laboratory findings supported autoinflammation as the underlying pathogenic mechanism of the syndrome. (ovid.com)
  • The data indicate that SCL-like syndrome can be considered a novel clinical syndrome, which can complicate APS. (ovid.com)
  • Rhabdomyolysis, which literally means striated muscle dissolution or disintegration, 1 is a potentially lethal clinical and biochemical syndrome. (aafp.org)
  • Rhabdomyolysis is a potentially life-threatening syndrome resulting from the breakdown of skeletal muscle fibers with leakage of muscle contents into the circulation. (aafp.org)