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Biomedical subjects

Nicholas E Vlahakis

Publications and source records attributed to Nicholas E Vlahakis.

10 recordsLinked to original sources
PubMed2006

Acute pancreatitis due to hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is an infrequent disorder characterized by abnormalities in the levels and/or function of complement C1 esterase inhibitor. Clinical manifestations of HAE are due to recurrent episodic swelling of the subcutaneous or submucosal tissue. When swelling involves the gastrointestinal mucosa, patients may present with nausea, vomiting, diarrhea, and severe abdominal pain. However, HAE is almost never suspected as a potential cause of acute pancreatitis. OBJECTIVE: To describe a patient with HAE-associated pancreatitis requiring intensive medical care that responded favorably to conservative and supportive measures. METHODS: Various tests were performed, including abdominal imaging, measurement of pancreatic enzymes levels, liver function tests, measurement of complement levels, and endoscopic retrograde cholangiopancreatography. RESULTS: The results of these tests confirmed the diagnosis of HAE-associated acute pancreatitis. No other obvious origin, such as gallstones or alcohol use, was identified. CONCLUSION: This case illustrates the need for a high clinical suspicion of acute pancreatitis when caring for patients with HAE who present with abdominal symptoms. There continues to be an urgent need for better and additional therapeutic options for HAE patients, including those to prevent and abort ongoing attacks.

Adult↗
PubMed2006

B-type natriuretic peptide in the assessment of acute lung injury and cardiogenic pulmonary edema.

OBJECTIVE: The role of plasma B-type natriuretic peptide (BNP) in critically ill patients with acute pulmonary edema is controversial. We postulated that a low BNP level would exclude cardiac dysfunction as the principal cause of pulmonary edema and therefore help in the diagnosis of acute lung injury. DESIGN: A retrospective derivation cohort was followed by a prospective validation cohort of consecutive patients with acute pulmonary edema admitted to three intensive care units. BNP was measured within 24 hrs from onset. Critical care experts blinded to BNP results integrated clinical data with the course of disease and response to therapy and served as the reference standard. SETTING: Three intensive care units at the tertiary center. PATIENTS: Consecutive critically ill patients with acute pulmonary edema. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In a derivation cohort of 84 patients, a BNP threshold of <or=250 pg/mL had a specificity of 87% and sensitivity of 48% for the diagnosis of acute lung injury. High specificity of BNP (90%, likelihood ratio of 3.9) was confirmed in a validation cohort of 120 consecutive patients, 52 (43%) of whom had acute lung injury. Notably, 32% of patients with acute lung injury had concomitant cardiac dysfunction. The median time from the onset of pulmonary edema to BNP testing was 3 hrs. The accuracy of BNP (area under receiver operator curve, 0.71) was comparable with pulmonary artery occlusion pressure (area under receiver operator curve, 0.66) and superior to ejection fraction (area under receiver operator curve, 0.60) in subgroups of patients in whom these tests were performed. The accuracy of BNP improved when patients with renal insufficiency were excluded (area under receiver operator curve, 0.82). CONCLUSION: When measured early after the onset of acute pulmonary edema, a BNP level of <250 pg/mL supports the diagnosis of acute lung injury. The high rate of cardiac and renal dysfunction in critically ill patients limits the discriminative role of BNP. No level of BNP could completely exclude cardiac dysfunction.

Acute Disease↗
PubMed2005

Cellular stress failure in ventilator-injured lungs.

The clinical and experimental literature has unequivocally established that mechanical ventilation with large tidal volumes is injurious to the lung. However, uncertainty about the micromechanics of injured lungs and the numerous degrees of freedom in ventilator settings leave many unanswered questions about the biophysical determinants of lung injury. In this review we focus on experimental evidence for lung cells as injury targets and the relevance of these studies for human ventilator-associated lung injury. In vitro, the stress-induced mechanical interactions between matrix and adherent cells are important for cellular remodeling as a means for preventing compromise of cell structure and ultimately cell injury or death. In vivo, these same principles apply. Large tidal volume mechanical ventilation results in physical breaks in alveolar epithelial and endothelial plasma membrane integrity and subsequent triggering of proinflammatory signaling cascades resulting in the cytokine milieu and pathologic and physiologic findings of ventilator-associated lung injury. Importantly, though, alveolar cells possess cellular repair and remodeling mechanisms that in addition to protecting the stressed cell provide potential molecular targets for the prevention and treatment of ventilator-associated lung injury in the future.

Animals↗
PubMed2004

The lymphangiogenic vascular endothelial growth factors VEGF-C and -D are ligands for the integrin alpha9beta1.

Mice homozygous for a null mutation of the integrin alpha9 subunit die 6-12 days after birth from bilateral chylothoraces suggesting an underlying defect in lymphatic development. However, until now the mechanisms by which the integrin alpha9beta1 modulates lymphangiogenesis have not been described. In this study we show that adhesion to and migration on the lymphangiogenic vascular endothelial growth factors (VEGF-C and -D) are alpha9beta1-dependent. Mouse embryonic fibroblasts and human colon carcinoma cells (SW-480) transfected to express alpha9beta1 adhered and/or migrated on both growth factors in a concentration-dependent fashion, and both adhesion and migration were abrogated by anti-alpha9beta1 function-blocking antibody. In SW-480 cells, which lack cognate receptors for VEGF-C and -D, both growth factors induced alpha9beta1-dependent Erk and paxillin phosphorylation. Human microvascular endothelial cells, which express both alpha9beta1 and VEGF-R3, also adhered to and migrated on both growth factors, and both responses were blocked by anti-alpha9beta1 antibody. Furthermore, in a solid phase binding assay recombinant VEGF-C and -D bound to purified alpha9beta1 integrin in a dose- and cation-dependent fashion showing that VEGF-C and VEGF-D are ligands for the integrin alpha9beta1. The interaction between alpha9beta1 and VEGF-C and/or -D may begin to explain the abnormal lymphatic phenotype of the alpha9 knock-out mice.

Animals↗
PubMed2004

Sirolimus-associated diffuse alveolar hemorrhage.

Sirolimus is an immunosuppressive medication used in transplant recipients. To our knowledge, we describe the third reported case of alveolar hemorrhage in association with sirolimus. Fever, dyspnea, hemoptysis, and lung infiltrates resolved rapidly with cessation of sirolimus therapy both initially and after reinstitution of the drug. Unlike previous reports, our patient had no evidence of lymphocytic alveolitis but rather marked macrophage hemosiderosis, suggesting that sirolimus pulmonary toxicity may manifest through 2 separate mechanisms. Our case highlights an uncommon but potentially lethal manifestation of sirolimus pulmonary toxicity.

Biopsy↗
PubMed2003

Response of alveolar cells to mechanical stress.

The purpose of this review is to highlight areas in alveolar cell biology in which our understanding of the effects of mechanical stress have been advanced in the last year, focusing on intracellular signal transduction pathways, the surfactant system, and cell injury and repair. Mechano-transduction pathways are only now beginning to be elucidated in alveolar cells. The importance of the mitogen-activated protein kinase, G protein, and growth factor systems is emphasized. The research conducted in the last year has also stressed the importance of alveolar cell cross-talk, with surfactant exocytosis being facilitated through parathyroid hormone-related peptide and leptin and calcium in interstitial fibroblasts and endothelial cells, respectively. Finally, the importance of deformation-induced plasma membrane breaks is emphasized. Alveolar cells were found to exocytose intracellular lipid vesicles to the plasma membrane-not only to prevent cell breaks but also to reseal cell breaks. This dynamic process was a stronger determinant of cell breaks than the prestress properties of the cytoskeleton. All of these exciting findings provide further potential treatment targets for ventilator-induced lung injury.

Animals↗
PubMed2003

Osteoarticular infection complicating enterococcal endocarditis.

Despite the common occurrence of musculoskeletal complaints in patients with infective endocarditis, infectious osteoarticular complications are diagnosed infrequently. Moreover, although enterococcal infection is the third most common cause of infective endocarditis, infectious osteoarticular complications are rare. We report a case of disk space infection in a patient with enterococcal endocarditis. Blood cultures and an L3-4 aspirate grew Enterococcus faecalis, and transthoracic echocardiography revealed a large vegetation on the posterior mitral valve leaflet. The osteoarticular infection resolved with antimicrobial treatment, but worsening heart failure necessitated valve replacement surgery. The patient had an uneventful recovery with no evidence of recurrence or complications. A review of the medical literature from 1966 through 1998 identified 13 additional cases, only 8 of which provided clinical and treatment data. We present the clinical and laboratory findings reported in these cases, along with data from our patient. This report highlights the rare occurrence of osteoarticular infection in the setting of enterococcal endocarditis and emphasizes early recognition and treatment.

Anti-Bacterial Agents↗
PubMed2002

Role of deformation-induced lipid trafficking in the prevention of plasma membrane stress failure.

Cells experience plasma membrane stress failure when the matrix to which they adhere undergoes large deformations. In the lung, such a mechanism might explain mechanical ventilation-associated cell injury. We have previously shown that in alveolar epithelial cells, deformation induces lipid trafficking to the plasma membrane, thereby accommodating the required increase in the cell surface area. We now show that cell wounding is strain amplitude and rate dependent and that under conditions of impaired exocytosis strain-induced cell wounding is significantly increased. In addition, the susceptibility of cells to mechanical injury was not correlated with changes in cell stiffness. Using a dual-labeling technique, we differentiated between cell populations that were reversibly and irreversibly injured and showed that interventions that impair deformation-induced lipid trafficking also reduce the likelihood of plasma membrane resealing. Our findings suggest that cell plasticity and remodeling responses such as deformation-induced lipid trafficking are more important for cytoprotection from strain injury than are the innate mechanical properties of the cell. We also conclude that in deformation experiments, tests of cell membrane integrity cannot be interpreted as tests of cell viability because an intact plasma membrane after deformation does not mean that no injury had occurred.

Animals↗