Impact of Pharmacologically Left Shifting the Oxygen-Hemoglobin Dissociation Curve on Arterial Blood Gases and Pulmonary Gas Exchange During Maximal Exercise in Hypoxia.

Stewart, Glenn M., Troy J. Cross, Michael J.

Effects of an allosteric hemoglobin affinity modulator on arterial blood gases and cardiopulmonary responses during normoxic and hypoxic low-intensity exercise.

Numerous pathophysiological conditions induce hypoxemia-related cardiopulmonary perturbations, decrements in exercise capacity, and debilitating symptoms. Accordingly, this study investigated the efficacy of an allosteric hemoglobin modulator (voxelotor) to enhance arterial oxygen saturation during low-intensity exercise in hypoxia. Eight normal healthy subjects (36 ± 7 yr; 73.

Nonleg venous thrombosis in critically ill adults: a nested prospective cohort study.

Importance: Critically ill patients are at risk of venous thrombosis, and therefore guidelines recommend daily thromboprophylaxis. Deep vein thrombosis (DVT) commonly occurs in the lower extremities but can occur in other sites including the head and neck, trunk, and upper extremities. The risk of nonleg deep venous thromboses (NLDVTs), predisposing factors, and the association between NLDVTs and pulmonary embolism (PE) or death are unclear.

Heparin-induced thrombocytopenia in medical surgical critical illness.

Background: In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to a lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (five vs 12 patients, P = .

The induction of angiogenesis by cerium oxide nanoparticles through the modulation of oxygen in intracellular environments.

Angiogenesis is the formation of new blood vessels from existing blood vessels and is critical for many physiological and pathophysiological processes. In this study we have shown the unique property of cerium oxide nanoparticles (CNPs) to induce angiogenesis, observed using both in vitro and in vivo model systems. In particular, CNPs trigger angiogenesis by modulating the intracellular oxygen environment and stabilizing hypoxia inducing factor 1α endogenously.

Dalteparin versus unfractionated heparin in critically ill patients.

Background: The effects of thromboprophylaxis with low-molecular-weight heparin, as compared with unfractionated heparin, on venous thromboembolism, bleeding, and other outcomes are uncertain in critically ill patients.

Methods: In this multicenter trial, we tested the superiority of dalteparin over unfractionated heparin by randomly assigning 3764 patients to receive either subcutaneous dalteparin (at a dose of 5000 IU once daily) plus placebo once daily (for parallel-group twice-daily injections) or unfractionated heparin (at a dose of 5000 IU twice daily) while they were in the intensive care unit. The primary outcome, proximal leg deep-vein thrombosis, was diagnosed on compression ultrasonography performed within 2 days after admission, twice weekly, and as clinically indicated.

Vascular endothelial growth factor A (VEGF-A) induces endothelial and cancer cell migration through direct binding to integrin {alpha}9{beta}1: identification of a specific {alpha}9{beta}1 binding site.

Integrin α9β1 mediates accelerated cell adhesion and migration through interactions with a number of diverse extracellular ligands. We have shown previously that it directly binds the vascular endothelial growth factors (VEGF) A, C, and D and contributes to VEGF-induced angiogenesis and lymphangiogenesis. Until now, the α9β1 binding site in VEGF has not been identified.

Lymphangioleiomyoma cells and lymphatic endothelial cells: expression of VEGFR-3 in lymphangioleiomyoma cell clusters.

This Correspondence addresses the use of LAM and LAM-derived cells in Issaka et al. (Am J Pathol 2009,175: 1410–1420)

Integrin alpha9beta1: Unique signaling pathways reveal diverse biological roles.

Integrins are transmembrane heterodimeric receptors responsible for transducing and modulating signals between the extracellular matrix and cytoskeleton, ultimately influencing cell functions such as adhesion and migration. Integrin alpha9beta1 is classified within a two member sub-family of integrins highlighted in part by its specialized role in cell migration. The importance of this role is demonstrated by its regulation of numerous biological functions including lymphatic valve morphogenesis, lymphangiogenesis, angiogenesis and hematopoietic homeostasis.

Vascular endothelial growth factors C and D induces proliferation of lymphangioleiomyomatosis cells through autocrine crosstalk with endothelium.

Lymphangioleiomyomatosis (LAM) is a potentially fatal lung disease characterized by nodules of proliferative smooth muscle-like cells. The exact nature of these LAM cells and their proliferative stimuli are poorly characterized. Herein we report the novel findings that the lymphangiogenic vascular endothelial growth factors (VEGF) C and D induce LAM cell proliferation through activation of their cognate receptor VEGF-R3 and activation of the signaling intermediates Akt/mTOR/S6.

Integrin alpha9beta1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase.

Integrins are important mediators of cell adhesion and migration, which in turn are essential for diverse biological functions, including wound healing and cancer metastasis. The integrin alpha9beta1 is expressed on numerous mammalian tissues and can mediate accelerated cell migration. As the molecular signaling mechanisms that transduce this effect are poorly defined, we investigated the pathways by which activated integrin alpha9beta1 signals migration.

Fetal outcomes of critically ill pregnant women admitted to the intensive care unit for nonobstetric causes.

Introduction: The outcome of the fetus in critically ill mothers has been briefly reported as a part of descriptive studies focusing on maternal risk factors for admission to the intensive care unit. We evaluated the risk factors for adverse fetal outcomes in critically ill pregnant women admitted to the intensive care unit for nonobstetrical reasons.

Design: Retrospective cohort study of all critically ill pregnant patients >18 yr; admitted to four (medical, surgical, trauma, and mixed medical-surgical) intensive care units at the Mayo Clinic in Rochester, MN; during the period of January 1995 to December 2005.

Six-month survival of patients with acute lung injury: prospective cohort study.

Objective: Both short- and long-term outcome studies in acute lung injury (ALI) performed thus far were conducted before the implementation of recent advances in mechanical ventilation and supportive care and/or in the context of clinical trials with restricted inclusion criteria. We sought to determine the outcome of consecutive acute lung injury patients after the implementation of these interventions.

Design: Prospective cohort study.

Infective endocarditis due to community-associated methicillin-resistant Staphylococcus aureus in injection drug users may be associated with Panton-Valentine leukocidin-negative strains.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates that cause infective endocarditis in injection drug users (IDUs) are distinct from CA-MRSA strains that cause endocardial infection as a complication of skin and soft tissue infections. We present a case of CA-MRSA infective endocarditis, review pertinent cases previously published, and describe the molecular characteristics of strains from IDUs and patients with skin and soft tissue infections.

Integrin alpha9beta1 directly binds to vascular endothelial growth factor (VEGF)-A and contributes to VEGF-A-induced angiogenesis.

Vascular endothelial growth factor A (VEGF-A) is a potent inducer of angiogenesis. We now show that VEGF-A-induced adhesion and migration of human endothelial cells are dependent on the integrin alpha9beta1 and that VEGF-A is a direct ligand for this integrin. Adhesion and migration of these cells on the 165 and 121 isoforms of VEGF-A depend on cooperative input from alpha9beta1 and the cognate receptor for VEGF-A, VEGF receptor 2 (VEGF-R2).

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.

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.

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.

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.

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.

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.

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.