ABSTRACT
INTRODUCTION: Cavernous sinus thrombosis (CST) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of CST, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: CST is a potentially deadly thrombophlebitic disease involving the cavernous sinuses. The most common underlying etiology is sinusitis or other facial infection several days prior to development of CST, though other causes include maxillofacial trauma or surgery, thrombophilia, dehydration, or medications. Staphylococcus aureus, streptococcal species, oral anaerobic species, and gram-negative bacilli are the most frequent bacterial etiologies. The most prevalent presenting signs and symptoms are fever, headache, and ocular manifestations (chemosis, periorbital edema, ptosis, ophthalmoplegia, vision changes). Cranial nerve (CN) VI is the most commonly affected CN, resulting in lateral rectus palsy. Other CNs that may be affected include III, IV, and V. The disease may also affect the pulmonary and central nervous systems. Laboratory testing typically reveals elevated inflammatory markers, and blood cultures are positive in up to 70% of cases. Computed tomography of the head and orbits with intravenous contrast delayed phase imaging is recommended in the ED setting, though magnetic resonance venography demonstrates the highest sensitivity. Management includes resuscitation, antibiotics, and anticoagulation with specialist consultation. CONCLUSION: An understanding of CST can assist emergency clinicians in diagnosing and managing this potentially deadly disease.
ABSTRACT
Oxidative damage to biomolecules such as lipids, proteins, nucleotides, and sugars has been implicated in the pathogenesis of various diseases. Superoxide radical anion (O 2 (*-)) addition to nitrones bearing an amide N-H has been shown to be more favored as compared to other nitrones [ Villamena, F. A. , ( 2007) J. Am. Chem. Soc. 129, 8177- 8191 ]. It has also been demonstrated by others [ Winterbourn, C. C. , ( 2004) Biochem. J. 381, 241- 248 ] that O 2 (*-) addition to tyrosine to form hydroperoxide is favored in the presence of basic amino groups, but the mechanism for this observation remains obscure. We, therefore, hypothesized that the alpha-effect resulting from the interaction of O 2 (*-) with N-H can play a crucial role in the enhancement of hydroperoxide formation. Understanding this phenomenon is important in the elucidation of mechanisms leading to oxidative stress in cellular systems. Computational (at the PCM/B3LYP/6-31+G**//B3LYP/6-31G level of theory) as well as experimental studies were carried out to shed insights into the effect of amide or amino N-H on the enhancement (or stabilization) of hydroperoxide formation in tyrosine. H-bond interaction of amino acid group with O 2 (*-) results in the perturbation of the spin and charge densities of O 2 (*-). A similar phenomenon has been predicted for non-amino acids bearing H-bond donor groups. Using the FOX assay, tyrosyl hydroperoxide formation was enhanced in the presence of H-bond donors from amino acids and non-amino acids. The role of H-bonding in either stabilizing the hydroperoxide adduct or facilitating O 2 (*-) addition via an alpha-effect was further theoretically investigated, and results show that the latter mechanism is more thermodynamically preferred. This study provides new mechanistic insights in the initiation of oxidative modification to tyrosyl radical.
