The inhibition of CXC chemokine receptor 2 (CXCR2), a key inflammatory mediator, is a potential strategy in the treatment of several pulmonary diseases and cancers. The complexity of endogenous chemokine interaction with the orthosteric binding site has led to the development of CXCR2 negative allosteric modulators (NAMs) targeting an intracellular pocket near the G protein binding site. Our understanding of NAM binding and mode of action has been limited by the availability of suitable tracer ligands for competition studies, allowing direct ligand binding measurements.
View Article and Find Full Text PDFG protein-coupled receptors (GPCRs) are widely therapeutically targeted, and recent advances in allosteric modulator development at these receptors offer further potential for exploitation. Intracellular allosteric modulators (IAM) represent a class of ligands that bind to the receptor-effector interface (e.g.
View Article and Find Full Text PDFObjective: Giant cell arteritis (GCA) is a systemic vasculitis, affecting medium- and large-sized vessels. Temporal artery biopsies (TABs) are currently the benchmark for diagnosing suspected cases of GCA. Often, the temporal artery is "skeletonized," and surrounding soft tissue is discarded at the time of biopsy.
View Article and Find Full Text PDFPurpose: A patient's presentation and clinical diagnosis can at times be clouded by their past medical history. Clinicians' anchoring bias towards initial information, such as a history of cancer, may lead them astray when creating a differential diagnosis for a patient who presents with new signs and symptoms of a mass lesion, assuming metastatic disease without seeking tissue confirmation.
Methods: The presentation, workup, diagnosis, and treatment of two patients who presented with orbital masses in the context of a primary prostate cancer are presented in this report.
Periorbital infections after strabismus surgery are rare. We describe the first reported case of necrotizing group A streptococcal infection of the conjunctiva and Tenon's capsule complicating uneventful strabismus surgery in a 23-month-old boy, successfully managed with conservative intraoperative debridement and with targeted local and systemic antibiotics.
View Article and Find Full Text PDFWe report a case of a 44-year-old man who presented with a left medial canthal mass and epiphora. Imaging was suggestive of a mass continuous with the nasolacrimal sac. Subsequent surgical exploration revealed a mass adherent to bone with invasion of the lacrimal system.
View Article and Find Full Text PDFPurpose: To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes.
Design: Randomized, double-masked, placebo-controlled trial.
Participants: Patients with primary open-angle or pseudo-exfoliation glaucoma.
Malignant melanoma of the conjunctiva is a relatively infrequent neoplasm that can be associated with significant morbidity and cause diagnostic difficulty to both the ophthalmologist and pathologist. We herein describe the first reported case in North American and European databases of a rare variant-signet ring cell melanoma - arising in the background of primary acquired melanosis (PAM) and use this case as a review of important diagnostic and therapeutic considerations when faced with this condition.
View Article and Find Full Text PDFBackground: Conjunctival lymphoproliferative lesions have not been selected for independent analysis with newer immunohistochemical and molecular genetic techniques to highlight their unique profile.
Methods: Retrospective case series examined biopsies from 16 consecutive patients with conjunctival lymphoproliferative lesions. The histopathologic, immunohistochemical, and molecular genetic features were characterized, as well as the frequency of tumour type, prognostic implications, clinical features, and treatments offered.
Case Report: A 57-year-old woman presented with a 16-month history of a slowly growing mass in the medial aspect of her right lower eyelid. On radiologic examination, the mass was seen to extend into the anterior orbit. Initial attempt at excision was complicated by problems with hemostasis and only a portion was removed.
View Article and Find Full Text PDFBackground: Lacrimal gland lymphoproliferative disorders are usually classified as orbital adnexal tumours. Because the lacrimal gland is the only orbital structure with native lymphocytes, we examined cases with primary involvement of the gland.
Methods: The 14 cases were selected from a review of all cases in the surgical pathology files of the Ottawa Hospital between 1992 and 2003.