PubMed Health⌕ Search

Biomedical subjects

Brian R Younge

Publications and source records attributed to Brian R Younge.

7 recordsLinked to original sources
PubMed2006

Treatment of giant cell arteritis using induction therapy with high-dose glucocorticoids: a double-blind, placebo-controlled, randomized prospective clinical trial.

OBJECTIVE: Glucocorticoid (GC) therapy for giant cell arteritis (GCA) is effective but requires prolonged administration, resulting in adverse side effects. The goal of the current study was to test the hypothesis that induction treatment with high-dose pulse intravenous (IV) methylprednisolone permits a shorter course of therapy. METHODS: Twenty-seven patients with biopsy-proven GCA were enrolled in a randomized, double-blind, placebo-controlled study to receive IV methylprednisolone (15 mg/kg of ideal body weight/day) or IV saline for 3 consecutive days. All patients were started on 40 mg/day prednisone and followed the same tapering schedule as long as disease activity was controlled. The numbers of patients with disease in remission after 36, 52, and 78 weeks of treatment and taking <or=5 mg/day prednisone were compared. Cumulative prednisone dose, number of relapses, and development of adverse GC effects were assessed. RESULTS: Ten of the 14 IV GC-treated patients, but only 2 of 13 control patients, were taking <or=5 mg/day prednisone at 36 weeks (P = 0.003). This difference was maintained; there was a higher number of sustained remissions after discontinuation of treatment in the IV GC-treated group and a lower median daily dose of prednisone at 78 weeks (P = 0.0004). The median cumulative dose of oral prednisone, excluding the IV GC dose, was 5,636 mg in the IV GC-treated group compared with 7,860 mg in the IV saline-treated group (P = 0.001). CONCLUSION: Initial treatment of GCA with IV GC pulses allowed for more rapid tapering of oral GCs and had long-term benefits, with a higher frequency of patients experiencing sustained remission of their disease after discontinuation of treatment.

Administration, Oral↗
PubMed2005

Oprelvekin-associated bilateral optic disk edema.

PURPOSE: To report a case of bilateral optic disk edema in a patient taking oprelvekin for radioimmunotherapy-induced thrombocytopenia. DESIGN: Observational case report. METHODS: A 38-year-old man with a history of relapsed non-Hodgkins follicular lymphoma complained of bilateral loss of vision following oprelvekin therapy for thrombocytopenia. RESULTS: Funduscopic examination demonstrated bilateral optic disk edema with exudates inferotemporal to the right nerve. The results of magnetic resonance imaging of the brain and orbits and lumbar puncture were normal. The disk edema resolved with discontinuation of oprelvekin therapy. CONCLUSIONS: Oprelvekin therapy may be associated with bilateral optic disk edema. This has been shown to be reversible in a primate model.

Adult↗
PubMed2004

Initiation of glucocorticoid therapy: before or after temporal artery biopsy?

OBJECTIVE: To identify clinical findings in patients with suspected giant cell arteritis (GCA) that may help clinicians decide when to initiate glucocorticoid therapy. PATIENTS AND METHODS: Medical diagnostic codes and surgical indexing were used to identify all patients who had temporal artery biopsy at the Mayo Clinic in Rochester, Minn, between January 1, 1988, and December 31, 1997. Patient medical records were abstracted for pertinent clinical data, glucocorticoid use, and final diagnoses. Sensitivities, specificities, predictive values, and likelihood ratios were calculated for the association of the various clinical findings and the presence of a positive biopsy result. Graphic and arithmetic models were constructed to predict positive temporal artery biopsy results. RESULTS: During the 10-year interval, 1113 patients had temporal artery biopsy. The results were positive for GCA in 373 patients (33.5%) and negative in 740 (665%). Twenty percent of all patients were taking glucocorticoids at the time of biopsy. The presence of jaw claudication had a positive predictive value of 78. Combinations of jaw claudication with new headache, scalp tenderness, and decreased vision had still higher values. Positive likelihood ratios in patients with these combinations and in those with diplopia were greater than 3. A normal erythrocyte sedi-mentation rate in patients not taking corticosteroids provided a high negative likelihood ratio of 40. An arithmetic equation provided the probability of a positive biopsy result on a continuous scale using 6 variables identified by logistic regression. Patients with a greater than 80% chance of a positive biopsy result and those with less than a 10% chance were identified. CONCLUSION: Positive predictive values, likelihood ratios, and an arithmetic formula identify patients who have an increased or decreased chance of a positive temporal artery biopsy result. Use of these methods to determine early initiation of glucocorticoid therapy before temporal artery biopsy or deferral until after biopsy may help reduce both vascular complications of GCA and adverse effects of corticosteroids.

Administration, Oral↗
PubMed2003

Rotatory nystagmus synchronous with heartbeat: a treatable form of nystagmus.

PURPOSE: To describe a treatable form of nystagmus. METHODS: Two patients recently evaluated at the Mayo Clinic had experienced various forms of oscillopsia, imbalance, and worsening symptoms with a Valsalva maneuver. Close inspection of the eye revealed a subtle rotatory nystagmus that was synchronous with the heartbeat. RESULTS: The two patients had surgical treatment for dehiscence of the superior semicircular canal; postoperatively, their symptoms completely resolved. This is a relatively newly discovered condition that has not been described on either slit-lamp or ophthalmoscopic examination. The cause is related to a dehiscence of the superior semicircular canal that permits communication of variable pressures between the intracranial cavity and the perilymphatic spaces of the semicircular canal. CONCLUSION: Being aware of this unusual form of nystagmus may permit physicians to diagnose it--one of the few treatable forms of nystagmus.

Humans↗
PubMed2002

Reactive nitrogen intermediates in giant cell arteritis: selective nitration of neocapillaries.

Arterial wall damage in giant cell arteritis (GCA) is mediated by several different macrophage effector functions, including the production of metalloproteinases and lipid peroxidation. Tissue-invading macrophages also express nitric oxide synthase (NOS)-2, but it is not known whether nitric oxide-related mechanisms contribute to the disease process. Nitric oxide can form nitrating agents, including peroxynitrite, a nitric oxide congener formed in the presence of reactive oxygen intermediates. Protein nitration selectively targets tyrosine residues and can result in a gain, as well as a loss, of protein function. Nitrated tyrosine residues in GCA arteries were detected almost exclusively on endothelial cells of newly formed microcapillaries in the media, whereas microvessels in the adventitia and the intima were spared. Nitration correlated with endothelial NOS-3 expression and not with NOS-2-producing macrophages, which preferentially homed to the hyperplastic intima. The restriction of nitration to the media coincided with the production of reactive oxygen intermediates as demonstrated by the presence of the toxic aldehyde, 4-hydroxynonenal. Depletion of tissue-infiltrating macrophages in human temporal artery-SCID mouse chimeras disrupted nitrotyrosine generation, demonstrating a critical role of macrophages in the nitration process that targeted medial microvessels. Thus, protein nitration in GCA is highly compartmentalized, reflecting the production of reactive oxygen and reactive nitrogen intermediates in the inflamed arterial wall. Heterogeneity of microvessels in NOS-3 regulation may be an additional determinant contributing to this compartmentalization and could explain the preferential targeting of newly generated capillary beds.

Animals↗
PubMed2002

Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis.

Immature dendritic cells (DCs) are scattered throughout peripheral tissues and act as sentinels that sample the antigenic environment. After activation, they modify their chemokine receptor profile and migrate toward lymphoid tissues. On arrival, they have matured into chemokine-producing DCs that express co-stimulatory molecules and can prime naive T cells. Normal temporal arteries contain immature DCs that are located at the media-adventitia border. In temporal arteries affected by giant cell arteritis, DCs are highly enriched and activated and have matured into fully differentiated cells producing the chemokines, CCL18, CCL19, and CCL21. In keeping with their advanced maturation, DCs in the granulomatous lesions possess the chemokine receptor, CCR7. CCR7 binds CCL19 and CCL21, causing the highly activated DCs to be trapped in the peripheral tissue site. The co-stimulatory molecule, CD86, which is critical for DC/T-cell interaction, is expressed by a subset of DCs captured in the arterial wall. DC/T-cell interaction does not involve interleukin-12; transcripts for interleukin-12 p40 are absent in the vasculitic infiltrates. We propose that differentiation of DCs and the autocrine and paracrine actions of chemokines in granulomatous lesions misdirect DCs away from their usual journey to lymphoid organs and are critical in maintaining T-cell activation and granuloma formation in giant cell arteritis.

Aged↗