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1.
Surv Ophthalmol ; 54(6): 697-704, 2009.
Article in English | MEDLINE | ID: mdl-19709708

ABSTRACT

Multiple myeloma is a plasma cell malignancy that destroys skeletal, renal, and neurological function. Orbital involvement is rare, but has been considered an initial presentation for the malignancy. Furthermore, an association between the subtype of multiple myeloma and the likelihood of orbital infiltration has been suggested. We present a case of an orbital mass that was a recurrence of multiple myeloma. A literature search was performed to evaluate the presentation characteristics of orbital multiple myeloma, plasmacytoma and primary (or solitary) extramedullary plasmacytoma. Past reports were analyzed for age, sex, symptoms at presentation, time from symptom onset to presentation, prior diagnosis before presentation for orbital symptoms, radiological characteristics, immunoglobulin subtype, and survival times. Less than half of published cases had orbital multiple myeloma as the primary presentation. Proptosis is the major presenting sign of orbital multiple myeloma, and radiological evaluation shows that the majority of masses originate in the superotemporal quadrant. The dominant immunoglobulin subtype was IgG.


Subject(s)
Multiple Myeloma/pathology , Orbital Neoplasms/pathology , Aged , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Humans , Immunoglobulin A/blood , Immunoglobulin kappa-Chains/analysis , Male , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/therapy , Ophthalmologic Surgical Procedures , Orbital Neoplasms/diagnostic imaging , Orbital Neoplasms/therapy , Retrospective Studies , Tomography, X-Ray Computed , Visual Acuity
2.
Arch Ophthalmol ; 125(12): 1635-42, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18071114

ABSTRACT

OBJECTIVE: To evaluate the clinical utility of time-resolved contrast-enhanced magnetic resonance angiography (MRA) in the evaluation of vascular orbital tumors. METHODS: Retrospective medical record review of patients with vascular orbital lesions imaged with Time-Resolved Imaging of Contrast KineticS (TRICKS; GE Healthcare [Chalfont St Giles, England]) MRA, a noninvasive dynamic imaging modality. RESULTS: Five patients with orbital vascular tumors were evaluated using TRICKS MRA. These included 1 patient with a cavernous hemangioma, 2 patients with orbital varices, 1 patient with an orbitocutaneous arteriovenous malformation, and 1 patient who had a solitary fibrous tumor with features of a hemangiopericytoma. In 2 patients, diagnoses were altered as a result of TRICKS MRA. In addition, a young patient with a large orbitocutaneous arteriovenous malformation involving the ophthalmic artery was followed perioperatively and noninvasively using TRICKS MRA, which produced exquisite images and added substantial value in the care of these patients. CONCLUSION: Dynamic MRA in the form of TRICKS is a newly available imaging modality with great potential for improving the evaluation and management of patients with complex orbital tumors.


Subject(s)
Arteriovenous Malformations/diagnosis , Hemangioma, Cavernous/diagnosis , Magnetic Resonance Angiography , Orbit/blood supply , Orbital Neoplasms/diagnosis , Solitary Fibrous Tumors/diagnosis , Varicose Veins/diagnosis , Adult , Aged , Blood Flow Velocity , Child , Female , Humans , Male , Middle Aged , Regional Blood Flow , Retrospective Studies , Time Factors
3.
WMJ ; 105(1): 58-61, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16676493

ABSTRACT

Infections affecting the central nervous system caused by Blastomyces dermatitidis are rare but curable. We describe a case of a 24-year-old man who presented to the emergency department with progressive bilateral lower extremity weakness over 1 month. On the day of admission, he had minimal muscle strength and was hyperreflexic in the lower extremities. Sensation, however, was intact. Skin examination revealed annular, raised, crusted lesions on his face and legs. A magnetic resonance imaging (MRI) scan showed marrow replacement of the T7 and T8 vertebral bodies and an epidural mass with cord compression. A chest radiograph showed an infiltrate, and a subsequent needle biopsy revealed yeast resembling B. dermatitidis. A skin biopsy was then obtained, and the culture grew out B. dermatitidis. He received 4 weeks of amphotericin B lipid complex (total of 6 grams), followed by oral itraconazole. After 1 week on antifungals, he was able to walk with a walker and the skin lesions virtually resolved. At 5 months he was ambulatory and riding a bicycle daily. Blastomycosis should be included in the differential diagnosis of epidural masses.


Subject(s)
Blastomycosis/diagnosis , Muscle Weakness/microbiology , Adult , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Blastomycosis/drug therapy , Diagnosis, Differential , Humans , Lower Extremity , Magnetic Resonance Imaging , Male
4.
Mol Pain ; 1: 17, 2005 Apr 27.
Article in English | MEDLINE | ID: mdl-15857517

ABSTRACT

Insulin and insulin-like growth factors (IGFs) maintain vital neuronal functions. Absolute or functional deficiencies of insulin or IGF-I may contribute to neuronal and vascular complications associated with diabetes. Vanilloid receptor 1 (also called TRPV1) is an ion channel that mediates inflammatory thermal nociception and is present on sensory neurons. Here we demonstrate that both insulin and IGF-I enhance TRPV1-mediated membrane currents in heterologous expression systems and cultured dorsal root ganglion neurons. Enhancement of membrane current results from both increased sensitivity of the receptor and translocation of TRPV1 from cytosol to plasma membrane. Receptor tyrosine kinases trigger a signaling cascade leading to activation of phosphatidylinositol 3-kinase (PI(3)K) and protein kinase C (PKC)-mediated phosphorylation of TRPV1, which is found to be essential for the potentiation. These findings establish a link between the insulin family of trophic factors and vanilloid receptors.


Subject(s)
Insulin-Like Growth Factor I/physiology , Insulin/physiology , TRPV Cation Channels/metabolism , Animals , Cell Line , Humans , Protein Transport/physiology , Rats , Signal Transduction/physiology , TRPV Cation Channels/physiology , Xenopus laevis
5.
J Neurosci ; 24(14): 3663-71, 2004 Apr 07.
Article in English | MEDLINE | ID: mdl-15071115

ABSTRACT

Vanilloid receptor 1 (TRPV1), a nonspecific cation channel expressed primarily in small sensory neurons, mediates inflammatory thermal pain sensation. The function and expression of TRPV1 are enhanced during inflammation and certain neuropathies, leading to sustained hyperalgesia. Activation of TRPV1 in the spinal cord and periphery promotes release of adenosine, which produces analgesia by activating A(1) and A(2A) adenosine receptor (AR) on central and peripheral neurons. This study provides evidence of a direct interaction of AR analogs with TRPV1. Adenosine analogs inhibit TRPV1-mediated Ca(2+) entry in human embryonic kidney (HEK293) cells stably expressing TRPV1 (HEK/TRPV1) and DRG neurons. This inhibition was independent of A(2A)AR activation. Specific binding of [(3)H]resiniferatoxin (RTX) in plasma membrane preparations was inhibited by CGS21680, an A(2A)AR agonist. Similar degrees of inhibition were observed with both agonists and antagonists of ARs. Adenosine analogs inhibited [(3)H]RTX binding to affinity-purified TRPV1, indicative of a direct interaction of these ligands with the receptor. Furthermore, specific capsaicin-sensitive binding of [(3)H]CGS21680 was observed in Xenopus oocyte membranes expressing TRPV1. Capsaicin-induced inward currents in DRG neurons were inhibited by adenosine and agonist and antagonist of A(2A)AR at nanomolar concentrations. Increasing the concentrations of capsaicin reversed the inhibitory response to capsaicin, suggesting a competitive inhibition at TRPV1. Finally, exposure of HEK/TRPV1 cells to capsaicin induced an approximately 2.4-fold increase in proapoptotic cells that was abolished by adenosine analogs. Together, these data suggest that adenosine could serve as an endogenous inhibitor of TRPV1 activity by directly interacting with the receptor protein.


Subject(s)
Adenosine/analogs & derivatives , Adenosine/metabolism , Receptors, Drug/metabolism , Adenosine/pharmacokinetics , Adenosine/pharmacology , Adenosine A2 Receptor Agonists , Adenosine A2 Receptor Antagonists , Animals , Apoptosis/drug effects , Apoptosis/physiology , Binding, Competitive/drug effects , Binding, Competitive/physiology , Capsaicin/metabolism , Capsaicin/pharmacokinetics , Cell Membrane/metabolism , Cells, Cultured , Diterpenes/metabolism , Diterpenes/pharmacokinetics , Dose-Response Relationship, Drug , Ganglia, Spinal/chemistry , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Humans , Kidney/cytology , Kidney/drug effects , Kidney/metabolism , Neurons/drug effects , Neurons/metabolism , Oocytes/metabolism , Phenethylamines/metabolism , Phenethylamines/pharmacokinetics , Protein Binding/drug effects , Protein Binding/physiology , Rats , Receptors, Drug/genetics , Xenopus laevis
6.
J Neurophysiol ; 91(3): 1442-9, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14973326

ABSTRACT

The search for an endogenous ligand for the vanilloid receptor (VR or TRPV1) has led to the identification of N-arachidonyl dopamine (NADA). This study investigates the role of protein kinase C (PKC)-mediated phosphorylation on NADA-induced membrane currents in Xenopus oocytes heterologously expressing TRPV1 and in dorsal root ganglion (DRG) neurons. In basal state, current induced by 10 microM NADA is 5-10% of the current induced by 1 microM capsaicin or protons at pH 5. However, PKC activator, phorbol 12,13-dibutyrate (PDBu) strongly potentiated ( approximately 15-fold) the NADA-induced current. Repeated application of NADA at short intervals potentiated its own response approximately fivefold in a PKC-dependent manner. PKC inhibitor, bisindolylmaleimide (BIM, 500 nM), a mutant TRPV1 (S800A/S502A), and maximal activation of PKC abolished the potentiation induced by repeated application of NADA. As a further confirmation that NADA could stimulate PKC, pretreatment with NADA potentiated the response of protons at pH 5 (approximately 20 fold), which was dramatically reduced in the mutant TRPV1. In DRG neurons, capsaicin (100 nM) induced a approximately 15 mV depolarization and initiated a train of action potentials compared with 1 microM NADA that produced a approximately 5 mV response. Pretreatment with PDBu induced significantly larger depolarization and potentiated NADA-induced current. Furthermore, exposure of NADA to the intracellular surface of the membrane-induced larger currents suggesting inaccessibility to the intracellular binding site might contribute to its weaker action. These results indicate that NADA is a potent agonist of VR when the receptor is in the PKC-mediated phosphorylation state.


Subject(s)
Arachidonic Acids/pharmacology , Dopamine/analogs & derivatives , Dopamine/pharmacology , Protein Kinase C/drug effects , Receptors, Drug/drug effects , Action Potentials/physiology , Animals , Electrophysiology , Female , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Lipids/physiology , Membrane Potentials/physiology , Microinjections , Oocytes/drug effects , Oocytes/physiology , Patch-Clamp Techniques , Phorbol 12,13-Dibutyrate/pharmacology , Phosphorylation , Pregnancy , Protons , Rats , Receptors, Drug/metabolism , Xenopus laevis
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