Faculty Bibliography

We demonstrate the detection of iron oxide nanoparticles taken up by macrophages in atherosclerotic plaque with differential phase optical coherence tomography (DP-OCT). Magneto mechanical detection of nanoparticles is demonstrated in hyperlipidemic Watanabe and balloon-injured fat-fed New Zealand white rabbits injected with monocrystalline iron oxide nanoparticles (MIONs) of < 40 nm diam. MIONs taken up by macrophages was excited by an oscillating magnetic flux density and resulting nanometer tissue surface displacement was detected by DP-OCT. Frequency response of tissue surface displacement in response to an externally applied magnetic flux density was twice the stimulus frequency as expected from the equations of motion for the nanoparticle cluster.

OBJECTIVES: This study prospectively evaluated the acute and chronic arterial blood flow and vascular pathology after vessel closure using two commonly used closure devices controlled by deploying both devices in each animal. BACKGROUND: Several vessel closure systems are approved for clinical use; however, few direct comparisons have ever been performed and no randomized case controlled study has been published using FDA-approved devices. METHODS: Nineteen Sous Scroufulae pigs underwent bilateral percutaneous arteriotomies using ultrasound-guided 6 Fr sheath insertion in both common femoral arteries. The femoral access site was then closed using either an Angio-Seal STS Plus, an absorbable collagen sponge, or StarClose, a self-closing nitinol clip. Angiograms and ultrasound of the site were performed prior to closure and immediately afterwards. At follow-up, ultrasound was performed at the site and the specimens were sent for histopathology. RESULTS: Baseline femoral artery diameters (centimeters) were similar in both groups by U/S (5.2 +/- 0.3, 5.3 +/- 0.3) and quantitative angiography (4.6 +/- 0.7, 4.6 +/- 0.8). Postdeployment angiograms showed a vessel diameter stenosis of 65%+/- 24% with Angio-Seal (n = 18) and 50%+/- 22% with StarClose (n = 18), P = 0.04. 2D U/S performed immediately postdeployment showed vessel diameter stenosis of 59%+/- 33.0 with Angio-Seal (n = 19), and 35%+/- 20 with StarClose (n = 19), P = 0.01. At 7-, 30-, and 60-day follow-up, no appreciable differences in the vessel diameter were observed by U/S. At early follow-up (7 and 30 days), Angio-Seal arteriotomy closure sites were associated with higher inflammatory and hemorrhage scores, but no difference was seen at late (60-day) follow-up. CONCLUSIONS: The StarClose closure device is associated with less short-term vessel injury compared to Angio-Seal STS Plus; however, this difference was not statistically significant after 60 days.

BACKGROUND: Clinically significant cardiac fistulas occur rarely and traditionally are surgically repaired. We describe the first known case of percutaneous closure of a left ventricular outflow tract (LVOT) to left atrium (LA) fistula formed as the result of aortic valve replacement surgery. CASE REPORT: The patient was an 86-year-old woman with a history of aortic valve replacement who began complaining of shortness of breath 7 years later. Initially she was misdiagnosed as having mitral regurgitation. However, a transesophageal echocardiography (TEE) showed the presence of a 7.5 mm fistula between her LVOT and LA, producing a large regurgitant jet. As she was not a good surgical candidate, she underwent percutaneous closure. An Amplatzer Duct Occluder 9-PDA-006 (10 mm x 8 mm) device was successfully deployed in the fistula using TEE guidance. On follow-up, the patient described marked improvement of her symptoms. DISCUSSION: In the rare case of cardiac fistulas that are deemed high risk for surgical intervention, a percutaneous approach with an occlusive device offers promise in treating these patients.

BACKGROUND AND OBJECTIVES: A novel method to detect tissue-based macrophages using a combination of superparamagnetic iron oxide (SPIO) nanoparticles and differential phase optical coherence tomography (DP-OCT) with an external oscillating magnetic field is reported. STUDY DESIGN/MATERIAL AND METHODS: Magnetic force acting on iron-laden tissue-based macrophages was varied by applying a sinusoidal current to a solenoid containing a conical iron core that substantially focused and increased magnetic flux density. RESULTS: Nanoparticle motion was detected with DP-OCT, which can detect tissue movement with nanometer resolution. Frequency response of iron-laden tissue movement was twice the modulation frequency since the magnetic force is proportional to the product of magnetic flux density and gradient. CONCLUSIONS: Results of our experiments indicate that DP-OCT can be used to identify tissue-based macrophage when excited by an external focused oscillating magnetic field.

Heart failure commonly manifests as a syndrome of salt and water retention. Arginine vasopressin plays an important role in volume homeostasis and may contribute to this syndrome seen in heart failure patients. Recently, a number of agents have been developed that antagonize the effects of vasopressin. Conivaptan, which is a dual antagonist of the V1a and V2 receptor, has shown promise in animal studies and in small scale human trials as a potential therapeutic option for the treatment of acute and chronic heart failure. Further large studies are being conducted, which may confirm the benefits of conivaptan and other vasopressin antagonists in heart failure patients.

Arginine vasopressin plays an important role in volume homeostasis. Patients with heart failure have chronically elevated plasma vasopressin concentrations which may contribute to their clinical syndrome of fluid retention. Recently, a number of agents have been developed to antagonize the effects of vasopressin by targeting its V1a and V2 receptors, which are involved in vascular tone and free water regulation, respectively. Two vasopressin antagonists, in particular, tolvaptan and conivaptan, have shown promise in animal studies and small-scale human trials. The following is a review of current experimental and clinical studies using vasopressin antagonists and their potential role in the treatment of heart failure.

OBJECTIVE: To report a case of severe dilated cardiomyopathy (DCMP) in a patient on bromocriptine therapy for a microprolactinoma. CASE SUMMARY: A 31-year-old African American female, who had been receiving bromocriptine 5 mg orally daily for a microprolactinoma during the preceding month, developed severe DCMP. An echocardiogram showed a markedly dilated left ventricle with severe reduction in the left-ventricular ejection fraction in the absence of any other identifiable causes of DCMP such as a peripartum state, ethanol use, preceding systemic viral illness, chronic hypocalcemia, chronic hypophosphatemia, or chronic uncontrolled tachycardia. She improved substantially (both symptomatically and echocardiographically) after cessation of bromocriptine therapy and initiation of supportive treatment of congestive heart failure (CHF). She showed no recurrence of CHF at a follow-up visit 2 months after withdrawal of the supportive care. The patient was not rechallenged with bromocriptine due to the clinical/ethical gravity of this probable adverse effect. DISCUSSION: Although cardiopulmonary adverse effects have been reported with the use of cabergoline (another dopamine agonist), to the best of our knowledge, this is the first case report of severe life-threatening DCMP associated with bromocriptine therapy. Causality assessment using the Naranjo probability scale revealed that the adverse drug event was probable. CONCLUSIONS: Bromocriptine was probably associated with DCMP in a patient being treated for a microprolactinoma. Severe DCMP needs to be considered a potentially life-threatening but reversible adverse effect of bromocriptine therapy for microprolactinoma of the pituitary gland.

We describe the unusual occurrence of atrial fibrillation immediately after a seizure in a young patient with cyclosporine toxicity. The new onset atrial fibrillation was triggered by high levels of cyclosporine and possibly facilitated by the electrolyte imbalances post seizure and the presence of underlying mild left atrial enlargement.

Varicella-Zoster Virus (VZV) is the second most common ocular pathogen in patients with HIV infection. VZV retinitis is estimated to occur in 0.6% of patients with HIV infection and may occur in one of two clinical syndromes. The first is the acute retinal necrosis syndrome, which also may be seen in immunocompetent hosts. The second clinical syndrome occurs in patients with CD4 cell counts typically < 50 x 10(6)/l and is termed progressive outer retinal necrosis. VZV retinitis has been reported to occur simultaneously with other VZV central nervous system manifestations such as encephalitis and myelitis in HIV-infected patients. In addition, VZV retrobulbar optic neuritis heralding VZV retinitis has recently been described in HIV-infected patients who had suffered a recent episode of dermatomal herpes zoster. Herein we report the case of an HIV-infected individual who presented with VZV meningitis and retrobulbar optic neuritis that preceded the onset of progressive outer retinal necrosis. We also review of the literature of seven additional reported cases of retrobulbar optic neuritis preceding the onset of VZV retinitis.