Ocular manifestations of sarcoidosis

Ophthalmic involvement in sarcoidosis may cause significant sight-threatening illness for patients. Studies of patients with histologically proven sarcoidosis have found 25 to 50% of patients to have ocular manifestations. The frequency in which eye disease is seen and the course that it takes vary with age, race, and geography. This article discusses relevant aspects of the ocular manifestations of sarcoidosis for the internist and pulmonologist. Overall disease presentation, specific types of ocular involvement, evaluation strategies, and treatment considerations are discussed.     

BAD and Bcl-2 regulation are early events linking neuronal endoplasmic reticulum stress to mitochondria-mediated apoptosis

The mechanism of endoplasmic reticulum (ER)-mediated apoptosis in neurons was examined. Using primary cortical neurons, we show that nordihydroguaiaretic acid (NDGA) and brefeldin A (BFA), two ER stressors, induce early ER stress as shown by Western blotting of the eukaryotic initiation factor-2alpha (eIF2alpha), an ER stress marker. This event was associated with an enhancement of neuronal apoptosis as demonstrated by the time-dependent increase in caspase-3 activity and by nuclear fragmentation. The study of the apoptotic signaling showed the translocation of cytochrome c from the mitochondrial matrix to the cytosol. Further evaluation of the apoptotic process revealed that NDGA and BFA induced a rapid dephosphorylation of BAD and decrease expression of Bcl-2. Altogether, our results indicate that neuronal ER stress is associated with an apoptotic cascade involving the mitochondria.     

Hepatitis A,hepatitis B,and combination hepatitis vaccines for immunoprophylaxis: an update

Since the publication of the last extensive review of hepatitis vaccines, use of inactivated hepatitis A vaccines has been extended to high-risk regions of the United States and specific patient groups, such as those with chronic liver disease, and use of the recombinant hepatitis B vaccines has been recommended for older adolescents. A combination hepatitis A and B vaccine, recently approved for licensure by the US Food and Drug Administration, should increase convenience and compliance, reduce the costs of vaccination, and provide prolonged and dual protection for those at risk for hepatitis. Although commercially available vaccines for hepatitis C, D, and E remain a distant goal, advances in vaccine and adjuvant technology, including immunization with DNA-based vaccines, hold promise for the future.     

Proton MR spectroscopic and diffusion tensor brain MR imaging in X-linked adrenoleukodystrophy: initial experience

PURPOSE: To compare conventional magnetic resonance (MR) imaging, proton MR spectroscopic imaging, and diffusion tensor (DT) MR imaging findings in patients with X chromosome-linked adrenoleukodystrophy (X-ALD). MATERIALS AND METHODS: Multisection proton MR spectroscopy and DT imaging were performed in 11 patients with X-ALD and in 11 healthy control subjects. Quantitative measures of N-acetylaspartate (NAA), choline, and creatine values and of isotropic apparent diffusion coefficient (IADC) and fractional anisotropy (FA) were obtained from coregistered regions of interest. DT imaging and metabolic parameters were compared by using regression analysis. In addition, differences in DT imaging and metabolite measurements between normal- and abnormal-appearing white matter on conventional MR images were evaluated by using a nonparametric (Mann-Whitney) test. RESULTS: A strong logarithmic relationship between NAA value and FA (r = 0.64, P <.001) and an inverse logarithmic relationship were found between NAA value and IADC (r = -0.69, P <.001). Creatine and choline values correlated poorly with IADC and FA. In the normal-appearing white matter of asymptomatic patients, the NAA value was 17% lower than that in the healthy control subjects (P =.016), whereas no significant difference in DT imaging measures was seen in these regions. CONCLUSION: In patients with X-ALD, MR spectroscopic imaging can depict abnormalities in white matter that have a normal appearance on both conventional MR and DT images; this finding suggests that it may be the most sensitive technique for detecting early abnormalities of demyelination or axonal loss in patients with X-ALD.     

Single-vessel coronary artery stenosis: myocardial perfusion imaging with Gadomer-17 first-pass MR imaging in a swine model of comparison with gadopentetate dimeglumine

PURPOSE: To evaluate the ability of Gadomer-17 to depict perfusion defects in a closed-chest swine model of single-vessel coronary artery disease. MATERIALS AND METHODS: Twelve pigs underwent closed-chest placement of a flow reducer for 70%-90% luminal stenosis in the proximal left anterior coronary artery. Magnetic resonance (MR) perfusion imaging with Gadomer-17 and gadopentetate dimeglumine, microsphere blood flow (MBF) testing, and technetium 99m ((99m)Tc) 2 methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) were performed during dipyridamole vasodilation. Comparisons of percentage signal intensity (SI) increase (PSIC) in remote and ischemic myocardium were made with repeated measurements analysis of variance after injection of both tracers. RESULTS: Perfusion defects and reduced PSIC in the anterior ischemic versus the inferior remote myocardium could be identified after injection of both Gadomer-17 (PSIC, 66% +/- 30 [mean +/- SD] vs 100% +/- 32, respectively; P <.001) and gadopentetate dimeglumine (PSIC, 49% +/- 31 vs 81% +/- 43, respectively; P <.005). The size of perfusion defect depicted with both tracers was highly correlated with defect size at (99m)Tc MIBI SPECT (r = 0.69, P <.05 for Gadomer-17 and r = 0.60, P =.05 for gadopentetate dimeglumine) and with areas of reduced MBF (r = 0.70, P <.05 for Gadomer-17 and r = 0.80, P <.05 for gadopentetate dimeglumine). PSIC also correlated with MBF (r = 0.89, P <.001 for Gadomer-17 and r = 0.75, P <.001 for gadopentetate dimeglumine). Gadomer-17 allowed differentiation of ischemic from nonischemic myocardium, as demonstrated by reduced PSIC (PSIC, 48% +/- 38 vs 72% +/- 31, respectively; P <.001) until 20 minutes after contrast material injection. In contrast, differentiation of ischemic from nonischemic myocardium was possible only until 55 seconds after injection of gadopentetate dimeglumine (PSIC, 36% +/- 24 vs 56% +/- 27, respectively; P <.005) but not at any time point thereafter. CONCLUSION: With the study conditions, Gadomer-17 provided more prolonged differentiation of ischemic from remote myocardium than that with gadopentetate dimeglumine.     

Use of the trispan device to assist coil embolization of high-flow arteriovenous fistulas

The Trispan device is a new tool designed for use in the endovascular treatment of wide-neck aneurysms with coils. We describe another application of this device to control coil deposition and to prevent coil migration during transvenous occlusion of high-flow arteriovenous fistulas.     

Endovascular treatment of experimental wide neck aneurysms: comparison of results using coils or cyanoacrylate with the assistance of an aneurysm neck bridge device

BACKGROUND AND PURPOSE: Endovascular treatment of wide neck aneurysms often results in incomplete occlusion or aneurysm recurrence. The two goals of the present study were to compare results of coil embolization with or without the assistance of an aneurysm neck bridge device (ANBD) and to explore the use of this instrument to control cyanoacrylate embolization. METHODS: Wide necked bifurcation aneurysms were constructed in 28 dogs. Coil embolization of the aneurysms was performed 2 to 4 weeks later, with (n = 11) or without (n = 10) ANBD assistance. In seven other animals, embolization was performed with cyanoacrylate, injected under the protection of ANBDs. Angiographic results were compared immediately after and at 3 and 12 weeks. Neointima formation at the neck was also compared between groups at 12 weeks. RESULTS: Initial angiographic results and recurrences at 12 weeks were not significantly different in aneurysms coiled with or without ANBDs. Neointimal scores were also similar. The use of one ANBD at the neck was not sufficient to safely deliver cyanoacrylate into aneurysms. Cyanoacrylate embolization led to improved angiographic results (P =.05) and to better neointimal sealing of the neck of the aneurysms at 12 weeks (P =.004). CONCLUSION: ANBDs did not prevent recanalization and recurrences after coil embolization of wide neck aneurysms in this animal study. ANBD-assisted cyanoacrylate embolization was unsafe but could decrease recurrences at 12 weeks.