Multidisciplinary approach to palliation of obstructive jaundice caused by a central hepatocellular carcinoma

BACKGROUND/AIMS: Obstructive jaundice due to intraductal tumour growth is a rare symptom in association with hepatocellular carcinoma (HCC). METHODS: We report a 65-year-old white male who was admitted to our department with a 2-week history of progressive jaundice. At laparotomy, the liver showed advanced cirrhosis due to long-standing biliary obstruction. Cholangiography confirmed total obstruction of the main bifurcation of the hepatic duct by intraductal tumour growth. Combination treatment with surgical segment III drainage, transcatheter arterial embolization and radioembolization with yttrium-90 resin particles and endoscopic stenting was performed. This form of treatment has never been reported before. RESULTS: With these combined procedures, relief of jaundice and a survival time of 32 months could be achieved. CONCLUSION: The combination of palliative methods may relieve jaundice, ensure a good quality of life and possibly prolong survival in patients with mechanical tumour obstruction of the biliary tree by HCC.     

Intravascular ultrasound-guided creation of re-entry sites to improve intermittent claudication in patients with aortic dissection.

PURPOSE: To report percutaneous fenestration of aortic dissection flaps to relieve distal ischemia using a novel intravascular ultrasound (IVUS)-guided fenestration device. CASE REPORTS: Two men (47 and 62 years of age) with aortic dissection and intermittent claudication had percutaneous ultrasound-guided fenestration performed under local anesthesia. Using an ipsilateral transfemoral approach, the intimal flap was punctured under real-time IVUS guidance using a needle-catheter combination through which a guidewire was placed across the dissection flap into the false lumen. The fenestration was achieved using balloon catheters of increasing diameter introduced over the guidewire. Stenting of the re-entry was performed in 1 patient to equalize pressure across the dissection membrane in both lumens. The procedures were performed successfully and without complications. In both patients, ankle-brachial indexes improved from 0.76 to 1.07 and from 0.8 to 1.1, respectively. Both patients were without claudication at the 3- and 6-month follow-up examination. CONCLUSION: Percutaneous intravascular ultrasound-guided fenestration and stenting at the level of the iliac artery in aortic dissection patients with claudication is a technically feasible and safe procedure and relieves symptoms.     

A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and mobility

Synaptic vesicles (SVs) from excitatory synapses carry vesicular glutamate transporters (VGLUTs) that fill the vesicles with neurotransmitter. Although the essential function of VGLUTs as glutamate transporters has been well established, the evidence for additional cell‐biological functions is more controversial. Both VGLUT1 and VGLUT2 disruptions in mice result in a reduced number of SVs away from release sites, flattening of SVs, and the appearance of tubular structures. Therefore, we analysed the morphology, biochemical composition and trafficking of SVs at synapses of VGLUT1^?/? mice in order to test for a function of VGLUTs in the formation or clustering of SVs. Analyses with high‐pressure freezing immobilisation and electron tomography pointed to a role of VGLUT1 transport function in the tonicity of excitatory SVs, explaining the aldehyde‐induced flattening of SVs observed in VGLUT1^?/? synapses. We confirmed the steep reduction in the number of SVs previously observed in VGLUT1^?/? presynaptic terminals, but did not observe accumulation of endocytotic intermediates. Furthermore, SV proteins of adult VGLUT1^?/? mouse brain tissue were expressed at normal levels in all subcellular fractions, suggesting that they were not displaced to another organelle. We thus assessed the mobility of the recently documented superpool of SVs. Synaptobrevin2–enhanced green fluorescent protein time lapse experiments revealed an oversized superpool of SVs in VGLUT1^?/? neurons. Our results support the idea that, beyond glutamate loading, VGLUT1 enhances the tonicity of excitatory SVs and stabilises SVs at presynaptic terminals.     

β‐amyloid and ATP‐induced diffusional trapping of astrocyte and neuronal metabotropic glutamate type‐5 receptors

β‐Amyloid (Aβ) oligomers initiate synaptotoxicity following their interaction with the plasma membrane. Several proteins including metabotropic glutamate type 5 receptors (mGluR5s) contribute to this process. We observed an overexpression of mGluR5s in reactive astrocytes surrounding Aβ plaques in brain sections from an Alzheimer's disease mouse model. In a simplified cell culture system, using immunocytochemistry and single molecule imaging, we demonstrated a rapid binding of Aβ oligomers on the plasma membrane of astrocytes. The resulting aggregates of Aβ oligomers led to the diffusional trapping and clustering of mGluR5s. Further, Aβ oligomers induced an increase in ATP release following activation of astroglial mGluR5s by its agonist. ATP slowed mGluR5s diffusion in astrocytes as well as in neurons co‐cultured with astrocytes. This effect, which is purinergic receptor‐dependent, was not observed in pure neuronal cultures. Thus, Aβ oligomer‐ and mGluR5‐dependent ATP release by astrocytes may contribute to the overall deleterious effect of mGluR5s in Alzheimer's disease. GLIA 2013;61:1673–1686     

Effects of probucol versus aspirin and versus brachytherapy on restenosis after femoropopliteal angioplasty: the PAB randomized multicenter trial.

PURPOSE: To evaluate the effect of probucol and/or of endovascular brachytherapy (EVBT) on restenosis after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. METHODS: A total of 335 patients (206 men; mean age 72+/-9 years) with intermittent claudication were randomized according to a 2x2 factorial design to 1 of the 4 groups: probucol, placebo, EVBT, and EVBT+probucol. Probucol (1 g/d) or placebo were given in double-blinded fashion 1 month before and for 6 months after PTA. Gamma irradiation (192Iridium, 14 Gy, 5-mm reference depth) was randomly applied in an unblinded manner from a noncentered endoluminal catheter. All patients received aspirin (100 mg/d). Primary endpoint was restenosis (>50% diameter reduction) detected by duplex ultrasound 6 months after PTA. Secondary endpoints included clinical and hemodynamic assessment. RESULTS: Restenosis in patients undergoing EVBT was 17% (23/133) versus 35% (50/142) in patients without EVBT (p<0.001); in patients treated with probucol versus placebo, the rates were 23% (31/135) and 30% (43/140, p<0.001). Three quarters (77%, 102/133) of patients were free of claudication after EVBT therapy versus 61% (87/142) without EVBT (p<0.05). Need for target vessel revascularization was 6% (8/133) with EVBT versus 14% (20/142) without EVBT (p<0.01). Late thrombotic occlusions occurred in 4% (6/133), exclusively in patients treated with EVBT after stent implantation. CONCLUSIONS: Endovascular brachytherapy significantly reduces restenosis, improves symptoms, and reduces reinterventions after PTA of femoropopliteal arteries. Probucol reduces restenosis but has no additive effect when combined with brachytherapy.     

Strychnine-blocked glycine receptor is removed from synapses by a shift in insertion/degradation equilibrium

The long-term inhibition by strychnine of glycine receptor activity in neurons provokes the receptor's selective intracellular accumulation and disappearance from synapses. This could result either from a disruption of the postsynaptic anchoring of the receptor or from an arrest of its exocytic transport. In this study we combined biochemical and fluorescence microscopy analyses to determine on a short time scale the fate of the strychnine-inactivated glycine receptor. Quantification of the cellular content of receptor showed that the rapid accumulation depends on protein synthesis. Cell surface biotinylation of neurons demonstrated that strychnine did not accelerate the turnover rate of the receptor. Labeling of endosomes indicated that, in strychnine-treated cells, the accumulated receptor is not blocked in the endosomal transport pathway. Taken together, these results indicate that strychnine does not destabilize the postsynaptic receptor but triggers its disappearance from synapses by a nondegradative sequestration of newly synthesized molecules in a nonendocytic compartment.     

Iliac graft access to facilitate endovascular repair of a ruptured thoracic aortic aneurysm -- a case report

Arterial access for endovascular aortic aneurysm repair is usually gained through a common femoral artery approach. In small femoral arteries this can be difficult or even impossible owing to the large size of the introduction sheath of the delivery system. In such cases the iliac arteries or the abdominal aorta can be used for vascular access, although, in heavily calcified arteries,even this can be hazardous. The authors report an 81-year-old woman with a contained rupture of the thoracic aorta in whom a polyester graft was used to facilitate vascular access to the common iliac artery for a safe two-stage endovascular repair of the aneurysm.     

Direct leukocyte migration inhibition by myelin basic protein in exacerbations of multiple sclerosis.

Studies in 13 normal subjects, 9 patients with multiple sclerosis (MS) within 3 weeks of exacerbation and 16 others 1 to 6 months after onset were carried out for evidence of cell-mediated hypersensitivity to myelin basic protein. Ten patients with stroke and 10 with Guillain-Barré syndrome were studied as additional controls. Peripheral leukocytes obtained by leukapheresis were packed into capillary tubes and allowed to migrate out onto glass in the presence or absence of myelin basic protein. Cells of patients within 3 weeks of an MS episode gave a mean migration index of 68 +/- 9%, and those 1 to 6 months after onset, 93 +/- 21%. For the entire MS group the mean index was 88 +/- 20%, for those with Guillain-Barré, 103 +/- 7%; and for the stroke patients, 107 +/- 11%. Results for the acutely ill MS patients were significant (P less than 0.005). The data are similar to those obtained using the migration inhibition factor assay but show that sensitized lymphocytes also elaborate a second mediator during acute exacerbations of illness. These observations strengthen evidence that sensitization to this potent encephalitogen occurs simultaneously with exacerbations of clinical illness.     

Coil embolization of an infected superior gluteal artery pseudoaneurysm caused by methicillin-resistant Staphylococcus aureus

We describe the successful selective coil embolization of an infected superior gluteal pseudoaneurysm secondary to methicillin-resistant Staphylococcus aureus (MRSA) in a 36-year old women. The patient presented with a long history of drug abuse and perisacral abscesses due to chronic sacroilitis. The chosen strategy provides a safe and successful management of infected false gluteal artery aneurysm.