Multidetector-Row Computed Tomography in the Evaluation of Transjugular Intrahepatic Portosystemic Shunt Performed with Expanded-Polytetrafluoroethylene-Covered Stent-Graft

We assessed, in a prospective study, the efficacy of multidetector spiral computed tomography (MDCT) in the evaluation of transjugular intrahepatic portosystemic shunt (TIPS) patency in patients treated with the Viatorr (Gore, Flagstaff, AZ) expanded-polytetrafluoroethylene (e-PTFE)-covered stent-graft. Eighty patients who underwent TIPS procedure using the Viatorr self-expanding e-PTFE stent-graft were evaluated at follow-up of 1, 3, 6, and 12 months with clinical and laboratory tests as well as ultrasound–color Doppler (USCD) imaging. In case of varices, upper gastrointestinal endoscopy was also performed. In addition, the shunt was evaluated using MDCT at 6 and 12 months. In all cases of abnormal findings and discrepancy between MDCT and USCD, invasive control venography was performed. MDCT images were acquired before and after injection of intravenous contrast media on the axial plane and after three-dimensional reconstruction using different algorithms. MDCT was successfully performed in all patients. No artefacts correlated to the Viatorr stent-graft were observed. A missing correlation between UCSD and MDCT was noticed in 20 of 80 (25%) patients. Invasive control venography confirmed shunt patency in 16 (80%) cases and shunt malfunction in 4 (20%) cases. According to these data, MDCT sensitivity was 95.2%; specificity was 96.6%; and positive (PPV) and negative predictive values (NPV) were 90.9 and 98.2%, respectively. USCD sensitivity was 90%; specificity was 75%; and PPV and NPV were 54.5 and 95.7%, respectively. A high correlation (K value = 0.85) between MDCT and invasive control venography was observed. On the basis of these results, MDCT shows superior sensitivity and specificity compared with USCD in those patients in whom TIPS was performed with the Viatorr stent-graft. MDCT can be considered a valid tool in the follow-up of these patients.     

Estimating the Prevalence of Severe Mental Illness in Mental Health Services in Lombardy (Italy)

Although many countries’ policies give Severe Mental Illness (SMI) priority inside Mental Health Services, researches assessing the prevalence of SMI in Mental Health Services according to operational criteria are still few. The aim of this is paper is to define annual SMI treated prevalence, describing socio-demographic and clinical characteristics, patterns of care and treatment costs of SMI and non-SMI patients. SMI prevalence in 10 Departments of Mental Health of the Lombardy Region (Italy) was assessed in 2000 by applying criteria concerning both severity, measured through HoNOS (Health of the Nation Outcome Scales), and utilisation patterns in the previous year. Annual SMI prevalence was equal to 3.1 cases per 1,000 inhabitants aged over 14; SMI patients’ costs were 5.5 times higher than those of non-SMI patients ($5,183 versus $939 per year) and patterns of care were different. The variables predicting the SMI status were diagnosis, presence of paid employment, duration of service contact, care packages delivered in 2000 and severity of some HoNOS items (self harm, drug abuse, cognitive problems, delusions, other symptoms, relationships, activities of daily living and housing). The use of the combined criteria of severity and intensity of contact with mental health services in the previous year seems to be able to define severely ill patients adequately. Funding for this work was provided by the Health Authority of the Lombardy Region. Antonio Lora is affiliated with the Department of Mental Health, Hospital of Desio, Milan, Italy. Roberto Bezzi is affiliated with the Department of Mental Health, Hospital of Legnano, Milan, Italy. Arcadio Erlicher is affiliated with the Department of Mental Health, Niguarda Ca′ Granda Hospital, Milan, Italy.     

The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals

Collective evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is non-cell-autonomous and requires the interaction with the neighboring astrocytes. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1(G93A) mouse model of ALS. Mechanistic studies in vitro identified a role for the excitatory amino acid glutamate in the gliodegenerative process via the activation of its inositol 1,4,5-triphosphate (IP(3))-generating metabotropic receptor 5 (mGluR5). Since non-physiological formation of IP(3) can prompt IP(3) receptor (IP(3)R)-mediated Ca(2+) release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca(2+) signaling that occurs downstream of mGluR5 in hSOD1(G93A)-expressing astrocytes. Contrary to wild-type cells, stimulation of mGluR5 causes aberrant and persistent elevations of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in the absence of spontaneous oscillations. The interaction of IP(3)Rs with the anti-apoptotic protein Bcl-X(L) was previously described to prevent cell death by modulating intracellular Ca(2+) signals. In mutant SOD1-expressing astrocytes, we found that the sole BH4 domain of Bcl-X(L), fused to the protein transduction domain of the HIV-1 TAT protein (TAT-BH4), is sufficient to restore sustained Ca(2+) oscillations and cell death resistance. Furthermore, chronic treatment of hSOD1(G93A) mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. Our results point at TAT-BH4 as a novel glioprotective agent with a therapeutic potential for ALS.     

The Competitive Transport Inhibitor L-trans-pyrrolidine-2,4-dicarboxylate Triggers Excitotoxicity in Rat Cortical Neuron-Astrocyte Co-cultures via Glutamate Release rather than Uptake Inhibition

We studied the early and late effects of L- trans -pyrrolidine-2,4-dicarboxylate (PDC), a competitive inhibitor of glutamate uptake with low affinity for glutamate receptors, in co-cultures of rat cortical neurons and glia expressing spontaneous excitatory amino acid (EAA) neurotransmission. At 100 or 200 μM, PDC induced different patterns of electrical changes: 100 μM prolonged tetrodotoxin-sensitive excitation triggered by synaptic glutamate release; 200 μM produced sustained, tetrodotoxin-insensitive and EAA-mediated neuronal depolarization, overwhelming synaptic activity. At 200 μM, but not at 100 μM, PDC caused rapid elevation of the glutamate concentration ([Glu]₀) in the culture medium, resulting in NMDA receptor-mediated excitotoxic death of neurons 24 h later. The increase in [Glu]₀ was largely insensitive to tetrodotoxin, independent of extracellular Ca²⁺, and present also in astrocyte-pure cultures. By the use of glutamate transporters functionally reconstituted in liposomes, we showed directly that PDC activates carrier-mediated release of glutamate via heteroexchange. Glutamate release and delayed neurotoxicity in our cultures were suppressed if PDC was applied in a Na⁺-free medium containing Li⁺. However, replacement of Na⁺ with choline instead of Li⁺ did not result in an identical effect, suggesting that Li⁺ does not act simply as an external Na⁺ substitute. In conclusion, our data indicate that alteration of glutamate transport by PDC has excitotoxic consequences and that active release of glutamate rather than just uptake inhibition is responsible for the generation of neuronal injury.     

Clinical Experience with Covered Wallstents for Biliary Malignancies: 23-Month Follow-Up

Purpose: To evaluate the effectiveness of partially covered metallic Wallstents to prevent tumoral ingrowth in patients with neoplastic obstruction of the biliary tract. Methods: Twenty-one patients with malignant obstructive jaundice have been treated with Wallstents partially covered with a polyurethane polymer. In total, 36 covered stents (8 and 10 mm in diameter, 70 and 90 mm long) were deployed. All the stents were free from covering at both ends. Results: Jaundice was successfully treated in 100% of cases. There were no problems related to the releasing system during stent positioning, no major complications, and no incompatibility reactions to the materials composing the endoprostheses. At 23-month follow-up, 6 patients are still alive and 15 are dead; of these 15 patients, 11 died in the first 6 months and the last 4 died between 6 and 23 months. Seven patients had an obstructed stent; in four of these, cholangioscopy showed the presence of tumoral ingrowth and in one it showed necrotic tissue with biliary pigments and inflammatory cells. No biopsy specimen was obtained in the remaining two patients with stent obstruction. The follow-up, ranging from 7 to 23 months, showed a primary patency of 46.8% and 24.6% and an assisted patency of 66.3% and 59% at 6 months and 23 months, respectively. Conclusions: Covered metallic stents are effective and may produce improved survival in patients with malignant biliary obstruction (27.8% at 23 months). Stent patency, however, is similar to that of uncovered stents. Modifications in the design of the covering membrane may reduce stent obstruction resulting from disruption of the plastic covering. Received: 0/00/00/Accepted: 0/00/00     

Magnetic Resonance-Guided Focused Ultrasound Ablation in Abdominal Moving Organs: A Feasibility Study in Selected Cases of Pancreatic and Liver Cancer

Purpose

This study was designed to evaluate preliminarily the feasibility and safety of magnetic resonance-guided focused ultrasound (MRgFUS) for treatment of solid tumors in the upper abdomen.

Methods

We enrolled one patient with hepatocellular carcinoma and two patients with pancreatic adenocarcinoma for MRgFUS ablation. Treatments were performed on a 3T scanner under controlled respiration. Treatment response was evaluated at 1, 3, and 6 months by assessing the nonperfused volume (NPV) of ablated tissue at MR and the degree of pain severity and pain interference.

Results

In the patient with HCC, NPV was 100 % after treatment and 85 % at 3 and 6 months follow-up. Histological analysis after liver transplantation showed fibrosis in the ablated area with minimal local tumor recurrence. In the two patients with pancreatic adenocarcinoma, NPV was 80 and 85 % after treatment and 70 and 80 % at 3 and 6 months follow-up. Pain severity and pain interference respectively decreased from a mean of 7 and 6.7 points, respectively, to a mean of 3 and 2 points after treatment.

Conclusions

MRgFUS can be feasible and safe in selected patients with solid tumors in abdominal moving organs. However, this technique has several limitations due to the interposition of the rib cage or intestinal loops into the path of the ultrasonic beam, as well as to organ motion. Future technical developments are needed to implement advanced motion detection within the system to control organ and lesion position in real-time and keep the focus of the ultrasound beam on the targeted lesion.