LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

CT renal planimetry: effectiveness in the evaluation of individual renal function.

Computed tomographic (CT) renal planimetry was used to study individual renal function in 32 adult patients with urologic disease. CT results were well-correlated to reference methods (r = 0.88, P < 0.001), which were radionuclide studies (N = 9) or separate creatinine clearance (N = 23). The difference between planimetric data and reference methods did not exceed 14% in any case and was less than 10% in 26 cases.     

Giant perimedullary arteriovenous fistulas of the spine: clinical and radiologic features and endovascular treatment.

PURPOSETo present the clinical and radiologic features of giant perimedullary arteriovenous fistulas (GAVFs) in 12 consecutive cases and to evaluate the results of endovascular treatment.METHODSWe retrospectively reviewed the clinical and radiologic data as well as the results of balloon endovascular treatment obtained from 1980 to 1989.RESULTSGAVFs, defined as large intradural perimedullary direct arteriovenous high-flow shunts, are revealed mainly in childhood either by subarachnoid hemorrhage or by progressive neurologic disorders. MR imaging and myelography show major vascular dilatations. The angioarchitecture of GAVFs can only be assessed by selective spinal angiography. Ten patients were treated by balloon occlusion resulting in eight anatomic cures and six good clinical results. One balloon migrated to the venous side, leading to clinical deterioration.CONCLUSIONGAVF is a special subgroup of intradural perimedullary arteriovenous fistula. The endovascular approach should be the first line of treatment, with surgery reserved for special circumstances. Nondetachable balloon occlusion is a safe and efficient method for treating GAVFs.     

Nano-C60 cytotoxicity is due to lipid peroxidation

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C₆₀, a fullerene aggregate that readily forms when pristine C₆₀ is added to water. Nano-C₆₀ was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses 50 ppb (LC₅₀=2–50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C₆₀ colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C₆₀ inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, l-ascorbic acid, the oxidative damage and resultant toxicity of nano-C₆₀ was completely prevented.     

Correlation between genotype,metabolic data,and clinical presentation in carnitine palmitoyltransferase 2 (CPT2) deficiency

Carnitine palmitoyltransferase 2 (CPT2) deficiency, the most common inherited disease of the mitochondrial long-chain fatty acid (LCFA) oxidation, may result in distinct clinical phenotypes, namely a mild adult muscular form and a severe hepatocardiomuscular disease with an onset in the neonatal period or in infancy. In order to understand the mechanisms underlying the difference in severity between these phenotypes, we analyzed a cohort of 20 CPT2-deficient patients being affected either with the infantile (seven patients) or the adult onset form of the disease (13 patients). Using a combination of direct sequencing and denaturing gradient gel electrophoresis, 13 CPT2 mutations were identified, including five novel ones, namely: 371G>A (R124Q), 437A>C (N146T), 481C>T (R161W), 983A>G (D328G), and 1823G>C (D608H). After updating the spectrum of CPT2 mutations (n=39) and genotypes (n=38) as well as their consequences on CPT2 activity and LCFA oxidation, it appears that both the type and location of CPT2 mutations and one or several additional genetic factors to be identified would modulate the LCFA flux and therefore the severity of the disease.     

Development of the biologically active Guglielmi detachable coil for the treatment of cerebral aneurysms. Part II: an experimental study in a swine aneurysm model

BACKGROUND AND PURPOSE: Ion implantation is a surface-modification technology that creates a borderless surface on protein-coated platinum; this change in physical and chemical properties on the surface of Guglielmi detachable coils (GDCs) appears to enhance cell proliferation and adhesion. Our purpose was to evaluate the effect of ion implantation on GDCs in an experimental aneurysm model. METHODS: GDCs were coated with either type I collagen, fibronectin, vitronectin, laminin, or fibrinogen. Using He+ or Ne+ 1 x 10(14-15) ions/cm2, ion implantation was performed on these protein-coated GDCs (GDC-Is). A total of 56 experimental aneurysms were constructed microsurgically in the common carotid arteries of 28 swine. These experimental aneurysms were embolized with standard GDCs (n = 23), collagen GDC-Is (n = 11), vitronectin GDC-Is (n = 6), laminin GDC-Is (n = 4), fibrinogen GDC-Is (n = 6), and fibronectin GDC-Is (n = 6). The animals were sacrificed at day 14 after coil embolization. The physical properties of the new coils (friction on delivery, deployment into aneurysms, trackability, etc) and the development of tissue scarring and neoendothelium across the aneurysm's orifice were evaluated macroscopically and microscopically. RESULTS: No evidence of increased coil friction/stiffness was observed during delivery of GDC-Is through microcatheters in this aneurysm model. A more intense scar formation and neoendothelium at the neck of aneurysms were observed macroscopically when treated with GDC-Is. Significant differences in the proportion of neck coverage between standard GDCs (48.3% +/- 20.5%) and all GDC-I groups were observed (collagen GDC-I-89.4% +/- 14.9%, P < .01; vitronectin GDC-I-71.5% +/- 7.0%, P < .05; laminin GDC-I-76.5% +/- 11.0%, P < .05; fibrinogen GDC-I-74.8% +/- 13.9%, P < .05; fibronectin GDC-I-87.5% +/- 15.0%, P < .01). Light microscopy showed a well-organized fibrous tissue bridging the aneurysm's neck when using GDC-Is, whereas only a fibrin-like thin layer covered the standard GDC surfaces. CONCLUSION: GDC-Is indicated a more intense inflammatory response in the aneurysm body and dome and faster re-endothelial coverage of the neck of the aneurysm. This accelerated histologic response may decrease the chances of coil compaction and aneurysm recanalization. This technology may improve anatomic and clinical outcomes in patients harboring intracranial aneurysms.     

Endovascular treatment of multiple intracranial aneurysms by using Guglielmi detachable coils

OBJECT: The purpose of this paper is to present the authors' experience with Guglielmi detachable coil (GDC) embolization of multiple intracranial aneurysms and to evaluate the results of this therapy in single-stage procedures. METHODS: Clinical and angiographic evaluations were performed in 38 consecutive patients with multiple intracranial aneurysms treated by GDC embolization between March 1990 and October 1997. Twenty-nine patients presented with subarachnoid hemorrhage (SAH), four with mass effect, and five were asymptomatic. These 38 patients harbored 101 aneurysms, 79 of which were treated with GDCs, 14 by surgical clipping, and eight were left untreated. Of the GDC-treated lesions, a complete endovascular occlusion was achieved in 55 aneurysms (70%), and 24 (30%) presented neck remnants. Twenty-five patients (66%) underwent GDC embolization of more than one aneurysm in the first session. Eighteen (86%) of 21 patients with acute SAH underwent treatment for all aneurysms within 3 days after admission (15 of 21 in one session). Follow-up angiographic studies in 30 patients demonstrated an unchanged or improved result in 94% of the aneurysms (59 lesions) and coil compaction in 6% (four lesions). The overall clinical outcome was excellent in 34 patients (89%), good in one (3%), fair in one (3%), and death in two (5%). CONCLUSIONS: Endovascular treatment of multiple intracranial aneurysms, regardless of their location, with GDCs was performed safely in one session, even during the acute phase of SAH. Treatment of all aneurysms in one session protected the patient from rebleeding and eliminated the risk of mistakenly treating only the unruptured aneurysms.     

Efficacy of Zoladex LA (goserelin) in the treatment of girls with central precocious or early puberty

OBJECTIVE: To assess the efficacy of a longer acting preparation of the gonadotrophin releasing hormone (GnRH) analogue goserelin (Zoladex LA, 10.8 mg) in 12 girls with central precocious or early puberty. METHODS: Two girls started treatment de novo; the remainder had been on suppressive treatment for a median duration of 1.5 (range, 0.2-5.6) years. Assessment comprising auxology, pubertal staging, and pelvic ultrasound examination was carried out at weeks 0, 4, 8, 10, and 12 (first cycle) and weeks 8, 10, and 12 (second cycle) to evaluate the required injection frequency. Thereafter, assessment was performed on the day of injection. Zoladex LA was given every 12 weeks unless pubertal progression occurred. RESULTS: Satisfactory control was achieved in eight patients using this regimen, and three patients required more frequent injections. One girl was removed from the study because of clinical progression and extreme mood swings. No serious adverse effects occurred. Mean height velocity during the study period was 4.5 cm/year (range, 3.1-6.6) compared with 6.5 cm/year (range, 3.8-9.6) before treatment in nine patients for whom data were available. CONCLUSIONS: Zoladex LA was effective in controlling precocious puberty in girls when given at intervals of 9-12 weeks and it is recommended that an initial assessment is made eight weeks after beginning treatment.