Endovascular coil trapping for ruptured vertebral artery dissecting aneurysms by using double microcatheters technique in the acute stage.

BACKGROUND: In the treatment of vertebral artery (VA) dissecting aneurysms, only proximal occlusion of the VA does not necessarily prevent rerupture. We evaluated the efficacy of coil trapping for the ruptured VA dissecting aneurysms using the double microcatheters technique. METHODS: We treated 11 patients who presented with subarachnoid haemorrhage (SAH) due to rupture of a VA dissecting aneurysm which did not involve the posterior inferior cerebellar artery at the site of dissection. All patients tolerated the balloon occlusion test. Within 3 days of the SAH, the dissection site was trapped with a Guglielmi detachable coil (GDC) using the double microcatheters technique. The proximal and distal sites of the dissecting aneurysm were embolized simultaneously. FINDINGS: GDC trapping at the affected site was successful in all 11 patients. Radiographic findings showed complete occlusion of the dissection site and patency of the unaffected artery. Although one patient experienced transient dysphagia, there were no major complications. INTERPRETATION: The double microcatheters technique is effective for coil trapping of ruptured VA dissecting aneurysms in selected patients. The risks posed by this simple technique are minimal, even in the acute stage.

[Treatment of spontaneous carotid-cavernous fistula by the transvenous approach via the facial and angular route].

We report a case of a patient with a spontaneous carotid-cavernous sinus fistula (CCF) who was successfully treated by the facial vein approach. This 66-year-old female had a 3-month history of right chemosis and exophthalmos. Angiograms showed a spontaneous right CCF with primary drainage via the superior ophthalmic vein. As both inferior petrosal sinuses were hypoplastic, the transvenous approach could not be used to gain access to the right cavernous sinus. With effort, we were able to traverse the sharp angle at the corner of the angular vein and the superior ophthalmic vein with a microcatheter. Thereafter, it was easily navigated into the right cavernous sinus. Successful placement of Guglielmi detachable coils resulted in complete closure of the fistula. When it is difficult to gain access to the cavernous sinus via the inferior petrosal sinus, the facial vein approach is a useful alternative.

Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis.

In highly vascular malignant glioma, glioma cells themselves may express angiogenic factors and induce angiogenesis. Recent studies have shown that novel angiogenic factors, angiopoietin-1 (Ang1) and -2 (Ang2), play important roles in the modulation of vasculogenesis and angiogenesis. In this study, we determined Ang2 mRNA expression in cultured human malignant glioma cells (U105, U251, and U373 MG) by reverse transcriptase-PCR. Western blot analysis and immunocytochemical analysis with antihuman Ang2 antibody revealed that Ang2 protein was expressed and secreted by these cells. Furthermore, hypoxia increased the Ang2 protein level in cultured glioma cells. Serial sections of 32 human glioma tissues (14 glioblastomas, eight anaplastic astrocytomas, seven astrocytomas, and three pilocytic astrocytomas) were immunostained against Ang2, vascular endothelial growth factor, Tie2, von Willebrand factor, and alpha smooth muscle actin. The immunoreactivity of each angiogenic factor was higher in malignant gliomas than in low-grade gliomas. Ang2 protein was detected not only in endothelial cells but also in glioma cells, and its expression was prominent in both the area surrounding the necrosis and the periphery of glioblastomas. In the area surrounding necrosis, Ang2 was highly expressed and tumor vessels showed regression. In the tumor periphery, Ang2 was highly expressed and many small vessels stained positively for von Willebrand factor but not for alpha smooth muscle actin, suggesting angiogenesis. Statistical analysis revealed that the Ang2 expression was negatively correlated with vessel maturation in malignant gliomas and that vascular endothelial growth factor expression was positively correlated with vessel maturation in low-grade gliomas (P < 0.05). These results suggest that glioma cells themselves express Ang2 and that expression may be induced by hypoxic stimulation and may play a crucial role in the vessel maturation, angiogenesis, and vessel regression in malignant glioma.

Intravenously injected FK506 failed to inhibit hippocampal calcineurin.

FK506 (tacrolimus) is known as an inhibitor for calcineurin and is used in numerous research fields. It is not clear whether intravenously injected FK506 inhibits neuronal calcineurin. We measured the calcineurin activities of normal and postischemic rat hippocampi after intravenous injection of FK506 (3 mg/kg). Intravenously injected FK506 had no inhibitory effect on calcineurin activity in the hippocampi of normal and postischemic rats, whereas FK506 inhibited the calcineurin in vitro (purified enzyme, hippocampal homogenate, and hippocampal slice culture homogenate). Thus, it is considered that intravenously injected FK506 does not act on intraneuronal calcineurin and that several effects of FK506 are not due to the inhibition of neuronal calcineurin.

[Follow-up survey of dioxins in the blood of Yusho patients (in 1998-1999)].

Follow-up survey of the blood concentration of PCDDs, PCDFs and non-ortho-chlorine substituted PCBs in Yusho patients is very important for their health control. We determined the blood concentration of these dioxin isomers in 119 blood samples collected in 1998 and 1999 using by a high-resolution gas chromatograph/high-resolution mass spectrometry (HRGC/HRMS). Thirty years had passed since the Yusho occurrence, and the total blood concentrations of PCDFs in the blood of Yusho patients were still as high as ever, except the patients with the PCB pattern C. Among the different groups of PCB patterns, the concentration of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF and 1,2,3,6,7,8-HxCDF showed significant differences, excluding the group BC because of the small number of cases. The findings indicate that these isomers are not decomposed in human body since they had highly contaminated the causal rice oil at the onset. In typical Yusho patients (Group A of PCB pattern), the mean TEQ concentrations of PCDDs, PCDFs and non-ortho-chlorine substituted PCBs in the blood collected in 1998 were 21, 206, and 14 pg-TEQ/g lipid, respectively, and in 1999, 30, 308 and 14 pg-TEQ/g lipid, respectively. The toxic contribution rate of PCDFs TEQ was still at high levels for total TEQ in both years. The patients of the group C, however, the mean blood levels of the dioxins TEQ in 1998 and 1999 did not differ from those of the normal controls determined in 1996 although some patients in this group showed a high toxic contribution rate of PCDFs TEQ for total TEQ. We will try the PCB isomer specific analysis of the Yusho patients blood, and will investigate the difference from normal controls blood.

[Endovascular treatment for facial arteriovenous malformations using new particles: report of two cases].

Facial arteriovenous malformations (FAVM) are difficult to treat because of their highly vascular networks. Intravascular treatment using liquid material to occlude the FAVM occasionally results in skin necrosis after embolization. The use of particulate materials to obliterate the nidus often fails to obtain a permanent cure due to arterial recanalization. We report two patients with FAVM who were successfully treated with endovascular embolization using a new type of particulate material. One patient was treated with embolization only, the other was treated with embolization followed by surgical resection. Both patients showed clinical and angiographic improvement. Intravascular treatment using particles with a smooth surface and optimal size is safe and effective in the treatment of patients with FAVM.

Treatment of dissecting vertebral aneurysm.

SUMMARY: We report 17 patients with dissecting aneurysm of the vertebral artery (VA) who were treated by direct surgery (n=8) or interventional surgery (n=9). Eight patients presented with subarachnoid hemorrhage (SAH) and nine with ischemia. Ten patients were treated by trapping of the aneurysm that was occlusion of the VA on both sides of aneurysm (direct surgery, n=2; interventional surgery, n=8). The other seven patients were treated by ligation of the VA proximal to the aneurysm (direct surgery, n=6; interventional surgery, n=l). Two patients underwent transposition of the posterior inferior cerebellar artery (PICA). In 15 patients, there were no major complications. Two patients who had been treated by proximal occlusion of the VA developed rebleeding and ischemia due to persistent retrograde filling of the dissecting site. We suggest that angiographic evidence of retrograde filling of the dissecting site should have been considered as an indication for trapping. Trapping of VA dissecting aneurysms is easier and safer by interventional surgery than by direct surgery.

The utility of the microcrystalline cellulose sphere as a particulate embolic agent: an experimental study.

BACKGROUND AND PURPOSE: Although various particulate materials have been developed as embolization agents, their biocompatibility remains unclear. We used an animal model to examine the possibility of using FDA-approved microcrystalline cellulose spheres (CELPHERE) as solid embolic material for the permanent occlusion of blood vessels. METHODS: Angiographic and histologic studies in 12 canine renal arterial systems were conducted to evaluate the performance of CELPHERE beads at 1 hour, and at 4 and 12 weeks after embolization. RESULTS: The CELPHERE beads traveled to vessels with diameters approximating their own. Larger vessels were occluded by aggregations of beads. There was no disruption of vessel walls and no evidence of perivascular hemorrhage or inflammatory changes. CONCLUSION: Because CELPHERE beads are easy to handle, highly biocompatible, and have few adverse effects, they are suitable for intravascular applications.

Purification and characterization of NAD-dependent morphine 6-dehydrogenase from hamster liver cytosol, a new member of the aldo-keto reductase superfamily.

Morphine 6-dehydrogenase, which catalyzes the dehydrogenation of morphine to morphinone, was purified 815-fold to a homogeneous protein from the soluble fraction of hamster liver with a yield of 15%. The enzyme was a monomeric protein with a molecular weight of 38 kDa and an isoelectric point of 5.6. Although both NAD and NADP served as cofactors, the enzyme activity with NADP was less than 5% that found with NAD at pH 7.4. With NAD, the enzyme gave the maximal activity at pH 9.3, and the K(m) and V(max) values toward morphine were 1.0 mM and 0.43 unit/mg protein, respectively. Among morphine congeners, normorphine exhibited higher activity than morphine, but codeine and ethylmorphine were poor substrates, and dihydromorphine and dihydrocodeine showed no detectable activity. The enzyme also exhibited significant activity for a variety of cyclic and alicyclic alcohols. In addition to xenobiotics, the enzyme catalyzed the dehydrogenation of 17beta-hydroxysteroids with much higher affinities than morphine. In the reverse reaction, the enzyme exhibited high activity for o-quinones, but morphinone, naloxone, and aromatic aldehydes and ketones were reduced at slow rates. Sulfhydryl reagents and ketamine strongly inhibited the enzyme, whereas pyrazole, barbital, and indomethacin had little effect on enzyme activity. 17beta-Hydroxysteroids inhibited the enzyme in a competitive manner against morphine. A total of 302 amino acid residues, which comprised approximately 94% of whole protein, were identified by sequencing of the peptides obtained by proteolytic digestion. This amino acid sequence of the enzyme showed significant homology to members of the aldo-keto reductase (AKR) superfamily and shared 63-64% identity with members of the AKR1C subfamily. These findings indicate that the enzyme is a new member of the AKR superfamily that is involved in steroid metabolism as 17beta-hydroxysteroid dehydrogenase as well as xenobiotic metabolism.

Treatment for Giant Aneurysms in the Cavernous Portion of the Internal Carotid Artery using Detachable Coils.

SUMMARY: We report 7 patients with symptomatic giant aneurysms in the cavernous portion of the internal carotid artery (ICA) who were treated by trapping the ICA on either side of the aneurysmal orifice using detachable coils. In all 7 patients the ICA was sacrificed; 5 patients subsequently underwent bypass surgery (STA-MCA bypass, n = 4; high-flow bypass, n = 1), the other 2 patients did not. In 6 patients, there were no post-treatment embolic episodes; one patient who had been treated by proximal occlusion of the ICA developed transient ischemia due to an intra-aneurysmal thrombus. Cranial nerve palsies were markedly improved in all patients. ICA trapping using detachable coils was a highly successful treatment method in these patients. We found the detachable coils effective and easy to use in the trapping methods applied in this series of 7 patients.

Purification and characterization of two major forms of naloxone reductase from rabbit liver cytosol, new members of aldo-keto reductase superfamily.

Rabbit liver cytosol produced approximately equal amounts of 6alpha-naloxol and 6beta-naloxol from naloxone in the presence of NADPH at pH 7.4, and contained at least four forms of naloxone reductase. The two major forms, NR1 and NR2, which catalyze the stereospecific reduction of naloxone to 6alpha-naloxol and 6beta-naloxol, respectively, were purified to apparent homogeneity by various chromatographic techniques. Both enzymes are monomeric proteins with similar molecular weights of 35000-36000, but NR1 is a basic protein with an isoelectric point (pI) of 9.3, while NR2 is an acidic protein (pI of 5.9). NR1 and NR2 gave the maximal activities at pH 8.0 and 6.1, respectively. NR1 exhibited considerable activity with NADH as well as with NADPH, whereas NR2 showed highly restricted specificity for NADPH. The Km and Vmax values of NR1 and NR2 for naloxone were 1.0 and 0.06 mM, and 76 and 162 munits/mg, respectively. In addition to naloxone, naltrexone and dihydromorphinone served as good substrates for NR2 but were poor substrates for NR1. Both enzymes reduced aliphatic and aromatic aldehydes, cyclic and aromatic ketones, and quinones at higher rates. The two enzymes catalyzed the dehydrogenation of 17beta-hydroxysteroids with low Km values, and NR2 showed an additional 3alpha-hydroxysteroid dehydrogenase activity. Amino acid sequence data of NRI (99% of whole protein) and NR2 (66%) showed that both enzymes belong to the aldo-keto reductase (AKR) superfamily and can be classified into the AKR1C subfamily. These findings therefore indicate that they are new members of the AKR superfamily and may be involved physiologically in the steroid metabolism as well as in the detoxification of xenobiotic carbonyl compounds.

Cosmetic osteoplastic craniotomy with a chisel and hammer.

BACKGROUND: Osteoplastic craniotomy has been performed recently with microfixation systems such as miniplates, burr hole buttons, and/or ceramic dust. However, these are costly methods of treatment. Without the use of these devices, we performed cosmetic osteoplastic craniotomy using an inexpensive chisel and hammer. METHODS: Our osteoplastic craniotomy with a chisel and hammer was used on 19 lesions in 15 patients. Using a chisel, the bone flap was cut gently from the calvarium to the skull base, the lamina externa to the diploe (finally the lamina interna), and both ends to the midportion between two holes. The lamina interna in the cranium was trimmed easily after removal of the bone flap. The bone defect was minimal because of the absence of a narrow cutting groove and because craniectomy was not performed. The bone flap was replaced by tapping and was tightly fixed. No special fixation system was needed, except for threads. RESULTS: Follow-up (mean follow-up, 5 months; range, 5 weeks to 9 months) skull X-ray and 3D-CT showed good fusion and inherent normal configuration of the bone flap. There were two minor dural tears and two minor bony fractures. CONCLUSION: A good cosmetic effect without the use of any additional instruments was accomplished with osteoplastic craniotomy using a chisel and hammer.

Gene transfer of human prostacyclin synthase prevents neointimal formation after carotid balloon injury in rats.

BACKGROUND AND PURPOSE: A disordered proliferative process in the vascular wall is thought to underlie the pathogenesis of restenosis after percutaneous transluminal angioplasty and carotid endarterectomy. A growth inhibitory property of overexpressed prostacyclin (PGI2) synthase (PGIS) was recently implicated in the pathological proliferation of vascular smooth muscle cells (VSMC) in vitro. Here, we investigated the effects of increased PGI2 synthesis on the pathological proliferation of VSMCs. METHODS: The cDNA encoding human PGIS was transfected into endothelium-denuded rat carotid arteries after arterial balloon injury with the use of hemagglutinating virus Japan (HVJ). HVJ liposome vector complex without PGIS cDNA was used for vehicle control. The level of 6-keto PGF1alpha, a stable hydrolyzed metabolite of PGI2, the histological distribution of the immunoreactivity for human PGIS and the ratio of neointimal/medial area were analyzed. RESULTS: In the analyses of 6-keto PGF1alpha, the level in the carotid arteries was significantly elevated 3 days after PGIS expression-vector transfection compared with that in the arteries after vehicle transfection. Seven days after human PGIS expression-vector transfection, the PGIS cDNA-transfected neointimal cells were strongly positive for human PGIS immunoreactivity in 81% sections examined. Fourteen days after the injury, the ratio of neointimal/medial area was 1.2+/-0.4 in the PGIS expression-vector transfected group, which was significantly smaller than that of the vehicle control group, 1.7+/-0.5; P<0.01. CONCLUSIONS: It was thus demonstrated that the gene transfer of human PGIS expression-vector into rat carotid arteries resulted in the increased production of human PGI2 in the vascular wall, the expression of human PGIS in the developing neointima and significantly inhibited the neointimal formation generated after balloon injury.

A novel hybrid biological embolic material: autologous fibroblast incorporated collagen (FC) beads.

If viable fibroblasts are used as an active ingredient of an embolic material, it is expected that proliferation and extracellular matrix production of fibroblasts incorporated at a vascular lesion will help restore tissues due to endovascular scar formation, resulting in progressive and permanent occlusion. Based on this working principle, we have devised a novel biological embolic material, hybrid fibroblast incorporated collagen (hybrid FC) beads composed of collagen microbeads and autologous fibroblasts harvested from the subcutaneous tissue of the host to be treated. Hybrid FC beads were prepared by culture of fibroblasts harvested from canine subcutaneous tissue on collagen microbeads (diameters ranging from around 100 µm to around 400 µm). Canine kidneys were embolized with either hybrid FC or cell-free collagen beads via a transarterial route. Histological examination up to 6 months after embolization revealed that, although both embolic materials effectively occluded the target vessels at the time of embolization, intravascular scar formation activity at the embolized sites was much more profound in the case of the hybrid FC beads than in that of the cell-free beads. Proliferation of autologous fibroblasts was verified by the expression of alkaline phosphatase activity of gene-transfected fibroblasts at the site of lodgement of the beads. It is expected that, using the novel hybrid biological embolic material, hybrid FC beads used for vascular lesions such as arteriovenous malformations can be treated more effectively to restore tissues, resulting in minimal recanalization which often occurs when synthetic embolic materials are used. Copyright 1999 Harcourt Publishers Ltd.

Expression of thioredoxin is enhanced in atherosclerotic plaques and during neointima formation in rat arteries.

Thioredoxin (TRX) is an intracellular enzyme that has a variety of activities as a hydrogen donor for various intracellular molecules. In the present study, we investigated the role of TRX in atherosclerotic lesions. In human atherosclerotic specimens, TRX and TRX mRNA were enhanced in endothelial cells and macrophages in the atherosclerotic plaques. In balloon-injured rat arteries, TRX expression increased from 2 to 6 weeks after injury; TRX was induced in the neointimal regenerating endothelial cells. In hybridization experiments, TRX mRNA was also induced from 2 to 6 weeks in the endothelium. In this model, inducible nitric oxide synthase immunoreactivity in the neointimal smooth muscle cells and endothelial cells increased from 2 to 6 weeks after surgical procedures were performed. During this period, the immunoreactivity of nitrotyrosine, which is a marker of nitric oxide (NO) production, also increased. We focused on the association between TRX and NO. In vitro studies using a murine endothelial cell line showed TRX and TRX mRNA induction by NO and peroxynitrite donors. Enhanced expression of TRX was detected mainly within the cytoplasm in immunocytochemical studies. In addition, TRX-transfected cells showed resistance to peroxynitrite-induced cytotoxicity. These findings indicate that TRX and the cellular redox state modified by TRX play a crucial role in arterial neointima formation in atherosclerosis.

Endosaccular embolization for internal carotid artery aneurysms at the c3 portion.

SUMMARY: Direct surgery for the aneurysms at the C3 portion of the internal carotid artery (ICA) requires relatively complicated procedures. We present three patients with this aneurysm who underwent endovascular embolization. The remodelling technique was utilized in two of these patients with unruptured aneurysms. Sufficient obliteration was achieved in every case. Endovascular embolization may be an important alternative for ICA C3 aneurysms.

Mechanism of intracranial rebleeding in moyamoya disease.

Intracranial hemorrhage is the major catastrophic event in the natural course of Moyamoya disease, and outcome of the patients with rebleeding is very poor. However, the mechanism underlying intracranial rebleeding is not well elucidated. We retrospectively analyzed 15 patients who bled two times or more among 46 bled patients with Moyamoya disease. The results indicated that there were two different types in the manner of rebleeding. One group consisted of seven cases, which bled two times or more at the same site than the original bleeding site. In four of these seven cases, a ruptured aneurysm was identified at the distal part of collateral vessel or on the major vessel. In the other three cases, no source of bleeding was identified. In all of these cases, rebleeding occurred within 2 months after the initial insult except for one case. Another group consisted of eight cases, which bled repeatedly but at different sites from the initial bleeding site. In any of these cases, neither aneurysms nor other vascular abnormalities were identified. In all of these cases, rebleeding occurred more than 2 months after the initial bleeding. The present result indicated that intracranial bleeding might occur as a result of rupture of a tiny aneurysm at the periphery of collateral vessels. These aneurysms may be blown out after initial bleeding. When they persist after the event, they may rupture again in a fairly short interval. In other cases, bleeding occur at different sites from the initial site. They are considered to be a result of ruptured weak Moyamoya vessels which are forced to act as collateral pathways and are under unusually increased hemodynamic stress.

Direct surgery for major artery aneurysm associated with moyamoya disease.

Moyamoya disease is often accompanied by intracranial major artery aneurysms in the posterior circulation which acts as collateral channels in place of the stenotic internal carotid arteries. These major artery aneurysms are considered to have high risk of enlargement and rupture due to increased hemodynamic stress. Direct surgical intervention has been recommended for the treatment of these aneurysms, but the direct approach to them is often difficult due to interference by intertwined abnormal vessels. We have performed direct surgery for seven major artery aneurysms in five patients with Moyamoya disease. Of these three aneurysms located in the anterior circulation were successfully clipped via pterional or interhemispheric approach. Of four posterior circulation aneurysms (two at the junction of the basilar artery and the superior cerebellar artery and two at the P1-P2 junction of the posterior cerebral artery), one was approached via pterional route because collateral vessels in the basal cistern was judged not to be rich on angiograms. However, the operative field was interfered by abundant fragile collateral vessels and it was difficult to reach the distal portion of the basilar artery. In contrast, in the other three cases in which the subtemporal approach was employed, there weren't any problems in exposures of the aneurysms. Our experiences indicate that subtemporal approach is superior than the pterional approach to reach the distal portion of the basilar artery in patients with Moyamoya disease.

Resection of a large, high-flow arteriovenous malformation during hypotension and hypothermia induced by a percutaneous cardiopulmonary support system. Case report.

The key to successful surgical resection of cerebral arteriovenous malformations (AVMs) is control of bleeding and cerebral swelling. Induced hypotension is one of the most valuable means of achieving this control. The authors introduced induced hypotension with mild hypothermia by using a percutaneous cardiopulmonary support system (PCPS) to resect a large, high-flow AVM. The efficacy and technical points of this method are discussed. The PCPS, whose entire intraluminal surface was coated with heparin, was established through a transfemoral route. During resection of the AVM, a mean arterial blood pressure of 60 mm Hg and a mean body temperature of 30 degrees C were easily maintained by regulating the flow rate of the PCPS and by blood cooling. The activated coagulation time was maintained at approximately 250 seconds with a minimum systemic administration of heparin. The authors report the case of a 30-year-old woman who presented with intraventricular hemorrhage and was diagnosed as having a large, high-flow AVM located in the left sylvian fissure. The AVM was fed by the left middle, posterior, and anterior cerebral arteries and drained by the many cortical ascending veins and the basal vein. The patient underwent surgery after hypotension and hypothermia had been induced via the PCPS method. Induced hypotension decreased the tension of the nidus and made its dissection easier. The AVM was totally resected and no hemostatic difficulties were encountered. On the basis of the authors' experience, they suggest that hypotension and hypothermia induced by using the PCPS is a powerful tool for the successful resection of large, high-flow AVMs.

[Detection of microemboli by transcranial Doppler sonography after carotid endarterectomy].

Transcranial Doppler sonography (TCD), a non-invasive monitoring technique, has potential for detecting microemboli caused by the extracranial internal carotid artery. Many previous reports have shown that TCD-detected microemboli may be a risk factor for stroke. The main purpose of this study is to verify whether microemboli cease after carotid endarterectomy (CEA). TCD monitoring was performed in 43 cases before and after CEA. TCD monitoring was carried out for an hour at the ipsilateral middle cerebral artery of each case using a 2-MHz pulse-wave transcranial Doppler device, and high intensity transient signals were counted as microemboli. Microemboli were detected preoperatively in 10 cases (23.3%). Microemboli were not detected in any case immediately after CEA, in either the subacute stage (from 14 to 21 days after CEA) or in the chronic stage (more than 3 months after CEA). In the acute stage (from 3 to 7 days after CEA), microemboli were detected in three cases (7.0%). The rate of TCD-detected microembolic was always significantly reduced after CEA. TCD monitoring can be helpful in assessing the effect of CEA for prevention of stroke by removing the suspected source of microemboli.