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ABSTRACT: We evaluated a new therapeutic strategy for malignant glioma, which combines intratumoral inoculation of mesenchymal stem cells (MSCs) expressing cytosine deaminase gene with 5-fluorocytosine (5-FC) administration. For in vitro and in vivo experiments, MSCs were transfected with adenovirus carrying either enhanced green fluorescent protein gene (AdexCAEGFP) or cytosine deaminase gene (AdexCACD), to establish MSC-expressing EGFP (MSC-EGFP) or CD (MSC-CD). Co-culture of 9L glioma cells with MSC-CD in a medium containing 5-FC resulted in a remarkable reduction in 9L cell viability. The migratory ability of MSC-EGFP toward 9L cells was demonstrated by double-chamber assay. For the in vivo study, rats harboring 9L brain tumors were inoculated with MSC-EGFP or MSC-CD. Immunohistochemistry of rat brain tumors inoculated with MSC-EGFP showed intratumoral distribution of MSC-EGFP. Survival analysis of rats bearing 9L gliomas treated with intratumoral MSC-CD and intraperitoneal 5-FC resulted in significant prolongation of survival compared with control animals. In conclusion, molecular therapy combining suicide gene therapy and MSCs as a targeting vehicle represents a potential new therapeutic approach for malignant glioma, both with respect to the antitumor potential of this system and its neuroprotective effect on normal brain tissue.
Cancer gene therapy 06/2012; 19(8):572-8. · 3.13 Impact Factor
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F Wang,
M Kameda,
T Yasuhara,
N Tajiri,
Y Kikuchi,
H B Liang,
J T Tayra,
A Shinko,
T Wakamori,
T Agari, I Date
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ABSTRACT: Cell transplantation has been shown to be an effective therapy for central nervous system disorders in animal models. Improving the efficacy of cell transplantation depends critically on improving grafted cell survival. We investigated whether glial cell line-derived neurotrophic factor (GDNF)-pretreatment of neural stem cells (NSCs) enhanced grafted cell survival in a rat model of Parkinson's disease (PD). We first examined the neuroprotective effects of GDNF on oxygen-glucose deprivation (OGD) in NSCs. Cells were pretreated with GDNF for 3 days before subjecting them to OGD. After 12h of OGD, GDNF-pretreated NSCs showed significant increases in survival rates compared with PBS-pretreated NSCs. An apoptosis assay showed that the number of apoptotic cells was significantly decreased in GDNF-pretreated NSCs at 1h and 6h after OGD. A PD rat model was then established by unilateral injection of 6-hydroxydopamine (6-OHDA, 9μg) into the medial forebrain bundle. Two weeks after 6-OHDA injection, GDNF-pretreated NSCs, PBS-pretreated NSCs, or PBS were injected into PD rat striatum. The survival of grafted cells in the striatum was significantly increased in the GDNF-pretreated NSC group compared with the control groups. GDNF pretreatment increased survival of NSCs following transplantation, at least partly through suppression of cell apoptosis.
Neuroscience Research 06/2011; 71(1):92-8. · 2.25 Impact Factor
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Y. Kikuchi,
T. Yasuhara,
T. Agari,
A. Kondo,
S. Kuramoto,
M. Kameda,
T. Kadota,
T. Baba,
N. Tajiri,
F. Wang,
J.T. Tayra,
H. Liang,
Y. Miyoshi,
C.V. Borlongan, I. Date
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ABSTRACT: Increased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8-hydroxy-2'-deoxyguanosine (8-OHdG), is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8-OHdG in PD patients. There are few basic laboratory data examining 8-OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). The urinary 8-OHdG level was measured in relation to behavioral and pathological deficits arising from 6-OHDA-induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6-OHDA injection. We collected urine samples with subsequent measurement of 8-OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8-OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8-OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8-OHdG level provides a good index of severity of parkinsonism. Urinary 8-OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6-OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8-OHdG level closely approximate onset and disease progression in PD. (c) 2010 Wiley-Liss, Inc
J.Cell Physiol. 10/2010;
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ABSTRACT: Bow hunter's syndrome is a unique clinical entity caused by mechanical occlusion of the vertebral artery on head rotation. Although it is usually treated by direct surgical intervention, we report successful treatment using endovascular stent placement for contralateral vertebral artery stenosis.
A 56-year-old man presented with repeated vertigo and loss of consciousness caused by turning his head to the left. Right vertebral angiogram showed no abnormalities with the head in the neutral position. However, with the head rotated 60 degrees to the left, the right vertebral artery was completely occluded at the C1-2 level. A three-dimensional angiogram with bone window clearly demonstrated vertebral artery compression at the C1-2 level by the bony structure. The left subclavian angiogram revealed severe stenosis at the origin of the left vertebral artery. Left vertebral artery angioplasty followed by stent placement was successfully performed under local anesthesia. The patient showed an uneventful postoperative course and his preoperative symptoms disappeared. At 6 months postoperatively, a left subclavian angiogram showed good patency of the stented left vertebral artery and the patient showed no recurrent symptoms.
Vertebral artery stenting is a useful and less invasive option in the treatment of bow hunter's syndrome in the setting of contralateral vertebral artery stenosis.
min - Minimally Invasive Neurosurgery 08/2009; 52(4):193-5. · 0.70 Impact Factor
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ABSTRACT: Neurovascular contact (NVC) of the trigeminal nerve is not only detected at the affected trigeminal nerve in patients with trigeminal neuralgia (TN) but is also observed at the asymptomatic nerves on the side contralateral to the TN as well as in normal nerves in control subjects. The frequency and severity of the NVC among the affected, contralateral, and normal trigeminal nerves were analyzed by 3D MR cisternogram and angiogram fusion imaging in relation to the cause of TN.
The inner view of the fusion MR imaging projected from inside the trigeminal nerve was used. The severity of the NVC was classified as none, simple, moderate, or severe, according to the nerve circumference in contact with the vessel. The NVC was analyzed in the affected nerves (n = 66) and the contralateral nerves (n = 66). Forty patients underwent microvascular decompression surgery, and 26 were treated medically. The NVC at the normal trigeminal nerves (n = 78) was studied in 39 control subjects without symptoms of TN.
The NVC in the affected trigeminal nerve was observed more frequently and much more severely than that at the contralateral and normal trigeminal nerves in controls (P < .01). Additionally, the NVC in the surgical patients was more severe than that in the medically treated patients (P < .01).
Severity analysis of the NVC with the inner view of the fusion MR imaging may provide useful information in the diagnosis of TN and can be a helpful adjunct in treatment planning for patients with TN.
American Journal of Neuroradiology 12/2008; 30(3):603-7. · 2.93 Impact Factor
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Tomoyuki Ogawa,
S. Ono,
T. Ichikawa,
H. Michiue,
S. Arimitsu,
K. Onoda,
K. Tokunaga,
K. Sugiu,
K. Tomizawa,
H. Matsui, I. Date
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ABSTRACT: BackgroundGene transfer with some vectors may be useful for treatment of cerebral vasospasm after subarachnoid haemorrhage (SAH) [2, 3, 6, 10, 12, 13, 19]. However, this method has some safety problems [18]. Previous studies have shown that direct delivery of therapeutic proteins by using protein transduction domain (PTD) may
reduce these problems [14, 15]. Here, we examined the transduction efficiency of eleven consecutive arginines (11R), which is one of the most effective
PTD [8, 9], into the rat cerebral arteries by using 11R-enhanced-green fluorescent protein (11R-EGFP).
Method11R-EGFP or EGFP was injected into the cisterna magna of the rats with SAH. SAH model was made by autologous blood injection.
The proteins were injected just after the autologous blood injection in SAH rats. The expression of 11R-EGFP or EGFP was observed
by fluorescence microscope.
FindingsThe signal of 11R-EGFP was much stronger than that of EGFP in all the layers of the rat basilar artery (BA). The 11R-EGFP
was especially transduced into the tunica media of the basilar artery 2 h after the injection.
ConclusionsOur results demonstrate that 11R-fused fluorescent protein effectively penetrates into the all layers of the rat BA, and especially
into the tunica media.
12/2007: pages 161-163;
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ABSTRACT: BackgroundUntil now, no absolute therapy for cerebral vasospasm (VS) after subarachnoid haemorrhage (SAH) has been established. Here
we examine the efficacy of intensive multimodality therapy, contrasting with the treatment in the non-multimodality period
in our institute.
MethodFor 10 years, a total of 108 patients who suffered subarachnoid haemorrhage (SAH) were divided into two groups. Group A patients
are from a period of time when there was no particular standardized protocol for treating SAH, i.e. 1996–2000. Group B patients
include the intensive care group for treating SAH, and we employed multimodality therapy on Group B by using intraventricular
urokinase (UK) injection, lumbar (LD) or cisternal drainages (CD) and timely intraarterial fasudil hydrochloride (FH) injection
in the second half of the period with a standardized protocol. Urokinase was given as a bolus administration from a ventricular
drain 12 h after surgery, and prophylactic mild hypertension and normovolemia were strictly performed. If symptomatic spasm
were detected, immediate intraarterial FH injection or percutaneous transluminal angioplasty was performed. Angiographic and
symptomatic vasospasm and the Glasgow outcome scale score 3 months post SAH were evaluated.
FindingsAngiographic vasospasm occurred in 64.2% and 59% in groups A and B, respectively. Symptomatic vasospasm was observed in 56.5%
of Group A and 37.1% of Group B. There was a statistical significance between the percentages of symptomatic vasospasm in
Groups A and B (p = 0.0422), but no significant differences were seen in angiographic vasospasm between these 2 groups. As for the outcome,
25.7% of Group A and 10.8% of Group B were poor outcome, and statistical significance (p = 0.001) was seen between these two groups. It is worth noting that there were no deaths due to vasospasm in Group B, in
contrast to the 14.8% death rate in Group A.
ConclusionsIntroduction of multimodality therapy was effective to prevent symptomatic vasospasm and improved the patients’ outcome.
12/2007: pages 279-281;
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ABSTRACT: BackgroundIn one of our studies we found that enhanced green fluorescent protein (EGFP) fused with consecutive 11 arginines (11R), one
of the protein transduction domains (PTDs) [1–6, 11], and effectively penetrated into all layers of the rat basilar artery (BA). We examined whether eNOS (140-kDa) fused 11R
(11R-eNOS) was also transduced into the BAs and had a positive effect on the attenuation of cerebral vasospasm.
Method11R-eNOS or saline was injected into the cisterna magna of male Sprague-Dawley rats. Two hours after the injection, the BAs
were extracted from the rats and transduction efficacy of 11R-eNOS in the BA was evaluated by immunofluorescence staining.
To examine the effect of 11R-eNOS on the cerebral arteries exposed to SAH, we measured the post SAH BA diameters six hours
after the injection of 11R-eNOS.
FindingsImmunofluorescent study confirmed the presence of 11R-eNOS protein in the layers of the cerebral arteries in vivo. 11R-eNOS had a positive effect on attenuation of cerebral vasospasm.
Conclusions11R-eNOS was effectively transduced into the walls of the BA. 11R-eNOS inhibited the vasoconstriction after SAH. These results
suggest that 11R-eNOS protein therapy has a potential in treating cerebral vasospasm.
12/2007: pages 165-167;
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ABSTRACT: BackgroundAlthough several tools are available for the detection of cerebral vasospasm after subarachnoid haemorrhage, it has remained
difficult to identify vasospasm timely and accurately. INVOS® monitoring measures the oxygen saturation by using near infrared spectroscopy, and in this study we examined the usefulness
of this system for the detection of vasospasm.
MethodFive patients who had suffered SAH were enrolled in this study. In view of the thickness of the clots, the probes of INVOS® were attached to the scalp in the areas where vasospasm was likely to occur, from day 3 to the end of vasospasm, up to 14
days post SAH. Patients were monitored every day by INVOS® and by neurological exams. Angiography was performed if regional oxygen saturation had continuously decreased by 10% or more
as compared to the contralateral side, or if patients showed additional neurological deficits. If vasospasm was detected,
interventional treatment using intraarterial fasudil injection or percutaneous transluminal angioplasty was performed. The
same interventional therapy was repeated until neurological deficits improved.
FindingsWhen the INVOS® value decreased to lower than 60, angiographic or symptomatic vasospasm tended to occur, and the response of regional oxygen
saturation correlated accurately, both symptomatically and angiographically, with brain ischemia due to vasospasm. Recovery
from ischemia on angiography or single photon emission CT also correlated with the return of regional oxygen saturation by
INVOS®.
ConclusionsINVOS® monitoring is handy and noninvasive; it is able to evaluate real-time regional oxygen saturation in the region of VS and
may be superior to the other existing monitoring systems.
12/2007: pages 215-218;
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ABSTRACT: BackgroundHypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates the expression of various neuroprotective genes.
The goal of this study was to clarify the relationship between HIF-1α expression and subarachnoid haemorrhage (SAH) and to determine the effects of the deferoxamine (DFO)-induced increase in
HIF-1α protein levels on the brainstem and the basilar artery (BA) following experimental SAH.
MethodRat single- (10min, 6 h, Day 1, Day 2) and double-haemorrhage (Day 7) models of SAH were used. The time course of HIF-1α protein levels of the brainstems and the diameter of the BA was assessed. After an induction of double-haemorrhage in rats,
DFO was injected intraperitoneally and HIF-1α protein expression, activity in the brainstems, the diameter of the BA and the brainstem blood flow were assessed.
FindingsThe expression of HIF-1α protein was significantly greater at 10 min and 7 days after SAH. The increase of HIF-1α protein correlated with the degree of cerebral vasospasm. An injection of DFO resulted in significant increases in HIF-1α protein expression and activity in the brainstem of rats with SAH.
ConclusionsThese results indicate that DFO-induced increase in HIF-1α protein levels and activity exerts neuroprotective and antivasospastic effects. DFO may be a potential therapeutic tool for
cerebral vasospasm after SAH.
12/2007: pages 69-73;
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ABSTRACT: Bedridden patients who receive good physical rehabilitation are able to exhibit clinical improvement. Accumulating evidence demonstrates that exercise increases endogenous neurogenesis and may even protect against central nervous system (CNS) disorders. Here, we explored the effects of lack of exercise on neurogenesis in rats by employing a routine hindlimb suspension (HS) model over a 2-week period, which consists of elevating their tails, thereby raising their hindlimbs above the ground and unloading the weights in these extremities. In addition, the effects of exercise and recovery time with normal caging after HS were also explored. BrdU (50 mg/kg, i.p.) was injected every 8 h over the last 4 days of each paradigm to label proliferative cells. Immunohistochemical results revealed that HS significantly reduced the number of BrdU/Doublecortin double-positive cells in the subventricular zone and dentate gyrus. Exercise and recovery time significantly improved atrophy of the soleus muscle, but did not attenuate the HS-induced decrement in BrdU/Dcx-positive cells. A separate cohort of animals was exposed to the same HS paradigm and enzyme-linked immunosorbent assay (ELISA) of neurotrophic factors was performed on brain tissue samples harvested at the end of the HS period, as well as plasma samples from all animals. ELISA results revealed that HS reduced the levels of brain-derived neurotrophic factor in the hippocampus and vascular endothelial growth factor plasma levels. This study revealed that lack of exercise reduced neurogenesis with downregulation of neurotrophic factors. The use of the HS model in conjunction with CNS disease models should further elucidate the role of exercise in neurogenesis and neurotrophic factors in neurologic disorders.
Neuroscience 11/2007; 149(1):182-91. · 3.38 Impact Factor
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M Kameda,
T Shingo,
K Takahashi,
K Muraoka,
K Kurozumi,
T Yasuhara,
T Maruo,
T Tsuboi,
T Uozumi,
T Matsui,
Y Miyoshi,
H Hamada, I Date
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ABSTRACT: Adult neural stem and progenitor cells (NSPCs) are important autologous transplantation tools in regenerative medicine, as they can secrete factors that protect the ischemic brain. We investigated whether adult NSPCs genetically modified to secrete more glial cell line-derived neurotrophic factor (GDNF) could protect against transient ischemia in rats. NSPCs were harvested from the subventricular zone of adult Wistar rats and cultured for 3 weeks in the presence of epidermal growth factor. The NSPCs were treated with fibre-mutant Arg-Gly-Asp adenovirus containing the GDNF gene (NSPC-GDNF) or enhanced green fluorescent protein (EGFP) gene (NSPC-EGFP; control group). In one experiment, cultured cells were transplanted into the right ischemic boundary zone of Wistar rat brains. One week later, animals underwent 90 min of intraluminal right middle cerebral artery occlusion followed by magnetic resonance imaging and behavioural tests. The NSPC-GDNF group had higher behavioural scores and lesser infarct volume than did controls at 1, 7 and 28 days postocclusion. In the second experiment, we transplanted NSPCs 3 h after ischemic insult. Compared to controls, rats receiving NSPC-GDNF had decreased infarct volume and better behavioural assessments at 7 days post-transplant. Animals were killed on day 7 and brains were collected for GDNF ELISA and morphological assessment. Compared to controls, more GDNF was secreted, more NSPC-GDNF cells migrated toward the ischemic core and more NSPC-GDNF cells expressed immature neuronal marker. Moreover, the NSPC-GDNF group showed more effective inhibition of microglial invasion and apoptosis. These findings suggest that NSPC-GDNF may be useful in treatment of cerebral ischemia.
European Journal of Neuroscience 10/2007; 26(6):1462-78. · 3.63 Impact Factor
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ABSTRACT: Cell therapy is thought to have a central role in restorative therapy, which aims to restore function to the damaged nervous system. The purpose of this study was to establish an autologous neural stem cell (NSC) transplantation model using adult rats and to compare survival, migration, and differentiation between this system and allogeneic NSC transplantation. Furthermore, we compared the immunologic response of the host tissue between autologous and allogeneic transplantation. NSCs were removed from the subventricular zone of adult Fischer 344 rats using stereotactic methods. NSCs were expanded and microinjected into normal hippocampus in the autologous brain. Allogeneic NSC (derived from adult Wistar rats) transplantation was performed using the same procedure, and hippocampal sections were analyzed immunohistologically 3 weeks post-transplantation. The cell survival and migration rate were higher for autologous transplantation than for allogeneic transplantation, and the neuronal differentiation rate in the autologous transplanted cells far exceeded that of allogeneic transplantation. Furthermore, there was less astrocyte and microglia reactivity in the host tissue of the autologous transplantation compared with allogeneic transplantation. These findings demonstrate that immunoreactivity of the host tissue strongly influences cell transplantation in the CNS as the autologous transplantation did not induce host tissue immunoreactivity; the microenvironment was essentially maintained in an optimal condition for the transplanted cells.
Experimental Neurology 07/2006; 199(2):311-27. · 4.70 Impact Factor
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ABSTRACT: Fusion imaging of 3D MR cisternography/angiography was used for the assessment of the vascular bulging finding detected by MR angiography from the viewpoint of the outer wall configuration of the corresponding internal carotid artery depicted by MR cisternography. With a fusion image, useful information was obtained to distinguish an infundibular dilation and enlarged origin of the normal posterior communicating artery from an aneurysm. This imaging technique can be a feasible addition to a noninvasive screening of cerebrovascular lesions with MR angiography alone.
American Journal of Neuroradiology 03/2006; 27(2):306-12. · 2.93 Impact Factor
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ABSTRACT: Collagen lattice contraction has been reported as another aspect of the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH). Recently, some authors have suggested that matrix metalloproteinase-1 (MMP-1) plays an important role in collagen lattice contraction. Therefore, this study aimed to clarify a role of MMP-1 during cerebral vasospasm in a rat SAH model.
We used a single-SAH model in rats and assessed the basilar arteries (BAs) at 30 minutes and on 2 days after SAH by cross-sectional area measurement and other histological parameters. Immunohistochemistry and Western blot analysis were used to quantify MMP-1 expression and activation.
BAs in rats significantly exhibited severe cerebral vasospasm at 30 minutes after SAH and moderate vasospasm on Day 2. The immunohistochemistry and Western blotting performed in BAs of rats demonstrated that both expression and activation in MMP-1 peaked at 30 minutes after SAH and then declined to the control level.
MMP-1 is expressed and activated in a parallel time course to the development of cerebral vasospasm in an experimental model of SAH.
Acta Neurochirurgica 03/2005; 147(2):187-92; discussion 192-3. · 1.52 Impact Factor
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ABSTRACT: The goal of this study was to evaluate the results of endovascular and surgical treatments for ruptured vertebral artery dissecting aneurysms (VADAs) to determine which treatment is preferable. We evaluated the cases of 25 consecutive patients with ruptured VADAs treated in our institution. From 1992 to 1997, five patients were treated surgically. Since 1998, 20 patients with VADAs have been treated with endovascular therapy. The goal of the treatment was to exclude the aneurysm from the circulation. Among the five patients undergoing surgery, three aneurysms were treated with proximal clipping, one with trapping, and one with dome clipping. None of the patients were treated during the acute stage of rupture. Transient complications occurred in two patients. Of the 20 patients treated through the endovascular approach, 15 were treated within 24 h of rupture, but 12 had rebleeding before treatment. Eighteen aneurysms were occluded, along with the affected vertebral artery (VA), by using detachable coils (internal trapping), and one was occluded with the VA preserved. A stent-assisted occlusion of one aneurysm was done in a patient who had a contralateral hypoplastic VA. In both groups, the outcome of each patient depended greatly on the patient's condition before treatment and whether there was rebleeding. No posttreatment bleeding occurred. All procedures were effective, but endovascular treatment was less invasive and easier to use during the acute stage of subarachnoid hemorrhage. Although this report does not describe a controlled study, we found that endovascular treatment is preferable for treating ruptured VADAs in the acute stage.
Neuroradiology 03/2005; 47(2):158-64. · 2.82 Impact Factor
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ABSTRACT: We report our results of endovascular treatment for elderly patients with ruptured aneurysm and discuss the indication for treatment. One hundred and thirty four consecutive patients with ruptured aneurysm treated in our institute during the last 4 years were retrospectively evaluated. Fifty eight patients were included in group A (over 70 years old), and 76 patients in group B (under 69 years old). In both groups, the outcome was strongly related to the preoperative Hunt & Kosnik grade. However, significant risk factors (i.e. pneumonia, rupture of extracranial aneurysm) which make prognosis poor were more common in group A. Group A showed poor outcome in grade III patients, although there were no outcome differences between the two groups in patients of other grades. Endovascular treatment for elderly patients with ruptured aneurysms seemed to be useful. Their outcome was strongly related to their preoperative condition. General risk factors should be evaluated before treatment, especially in elderly patients. Patients with low Hunt & Kosnik grade seem to be most suitable for endovascular treatment. On the other hand, outcome of patients with poor preoperative grade was worse despite the less invasive nature of endovascular treatment. An improvement of outcome in grade III patients is desirable.
Acta neurochirurgica. Supplement 02/2005; 94:7-9.
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ABSTRACT: Embolization is recognized as an important adjunct in the treatment of cerebral arteriovenous malformations (AVMs). We reviewed our results of embolizations for AVMs and discussed procedure-related complications. Eleven complications were recorded in 68 consecutive patients (16%). Of these, four were technical problems including a glued catheter, inability to withdraw the catheter, vessel perforation by the microcatheter, and coil migration. Other complications included three cases of ischemic symptoms due to retrograde thrombosis, two cases of asymptomatic cerebral infarction, one case of asymptomatic small haemorrhage due to venous occlusion, and one case of post-embolization haemorrhage of unknown etiology. Our morbidity rate was 7%, mortality rate was 0%, and asymptomatic complication rate was 9%, retorospectively. Further improvements to endovascular techniques and devices are required.
Interventional Neuroradiology 12/2004; 10 Suppl 2:59-61. · 0.56 Impact Factor
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ABSTRACT: The present case involves a 47-yr-old woman with Cushing's disease due to pituitary macroadenoma. The patient had suffered from hypertension and obesity for two yr. Her serum cortisol levels were moderately elevated throughout the observation period, and dexamethasone failed to suppress the cortisol secretion. Plasma ACTH levels were markedly high (>100 pg/ml) and did not respond to CRH provocation. Gel filtration analysis of the patient's plasma detected the existence of big ACTH molecules, which eluted with a peak of authentic 1-39 ACTH. Cranial magnetic resonance imaging (MRI) revealed a 3 cm pituitary tumor occupying the sellar region and right cavernous sinus with diffuse enhancement by gadolinium. The pituitary mass was removed by transsphenoidal surgery, and was pathologically identified as compatible to ACTH-producing pituitary adenoma by immunohistochemistry. RT-PCR analysis of total cellular RNA extracted from the resected adenoma revealed a relatively high expression level of dopamine D2 receptor (D2R) mRNA. Therefore, a long-acting D2R agonist, cabergoline (0.25 to 0.5 mg/week), was administered for the remnant adenoma, which gradually reduced ACTH levels in 90 days. In addition, cranial MRI exhibited shrinkage of the remnant pituitary mass after a 6-month treatment with cabergoline. This case demonstrates the efficacy of cabergoline to treat Cushing's disease caused by pituitary macroadenoma secreting aberrant ACTH molecules.
Journal of endocrinological investigation 12/2004; 27(11):1055-9. · 1.57 Impact Factor
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ABSTRACT: We introduce our training tools and system of neurovascular intervention. An in vitro cerebral vascular model was used for the young residents to understand the basic interventional techniques and devices. The model included several vascular lesions such as cerebral aneurysm, dural arterio-venous fistula, or carotid artery stenosis. Endovascular procedures in the model were performed under fluoroscopic or direct visual control, and consecutive haemodynamic changes were visualized by using digital subtraction angiography and direct observation. Thus, traineess could have an easy understanding of clinical conditions. New medical devices, such as platinum coils, were successfully implanted in the model under stable conditions. After the initial training using vascular model, the residents had started clinical experiences under the control of senior surgeons. Although it is difficult to describe usefulness of our clinical training, we believe that we provide enough good quality and quantity of clinical cases to the residents. Because our endovascular team has recently had150-200 interventional procedures every year, one resident can have experienced more than 100 cases per year. The qualification of a Board Certified Specialist of the Japanese Society of Intravascular Neurosurgery (JSIN) requires that the applicant must have experienced more than 100 cases for four years. So our residents can have enough case materials to qualify the board examination.
Interventional Neuroradiology 03/2004; 10 Suppl 1:107-12. · 0.56 Impact Factor
