Recanalisation of the internal carotid artery via the vasa vasorum after coil occlusion.

Antegrade recanalisation of a completely occluded internal carotid artery (ICA) via the vasa vasorum is extremely rare. Here, we report such a case after proximal endovascular coiling in a case of dissected (i.e. non-atherosclerotic) ICA. A 42-year-old man presented with thromboembolic stroke of the left frontal lobe owing to pseudo-occlusion of the left ICA manifesting as motor aphasia and right hemiparesis. There were abundant floating thrombi in the petrous portion of the left ICA. Because of good collateral flow in the left middle cerebral artery territory through the anterior communicating artery and external carotid artery system, endovascular coil embolisation of the left ICA was performed for prevention of further thromboembolic stroke. The patient showed progressive recovery following endovascular treatment, and was discharged with mild right hemiparesis 1 month later. He maintained a regimen of aspirin and physical rehabilitation. At follow-up, 38 months later, the patient was asymptomatic. Angiography demonstrated occlusion of the left ICA and multiple serpiginous vessels originating from the proximal internal and external carotid arteries and which filled the ICA distal to the occlusion. This case suggests that an ICA occluded by proximal coil embolisation-even in a non-atherosclerotic case-might be recanalised via the vasa vasorum.

[Does transradial cardiac catheterization affect coronary artery bypass grafting?].

Recent technological advances have enabled the miniaturization of catheters for coronary angiography and intervention. As a result of this advancement, the transradial approach is becoming more popular. The advantages of this approach include a lower incidence of access site complications, earlier patient ambulation, improved patient satisfaction, and lower cost. The cardiologists of our institute have introduced this technique without delay and have taken the initiative in Japan. However, there are concerns regarding the effect of transradial cardiac catheterization on the condition of radial artery grafts for coronary artery bypass grafting (CABG). In this study, we evaluated the influence of transradial catheterization on CABG. We retrospectively evaluated 157 patients who had undergone CABG using the radial artery. The condition of the grafts was assessed intraoperatively. Postoperative coronary angiography was carried out 3 months after the surgical intervention. The patency of the grafts was assessed by 2 cardiologists. One-quarter of the radial artery grafts were affected by transradial catheterization. Since most of them were located only at the puncture site, the graft itself was capable of being used for grafting after the resection of its affected distal end. The patency rate was not affected by transradial catheterization.

Endovascular treatment of aneurysmal subarachnoid hemorrhage associated with bilateral common carotid artery occlusion.

SUMMARY: Cases of aneurysm associated with the occlusion of both common carotid arteries are very rare.We present a case of ruptured aneurysms of the basilar bifurcation and posterior cerebral artery coexisting with bilateral common carotid artery occlusion, successfully treated by endovascular coil embolization with a double-balloon remodeling technique. Finally, we review the literature. A 62-year-old woman presented with severe headache; a computed tomography scan demonstrated subarachnoid hemorrhage. Angiography revealed that the bilateral common carotid arteries were occluded. The muscle branches of the vertebral arteries had anastomosed to the bilateral external carotid arteries. Bilateral posterior communicating arteries had developed and supplied the bilateral internal carotid arteries. Two aneurysms (a saccular aneurysm of the P1 portion of the left posterior cerebral artery and a wide-necked aneurysm of the basilar bifurcation) were also observed. Endovascular embolization of the aneurysms was successfully performed using a double-balloon remodeling technique. The patient made a full recovery after treatment, and the aneurysms remained obliterated 12 months after embolization. We believe that this is the first report of ruptured aneurysms associated with bilateral common carotid artery occlusion successfully treated by endovascular coiling. The double-balloon remodeling technique was useful for treatment of wide-necked basilar bifurcation aneurysm.

Unusual variant of persistent primitive hypoglossal artery.

Here, we present a case of an unusual variant of a persistent primitive hypoglossal artery, which was found incidentally during an examination for a hypertensive thalamic haemorrhage. The anastomotic vessel arose from the external carotid artery and joined the vertebral artery through the hypoglossal canal. The embryology of the anomaly is briefly discussed.

Early embolization for ruptured aneurysm in acute stage of subarachnoid hemorrhage with neurogenic pulmonary edema.

SUMMARY: Four cases of ruptured aneurysmal subarachnoid hemorrhage (SAH) presented with severe neurogenic pulmonary edema (NPE). On admission, two patients were grade IV and two were grade V according to Hunt and Hess grading. All patients needed respiratory management with the assistance of a ventilator. Three of them underwent endovascular treatment for the ruptured aneurysms within three days from onset after ensuring hemodynamic stability. Immediately after the endovascular treatment, lumbar spinal drainage was inserted in all the patients. The pulmonary edema findings disappeared rapidly after the respiratory management. The results were good recovery in two, and moderate disability in two. We concluded that early embolization of ruptured aneurysm and placement of spinal drainage is a satisfactory option for severe SAH with NPE.

Randomized, double-blind, placebo-controlled crossover trial of famotidine in patients with functional dyspepsia.

BACKGROUND: Histamine 2-receptor antagonists were used as a first therapy against functional dyspepsia. However, few clinical studies with famotidine for functional dyspepsia have been reported. AIM: To evaluate the effectiveness of famotidine for functional dyspepsia patients. METHODS: A multicentre, randomized, double-blind, placebo-controlled crossover trail was conducted. Patients diagnosed with functional dyspepsia by the Roma II criteria were included. Subjects were randomized into two groups, and received either famotidine or placebo as the first 4 weeks medication. After a 1-week washout period, they were switched to the other regimen for another 4 weeks. Evaluation was made prior to the start of study, upon completion of the first drug cycle, and the second drug cycle, by Gastrointestinal Symptoms Rating Scale for the seriousness of abdominal symptoms, and by Short Form-36 for the level of quality of life. RESULTS: Nineteen of 21 enrolled patients successfully completed this study. Significant improvement in Gastrointestinal Symptoms Rating Scale scores was observed in abdominal pain (P = 0.007), indigestion and reflux syndrome after famotidine treatment. Also quality of life scores showed significant improvement in body pain, vitality and general health perceptions after famotidine treatment. There was no improvement of symptoms and quality of life scores after administration of placebo. CONCLUSIONS: Famotidine was effective for improving symptoms and quality of life in functional dyspepsia patients.

Intrathecal application with liposome-entrapped Fasudil for cerebral vasospasm following subarachnoid hemorrhage in rats.

To date, the pharmacological approach to cerebral vasospasm following subarachnoid hemorrhage has been hampered in part by an inability to attain sufficiently high concentrations of vasodilator drugs in the cerebrospinal fluid (CSF). To overcome this limitation of current drug therapy, we have developed a sustained-release preparation of protein kinase inhibitor Fasudil. Cerebral vasospasm in rats was induced by double-injection method. Treated rats received 0.417 mg liposome-entrapped Fasudil via the cisterna magna and control rats received drug-free liposomes in the same manner. The diameter of the basilar artery was assessed at 7 days after the initial blood injection. Vasoconstriction of the rat basilar artery was significantly reduced in group treated with liposomal Fasudil compared to the control group (treated group: 87.7 +/- 6.18%, n= 10; control group: 66.3 +/- 9.82%, n = 10; ***P< 0.001). This new approach for cerebral vasospasm may have significant potential for use in the clinical setting.

Improved rat model for cerebral vasospasm studies.

While the rat has been used extensively in subarachnoid hemorrhage (SAH)-cerebral vasospasm studies, concerns exist whether this animal represents a usable model because its time course and pattern of cerebral vasospasm following SAH is not comparable to that observed in man. At present, our knowledge of the rat model is based almost exclusively on studies using a 'single hemorrhage' method. Since there is a positive correlation between severity of cerebral vasospasm, and volume of subarachnoid blood, an obvious question is whether the rat will show modifications in vascular responses when insulted by a second SAH. Here, an SAH was produced in rats using a 'double hemorrhage' method. Following SAH, cerebral arteries showed pathological alterations, significant decreases in luminal perimeter, and increases in arterial wall thickness, over a 7-day post-SAH period. The above vascular features are considered to be indicative of cerebral vasospasm and their presence over a 7-day post-SAH period represents a significant time extension when compared to a single hemorrhage. These modified vascular responses made the double hemorrhaged rat a much-improved animal model.

Transactivation of core binding factor alpha1 as a basic mechanism to trigger parathyroid hormone-induced osteogenesis.

During 28-day culture of bone marrow- and calvaria-derived osteoblasts, the constant presence of parathyroid hormone (PTH)(1-34) retarded differentiation and nodule formation (NF) in a dose-dependent fashion (C-phase). In contrast, addition of PTH(1-34) in late stage cultures (from day 10 to 21) accelerated NF (A-phase). The stable production of such an A-phase allowed us to study the mechanism of bone anabolic action of PTH(1-34). Subcellular localization studies of core binding factor alpha1 (Cbfa1) and reporter assays provided the results indicating that in the A-phase, PTH(1-34) triggers its bone anabolic action via enhancement of Cbfa1 transactivation. RT-PCR and Northern blot analyses revealed that alkaline phosphatase, osteocalcin and bone sialoprotein expression decreased in the C-phase and increased in the A-phase; however, expression of other bone proteins (Cbfa1, PTH/PTH-related peptide-receptor, osteopontin, collagen I alpha1, collagen I alpha2, vitamin K-dependent gamma-glutamyl carboxylase) did not change in a phase transition-related manner. Ovariectomized osteopenic mice, treated with PTH(1-34) (4 and 40 microg/kg, s.c., every other day, 4 or 6 weeks), recovered lost bone, displayed elevated nuclear localization of Cbfal in tibiae without alteration of its cytosolic level and exhibited upregulation of expressions of the same set of proteins (alkaline phosphatase, osteocalcin and bone sialoprotein) in femora. These results obtained by a concerted study in vitro and in vivo suggest that PTH triggers its osteogenic action via promotion of the transactivation of Cbfa1.

Thoracodorsal artery as a free arterial graft for myocardial revascularization.

When complete arterial revascularization of coronary circulation cannot be accomplished using the internal thoracic artery and other conventionally used arterial conduits, the thoracodorsal artery may be an excellent alternative. We report the use of the thoracodorsal artery as a free arterial graft in 3 patients, describe the harvesting technique, and review the anatomy.

Change in the diameter of the radial artery transradial intervention using a 6 French system in Japanese patients.

We examined the change in the diameter of the radial artery after transradial intervention (TRI) using a 6 French system in 50 Japanese patients in order to investigate whether the radial artery would be preserved after TRI. In all cases, the Allen test was normal and repeated puncture was possible at the TRI site 3 months after TRI. Moreover, the appearance of new stenosis or thinning throughout the radial artery at the TRI site was not seen. The diameter of the radial artery 3 months after TRI tended to be somewhat smaller at both the proximal and distal sites; however, there was not a statistically significant change between the diameter before and 3 months after TRI. Our results show that the radial artery will be preserved after TRI using a 6 French system in selected Japanese patients.

Cyclosporine reduces left ventricular mass with chronic aortic banding in mice, which could be due to apoptosis and fibrosis.

A tacit assumption in studies of left ventricular (LV) hypertrophy is that left ventricular/body weight (LV/BW) reflects the extent of myocyte hypertrophy. The goal of the current investigation was to determine if there was another explanation for the reduced LV/BW observed after inhibiting calcineurin with cyclosporine during the development of pressure overload LV hypertrophy as compared with animals that did not receive cyclosporine. Accordingly, we examined the prevalence of fibrosis and apoptosis and measured cell size in the hearts from mice at 1 and 3 weeks after transverse aortic banding with and without chronic cyclosporine. Although LV/BW, compared to aortic banded vehicle treated mice, was reduced by 30% in aortic banded cyclosporine treated mice, myocyte cross sectional area was similar in both banded groups (346+/-9 microm2 v 336+/-13 microm2). The volume percent interstitial fibrosis was greater in aortic banded cyclosporine treated animals (1.4+/-0.2%) compared with aortic banded vehicle treated animals (0.9+/-0.2%, P<0.05) or in sham animals (0.6+/-0.1%). Surprisingly, lesions including myocytes containing iron were observed and were most prominent in aortic banded cyclosporine treated animals. Apoptosis, quantitated with TUNEL staining as percent of myocytes, was increased in aortic banded cyclosporine treated animals at 7 days (1.6+/-0.4%) compared with aortic banded vehicle treated animals (0.4+/-0.1%, P<0.01) and was still increased at 21 days. Immunoblotting demonstrated a decrease in the phosphorylation of Akt and Bad, and also Bcl-2 levels were reduced in aortic banded cyclosporine treated animals at 7 days compared with aortic banded vehicle treated animals. These proteins protect against apoptosis, and support the concept that cyclosporine inhibited the calcineurin pathway, resulting in enhanced apoptosis. Thus, the decrease in LV/BW in the aortic banded cyclosporine treated animals actually may be due, at least in part, to cell loss and death, as reflected by the enhanced fibrosis and apoptosis and the focal iron deposits in myocytes.

Mitral exposure technique for redo cardiac surgery. A left mediastinal pleurotomy and minimal adhesiotomy method.

We report an improved mitral exposure technique for mitral valve re-operation. Left mediastinal pleurotomy through a median sternotomy achieves rotation of the heart and excellent exposure of the mitral valve allowing the apex to drop posteriorly. We employed this technique in redo mitral valve surgeries for over a 3-year period. This minimal adhesiotomy method is technically simple, safe and time-saving.

Percutaneous ulnar artery approach for coronary angiography: a preliminary report in nine patients.

The radial artery approach is becoming more popular for diagnostic cardiac catheterization and interventional procedures because of its lower incidence of access site complications and decreased patient discomfort after the procedure. However, Allen's test reveals inadequate blood supply through the ulnar artery to the hand, and therefore the approach does not seem to be suitable in 10%-30% of patients. Here we demonstrated a new percutaneous ulnar artery approach for coronary angiography in nine patients. We succeeded in obtaining an entry site into the left ulnar artery in seven patients. The average time for cannulation and that for catheterization procedure were comparable with those of the radial approach previously reported from other laboratories. Complications such as bleeding, loss of an ulnar pulse, ulnar nerve injury, and the formation of an aneurysm or fistula were not observed in any patient. The ulnar approach may be another technique that decreases patient discomfort and risk, while preserving the radial artery as a potential coronary bypass graft for surgical myocardial revascularization. Cathet Cardiovasc Intervent 2001;53:410-414.

Incadronate and etidronate accelerate phosphate-primed mineralization of MC4 cells via ERK1/2-Cbfa1 signaling pathway in a Ras-independent manner: further involvement of mevalonate-pathway blockade for incadronate.

Two types of bisphosphonates (BPs), incadronate (INC) and etidronate (ETI) accelerated phosphate (Pi)-primed mineralization of MC4 cells in a subnanomolar dose range. Intracellular signaling pathways involved were examined. 1) The effect of INC but not ETI was partially suppressed by two mevalonate (MVA) pathway metabolites, farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP). 2) The BP-like accelerating effect was produced by statins and also by Toxin B, a Rho GTPases-specific inhibitor. 3) INC induced Cbfa1-nuclear localization within hours; and in an in vivo experiment using ovariectomized mice, its 3 weeks dosing exhibited the same effect in tibial extracts. 4) BPs promoted luciferase expression in murine p1.3-osteocalcin gene 2-luc and p6-osteoblast specific element 2-luc transfected cells, just as MVA, FPP and GGPP did independently and additively to INC. 5) BPs activated extracellular signal-regulated kinase (ERK1/2) in a Ras-independent manner within 5 min, and Pi was found to sensitize MC4 cells to BPs. MVA and its metabolites also activated ERKs but in a Ras-dependent manner and additively to INC. Ras dependency was determined using N17Ras-transfected cells. A MEK (MAP kinase-ERK kinase)-specific inhibitor PD98059 alone partly and with FPP completely blocked INC-induced mineralization. The results suggest that BPs act on Pi-sensitized MC4 cells to accelerate mineralization via nonRas-MEK-ERK1/2-Cbfa1 transactivation pathway and INC additionally acts by inhibiting the MVA pathway.

Absence of BAT-26 instability in gastric intestinal metaplasia.

BAT-26 instability, a sensitive marker for the high-frequency microsatellite instability (MSI-H) phenotype, was analyzed in samples of gastric cancer and in adjacent intestinal metaplastic mucosae. Although all MSI-H gastric cancer samples showed BAT-26 instability, as assessed using 12 dinucleotide microsatellite markers, BAT-26 instability was not found in the adjacent intestinal metaplastic mucosa in any of the samples.

Oxyhemoglobin induces caspase-mediated cell death in cerebral endothelial cells.

Damaged endothelium is one of the pathological changes of the cerebral vasospastic vessels following subarachnoid hemorrhage. Our recent study shows that oxyhemoglobin (OxyHb) induces apoptosis in vascular endothelial cells. Apoptosis generally requires the action of various classes of proteases, including a family of cysteine proteases, known collectively as the caspases. This study was undertaken to investigate the activation of caspases and the efficacy of caspase inhibitors, z-IETD-fmk and z-LEHD-fmk, for oxyhemoglobin-induced apoptosis in vascular endothelial cells. Cultured bovine brain microvascular endothelial cells (passages 5-9) were used for this study. OxyHb (10 micromol/L) was added during the 24-72 h incubation with and without caspase-8 or - 9 inhibitors (z-IETD-fmk and z-LEHD-fmk). Counting surviving cells, DNA laddering, western blotting of poly(ADP-ribose) polymerase, and measurement of caspase activities were employed to confirm the cytotoxic effects of OxyHb and the protective effects of the caspase inhibitors. OxyHb produced cell detachment in a time-dependent manner and increased caspase-8 and -9 activities in the cells. z-IETD-fmk and z-LEHD-fmk (100 micromol/L) attenuated OxyHb-induced cell loss, DNA laddering, and proteolytic cleavage of PARP, although a lower concentration (10 micromol/L) of caspase inhibitors showed partial effects. OxyHb activates caspase-8 and -9 in cultured vascular endothelial cells, and blocking the action of the caspases with the inhibitors efficiently prevents loss of vascular endothelial cells from OxyHb-induced apoptosis in vitro. These results suggest that the caspase cascade participates in OxyHb-induced apoptosis.

Efficacy of intrathecal liposomal fasudil for experimental cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVE: To investigate the safety and efficacy of liposomal fasudil in a sustained-release form for the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: Eighteen rats were divided into three groups, each of which received 2.5 mg/kg of liposomal fasudil, 5 mg/kg of liposomal fasudil, or drug-free liposomes after SAH. Next, experimental SAH was induced in 15 dogs by injection of autologous arterial blood into the cisterna magna twice after baseline vertebral angiography. In six dogs, 0.94 mg/kg of liposomal fasudil was injected into the cisterna magna (treatment group). In four dogs, drug-free liposomes were similarly injected (placebo group), and the remaining five dogs were not treated with liposomal injection after SAH (control group). Angiography was repeated on Day 7, and cerebrospinal fluid was collected before the dogs were killed. RESULTS: A high dose of liposomal fasudil caused no significant changes in mean arterial blood pressure and did not induce seizures during the observation period. Gross and microscopic examination of the brains revealed no abnormalities, but severe vasospasm was noted in the rat basilar artery, mainly in the group treated with drug-free liposomes. Likewise, in the canine placebo and control groups, significant vasospasm occurred in the basilar artery on Day 7. In the treatment group, vasospasm in the basilar artery was significantly ameliorated (P < 0.01). In vivo, 90% of fasudil was released from liposomes in the cerebrospinal fluid. CONCLUSION: A single injection of intrathecal liposomal fasudil is safe and effective for the prevention of vasospasm in experimental SAH.