Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activator-related brain damages in mice.

Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA+nPt, and nPt. At 48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2h after tMCAO was also examined with hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and infarct volume as compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent signals in affected regions of tMCAO groups. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke.

Abnormal response to sodium channel blockers in patients with Brugada syndrome: augmented localised wall motion abnormalities in the right ventricular outflow tract region detected by electron beam computed tomography.

OBJECTIVE: To investigate the relation between the wall motion abnormalities and sodium channel abnormalities in cases of the Brugada syndrome. DESIGN: Consecutive prospective case-control study in a single hospital. SETTING: Tertiary referral centre. PATIENTS: 13 consecutive patients with Brugada syndrome and 13 age and sex matched control subjects. INTERVENTIONS: Each subject underwent electron beam computed tomography (EBT) and a 12 lead ECG before and after disopyramide injection. MAIN OUTCOME MEASURES: QRS width and the magnitude of ST segment elevation in the 12 lead ECG; wall motion by EBT. RESULTS: After disopyramide, EBT revealed deterioration of focal wall motion abnormalities in the right ventricular outflow tract region in eight of the 13 patients (62%). Prolongation of the QRS width after disopyramide injection in lead V2, which usually reflects the electrical activity in right ventricular outflow tract region, was greater in these eight patients (p < 0.01) than in the other five patients, in whom wall motion did not change after disopyramide. The degree of augmentation of ST segment elevation did not differ significantly between the two groups CONCLUSIONS: The deterioration of wall motion abnormalities in the right ventricular outflow tract region after disopyramide suggests the presence of functional abnormalities of the sodium channel. Some patients with Brugada syndrome may have arrhythmogenic substrates with abnormal responses to sodium channel blockers.

Complete genome sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7.

The complete genomic sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7 which optimally grows at 80 degrees C, at low pH, and under aerobic conditions, has been determined by the whole genome shotgun method with slight modifications. The genomic size was 2,694,756 bp long and the G + C content was 32.8%. The following RNA-coding genes were identified: a single 16S-23S rRNA cluster, one 5S rRNA gene and 46 tRNA genes (including 24 intron-containing tRNA genes). The repetitive sequences identified were SR-type repetitive sequences, long dispersed-type repetitive sequences and Tn-like repetitive elements. The genome contained 2826 potential protein-coding regions (open reading frames, ORFs). By similarity search against public databases, 911 (32.2%) ORFs were related to functional assigned genes, 921 (32.6%) were related to conserved ORFs of unknown function, 145 (5.1%) contained some motifs, and remaining 849 (30.0%) did not show any significant similarity to the registered sequences. The ORFs with functional assignments included the candidate genes involved in sulfide metabolism, the TCA cycle and the respiratory chain. Sequence comparison provided evidence suggesting the integration of plasmid, rearrangement of genomic structure, and duplication of genomic regions that may be responsible for the larger genomic size of the S. tokodaii strain7 genome. The genome contained eukaryote-type genes which were not identified in other archaea and lacked the CCA sequence in the tRNA genes. The result suggests that this strain is closer to eukaryotes among the archaea strains so far sequenced. The data presented in this paper are also available on the internet homepage (http://www.bio.nite.go.jp/E-home/genome_list-e.html/).

Prostaglandin I(2)/E(2) ratios in unilateral renovascular hypertension of different severities.

Differences between prostaglandins I(2) and E(2) in their renal synthesis and pathophysiological roles were investigated in unilateral renovascular hypertension of different severities in 18 patients: 6 with mild stenosis (<75% of the diameter) of the renal artery, 7 with moderate stenosis (75% to 90%), and 5 with severe stenosis (>90%). Before and after aspirin administration (10 mg/kg), renal venous and aortic plasma was assayed for 6-ketoprostaglandin F(1alpha) (instead of prostaglandin I(2)), prostaglandin E(2), and renin activity. In mild or moderate stenosis, the mean 6-ketoprostaglandin F(1alpha) level in renal venous plasma from the stenotic side was not different from that from the normal side or from aortic plasma. Prostaglandin E(2) levels and renin activity in such patients were higher on the stenotic side than on the normal side and higher in venous than in aortic plasma. Aspirin inhibited prostaglandin E(2) synthesis and suppressed renin release from stenotic kidneys and lowered blood pressure as the renin activity decreased in patients with mild or moderate stenosis. In severe stenosis, levels of 6-ketoprostaglandin F(1alpha) and prostaglandin E(2) were higher on the stenotic side than on the normal side and higher in venous than in aortic plasma. Aspirin inhibited the synthesis of both prostaglandins and suppressed renin release from the stenotic kidney. In patients with unilateral renovascular hypertension with mild or moderate stenosis of the renal artery, prostaglandin E(2), rather than I(2), seems to contribute to further acceleration of renin release. Prostaglandin I(2) may increase and participate in further renin release when the stenosis is severe.

Localized right ventricular morphological abnormalities detected by electron-beam computed tomography represent arrhythmogenic substrates in patients with the Brugada syndrome.

AIMS: This study was designed to determine, using electron-beam CT, whether there are morphological abnormalities in patients with the Brugada syndrome and to elucidate the relationship between those abnormalities and arrhythmogenesis. METHODS AND RESULTS: Twenty-six consecutive patients with the Brugada syndrome and 23 age- and gender-matched control subjects (controls) were evaluated for morphological abnormalities using electron beam CT. Electron beam CT demonstrated morphological abnormalities of the right ventricle in 21 (81%) of 26 patients, but in only two (9%) of 23 controls. The sites of morphological abnormalities were the right ventricular outflow tract area in 17 patients and the inferior wall of the right ventricle in four patients. Of the seven patients with monoform premature ventricular contractions recorded only in the acute phase, four of the five patients with premature ventricular contractions from the right ventricular outflow tract area had morphological abnormalities in the right ventricular outflow tract area, and the other two patients with premature ventricular contractions from the inferior wall of the right ventricle had morphological abnormalities in the inferior wall of the right ventricle. CONCLUSION: The sites of morphological abnormalities detected by electron beam CT in patients with the Brugada syndrome were related to the origins of premature ventricular contractions recorded only in the acute phase, which may trigger ventricular fibrillation. These morphological abnormalities may be related to arrhythmogenic substrates in patients with the Brugada syndrome.

Action kinetics of a prothoracicostatic peptide from Bombyx mori and its possible signaling pathway.

A prothoracicostatic peptide (PTSP), purified from the brains of Bombyx mori, was found to inhibit ecdysteroidogenesis in the prothoracic glands (PGs) of this insect. This peptide was active at inhibiting ecdysteroidogenesis in the PGs at concentrations higher than 23 nM and glands incubated in 230 nM PTSP in vitro exhibited maximum inhibition of ecdysteroid production. By incubating PGs in vitro at different incubation periods it was observed that the first statistically significant inhibitory effect occurred after 30 min incubation in the presence of PTSP. Transferral of PGs from a medium with PTSP to a medium without PTSP resulted in the resumption of ecdysteroid production. Statistically significant inhibition of ecdysteroid production by PTSP was observed only in day 6 and in day 3 PGs of the 5th instar. The extracts of day 6 glands incubated in the presence of PTSP did not contain elevated amounts of ecdysteroid relative to controls after the incubations, indicating that PTSP does not inhibit the secretion, rather the synthesis, of ecdysteroid in the PGs. The presence of PTSP completely blocked the increased ecdysteroid production via L-type Ca(2+) channel activation by S(-)*Bay K 8644. There was no inhibition of ecdysteroid production by PTSP with glands incubated in Ca(2+)-free medium. The combined results suggest that PTSP regulates ecdysteroid synthesis only during specific stages of the 5th instar through a mechanism that likely involves the blocking of Ca(2+) influx through voltage-sensitive Ca(2+) channels in the PG cells of B. mori.

A system for computer-assisted design of stent-grafts for aortic aneurysms using 3-D morphological models.

A three-dimensional model was constructed from helical CT images for abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). A stent-graft was designed and positioned endoluminally on the computer. One hundred and nine stent-grafts for 101 patients were designed by this method and deployed well in all patients. The design time was reduced from 4 to 0.5 hr.

A histological study on the mechanism of epidermal nuclear elongation in electrical and burn injuries.

Epidermal nuclear elongation is one of the most important signs for the diagnosis of electrical injury. In this study, we investigated the mechanism responsible for this phenomenon by comparing the findings from burn injuries and those from contusions. Electrical and burn injuries were made in the dorsal skin of rats using energy ranging from 100 to 790 joules for electrical injury, and 170-690 joules for burn injury. Contusions were also made by compressing the skin with a vice. In electrical and burn injuries, the dermis under the epidermal elongated nuclei was homogeneous and without empty spaces between collagen bundles and the number of dermal fibroblasts per 0.01 mm2 below the damaged epidermis decreased significantly (P < 0.05). The incidence of this change correlated with the depth of denatured dermal collagen fibres and in both types of injuries, dermal cells had no nuclear antigenicity for ubiquitin. The width of the injured epidermis with nuclear elongation decreased significantly (P < 0.05) and the elongated nuclei were parallel to the basal membrane. In electrical injury however, nuclear elongation occurred more frequently near the external root sheath. Nuclear elongation of fibroblasts and external root sheath cells was also found, but those of sebaceous gland cells were not detected. Epidermal elongated nuclei were also found in contusions. The evidence strongly suggests that epidermal nuclear elongation in electrical and burn injuries is due to dermal expansion by heat.

Case report: stent placement in support of intravascular ultrasound in a woman with atypical lower abdominal aortic stenosis.

Localized stenosis confined to the distal abdominal aorta near the bifurcation is an atypical manifestation of atherosclerosis, particularly in a woman. We report the case of a middle-aged woman who presented with a focal stenosis accompanied by heavy calcification in the distal abdominal aorta. The lesion was successfully treated by Palmaz stent placement under intravascular ultrasound guidance.

Estimation of myocardial perfusion and viability using simultaneous 99mTc-tetrofosmin--FDG collimated SPECT.

UNLABELLED: This study was designed to elucidate the usefulness of crosstalk correction for dual-isotope simultaneous acquisition (DISA) with 99mTc-tetrofosmin and FDG in estimating myocardial perfusion and viability. METHODS: Eighteen patients with coronary artery disease were studied. First, SPECT was performed with a low-energy high-resolution collimator after a single injection of 99mTc-tetrofosmin (single 99mTc-tetrofosmin). Second, PET and DISA with an ultra-high-energy collimator were performed after glucose loading and an injection of FDG. DISA was designed to operate with simultaneous 3-channel acquisition, and weighted scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak was performed by modification of an existing dual-window technique. The FDG SPECT images were compared with the images obtained by PET. Both crosstalk-corrected and uncorrected 99mTc-tetrofosmin images were generated and compared with the single 99mTc-tetrofosmin images. RESULTS: Regional percentage uptake of FDG agreed well between DISA and PET. However, regional percentage uptake of 99mTc-tetrofosmin was generally higher on the uncorrected 99mTc-tetrofosmin images than on the single 99mTc-tetrofosmin images, especially in areas of low flow (percentage count of 99mTc-tetrofosmin > or = 50%). The crosstalk correction contributed to improving the agreement between regional percentage uptakes and significantly improved the detectability of myocardial perfusion-metabolism mismatching. CONCLUSION: With 3-channel acquisition and weighted-scatter correction of crosstalk from the 18F photopeak to the 99mTc photopeak, DISA with 99mTc-tetrofosmin and FDG is feasible for assessing regional myocardial perfusion and viability.

Use of ECG-gated SPET to assess the evolution of perfusion after acute myocardial infarction.

Serial improvement in myocardial perfusion images from the acute or subacute to the chronic stage of acute myocardial infarction (AMI) has been attributed to improved coronary microcirculation or cell function after acute ischaemia and reperfusion. However, conventionally used non-gated imaging cannot eliminate the effect of improved regional contraction. We studied the possibility that such scintigraphic improvement reflects the functional recovery by using ECG-gated myocardial perfusion imaging with technetium-99m sestamibi. Nineteen AMI patients who received acute reperfusion therapy underwent ECG-gated myocardial single-photon emission tomography (SPET) in the subacute and chronic stages. Serial changes in regional image count distributions were analysed on the non-gated, end-diastolic (ED) and end-systolic (ES) images by using segmental mean percent peak activity (MPA) and AMPA (MPA in chronic stage - MPA in subacute stage) on bull's-eye polar maps. These changes were compared with those in regional wall motion on biplane left ventriculography (LVG) from the acute (just after reperfusion) to the chronic stage. During the follow-up, regional wall motion remained the same in 42 (group A) but improved in 17 (group B) of the 59 ischaemically compromised segments. MPA showed no improvement in group A but significant improvement in group B on the non-gated and ES images (P<0.0001 and P<0.001, respectively). However, MPA on the ED images showed no improvement in either group. In the follow-up study of AMI, the scintigraphic improvement documented on the non-gated myocardial images appears to be mainly related to the recovery of wall thickening and not to a real improvement in myocardial perfusion. Therefore, ECG-gated myocardial imaging, which enables simultaneous assessment of changes in perfusion and contraction, is preferable to conventional non-gated imaging for follow-up of AMI.

Preoperative demonstration of the Adamkiewicz artery by magnetic resonance angiography in patients with descending or thoracoabdominal aortic aneurysms.

OBJECTIVE: Investigating the possibility of magnetic resonance angiography (MRA) to visualize the Adamkiewicz artery of as a preoperative study of thoracic aortic aneurysms. METHODS: From February 1998 to March 1999, 26 consecutive patients who had aneurysms of the thoracoabdominal or descending aorta underwent preoperative MRA to visualize the Adamkiewicz artery. Mean age was 60.5+/-11.5 years. Fifteen patients had non-dissecting aneurysm and 11 had aortic dissections. Nineteen patients underwent replacement of the aneurysms, four patients underwent endovascular stent-graft repair, and three patients were discharged without treatment of aneurysm. MRA was performed on a 1.5-T system (Magnetom, Siemens) and data acquisition was repeated two times following injection of gadolinium-DTPA. Source images were reconstructed with multiplanar reconstruction and maximum intensity projection. Criteria for the Adamkiewicz artery of were that the artery ascends from the dorsal branch of the intercostal or lumbar artery to the anterior mid-sagital surface of the spinal cord in the early phase. RESULTS: The Adamkiewicz arteries were demonstrated in 18 patients (69%). These arteries were originated from the left intercostal or lumbar arteries in 13 (72.2%) patients and from the right in 5 (27.8%) and from the Th8 branch in three, Th9 in seven, Th10 in two, Th11 in four, and L1 in two. All patients had graft replacement of the aorta using a partial bypass. All intercostal or lumber arteries, which were visualized as the origin of the Adamkiewicz artery, were reattached to the grafts. No spinal cord injury occurred. CONCLUSION: Preoperative detection the Adamkiewicz artery was possible by MRA and was very useful to reduce the incidence of ischemic injury of the spinal cord during surgery of the thoracoabdominal or descending aorta.

Phylogeny of the lady fern group, tribe Physematieae (Dryopteridaceae), based on chloroplast rbcL gene sequences.

Nucleotide sequences of the chloroplast gene rbcL from 42 species of the fern tribe Physematieae (Dryopteridaceae) were analyzed to gain insights into the inter- and intrageneric relationships and the generic circumscriptions in the tribe. The phylogenetic relationships were inferred using the neighbor-joining and maximum-parsimony methods, and both methods produced largely congruent trees. These trees reveal that: (1) Athyrium, Cornopteris, Pseudocystopteris, and Anisocampium form a clade and Athyrium is polyphyletic; (2) Deparia sensu lato is monophyletic and Dictyodroma formosana is included in the Deparia clade; (3) Diplaziopsis forms a clade with Homalosorus, which is isolated from the other genera of the Physematieae; (4) Monomelangium is included in the monophyletic Diplazium clade; and (5) Rhachidosorus is not closely related to either Athyrium or Diplazium.

MRA of the Adamkiewicz artery: a preoperative study for thoracic aortic aneurysm.

PURPOSE: The purpose of this work was to investigate the ability of MR angiography (MRA) to visualize the Adamkiewicz artery (AKA) as a preoperative study of thoracic aortic aneurysm to prevent ischemic injury of the spinal cord. METHOD: Twenty-six patients scheduled for surgical or endovascular stent-graft repair of thoracic aortic aneurysm were studied with a three-dimensional contrast MRA. Data acquisition was repeated two times following injection of Gd-DTPA. Source images were processed with multiplanar reconstruction and maximum intensity projection. RESULTS: The AKA was identified in 69% (18/26). In three patients, selective angiography of the intercostal artery confirmed the AKA at the same level and side predicted by MRA. The anterior spinal artery and the anterior medullary vein were observed in 50% (13/26) and 65% (17/26), respectively. CONCLUSION: Contrast MRA is a promising technique to visualize the AKA noninvasively as a preoperative evaluation of thoracic aortic aneurysms.

Attenuation correction for cardiac dual-head gamma camera coincidence imaging using segmented myocardial perfusion SPECT.

UNLABELLED: The diagnostic accuracy of cardiac FDG imaging obtained with the dual-head coincidence gamma camera (DHC) is impaired by artifacts induced by nonuniform attenuation. This study proposed a new method (registration and segmentation method for attenuation correction [AC-RS]) to correct these attenuations in the chest region without the need for additional hardware or expensive transmission scanning equipment. METHODS: Before DHC imaging, 99mTc-tetrofosmin SPECT was performed using dual-energy acquisition from both the photopeak and Compton scatter windows. The scatter window images of the 99mTc-tetrofosmin were then registered 3-dimensionally with the cardiac DHC images and segmented into anatomic regions to obtain body and lung contours by applying the optimal threshold method on localized histograms. Theoretic attenuation coefficient values were assigned to the corresponding anatomic regions, and the DHC emission images were reconstructed using these attenuation correction factors. The results were quantitatively evaluated by imaging a cardiac phantom filled with a uniform solution and placed in a chest phantom. Eight nondiabetic subjects were also examined using this technique, and the results were compared with those of measured attenuation-corrected PET images. RESULTS: Use of this technique in phantom and clinical studies decreased the degree of artifacts seen in the inferior wall activity and corrected the emission images. When the results were compared with those of PET scans, the regional relative counts of the uncorrected DHC scan did not correlate with the results of the PET scan. However, the regional relative counts of the AC-RS-corrected DHC scan exhibited a linear correlation with the results of the PET scan (r = 0.73; P < 0.001). CONCLUSION: Reasonably accurate attenuation-corrected cardiac DHC images can be obtained using AC-RS without the need for transmission scanning.

Brain fluorine-18 fluorodeoxyglucose imaging with dual-head coincidence gamma camera: comparison with dedicated ring-detector positron emission tomography.

BACKGROUND AND PURPOSE: Dual-head coincidence gamma camera (DHC) imaging has been proposed as an alternative to dedicated ring-detector positron emission tomography (dr-PET) for clinical fluorodeoxyglucose (FDG) studies. The purpose of this investigation was to assess the quality of DHC images in FDG studies of the human brain. METHODS: Seven healthy volunteers and 12 patients with various cerebral disorders underwent consecutive brain dr-PET and DHC with FDG. All sets of images were compared semiquantitatively using regions of interest. RESULTS: Cortical count ratios to the cerebellum on DHC and dr-PET images did not differ significantly among the volunteers, except in the superior frontal cortex and thalamus. In all studies including those of cerebral disorders, the mean cortical-to-cerebellar ratios of DHC and dr-PET images correlated closely. CONCLUSION: FDG imaging with DHC delineated the metabolic distribution of glucose in the brain as well as dr-PET did, except in the superior frontal cortex and thalamus. Therefore, DHC may be a dedicated cost-effective means of detecting metabolic abnormalities in the brain.

An application of PCR-single strand conformation polymorphism to MN genotyping.

A PCR-based genotyping of MN blood group system was investigated for DNA samples taken from a population of 409 northern Japanese. DNA fragment (257bp) including exon 2 of glycophorin A (GPA) gene, in which encodes the determinants of MN antigens, was specifically amplified. On the analysis of PCR-single-strand conformation polymorphism (PCR-SSCP) for M alleles, band patterns of M(G) and M(T) were easily discriminated each other. For N alleles, three band patterns were observed, and we tentatively named these alleles as N(1), N(2) and N(V). The N(1) allele appeared predominantly and N(2) had two base substitutions at 1st (C-->A) and 56th (C-->T) in exon 2 of N(1). The other N(V), which was detected from a pair of a mother and her child, possessed a single base substitution at 23rd (A-->G) in intron 2. The allele frequencies of M(G), M(T), N(1) and N(2) were 0.4450, 0.0978, 0.4303 and 0.0269, respectively. The polymorphism information content and the probability of paternity exclusion by this MN genotyping were estimated to be 0.5252 and 0.3219, respectively.

Histologic comparison of coronary and iliac atherectomy tissue from cases of in-stent restenosis.

Pathologically, restenotic lesions after stenting were investigated by use of atherectomized tissues of seven coronary and seven iliac arteries. The mean interval of the stent deployment to restenosis was 9.1 months for the coronary artery and 33.7 months for the iliac artery, indicating a 3.7-fold longer interval for the latter. This study does not include cases of acute thrombotic occlusion. The atherectomized tissue from restenotic coronary arteries showed abundant neointima with alpha-actin-positive and ultrastructually synthetic-type smooth muscle cells in a rich myxomatous extracellular matrix. In the iliac arteries, the predominant component of restenosis consisted of organized thrombi. The neointima of the iliac arteries was mature, and only a small amount of spindle cells were observed in the hyalinized matrix. The tissue that developed restenosis after stenting was different in the coronary and iliac arteries included in this series. This study on the atherectomized tissue suggests that even in the chronic stage, a major cause of in-stent restenosis among the larger caliber vessels such as the iliac artery is not neointima but stent thrombosis.

[MR angiography of steno-occlusive lesions of intracranial arteries: a comparative study between turbo MRA and conventional MRA].

PURPOSE: To compare the quality and diagnostic accuracy of images of intracranial steno-occlusive lesions obtained by conventional MRA and turbo MRA reconstructed using the zero-filled interpolation technique in the slice-select direction. MATERIALS AND METHODS: Eighteen patients with suspected steno-occlusive lesions of the intracranial arteries were studied with two types of three-dimensional time-of-flight angiography and conventional digital subtraction angiography. In total, 45 steno-occlusive lesions were quantitatively measured using calipers and correlated with DSA stenosis. A phantom that simulated vessels with stenosis was also imaged using the two types of MRA under the same conditions as those employed in the clinical study. RESULTS: Compared with conventional MRA, turbo MRA reduced the jaggedness of vessels and offered appearances more similar to those of DSA in the antero-posterior and lateral views. The severity of stenosis was classified into five grades based on the percentage of occlusion: not significant (0-24%), mild (25-49%), moderate (50-74%), severe (75-99%), and occlusive (100%). Neither turbo MRA nor conventional MRA showed any discrepancy from DSA above grade-1 stenosis. CONCLUSION: The advantage of turbo MRA is its ability to reduce the jaggedness of vessels on conventional MRA, and to simplify the recognition of vessel contours without prolonging acquisition time. Turbo MRA and conventional MRA have equally high diagnostic accuracy for steno-occlusive lesions.