The efficacy of eribulin mesylate for patients with cutaneous angiosarcoma previously treated with taxane: a multicentre prospective observational study.

BACKGROUND: Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established. METHODS: We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m-2 on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment. RESULTS: We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. CONCLUSIONS: ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.

Possible presence of hydrophilic SO3H nanoclusters on the surface of dry ultrathin Nafion® films: a positron annihilation study.

Solutions of Nafion® with an ion exchange capacity (IEC) of 0.91 meq g(-1), which are on the verge of the formation of SO(3)H nanoclusters, were spin coated on silicon (Si), glassy carbon (GC) and platinum/silicon (Pt/Si) substrates to form films of up to 256 nm thickness. Nanostructure of the films was studied using Doppler broadening of annihilation radiation (DBAR), positron annihilation lifetime (PAL), X-ray photoelectron spectroscopy (XPS), an atomic force microscope (AFM) and contact angle measurements. Contact angles as low as 10 degrees indicate that the surface of dry ultrathin Nafion® films on Si is highly hydrophilic. XPS data of 10 nm thick, ultrathin film on Si show that oxygen concentration is enhanced and the SO(3)H group concentration, in other words, IEC on the surface is much higher than other films. The S parameter measured by DBAR of an ultrathin Nafion® film on Si is much higher than that of the films on the other substrates. We consider that a large number of hydrophilic, reversed micelle like SO(3)H groups are on the surface of the ultrathin Nafion® film on Si but not on the surface of other films. Positrons implanted into the film are trapped by the SO(3)H clusters, annihilating with the electrons of oxygen and exhibit the high S parameter. The SO(3)H concentration on the surface of thin Nafion® films on GC and Pt/Si substrates may not be so high as the threshold for the formation of a large number of SO(3)H clusters. Positrons implanted into the films annihilate mostly with fluorine atoms, resulting in a low S parameter. The film-substrate interaction plays an essential role in nanostructuring of Nafion® thin films, which may also be the case for Nafion® on the catalysts of polymer electrolyte fuel cells.

Positronium formation in aromatic polymer electrolytes for fuel cells.

We measured the yield of positronium (Ps) in sulfonated aromatic proton conducting membranes for the polymer electrolyte fuel cell (PEFC) with and without -SO(2)- in their chemical structures by positron annihilation lifetime spectroscopy (PALS). It was observed that Ps formation is almost totally inhibited in the polymers without -SO(2)- such as sulfonated poly(ether ether ketone) (SPEEK). On the other hand Ps favorably forms in those with -SO(2)- as sulfonated polyether sulfone (SPES), which is due to the anti-inhibition effect of -SO(2)-. The high probability of Ps formation in these polymers enables the study of the free volume and the mechanism of gas permeation by PALS.

Effects of ion exchange on the free volume and oxygen permeation in Nafion for fuel cells.

Variations of the free volume, O2 permeability, and structure of the Nafion membrane upon ion exchange of H+ with Na+ and K+ were studied. The free volume was quantified using the positron annihilation lifetime (PAL) technique, whereas the polymer structure was characterized by dynamic mechanical analysis (DMA), nanoindentation, and wide-angle X-ray diffraction (WAXD). It was found that the ion exchange significantly expands the free volume and at the same time decreases the O2 permeability. This is opposed to the simple free volume model in which the structure with less open volume is more amenable to lower permeability. Comparison of experimental data collected by different techniques revealed that not only the free volume but also the polymer stiffness plays an essential role in O2 permeation.

Analysis of localization of adult T-cell leukemia-derived factor in the transient ischemic rat retina after treatment with OP-1206 alpha-CD, a prostaglandin E1 analogue.

Prostaglandin E1 (PGE1) is commonly used in therapy for obstructive diseases, including ischemic retinopathy, in which pathogenetic reactive oxygen intermediates are responsible. However, the mechanism(s) of PGE1 in reducing tissue damage is still unclear. Adult T-cell leukemia-derived factor/human thioredoxin (ADF) is induced by oxidative stresses and has protective activity against oxidative cellular injury. To evaluate the possible involvement of ADF in the tissue-protective effect of PGE1, we analyzed ADF expression immunohistochemically using a rat transient retinal ischemia model. Rats were treated orally with 300 micrograms/kg/day OP-1206 alpha-cyclodextrin clathrate (OP-1206), a stable PGE1 analogue, for 14 days after photodynamic retinal vascular thrombosis by rose Bengal. Rats without any OP-1206 treatment were used as controls. In the OP-1206-treated rats, minimal retinal atrophy due to ischemia/reperfusion was observed histologically up to 14 days, whereas in the non-treated rats the inner layer of the retina became markedly atrophic. In parallel with the histological change, after 14 days following thrombosis ADF immunoreactivity was preserved on retinal pigment epithelial cells in the OP-1206-treated rats, whereas it was diminished in the non-treated rats. These findings suggest an important role for ADF in the OP-1206-dependent suppression of retinal tissue damage caused by oxidative insult.

Basic fibroblast growth factor stimulates 3H-thymidine uptake in retinal venular and capillary endothelial cells in vivo.

Recent studies have found basic fibroblast growth factor (bFGF), an angiogenic peptide, in retina and have suggested that bFGF is responsible for retinal vascular proliferation. To test the hypothesis that bFGF stimulates 3H-thymidine uptake in retinal vascular cells in vivo, we injected bFGF (100 ng) into the vitreous cavity of six cats at 0 hr and again at 24 hr. Eight control eyes received boiled bFGF or no injection. After 46 hr, 3H-thymidine was injected into the vitreous cavity of all eyes and 2 hr later the eyes were enucleated. Intense 3H-thymidine uptake was seen in eyes with bFGF (56 +/- 20 SD positive cells per section) but not in control eyes (7-10 positive cells per section (P less than 0.001). Trypsin digest preparations showed that the thymidine uptake was predominantly in the venular (89%) and capillary (10%) endothelium and not in arterioles (1%) (P less than 0.001). The data suggest that retinal venular endothelial cells respond preferentially to exogenous bFGF, and in part may explain their prominent role in the neovascular process. In a second group of experiments to test the hypothesis that retinal ischemia releases a diffusable factor similar to bFGF that can cause 3H-thymidine uptake in retinal vascular cells, we created branch retinal vein occlusion in six cat eyes. The fellow eyes received no injections. In the eyes with branch vein occlusion there was an intense 3H-thymidine uptake within the distribution of the occluded vein (84 +/- 77 SD positive cells per section), but none in the areas outside the occluded vein (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Mitochondrial induction of adult T cell leukemia derived factor (ADF/hTx) after oxidative stresses in retinal pigment epithelial cells.

PURPOSE: Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhibits scavenging activity with reactive oxygen intermediates. In their previous study, the authors found that after transient retinal ischemia, the expression of thioredoxin in rat retinal pigment epithelium (RPE) layer increased markedly. The present investigation is to determine intracellular ADF localization in RPE after transient ischemia and in cultured human RPE cells after oxidative insult by H2O2. METHODS: The authors employed immunoelectron microscopy to examine ADF localization in RPE. Labeling density analysis was performed to supplement the main observation in the experiment of transient retinal ischemia. 3-(4,5-dimethylthiazol-2yl)-2-5-diphenyltetrazolium bromide (MTT) assay was performed to verify the protective role of recombinant ADF (rADF) against H2O2. RESULTS: In immunogold electron microscopy, sparse ADF-positive labeling was seen in the cytosol and mitochondria in normal rat RPE and in untreated cultured RPE cells. After oxidative stress, it was concentrated in mitochondria in both groups. MTT assay proved that rADF protected cultured RPE from the toxicity of H2O2. CONCLUSIONS: This study shows the induction of ADF/hTx in mitochondria of RPE after oxidative stresses and its protective effect on cultured RPE exposed to H2O2. The data indicate the possibly important role of ADF/hTx in the protection of retinal cells from the oxidative stresses associated with retinal ischemic disease and probably with regular visual activity.

Effect of gonadal steroids on gonadotropin-releasing hormones stimulated human chorionic gonadotropin release by trophoblast cells.

The effect of gonadal steroids on basal and GnRH-stimulated hCG release was studied using collagenase-dispersed trophoblast cells from early pregnancy. Both GnRH and a GnRH superagonist, Buserelin, stimulated hCG release with a similar dose dependency. Progesterone (0.1 to 10 micrograms/ml) inhibited GnRH-stimulated hCG release in a dose dependent manner as well as basal hCG release. Relatively high concentrations of estradiol (10 micrograms/ml) stimulated both basal and GnRH-mediated hCG release and antagonized the inhibitory effect of progesterone on hCG release at 1 micrograms/ml as well as RU486 (1 microgram/ml). These results indicate that progesterone has an important role in both basal and GnRH-mediated hCG regulatory system in the placenta.

Markedly increased unilateral intraocular pressure during hemodialysis in a patient with ipsilateral exfoliative glaucoma.

PURPOSE: To report a man with markedly increased intraocular pressure in a unilateral exfoliated eye during hemodialysis. METHOD: Case report. RESULTS: A 75-year-old man with unilateral exfoliative glaucoma complained of blurred vision in his right eye during hemodialysis. The blurred vision always occurred during hemodialysis, and the intraocular pressure was increased during hemodialysis. The average increase in intraocular pressure during hemodialysis in the right eye was 22.5 mm Hg, and the intraocular pressure in the left eye remained in the normal range during hemodialysis. Argon laser trabeculoplasty was performed on the right eye, and a decrease in intraocular pressure was attained. CONCLUSION: Physicians must be alert to intraocular pressure increases in these eyes during hemodialysis.

Surgical outcome of combined trabeculotomy and cataract surgery.

PURPOSE: To evaluate the efficacy of combined trabeculotomy and cataract surgery in lowering intraocular pressure and improving visual acuity in adults with primary open-angle glaucoma. PATIENTS AND METHODS: A consecutive series of 141 eyes with primary open-angle glaucoma or ocular hypertension was prospectively recruited. One hundred five eyes with visual field defects were treated by trabeculotomy combined with phacoemulsification and intraocular lens implantation (TPI group), and 36 eyes without visual field defects underwent cataract surgery (PI group). Patients in the TPI and PI groups were followed for more than 6 months after surgery (578.1 +/- 35.8 days and 616.0 +/- 58.5 days, respectively). The intraocular pressure reductions after surgery were compared between the groups to evaluate the effect of combined trabeculotomy and cataract surgery. Visual acuity and the complication rate in the two groups were secondary outcomes. The success probabilities of both groups were evaluated by Kaplan-Meier life table analysis with log rank test. RESULTS: A significant intraocular pressure reduction was observed in the TPI and PI groups up to 3 years and up to 1 year and 6 months after surgery, respectively; the magnitude of the reduction was significantly larger in the TPI group up to 3 years after surgery. The success probabilities of TPI group for intraocular pressure control under 21, 17, and 15 mm Hg were 95.8%, 58.7%, and 30.0%, respectively, 1 year after surgery, and 84.9%, 29.5%, and 13.5%, respectively, 3 years after surgery; the success probabilities were significantly higher than those of the PI group. Of 105 eyes, 104 (99.0%) had visual acuity equal to or better than the baseline acuity 3 months after combined trabeculotomy and cataract surgery. CONCLUSION: Combined trabeculotomy and cataract surgery normalizes intraocular pressure and improves visual acuity in adults with glaucoma and coexisting cataract.

Egress route of emulsified 20 centistokes silicone oil from anterior chamber of rabbit.

Silicone oil is used in recent clinical practice, however, it may cause adverse reactions in the eyes. When the high viscosity silicone oil is contaminated with low molecular weight silicone oil, the contamination may cause ocular toxicity or elevation of the intraocular pressure. To obtain information on the distribution of this preparation, emulsified 20 centistokes silicone oil was injected into the anterior chamber of rabbit eyes. The silicone oil droplets were visualized by light and electron microscopy by using oil soluble phthalocyanine blue. This copper containing dye remains in the tissue after removal of the silicone oil by organic solvents. Two and 4 weeks after an injection, the silicone emulsion was observed as numerous small vacuoles with blue precipitate at the margin of vacuoles within elongated trabecular endothelial cells, fibroblasts along the route of uveoscleral outflow and cells of the iris. Three hours after the injection, only a few vacuoles were present in these cells. These results demonstrated that the emulsified silicone oil leaves the anterior chamber through the conventional and unconventional routes. Phagocytosis by the trabecular endothelial cells and fibroblasts along the uveoscleral route caused an accumulation of the emulsified silicone oil in these cells. With chronic exposure to emulsified silicone oil, changes in the trabecular meshwork may lead to a reduction in the outflow of aqueous humor and cause glaucoma.

Superoxide dismutases in retinal degeneration of WBN/Kob rat.

PURPOSE: To examine the relationship between retinal degeneration and superoxide dismutase (SOD) in the degenerative retina of the WBN/Kob rat. METHODS: The retinas of 4-week-old and 10-month-old WBN/ Kob rats were examined with immunohistochemistry and immunoblotting. Wistar Kyoto rats were used as controls. RESULTS: Retinal degeneration began 4 weeks after birth. Four-week-old WBN/Kob rats showed no manganese superoxide dismutase (Mn-SOD) immunoreactivity in the photoreceptor inner segments or copper-zinc superoxide dismutase (CuZn-SOD) immunoreactivity in the outer nuclear layer or photoreceptor inner segments. Control 4-week-old Wistar Kyoto rats showed positive immunoreactivities at these sites. CONCLUSIONS: The retinal degeneration of WBN/Kob rats begins in the outer retina. The lack of SODs in the outer retina may contribute to retinal degeneration in the WBN/Kob rats.

TNP-470 (a fungus-derived inhibitor of angiogenesis) reduces proliferation of cultured fibroblasts isolated from primary pterygia: a possible drug therapy for pterygia.

PURPOSE: To study drug therapy for pterygium, especially the effect of a fumagillin analog, TNP-470, a potent anti-angiogenic compound, on the growth of cultured fibroblasts obtained from primary pterygia and normal human conjunctiva. METHODS: Cultured pterygium fibroblasts (PF) were exposed to different concentrations of TNP-470 every other day for 7 days (Treatment A) and to a single dose before 4 days of culture (Treatment B). Human normal conjunctival fibroblasts (HCF) were treated with TNP-470 every other day for 7 days. The cells were observed daily by phase contrast microscopy. Cell proliferation was assessed by counting cells with a hemocytometer. Trypan blue uptake was used to determine cell viability at harvest. RESULTS: TNP-470 induced a significant inhibition of PF and HCF proliferation in a dose-dependent manner (P < .0001). At the lowest dose of TNP-470 (100 pg/ml), the cumulative inhibitory effect of TNP-470 was more potent than the sustained inhibitory effect observed by treatment B in one high dose. Nevertheless, the cytotoxic effect was dose-dependent and more marked after treatment A than after treatment B. After washing out of the drug, partial reversibility was observed at doses lower than 5 mg/ml with a significant increase of viability. HCF were less sensitive to TNP-470 and doses less than 5 mg/ml were not cytotoxic. CONCLUSIONS: TNP-470 appears to have a marked inhibitory effect on PF proliferation, and it may be of considerable value in the prevention of pterygium growth and recurrence.

Localization and possible gene expression of proteoglycan decorin in the trabecular meshwork.

It is known that trabecular meshwork cells produce proteoglycans and that local production may be associated with aqueous outflow resistance. In an attempt to identify intraocular production of proteoglycan decorin in the anterior chamber angle of mammalian eyes, we conducted a Northern blot analysis and immunohistochemical studies. Northern blot analysis suggested gene expression of proteoglycan decorin in trabecular meshwork cells. Also, immunohistochemical studies using anti-decorin antibody demonstrated decorin-like immunoreactivity in the trabecular meshwork and around the Schlemm's canal. Our data demonstrate the presence of proteoglycan decorin in the outflow pathway, suggesting that decorin is a component of extracellular matrices in these regions and may be associated with outflow resistance.

Detached retina affects morphologic and biochemical changes in the retina adjacent to bullous retinal detachment in rabbits.

PURPOSE: Long-term results, more than 10 years after successful retinal detachment surgery, have shown gradually decreasing visual acuity in some cases. It is unclear if reduced functional recovery postoperatively is caused by anatomic changes or biochemical disorders. To determine the etiology of the reduced visual acuity, we cytochemically examined the changes in the cellular responses of the edges of retinal detachments. METHODS: We histochemically studied the glucose-6-phosphatase (G6P) and 5'-nucleotidase (5'-Nase) activity in the rabbit retina. Experimental rhegmatogenous retinal detachment was produced in a rabbit model after partial vitrectomy, followed by retinal tear formation. RESULTS: Although 5'-Nase activity gradually decreased during the period of detachment, activity was still detectable after 24 weeks. G6P activity increased in the region of the detached neural retina. Around the border of the detached retina, the decrease in 5'-Nase activity extended approximately 140 micrometers into the adjacent attached retina at 2 weeks after detachment and 270 micrometers at 24 weeks. CONCLUSIONS: These observations suggest that some anatomical and biochemical damages may occur in the retina adjacent to bullous retinal detachment and may explain the reduction in postoperative vision in some clinical cases.

Glial-, neuronal- and photoreceptor-specific cell markers in rosettes of retinoblastoma and retinal dysplasia.

Previous studies have shown that a rosette formation represents an attempt to form embryonic retinal tissue, primarily rods and cones. To test the theories as to the origin and characteristics of retinoblastoma cells, we compared the characteristics of tumor rosettes with those of dysplastic rosettes seen in retinal dysplasia using the glial, neuronal and photoreceptor markers. Forty-four retinoblastoma and one retinal dysplasia specimens were analyzed by indirect immunohistochemistry, using specific antibodies against glial fibrillary acidic protein, S-100 protein, myelin basic protein, neuron-specific enolase, neurofilament, retinal S-antigen and retinal pigment epithelial antigen. In human retinoblastoma, all the glial, neuronal, retinal pigment epithelial, and photoreceptor cell markers, except for the neurofilament, were present in parts of rosette-forming tumor cells. However, their localization was different for each antigen and it was not clear whether each tumor cell possesses several antigens. These immuno-positive tumor cells were cytologically indistinguishable from other rosette-forming cells at the light microscopic level. In retinal dysplasia, neuron specific enolase and retinal S-antigen were diffusely expressed in the dysplastic rosettes, however, other antigen were not seen in those rosettes. The staining pattern by immunocytochemistry is totally different in tumor rosettes from dysplastic ones. We found varying localizations of different immunoreactivities within tumor rosettes. These results led us to suggest that tumor cells in the rosettes of retinoblastoma may have the ability to differentiate into neural and glial cells. To prove the theory that retinoblastoma cells may have originated from a primitive neuroectodermal cell capable of multipotentiality, further investigation is needed.

Manganese and copper-zinc superoxide dismutases in the developing rat retina.

To determine whether superoxide dismutases (SODs) may be connected with cellular differentiation in the retina, we studied these enzymes by immunolocalization and immunochemical quantitative analysis in developing rat retinas. Four days after birth, manganese superoxide dismutase (Mn-SOD) and copper-zinc superoxide dismutase (CuZn-SOD) immunoreactivities were observed in the neural retina but not in immature neuroblasts. In 9-day-old rats, Mn-SOD immunoreactivity was located in the ganglion cell layer, inner plexiform layer, some cells of the inner nuclear layer, outer plexiform layer, and photoreceptor inner segments differentiated from immature neuroblasts. CuZn-SOD immunoreactivity was found in the same sites except the photoreceptor inner segments. The immunohistochemical staining in 9-day-old rat retinas was the same as in adult retinas. Our quantitative analysis showed increased SODs when retinal cell differentiation ceased. Our results suggest that the concentration of SODs in retinal neuroblasts is too low that immunoreactivity of SODs cannot be visualized. When the differentiation of retinal neuroblasts progresses, SODs appear to be increased in mature retinal cells to protect them from oxidative stress induced by light exposure when the eyes are open.

Immunohistochemical localization of basic fibroblast growth factor, platelet derived growth factor, transforming growth factor-beta and tumor necrosis factor-alpha in the pterygium.

Some fibroangiogenic factors have recently been shown to play potential roles in fibrovascular diseases. The aim of this study was to examine whether there is any relationship between growth factors and pterygium genesis. Twenty-three primary pterygia and 4 normal conjunctiva specimens were analyzed by indirect immunohistochemistry using specific antibodies against basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). Positive immunostaining of these growth factors was located in the epithelial cells, endothelial cells of vessels, basement membranes of vessels and epithelium, fibroblasts and infiltrating inflammatory cells in the pterygium. In the normal conjunctiva, positive immunolabeling for TGF-beta and PDGF was much weaker than in the pterygium. We conclude that growth factors may interact directly or indirectly in the pathogenesis of pterygium although proof of this awaits further studies.

Immunohistochemical study of p53, p21 and PCNA in pterygium.

Since mutated p53 is one of the most frequent gene abnormalities in human cancer, we hypothesized that mutation of p53 may play an important role in growth and recurrence of pterygia, a dysplasia of the conjunctiva. Therefore, we compared pterygia of Japanese and Tunisian patients using antibodies against p53, p21 and proliferating cell nuclear antigen (PCNA). In Nagasaki, 21 pterygia of Japanese individuals were removed and in Gabes, 19 primary pterygia of Tunisian individuals. Positive staining of wild type p53 was not found in the Japanese pterygia, whereas 38.1% were positive for mutant p53, none were positive for p21 and 76.2% were positive for PCNA. The incidence of mutant p53-positive staining was 50.0% in males and 22.2% in females, which was statistically significant. In the 19 Tunisian patients, positive staining of wild type p53 was not found, whereas 36.8% were positive for mutant p53, 0% for p21 and 63.1% for PCNA. Differences between Japanese patients and Tunisian patients were not significant. There were 2 types of pterygium. One type did not show mutant p53 and the other showed mutant p53 caused by ultraviolet light. However, damage caused by p53-dependent programmed cell death of pterygium cells may lead to mutations in other genes which may allow the progressive multistep development of limbal tumors. It is possible that mutant p53-positive pterygia can develop into limbal tumors.

Noninvasive detection of iliac artery disease and prediction of its severity from Doppler spectral analysis in common femoral artery.

The direct interrogation of iliac artery disease (IAD) with color-coded duplex scanning is limited by the presence of intestinal gas or obesity. The purposes of this study were to examine the diagnostic accuracy of duplex ultrasound (DUS) analysis of spectral waves in common femoral artery (CFA) for detection of IAD and to predict its severity. DUS and arteriography were performed in 107 lower extremities in this study. The following were calculated from the CFA spectral waves obtained by DUS: peak systolic velocity (PSV), acceleration (PSV/pulse rise time), and deceleration (PSV/pulse decay time). In patients with isolated IAD, the treadmill exercise test was also performed to evaluate the ischemic severity expressed as recovery rate of ankle pressure index five minutes after exercise (RR-API). Forty-six lower extremities with IAD and 61 without IAD were diagnosed by arteriography. PSV was significantly reduced in lower extremities with IAD (109.5 +/- 32.7 vs 59.8 +/- 32.9 cm/s, P < 0.05). The deceleration detected IAD with a greater specificity and sensitivity vs acceleration (100.0 vs 82.0% and 97.8 vs 82.6%, respectively). Moreover, the acceleration and deceleration significantly correlated with the RR-API (r = 0.589, P < 0.05 and r = 0.779, P < 0.01, n = 14, respectively). The present evaluation is a simple and accurate technique to augment other examinations for detection of IAD and to assess its ischemic severity.