Metal doped polyaniline as neuromorphic circuit elements for in-materia computing.

Polyaniline-based atomic switches are material building blocks whose nanoscale structure and resultant neuromorphic character provide a new physical substrate for the development next-generation, nanoarchitectonic-enabled computing systems. Metal ion-doped devices consisting of a Ag/metal ion doped polyaniline/Pt sandwich structure were fabricated using an in situ wet process. The devices exhibited repeatable resistive switching between high (ON) and low (OFF) conductance states in both Ag+ and Cu2+ ion-doped devices. The threshold voltage for switching was>0.8 V and average ON/OFF conductance ratios (30 cycles for 3 samples) were 13 and 16 for Ag+ and Cu2+ devices, respectively. The ON state duration was determined by the decay to an OFF state after pulsed voltages of differing amplitude and frequency. The switching behaviour is analagous to short-term (STM) and long-term (LTM) memories of biological synapses. Memristive behaviour and evidence of quantized conductance were also observed and interpreted in terms of metal filament formation bridging the metal doped polymer layer. The successful realization of these properties within physical material systems indicate polyaniline frameworks as suitable neuromorphic substrates for in materia computing.

Investigation of Ag and Cu Filament Formation Inside the Metal Sulfide Layer of an Atomic Switch Based on Point-Contact Spectroscopy.

The atomic switches have attracted wide attention owing to their applications in nonvolatile electric devices. The atomic switch is operated by the formation and dissipation of a metallic filament inside a metal sulfide film, which is controlled by a solid electrochemical reaction. Although the metallic filament is considered to consist of metal atoms, the chemical species of the metallic filament are difficult to be identified due to challenges in observing the metallic filament inside the solid. In this study, we report the investigation on the metallic filament in the atomic switch with metal sulfide based on point-contact spectroscopy (PCS). By cooling the atomic switch, the switch voltage increased to 1 V, which allowed for the PCS measurement. The PCS revealed that the metallic filament was composed of Ag atoms in the case of the Pt/Ag2S/Ag atomic switch. We applied this technique to the Pt/Cu2S/Ag and Pt/Ag2S/Cu atomic switches to uncover the formation process of the metallic filament. In both atomic switches, the chemical species of the metallic filament were Ag. The metal atoms were supplied from both the metal electrode and the sulfide layer.

Volatile and nonvolatile selective switching of a photo-assisted initialized atomic switch.

A photo-assisted atomic switch, which has a photoconductive molecular layer in a gap of about 20 nm between an Ag2S electrode and a Pt electrode, is set to a conventional gap-type atomic switch operation mode by light irradiation with the application of a small bias that precipitates Ag atoms from an Ag2S electrode. After this initialization, the switch operates only with application of a bias. In this study, we also found that after the set-operation a photo-assisted initialized atomic switch shows different switching modes depending on the bias range, i.e., volatile switching when the applied bias is smaller than the threshold bias, and nonvolatile switching when the applied bias is larger than the threshold bias. These characteristics can be useful in reconfiguring a circuit such as in neural computing systems.

Forming and switching mechanisms of a cation-migration-based oxide resistive memory.

We report detailed current-voltage and current-time measurements to reveal the forming and switching behaviors of Cu/Ta(2)O(5)/Pt nonvolatile resistive memory devices. The devices can be initially SET (from the OFF state to the ON state) when a low positive bias voltage is applied to the Cu electrode. This first SET operation corresponds to the first formation of a metal filament by inhomogeneous nucleation and subsequent growth of Cu on the Pt electrode, based on the migration of Cu ions in the stable Ta(2)O(5) matrix. After the forming, the device exhibits bipolar switching behavior (SET at positive bias and RESET (from the ON state to the OFF state) at negative bias) with increasing the ON resistance from a few hundred Ω to a few kΩ. From the measurements of the temperature stability of the ON states, we concluded that the RESET process consists of the Joule-heating-assisted oxidation of Cu atoms at the thinnest part of the metal filament followed by diffusion and drift of the Cu ions under their own concentration gradient and the applied electric field, disconnecting the metal filament. With ON resistances of the order of a few kΩ, the SET and RESET operations are repeated by the inhomogeneous nucleation and the Joule-heating-assisted dissolution of a small filament on a remaining filament. This switching model is applicable to the operation of cation-migration-based resistive memories using other oxide materials.

Usefulness of (123)I-BMIPP with myocardial imaging for evaluation of the efficacy of drug therapy in patients with chronic heart failure.

BACKGROUND: Fatty acid is a main source of cardiac energy in aerobic conditions. We used iodine-123-beta-methyl-iodophenyl pentadecanoic acid ((123)I-BMIPP) myocardial scintigraphy to study the efficacy of the angiotensin-converting enzyme inhibitor (ACEI) enalapril in the treatment of chronic heart failure (CHF) by evaluating its therapeutic effects on myocardial fatty acid metabolism. METHODS AND RESULTS: New York Heart Association functional class status, left ventricular end-diastolic diameter, percent fractional shortening, the ratio between early and late peaks of flow velocity, (123)I-BMIPP myocardial-to-mediastinal uptake ratio, and mean washout rate were measured in 42 patients (31 men and 11 women; mean age, 58 +/- 3 years) with CHF before treatment and 3 months after treatment. There was a significant correlation between myocardial fatty acid metabolism and other variables as well as between the degree of improvement in myocardial fatty acid metabolism and the degree of improvement in other variables. CONCLUSIONS: Enalapril improved symptoms and cardiac function in patients with CHF. These improvements significantly correlated with improvement of (123)I-BMIPP metabolism in the myocardium. (123)I-BMIPP scintigraphy is useful for evaluating the efficacy of drug therapy for CHF based on myocardial fatty acid metabolism.

Effect of sealing and Tween 80 on the antifungal susceptibility testing of essential oils.

Concentrations of essential oils showing high volatility decreased substantially in broth and agar media when incubated under open conditions. The decrease in the half life was from 0.7 to 38 hr in broth medium at 27 C. When evaporation was prevented by sealing, MIC values against Aspergillus fumigatus, Candida albicans and Trichophyton mentagrophytes by broth or agar dilution assay were lowered two to eight-fold, as compared with those obtained under open conditions. Addition of Tween 80 caused a rise of the MICs against A. fumigatus by two to four-fold in broth dilution assay, but little affected the MICs in agar dilution assay.

Subacute and chronic effects of DDD pacing on left ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy.

The present study examined the ability of dual-chamber (DDD) pacing to improve symptoms and exercise tolerance in patients with non-obstructive hypertrophic cardiomyopathy (HNCM). Seven patients with HNCM who had failed to benefit from pharmacotherapy participated in the study. The New York Heart Association (NHYA) functional class status and exercise tolerance, which was determined by the treadmill exercise test, were recorded and an echocardiographic observation was performed before, and 1 week, 3 months and 1 year after the implantation of a permanent DDD pacemaker. The atrioventricular delay (AVd) was determined by measuring the point of peak rapid filling velocity and maximum cardiac output (CO). Two patients were not implanted with a permanent pacemaker because their CO and blood pressure decreased or because palpitation occurred during temporary pacing. The ratio between early and late peaks of flow velocity (1.56, 1.21,0.95, and 0.86 before implantation and 1 week, 3 months and 1 year after implantation, respectively); deceleration time (ms: 263.2, 217.6, 204.6, 187.0); peak filling rate (ml/s: 146.2, 204.0, 233.2, 243.6); NYHA functional class status (2.0, 1.8, 1.6, 1.4); and exercise tolerance (s: 203, 264, 403, 480) were significantly improved after implantation. However, left ventricular dimension, percent fractional shortening, ejection fraction, acceleration time and the isovolumic relaxation time were not changed significantly. In conclusion, DDD pacing improved symptoms and the NYHA functional class status, which is associated with improvement of left ventricular diastolic function. It is proposed that DDD pacing would be useful in patients not only with obstructive but also non-obstructive hypertrophic cardiomyopathy refractory to medical treatment, depending on the careful selection of subjects.

[Effects of cilostazol in patients with bradycardiac atrial fibrillation].

OBJECTIVES: Cilostazol, an antithrombotic agent, directly and indirectly increases the heart rate. This study investigated whether cilostazol increases the heart rate, and whether it has chronotropic effects on cardiac failure in patients with bradycardiac atrial fibrillation. METHODS: Twelve patients (6 males and 6 females) with bradycardiac atrial fibrillation underwent Holter monitoring (24-hour total heartbeat counts and frequency of pause), echocardiography (left ventricular end-diastolic diameter, percentage fractional shortening), chest roentgenography (cardiothoracic ratio), and measurements of brain natriuretic peptide and atrial natriuretic peptide before and 6 months after daily oral administration of 100-200 mg cilostazol. RESULTS: Cilostazol administration increased the 24-hour total heartbeat counts from 69,685 +/- 1,690 (mean +/- SE; mean heart rate: 48 beats/min) to 87,352 +/- 3,123 (60), and decreased the frequency of pause from 362.3 +/- 72.9 to 112.3 +/- 41.0. Cardiothoracic ratio decreased from 55.8 +/- 1.1% to 52.5 +/- 1.1%, left ventricular end-diastolic diameter from 56.1 +/- 0.9 to 52.9 +/- 0.8 mm, but percentage fractional shortening was not significantly changed (from 33.0 +/- 2.2% to 33.7 +/- 2.1%). Brain natriuretic peptide decreased from 97.9 +/- 20.5 to 33.5 +/- 4.8 pg/ml, and atrial natriuretic peptide from 69.5 +/- 12.1 to 46.7 +/- 8.3 pg/ml. CONCLUSIONS: Cilostazol has beneficial effects in patients with bradycardiac atrial fibrillation. The increase of heart rate may be mediated by improvement of conductivity in the atrioventricular node and increase of coronary blood supply caused by dilation of vessels.

[Usefulness of washout rate analysis in adenosine triphosphate-stress thallium-201 myocardial scintigraphy in patients with vasospastic angina].

OBJECTIVES: This study evaluated the usefulness of washout rate analysis in adenosine triphosphate(ATP) stress thallium-201 scintigraphy for the diagnosis of vasospastic angina. METHODS: This study included 76 patients with vasospastic angina and 18 normal controls undergoing coronary arteriography. If significant coronary artery stenosis (> or = 50%) was pointed out, the subject was excluded from this study. 111 MBq of thallium-201 was intravenously injected 3 min after ATP loading (0.16 mg/kg/min) was started. Single photon emission computed tomography (SPECT) was performed 10 min and 4 hr after intravenous injection of ATP. The mean washout rate (%) was calculated based on a bull's eye map and was divided into 3 regions, the antero-septal/lateral/inferior regions. The washout rate in each region was calculated. Regional uptake was visually estimated based on the 17 segments of SPECT images. RESULTS: The washout rate in the normal control group was 48.9 +/- 4.1 (mean +/- SD)%. In patients with vasospastic angina, the washout rate in areas with coronary vasospasm was 33.4 +/- 5.5%. This value was significantly lower than in the areas without coronary vasospasm (42.8 +/- 3.6%). The usefulness of washout rate analysis in the diagnosis of vasospastic angina with a cut-off value of less than -2SD from normal washout rate in the 3 regions was examined. A significantly higher diagnostic value was found by washout rate analysis (sensitivity 72.3%, specificity 79.7%, and accuracy 74.6%) compared with visual evaluation of early images (sensitivity 50.3%, specificity 73.9%, and accuracy 57.5%). CONCLUSIONS: The diagnostic value of washout rate analysis was significantly higher (73.1%) compared with visual evaluation of early images (50.3%) in patients with multivessel vasospastic angina.

Major complications during spasm provocation tests with an intracoronary injection of acetylcholine.

This study sought to clarify major complications associated with acetylcholine testing. Serious major complications, such as sustained ventricular tachycardia, shock, and cardiac tamponade were determined in 4 of 715 patients (0.56%), but no cases of death or irreversible complications occurred. The spasm provocation test using acetylcholine should be performed carefully, although it is considered a safe and reliable method.

New combined spasm provocation test in patients with rest angina: intracoronary injection of acetylcholine after intracoronary administration of ergonovine.

The incidence of provoked coronary spasm with the standard single spasm provocation test has been relatively low in patients with rest angina. The present study examined the clinical usefulness of a newly designed spasm provocation test, an intracoronary injection of acetylcholine (ACh) following an ergonovine (ER) test, in patients with rest angina who demonstrated low disease activity and atypical chest pain. Triple sequential spasm provocation tests were performed in 24 patients with atypical chest pain who had no ischemia and in 40 patients with rest angina who had distinct ischemia. Initially, an ACh test (20-100 microg) and then an ER test (40-64 microg) were performed and then, if no spasm was provoked, an intracoronary injection of ACh was given after the ER test to evaluate coronary spasm. Coronary spasm was defined as total or subtotal occlusion. In the 24 patients with atypical chest pain, no spasm was provoked by intracoronary injection of either ACh or ER, but coronary spasms were induced in 2 patients using the new method, with the remaining 22 not experiencing spasm (specificity of new method, 92%). In the 40 patients with rest angina, intracoronary injection of ACh induced coronary spasm in 22 patients (group I) and 6 (group II) demonstrated spasm with intracoronary injection of ER. Coronary spasm was not induced by either the ACh test or the ER test in 12 patients (group III). The intracoronary administration of ACh after the ER test provoked spasm in 11 of 12 patients. Diffuse spasms were provoked in 10 of 11 patients. In patients with rest angina, the frequency of chest pain attacks in 1 month experienced by patients in group III (0.8+/-0.8) was significantly lower than that of patients in group I (7.0+/-5.3, p<0.01) or II (3.5+/-2.3, p<0.05). No serious or irreversible complications related to this new combined method were observed. In conclusion, this method was safe and reliable for the induction of coronary spasm in patients with rest angina who may have low disease activity.

[Usefulness of nitrendipine and its effects on quality of life and brain blood flow in elderly hypertensive patients].

There are many reports on the efficacy of Ca-antagonists for treatment of elderly essential hypertension. In particular, many studies have noted the beneficial effects of antihypertensive therapy on the quality of life (QOL). Nevertheless, there are no reports on antihypertensive therapy regarding the relationship between brain blood flow (BBF) and QOL. Therefore, we examined the efficacy of nitrendipine, a Ca-antagonist, on the brain blood flow and QOL, and its side effects in elderly essential hypertensive patients. The subjects were 17 (males: 4, females: 13) patients with untreated hypertension of WHO stage I or II, aged 70 years or older. The mean dose of nitrendipine was 9.4 +/- 0.4 mg daily. Before and 6 months after treatment, we examined blood pressure (BP), heart rate (HR), echocardiography (left ventricular mass index [LVMI], % fractional shortening [% FS]), plasma noradrenaline (Nad), plasma renin activity (PRA), BBF using the IMP-ARG method with BBF scintigraphy, and QOL was examined with a questionnaire. Two patients were excluded from this study because 1 had no decrease in BP, and another was moved to a different hospital. BP significantly decreased from 178/93 to 137/77 mmHg, but HR was not changed after treatment. BBF significantly increased from 37.0 +/- 4.9 to 41.0 +/- 4.9 ml/dl/min, but % FS, Nad, and PRA did not significantly change. The degree of QOL was improved by 4.2 +/- 1.2 points and there was a significant positive correlation between the changes of BBF and of QOL (r = 0.66, p = 0.04). However, moderate pharmacotherapy for BP seems to be necessary because there were 2 patients whose BBF decreased accompanied by excessive drop in BP after treatment. In conclusion, it is possible to safely use nitrendipine for elderly essential hypertensive patients. Nitrendipine has beneficial effects on BBF, and it was suggested that the increase of BBF is one of the most important factors in improvement of QOL.

Inhibitory effect of essential oils on apical growth of Aspergillus fumigatus by vapour contact.

The inhibitory effect of seven essential oils on the apical growth of hyphae of Aspergillus fumigatus was studied using a bio cell tracer by vapour contact in a sealed vessel. Based on the inhibitory pattern, these essential oils were classified into three groups. The first group, composed of citron, lavender and tea tree oils, stopped the apical growth in a loading dose of 63 micrograms ml-1 air, but allowed the regrowth of the hyphae after removal of the vapour, indicating fungistatic action. The second group, consisting of perilla and lemon-grass oils, stopped the apical growth in a loading dose of 6.3 micrograms ml-1 air, and did not allow the regrowth after gaseous contact at 63 micrograms ml-1 air, indicative of fungicidal action. The third group, consisting of cinnamon bark and thyme oils, retarded the growth in a dose of 6.3 micrograms ml-1 air, stopped it in a dose of 63 micrograms ml-1 air, and incompletely suppressed regrowth of the hyphae. Gas chromatographic analysis revealed that vapours of essential oils were absorbed on fungal mycelia and agar medium most abundantly by the first group, followed by the second and third groups, reflecting the volatility of the respective groups. Suppression of the apical growth by vapour contact was ascribed to the direct deposition of essential oils on fungal mycelia, together with an indirect effect via the agar medium absorbed.

Clinical characteristics of female patients with coronary spastic angina: comparison with male patients.

There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.

Limited efficacy of magnesium for the treatment of variant angina.

Some patients with variant angina show both ST segment elevation at rest and exercise-induced ST segment elevation. Magnesium deficiency has also been observed in patients with variant angina. This study investigated the correlation between the degree of magnesium deficiency and the efficacy of intravenous administration of magnesium in patients with variant angina. Fifteen patients with angiographically confirmed variant angina were assessed for magnesium deficiency and whether intravenous administration of magnesium (19.2 mEq/l) suppressed exercise-induced ST segment elevation. All 15 patients were studied with a magnesium retention test (0.2 mEq/kg over 4 hr) to analyze magnesium deficiency. In our study, magnesium retention rate in patients with variant angina was not higher than that of controls (57 +/- 24% vs 45 +/- 10%, NS). All 15 patients had anginal attacks during accelerated exercise combined with hyperventilation after placebo infusion, whereas only 8 patients had anginal attacks after magnesium administration. ST segment elevation occurred in 14 patients after placebo infusion, but in only 4 patients after magnesium administration. There were no correlations between disease activity, degree of magnesium deficiency or failure of suppression of ST elevation by the intravenous administration of magnesium. Intravenous administration of magnesium can suppress exercise-induced coronary spasms in some patients with variant angina, but the degree of magnesium deficiency did not correlate with the suppressions of exercise-induced ST elevation after magnesium administration. Intravenous administration of magnesium had limited efficacy in patients with variant angina and exercise-induced ST segment elevation.

Effect of insulin resistance on left ventricular hypertrophy and dysfunction in essential hypertension.

BACKGROUND: In hypertensive patients, the relationships between glucose tolerance and left ventricular hypertrophy (LVH) and left ventricular diastolic function (LVDF) have been described in several reports. OBJECTIVE: In this study, we examined the relationships between insulin resistance and LVH and LVDF in hypertensive patients from the therapeutic perspective. METHODS AND RESULTS: The study participants were essential hypertensive patients with impaired glucose tolerance (IGT-HT, n = 26), hypertensive patients with normal glucose tolerance (NGT-HT, n = 39), and normotensive control individuals (n = 18). Insulin resistance was evaluated by the insulin suppression test by use of the steady-state plasma glucose (SSPG) level. Left ventricular mass index (LVMI) and LVDF, which was determined by the E:A ratio, were estimated by echocardiography. Temocapril, an angiotensin-converting enzyme inhibitor, was administered in an open, non-randomized manner with a mean dose of 2.8+/-0.2 mg/ day, and the mean administration period was 18 weeks. The systolic and diastolic blood pressure, the LVMI, and the SSPG level were significantly higher in the hypertensive patients than in the control individuals. The mean systolic and diastolic blood pressures were significantly decreased by treatment with Temocapril. Before treatment, stepwise regression analysis showed that SSPG is an independent predictor for LVMI and LVDF. After treatment, the changes in LVMI (D-LVMI; %) (-15.1+/-1.5), the changes in LVDF (D-E:A; %) (-38.2+/-4.1), and the changes in insulin resistance (D-SSPG; %) (-13.7+/-1.7) were significantly higher in the IGT-HT group than in the NGT-HT group (-11.4+/-1.1, -18.1+/-1.7, -9.4+/-1.4, respectively), and the D-SSPG was an independent predictor for D-LVMI and D-E :A. CONCLUSIONS: The results of this study indicate that insulin resistance is an important factor affecting LVH and LVDF.

Relationship between insulin resistance and cardiac sympathetic nervous function in essential hypertension.

BACKGROUND: It has been suggested that hyperinsulinemia and insulin resistance participate in the pathogenesis of hypertension, in part by activating sympathetic activity. OBJECTIVE: We aimed to examine the relationship between insulin resistance and cardiac sympathetic nervous function in patients with essential hypertension using 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy. METHODS AND RESULTS: Twenty-eight patients (18 men) with essential hypertension and 11 (seven men) control individuals with a mean age of 55.8+/-3.3 years were recruited. Patients with diabetes mellitus, congestive heart failure or coronary artery disease were excluded from this study. To evaluate insulin resistance, we used steady-state plasma glucose (SSPG; mg/dl) levels measured by the SSPG method. To evaluate cardiac sympathetic nervous function, we calculated the heart-to-mediastinum ratio from the delayed MIBG image (H:M-D) and the mean washout rate (WOR, %). There were significant differences (P<0.01) in SSPG, H:M-D and WOR between the essential hypertension and control individual groups (125 versus 103 mg/dl, 2.2 versus 2.4, and 32 versus 23%, respectively). Stepwise regression analysis showed that SSPG and plasma norepinephrine level are independent predictors for the cardiac sympathetic nervous function obtained from MIBG scintigraphy. CONCLUSIONS: These findings indicate that insulin resistance is significantly related to activation of the cardiac sympathetic nervous function associated with left ventricular hypertrophy in patients with essential hypertension.

[Pathogenecity of fosfomycin-resistant strains isolated from Escherichia coli].

Two fosfomycin-resistant strains, FRC14 (parent strain, Escherichia coli [E.coli] c73-18) and FRK104 (parent strain, E. coli O124), were isolated from spleens before the bacterial disappearance, after inoculating the parent strains intraperitoneally into mice and treating them with a single oral dose of fosfomycin. The resistant strains were successfully isolated by a replica method from a mass of sensitive cells of respective parent. To elucidate the pathogenesis of the resistant strains, their characteristics were investigated. The MIC of fosfomycin for FRC14 was 25 micrograms/ml (4 times the MIC for the parent) and that for FRK104 was 100 micrograms/ml (8 times the MIC for the parent). The strain FRC14 showed a defective utilization of sn-glycerol 3-phosphate (G3P), but utilization of other carbohydrates was similar to that of the parent strain. Thus, the strain FRC14 seemed to be a glpT mutant. The strain FRK104 did not use variety of carbohydrates including G3P, but used glucose 6-phosphate. The utilization of G3P was recovered in the presence of cAMP. Thus, the strain FRK104 seemed to be a ptsI mutant. These resistant strains were diminished their killing activity for mice in comparison to that of the each parent strain when they were inoculated intraperitoneally. The cell number of FRC14 decreased or disappeared in blood and spleen in mice, while that of the parent increased. The strain FRK104 diminished its ability of producing keratoconjuctivitis in guinea pigs in comparison to that of the parent strain.

Inhibitory effect of ND2001 on spontaneous multiple metastasis of NC 65 tumors derived from human renal cancer cells intradermally transplanted into nude mice.

The NC 65 tumor cell line derived from human renal cell carcinoma was selected from among nine human cell lines by determining the inhibition of invasion by ND2001 (sodium D-glucaro-delta-lactam) in vitro. The efficacy of this agent against these tumor cells was investigated in an experimental metastatic model of human tumors in vivo. Although ND2001 did not inhibit growth of NC 65 cells intradermally transplanted into male KSN mice (nu/nu), this agent inhibited multiple spontaneous metastasis.

Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine.

This study examines the incidence of spasm by intracoronary injection of acetylcholine in Japanese patients who underwent coronary angiography. The subjects were 685 consecutive patients (477 men, mean age 63.2 +/- 7.5 years) who were studied with an acetylcholine test. Acetylcholine was injected in incremental doses of 20, 50, and 80 microg into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Spasm was defined as total or subtotal occlusion. Coronary vasospasm was determined in 221 patients (32.3%). Spasm occurred often during effort and rest in patients with angina (25 of 51, 49.0%), exertional angina (25 of 74, 33.8%), recent myocardial infarction (30 of 80, 37.5%), healed myocardial infarction (14 of 37, 37.8%), and especially in patients with rest angina (83 of 124, 66.9%), whereas spasm was relatively uncommon in patients with nonischemic heart disease (23 of 252, 9.1%). Spasm was superimposed on significant atherosclerotic lesions in 35.9% of patients as well as on nonfixed atherosclerotic lesions in 30.8% of patients. We conclude that >9% of Japanese patients may have coronary vasospasm with intracoronary injection of acetylcholine and recommend the provocation test for evaluating coronary vasospasm if coronary angiography is undertaken.