[Long-term survival of patient with brain metastases from lung cancer treated by pemetrexed monotherapy].

A 61-year-old female was diagnosed with cT2N1M0 adenocarcinoma in the right lung. Following resection of the right middle lobe and dissection of the second group of lymph nodes in July 2007, she was found to have pN2 disease, and carboplatin plus paclitaxel was administered as postoperative chemotherapy. Recurrence was found and gefitinib was administered as first-line chemotherapy. While the patient was followed on an outpatient basis, dysgeusia and headache developed in March 2009. As multiple brain metastases were confirmed by contrast-enhanced computed tomography, cranial irradiation (30 Gy in 10 fractions)was administered. Upon improvement of the patient's status to a level treatable by chemotherapy, a new second-line chemotherapy with pemetrexed was started. Since then, the patient has been followed on an outpatient basis and has currently completed 21 courses of chemotherapy. No recurrence has been observed thus far. The results suggest that pemetrexed is an effective agent for the treatment of brain metastases from lung adenocarcinoma.

Secondary preventive effects of a calcium antagonist for ischemic heart attack: randomized parallel comparison with ß-blockers.

BACKGROUND: Beta-blockers (BB) have been widely used in the management of hypertension and acute myocardial infarction (AMI), and both national and international guidelines have recommended them as first-line agents. Calcium channel antagonists (CCA) are also effective in the treatment of hypertension and angina pectoris. However, the efficacy of CCA in the prevention of cardiovascular events in post-myocardial infarction (MI) patients in comparison to that of BB remains unclear. METHODS AND RESULTS: A total of 120 post-MI patients (71 patients who were at least 1 month after the onset AMI and 49 stable coronary artery disease patients with a history of MI) were randomly assigned to receive a BB (atenolol, 25-50mg/day, n=60) or a CCA (benidipine, 4-8 mg/day, n=60). All patients with AMI within the previous 1 month or with vasospastic angina were excluded from the present study. The baseline clinical characteristics were generally similar in the BB and CCA groups. The rate of primary composite outcome was 26.3% in the BB group in comparison to 13.3% in the CCA group, with no significant between-group differences (hazard ratio with the CCA group 0.640, P=0.276). Both treatments were well tolerated with few severe adverse events. CONCLUSIONS: CCA treatment was found to be as effective as BB in reducing cardiovascular events in post-MI patients.

[The value of transbronchial lung biopsy findings in the diagnosis of a case of TS-1-induced pulmonary toxicity].

We report the case of a 67-year-old man with a diagnosis of stage IV stomach cancer in May 2010 who was treated with outpatient chemotherapy using TS-1, paclitaxel and lentinan. Dyspnea and coughing developed after drug administration in November and the patient was hospitalized on day 5 after the appearance of symptoms due to hypoxemia and the presence of ground-glass opacities in the right middle and lower lung fields. On the same day, bronchoscopy was performed for differentiation from infection and lymphangitic carcinomatosis. A transbronchial lung biopsy suggested drug-induced pulmonary toxicity, and a drug lymphocyte stimulation test was highly positive for TS-1. Discontinuation of TS-1 alone improved his respiratory status and imaging findings. TS-1 is available only in Japan, and because it is administered orally and its toxicity is minimal, its use has been expanded to treat a variety of malignancies. Drug-induced pulmonary toxicity due to TS-1 occurs in only 0.03% of all cases, and there are few reports regarding the histopathological findings of TS-1-related pulmonary toxicity. Although it can be difficult to diagnose drug-induced pulmonary toxicity because it demonstrates a variety of imaging findings, the present case suggests that it is important to proactively perform transbronchial lung biopsy at the early stage of diagnosis and promptly determine a course of treatment.

Regional left-ventricular diastolic wall motion assessed by a new program for ECG-gated myocardial perfusion SPECT in early-stage heart failure.

BACKGROUND: We developed a new program for gated single-photon emission computed tomography to estimate regional left-ventricular (LV) wall motion. We classified and graded diastolic wall motion, and compared its grading with global LV functions. METHODS AND RESULTS: Forty New York Heart Association functional class I (NYHA class I) patients and 15 control subjects were examined. The global time to peak filling and the regional diastolic wall motion synchrony, as estimated by the time lag between the earliest and latest regional peak filling, were evaluated. Using the control group's mean + 2 SD, diastolic wall motions were classified into four subsets: globally normal and regionally synchronous, globally normal but regionally dyssynchronous, globally prolonged and regionally dyssynchronous, and globally prolonged but regionally synchronous. These subsets were graded 0 to 3, respectively. Grade 0 was defined as normal. Grading was compared with global LV functions. Although 67.5% of patients demonstrated abnormal motion, the global diastolic parameter less frequently detected an abnormality (22.5% to 32.5%). Grading correlated with the first-third filling fraction (Spearman's rank correlation coefficient [rs] = -0.74, P = 3.8 x 10(-6)) and the first-third filling rate (rs = -0.49, P < .005). CONCLUSIONS: Regional diastolic wall motion abnormality was frequently detected even in early-stage heart failure. Grading reflected early diastolic dysfunction.

Relationship between left ventricular function and wall motion synchrony in heart failure assessed by ECG-gated myocardial perfusion SPECT.

OBJECTIVE: To confirm the relationship between left ventricular (LV) function and wall motion synchrony, and to identify the difference of synchrony between an ischemic heart disease (IHD) patient group and other heart disease (OHD) patient group among classified groups in heart failure, systolic, and diastolic parameters were compared using electrocardiograph-gated single-photon emission computed tomography. METHODS AND RESULTS: Twenty IHD and 30 OHD patient groups, comprised New York Heart Association functional class I-III (IHD1-3 and OHD1-3), and 15 controls were examined. The LV functions (ejection fraction, EF; peak-filling rate, PFR) and synchrony, which was estimated from the time lag between the earliest and latest regional systolic or diastolic temporal parameters (maximum difference of regional time to end-systole, MD-TES, or maximum difference of regional time to peak filling, MD-TPF), were compared. The LV function correlated with its synchrony in IHD and OHD (EF vs. MD-TES: r = -0.86, P = 1.3 x 10(-6) in IHD and r = -0.69, P = 2.8 x 10(-5) in OHD. PFR versus MD-TPF: r = -0.67, P < 0.002 in IHD and r = -0.63, P < 0.0002 in OHD). Dyssynchronous normal EF was observed in three IHD (15%) and six OHD (20%). Dyssynchronous normal PFR was observed in six IHD (30%) and six OHD (20%). MD-TES was significantly smaller in control group (CG) than in IHD3 and OHD3 (P < 0.005), and in IHD1 than in IHD3 and OHD3 (P < 0.05). MD-TPF was significantly smaller in CG than in IHD2, IHD3, and OHD3 (P < 0.05). However, there was no significant difference between LV synchrony in IHD and OHD, or among LV synchrony of the same functional classes between these two groups. CONCLUSIONS: This study confirms that LV function is correlated with wall motion synchrony. No statistically significant difference was confirmed in wall motion synchrony between IHD and OHD. However, dyssynchrony appears in the patients without apparent global LV dysfunction. This feature may facilitate identification of synchronous disorder in HF patients with preserved global LV function. It is expected that detection of such a disorder may lead to the initiation of appropriate treatments for early stage HF and prevent its progression.

[QT dispersion increases during hemodialysis procedures in patients undergoing maintenance dialysis: association with an RA system and holter electrocardiogram].

BACKGROUND: Patients undergoing maintenance dialysis have been associated with a high incidence of arrhythmias, which increases with hemodialysis (HD) procedures. In recent years, QT dispersion (QT-d), which is defined as the difference between the maximum and minimum QT intervals (QTmax, QTmin) on an electrocardiogram (ECG), has attracted attention as a useful tool for predicting and evaluating ventricular arrhythmias. AIM: To determine the QT interval and QT-d before and after HD in stable subjects on maintenance dialysis. Further, to analyze the association of changes (Delta) in the QT interval and QT-d with the fluid removal ratio and changes in laboratory data. PATIENTS AND METHODS: We selected 82 patients undergoing maintenance dialysis who were less than 80 years of age. QT intervals before and after HD were obtained, and laboratory data including neurohumoral factors and the RA system were carried out. Of all the patients, 63 underwent a 24-hour holter-monitoring ECG. RESULTS: QTmax was significantly prolonged with QTmin remaining unchanged, and QT-d was significantly increased. DeltaQT-d demonstrated a significant correlation with DeltaQTmax, DeltaQTmin and Deltaaldosterone, but showed no correlation with the fluid removal ratio and changes in laboratory data. Results of the holter ECG revealed that in the grade 0 (Lown's classification) group, no change was obtained in DeltaQTmax, DeltaQTmin and DeltaQT-d, and in groups 1 to 5, significant increases were noted in DeltaQTmax and DeltaQT-d. CONCLUSIONS: The increase in QT-d has a possible link with arrhythmia inducibility during HD, and the results of the holter ECG suggest that an increase in QT-d may predict the frequency of arrhythmias. Change in the RA system appeared to have an impact on QT-d, but there was no impact of this parameter on the fluid removal ratio or changes in the laboratory data.

Global and regional evaluation of systolic and diastolic left ventricular temporal parameters using a novel program for ECG-gated myocardial perfusion SPECT--validation by comparison with gated equilibrium radionuclide angiography and speckle-tracking radial strain from echocardiography.

BACKGROUND: A newly developed program, named cardioGRAF, enabled the evaluation of left ventricular (LV) systolic and diastolic temporal parameters for the estimation of heart failure using ECG-gated myocardial perfusion SPECT (GMPS). OBJECTIVE: The feasibility of those global (g-) and regional (r-) parameters was validated to compare with gated equilibrium radionuclide angiography (ERNA) and speckle-tracking radial strain (STS) from echocardiography. METHODS: Thirty-three patients were studied using GMPS and ERNA (n=11) or GMPS and STS (n=22). The following g- or r-parameters obtained by cardioGRAF and ERNA or STS were compared: time to end systole (TES), time from end systole to peak filling rate (TPF1), time from 0 to peak filling rate (TPF2), time to peak radial strain (TPS), time from peak strain to peak negative strain rate (TP-SR1), and time from 0 to peak negative strain rate (TP-SR2). RESULTS: All g-parameters were successfully obtained by cardioGRAF and ERNA. The results demonstrated good correlations (g-TES: r = 0.79, p < 0.005; g-TPF1: r = 0.75, p < 0.02; TPF2: r = 0.83, p < 0.005). The differences were 11.9 +/- 31.8 ms in g-TES, 19.9 +/- 65.4 ms in g-TPF1, and 37.7 +/- 67.4 ms in g-TPF2. All r-parameters were successfully obtained by cardioGRAF. Eight patients and 12 segments were excluded because of the inadequate quality of routine echocardiography for STS analysis. However, r-parameters obtained by cardioGRAF were significantly correlated with those of STS (r-TES and r-TPS: r = 0.61, p = 1 x 10(-8); r-TPF1 and r-TP-SR1: r = 0.69, p = 3 x 10(-11); r-TPF2 and r-TP-SR2: r = 0.76, p = 2 x 10(-15)). The differences were 22.1 +/- 38.2 ms between r-TES and r-TPS, 7.0 +/- 123.4 ms between r-TPF1 and r-TP-SR1, and 38.1 +/- 111.5 ms between r-TPF2 and r-TP-SR2. CONCLUSION: The feasibility of evaluating systolic and diastolic temporal parameters by a new program was validated. This program has the potential to evaluate both diastolic and systolic heterogeneous wall motions which express dyssynchrony in heart failure.

Relationships among regional diastolic impairment, elongation of global time to peak filling rate, and global diastolic function using ECG-gated myocardial perfusion SPECT in heart failure.

OBJECTIVE: The relationships among regional diastolic impairment, the elongation of global time to peak filling rate (g-TPF), and global diastolic function were examined by a novel program using electrocardiography-gated myocardial perfusion single-photon emission computed tomography (SPECT) (GMPS) in heart failure (HF). METHODS: Fifteen control subjects and 70 HF patients, New York Heart Association functional classification I (N-1) 41 cases, classification II (N-II) 15 cases, and classification III (N-III) 14 cases, were examined by GMPS. Using the reference mean +2 SD (standard deviation) of g-TPF derived from control group (CG), HF patients were divided into a normal g-TPF group (NG) and elongated g-TPF group (EG). The distributions of g-TPF and regional (r-) TPF were estimated by histograms. The extension of regional diastolic impairment was estimated by the number of r-TPF elongated segments (NES). RESULTS: g-TPF and r-TPF mainly distributed from 100 ms to 220 ms and demonstrated a peak around 150 ms in CG and NG. g-TPF distributed from 240 ms to 560 ms, but r-TPF distributed from 90 ms to 690 ms and demonstrated two peaks around 150 ms and 350 ms in EG. NES significantly correlated with g-TPF (r=0.79, P=6x10(-10) in N-I; r=0.69 and P<0.005 in N-II; r=0.89, P=2x10(-5) in N-III). NES negatively correlated with first third filling fraction (1/3FF) (r=-0.83, P=3x10(-11) in N-I; r=-0.72, P<0.0005 in N-II) and first third filling rate (1/3FR) (r=-0.49, P=0.002 in N-I; r=-0.52, P=0.002 in N-II; r=-0.81, P<0.0005 in N-III). g-TPF significantly correlated with 1/3FF (r=-0.67, P=1.5x10(-6) in N-I; r=-0.69, P<0.005 in N-II) and 1/3FR (r=-0.41, P<0.01 in N-I; r=-0.69, P<0.01 in N-III). CONCLUSIONS: The development of regional early diastolic impairment makes g-TPF elongation and induces global dysfunction in early diastole.

Quantification of left ventricular regional functions using ECG-gated myocardial perfusion SPECT--validation of left ventricular systolic functions--.

OBJECTIVE: We have developed a program to quantify regional left ventricular (LV) function and wall motion synchrony using ECG-gated myocardial perfusion SPECT (MPS). This preliminary study was undertaken to validate the use of this program for estimating regional LV systolic function. METHODS: Patients were subjected to MPS by 99mTc-sestamibi at rest. The study included 20 patients who were confirmed to have a low probability of coronary artery disease (LPG; low probability group), 19 heart disease patients who were examined by MPS and equilibrium radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The values of the ejection fraction (EF) and peak ejection rate (PER) were estimated. The global functions evaluated by this program were compared with those obtained by ERNA in the ERG. For regional assessment, the reference values of the functional indices were obtained for 17 LV segments in LPG. The Z score, (reference average value of the segment--patient's value of the segment)/reference standard deviation of the segment, was used for the evaluation of regional functions; a score equal to or greater than 2 was defined as abnormal. Semiquantitative visual interpretation of 2DE was used as the standard to assess wall motion. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these criteria and the relationship between 2DE grading and Z scoring were validated in 2DEG. RESULTS: The values of the global EF and PER evaluated by this program correlated with those determined by ERNA (r = 0.76 and 0.58, respectively; p < 0.005 and 0.01, respectively). The sensitivities of regional EF and PER for segmental wall motion abnormalities were 86.7% and 68.7%, respectively; their specificities were 86.7% and 95.5%, respectively; their PPVs were 64.3% and 79.2%, respectively; and their NPVs were 96.0% and 91.7%, respectively. The Z scores of these indices significantly correlated with the scores determined by 2DE (rs = 0.70 and 0.68, respectively; p < 10(-10)). CONCLUSION: The potential of this program to quantify the regional systolic function was validated.

Serial assessment of left ventricular performance at rest and during bicycle exercise by ECG-gated myocardial perfusion SPECT.

UNLABELLED: The present study evaluates left ventricular performance during exercise by ECG-gated myocardial perfusion SPECT with short-time data collection. METHODS: The study population consisted of 10 healthy volunteers (Group N) and 9 patients with ischemic heart disease (Group I). Seven patients in Group I had a history of prior myocardial infarction. Rest ECG-gated SPECT was performed 40 min after an injection of Tc-99m-tetrofosmin (555-740 MBq). After resting data acquisition, Group N underwent up to two 5-min stages of exercise (75 and 125 watts) on a detachable bicycle ergometer. The Group I patients all underwent symptom-limited, maximal testing on the ergometer. ECG-gated SPECT data were acquired from both groups for 3 min at rest and during the last 3 min of each exercise stage. RESULTS: Significant increases occurred in LVEF from rest to peak stress in both groups (from 55.4 +/- 5.8 to 66.6 +/- 4.1% in group N, p < 0.0001; from 49.0 +/- 12.8 to 56.7 +/- 13.8% in Group I, p < 0.001). The LVESV values significantly decreased to peak stress in Group N (from 49.9 +/- 13.1 to 37.8 +/- 10.0 ml, p < 0.0001), whereas LVEDV did not change (from 110.6 +/- 18.9 to 112.0 +/- 19.0 ml). In contrast, the LVESV values at rest and under peak stress were similar in Group I (from 52.6 +/- 23.9 to 51.7 +/- 31.4 ml) and LVEDV in Group I at peak exercise tended to increase (from 102.8 +/- 36.7 to 111.3 +/- 39.0 ml). The changes in LVESV from rest to peak stress were significantly different between Groups N and I (-12.1 +/- 6.3 vs. -0.9 +/- 11.6 ml, p < 0.02). CONCLUSION: ECG-gated SPECT with short-time data collection can assess left ventricular function during exercise and may offer useful information for evaluating patients with ischemic heart disease.

Age-adjusted level of circulating elastin as a cardiovascular risk factor in medical check-up individuals.

AIMS: The level of circulating soluble elastin (CSE) is reported to increase proportionally with the degree of clinical atherosclerosis; however, its diagnostic use is limited because CSE also increases with age. We aimed to investigate whether alterations in CSE concentrations are implicated in potential cardiovascular dysfunctions (indicated by standard physiological parameters) in medical check-up individuals, taking age into consideration. METHODS: In a total of 531 individuals (age 20-89 years), CSE levels were correlated most significantly with age. The groups of male and female individuals were each further divided into two subgroups: those with higher and those with lower CSE levels than the reference values determined by polynomial regression. RESULTS: Male participants with lower CSE levels (n = 128) than the age-adjusted reference baseline levels showed higher serum glucose (P < 0.008), uric acid (P < 0.008) and triglyceride (P < 0.02) levels than those with higher CSE levels (n = 126). However, most of the parameters tested in female participants with lower CSE levels (n = 140) were statistically comparable to those with higher CSE levels (n = 137). The ratio of CSE level to the age-adjusted reference level was calculated in each of the male participants, and declines in the ratio were significantly correlated with increases of serum glucose, uric acid and triglyceride levels (P < 0.005, P < 0.02 and P < 0.006, respectively). CONCLUSION: The decrease in age-adjusted CSE levels is a potential indicator of eventual cardiovascular dysfunction in medical check-up individuals, as predicted by the risk factors dyslipidemia, hyperuricemia or diabetes.

Usefulness of rosuvastatin to prevent periprocedural myocardial injury in patients undergoing elective coronary intervention.

The aim of the present study was to investigate whether percutaneous coronary intervention-related periprocedural myocardial infarction (MI) can be suppressed more significantly with high- compared with low-dose rosuvastatin. A total of 232 patients scheduled to undergo elective percutaneous coronary intervention within 5 to 7 days were assigned to groups that would receive either 2.5 or 20 mg/day of rosuvastatin (n = 116 each). The incidence of periprocedural MI did not significantly differ between the high and low-dose groups (8.7% vs 18.7%, p = 0.052). In patients who were not taking statins at the time of enrollment, high-dose rosuvastatin significantly suppressed periprocedural MI compared with the low dose (10.5% vs 30.0%, p = 0.037). The difference was not significant in patients who were already taking statins (high vs low dose 7.6% vs 10.6%, p = 0.582). In conclusion, the incidence of percutaneous coronary intervention-related periprocedural MI was reduced more effectively by high-dose than by low-dose rosuvastatin in statin-naive patients. However, low-dose rosuvastatin is sufficient for patients who are already taking statins.

Two cases of food additive-induced severe liver damage associated with positive results on lymphocyte stimulation test and for antinuclear antibodies.

Two cases of severe liver injury and positive result for antinuclear antibodies induced by food additives are reported. The first patient reported long-term intake of Mabo Ramen(®) noodle soup, nutritional supplements, and over-the-counter drugs. Total bilirubin, aspartate aminotransferase, and alanine aminotransferase were 9.6 mg/dL, 1,048, and 1,574 IU/L, respectively. Antinuclear antibody was 80×. The drug-induced lymphocyte stimulation test (DLST) was positive for Mabo Ramen(®) and its additives such as Xanthan gum, guar gum, and Doubanjiang. Histologic examination of a liver biopsy specimen showed lymphocyte infiltration and necrosis. The autoimmune hepatitis score was 3. The second patient reported intake of dietary supplements, including Bimore C(®) and Chokora BB(®). Laboratory tests revealed that total bilirubin was 9.8 mg/dL, aspartate aminotransferase was 1,130 IU/L, and alanine aminotransferase was 1,094 IU/L. Antinuclear antibody was 320×. Co-existing pancreatic damage was confirmed by the findings on abdominal CT and elevation of serum lipase, span-1, and DUPAN-2. DLSTs were positive for both supplements. These two supplements contained additives such as titanium oxide, magnesium stearate, and hydroxypropylcellulose. DLSTs for all three additives were positive. Histologic examination revealed periportal necrosis and lymphocyte infiltration of lobular and portal areas. These two cases demonstrate that repeating DLSTs is useful for identifying causative constituents in foods and supplements.

Baroreflex mechanisms and response to exercise in patients with heart disease.

BACKGROUND: Past reports showed that the baroreflex continuously regulates hemodynamics during exercise. However, it is still clinically unclear. If baroreflex mechanism is able to influence actually exercise cardiovascular control, baroreflex sympathetic and/or parasympathetic function relates to response to exercise. Therefore, we examined the relationship of heat rate changes to both blood pressure increment and decrement with tolerance and chronotropic response to peak exercise in patients with heart disease. METHODS: In 25 male heart disease patients (60 ± 9 years) without decompensated heart failure, baroreceptor reflex sensitivity (BRS ms mmHg(-1) ) was measured by reflex heart rate responses to changes in blood pressure after phenylephrine (P-BRS) and nitroglycerin (N-BRS) injection, respectively. Symptom-limited treadmill exercise test was performed according to Bruce's protocol. RESULTS: (i) The absolute values of blood pressure change after the administrations were similar between the agents because the dosages of nitroglycerin and phenylephrine were set to equalize absolute changes in blood pressure. (ii) In this study population, the ratio of N-BRS to P-BRS was not significantly correlated with hypertension and diabetes mellitus. (iii) Exercise capacity (METs) (r= -0.626) and heart rate response to exercise per METs (r=0.670) was significantly related to N-BRS but not to P-BRS. CONCLUSION: We found that the abnormality of baroreflex function in the presence of blood pressure decrements can lead to insufficient capacity and easy sympathetic activation during exercise.

Clinico-epidemiologic study of the metabolic syndrome and lifestyle factors associated with the risk of colon adenoma and adenocarcinoma.

BACKGROUND: The numbers of patients with colorectal cancer and associated deaths have been increasing in Japan, probably due to rapid lifestyle changes. Prevention is clearly important and the present study aimed to clarify risk factors and to promote colon cancer screening. METHODS: We investigated lifestyle factors, biochemical data, and pathological features of 727 individuals who underwent colonoscopy. Data were subjected to statistical analysis using SPSS software. RESULTS: Low-grade adenoma was more frequent among the elderly and in men. All of the men and 87.5% of the women with high-grade adenoma or adenocarcinoma were aged≥45 and≥50 years, respectively. In women, a larger waist circumference (=80 cm) increased the odds ratio for colon adenoma or adenocarcinoma (colon tumors) by 1.033 (95% confidence index (CI), 1.001-1.066; p=0.040). Metabolic syndrome significantly increased the odds ratio of colon tumors in men, but not in women. Cigarette smoking, drinking alcohol, and increased physical activity were significant risk factors for colon tumors in men, with odds ratios of 1.001 (95% CI, 1.000-1.002; p=0.001), 1.001 (95% CI, 1.000-1.003; p=0.047), and 1.406 (95% CI 1.038-1.904; p=0.028), respectively. CONCLUSIONS: Colon tumors have a high prevalence in the elderly. A larger waist circumference in women and metabolic syndrome in both men and women elevate the risk of colon tumors. In addition, smoking, drinking, and excessive physical activity are risk factors for adenoma and adenocarcinoma in men. For early detection of colorectal cancer, men older than 45 years and women older than 50 years with these risk factors are recommended to undergo colonoscopy.

Efficacy of high-throughput leukocytapheresis for rheumatoid arthritis with a reduced response to infliximab.

Infliximab (INF), a tumor necrosis factor-alpha (TNF-alpha) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high-throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS-180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28-joint disease activity score with C-reactive protein (DAS28-CRP) and with the erythrocyte sedimentation rate (DAS28-ESR). DAS28-CRP decreased significantly from 5.8 +/- 0.6 before LCAP to 3.9 +/- 0.7 (P = 0.0182) at 1-2 weeks after completion of five sessions of LCAP, and DAS28-ESR decreased significantly from 6.4 +/- 0.6 to 4.6 +/- 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF.

Assessment of left ventricular dyssynchrony during development of heart failure by a novel program using ECG-gated myocardial perfusion SPECT.

BACKGROUND: A novel program, "cardioGRAF", has been developed to analyze regional left ventricular (LV) systolic/diastolic function and dyssynchrony, so the present study aimed to use it confirm the presence of LV dyssynchrony, and to correlate LV function and dyssynchrony with plasma B-type natriuretic peptide (BNP) levels during the early to advanced stages of heart failure (HF). METHODS AND RESULTS: Fourteen control subjects (G-C) and 50 patients (New York Heart Association functional class I: G-1, 21 patients; class II: G-2, 15 patients; and class III: G-3, 14 patients) were examined by ECG-gated myocardial perfusion single-photon emission computed tomography, using the new index of dyssynchrony, maximal difference (MD), which is the difference between the earliest and latest temporal parameters among 17 segments. First-third filling rate (FR) and the MD of time to peak FR revealing diastolic dyssynchrony were significantly different between G-C subjects and G-1 patients. Ejection fraction, peak ejection rate, peak FR, MD of time to end-systole, and MD of time to peak ejection rate were significantly correlated with plasma BNP levels. CONCLUSION: Diastolic dyssynchrony was demonstrated even in the early stage of HF, but, although not correlated with the plasma BNP level, systolic dyssynchrony might affect it.

Improved stratification of perioperative cardiac risk in patients undergoing noncardiac surgery using new indices of dobutamine stress echocardiography.

OBJECTIVES: Prediction of perioperative cardiac events associated with noncardiac surgery remains difficult in patients whose functional capacity cannot be evaluated by exercise testing. Dobutamine stress echocardiography (DSE) has been used in these patients to improve risk stratification, but the results of standard DSE provide only a binary index of risk (positive or negative). Two new semiquantitative indices of DSE (semi-DSE) were retrospectively examined to determine the prediction of perioperative cardiac events compared to standard DSE. METHODS AND RESULTS: Clinical assessment of cardiac risk factors and standard DSE were performed safely in 122 consecutive patients (73 men, 49 women) undergoing noncardiac surgery. Preoperative revascularization was performed in 12 patients. The perioperative cardiac events consisted of 2 deaths, 4 cases of heart failure, and 2 cases of angina pectoris. For the semi-DSE indices, the extent of ischemia was indexed as the number of wall segments (SEG) displaying biphasic or worsening segmental wall-motion score, and the severity of ischemia (SI) was indexed as the sum of the differences in wall-motion scores between peak stress and rest divided by the number of affected segments. The optimal cut-off values of these indices for predicting cardiac events were 4.0 for SEG and 1.0 for SI. The risk stratification was further refined by these indices (high-, moderate-, and low-risk groups). The diagnostic accuracy of the semi-DSE indices, evaluated by the area under the receiver operating characteristic curves, was better than that of standard DSE (p < 0.001). CONCLUSIONS: Semi-DSE may improve cardiac-event risk stratification compared to standard DSE in patients undergoing noncardiac surgery whose functional capacity cannot be evaluated by exercise stress testing.

Effects of a single oral dose of cilostazol on epicardial coronary arteries and hemodynamics in humans.

Cilostazol, a novel cyclic adenosine monophosphate phosphodiesterase type III inhibitor, has been developed as an antiplatelet drug with a vasodilating action on peripheral arteries. The present study was designed to test, in humans, whether cilostazol can dilate the epicardial coronary arteries and what are its hemodynamic effects. Eight patients with chest pain syndrome were subjected to serial quantitative coronary arteriography immediately before and at 30, 60 and 150min after a single oral dose of cilostazol (200mg). Luminal cross-sectional areas (mm2) at the proximal and distal sites of major coronary arteries (6 segments at each sampling time) were significantly increased at 150 min after taking the drug. The percent increases relative to the baseline values were 25+/-7 (6.8+/-0.8-->8.3+/-1.0*) and 42+/-7% (2.1+/-0.3-->3.0+/-0.4*) in the right coronary artery, 24+/-5 (5.1+/-0.7-->6.1+/-0.8*) and 28+/-10% (1.6+/-0.31-->9+/-0.3*) in the left anterior descending artery, and 14+/-6 (5.9+/-0.9-->6.6+/-0.9*) and 24+/-10% (1.3+/-0.2-->1.5+/-0.2*) in the left circumflex artery, respectively (*p<0.05 vs baseline). This action, relative to that of nitroglycerine, was between 27% and 54%. Moreover, small but sustained decreases in systolic pulmonary pressure and stroke work index were observed. Thus, cilostazol has a mild coronary vasodilating action with minimal hemodynamic effects, thereby giving it a possible role in the treatment of coronary artery disease.