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Biomedical subjects

Masato Nakamura

Publications and source records attributed to Masato Nakamura.

At least 55 records · Page 3Linked to original sources

Chlamydia pneumoniae immunoreactivity in coronary artery plaques of patients with acute coronary syndromes and its relation with serology.

BACKGROUND: An association between Chlamydia pneumoniae (Cpn) infection and coronary artery disease has been reported and examined by different techniques. However, its immunoreactivity in coronary artery plaques of patients with acute coronary syndrome (ACS) and its relation with serology are less well defined. METHODS: We divided 40 coronary plaque specimens from 40 patients who underwent thrombectomy or directional coronary atherectomy into an ACS group (n = 22) and a non-ACS group (n = 18). Cpn in specimens was detected immunohistochemically and compared quantitatively. Serum immunoglobulin (Ig)A and IgG antibodies to Cpn and high-sensitivity C-reactive protein (hs-CRP) were measured. The relation between serology and immunohistochemical analysis was also investigated. RESULTS: Cpn immunopositive cells per square millimeter (Cpn+ cells/mm2) in the ACS group were significantly more numerous than in the non-ACS group (median 7.44 vs 1.50, P = .0018). Cpn IgA seropositivity rates and titers in the ACS group were significantly higher than those in the non-ACS group (86.3% vs 22.2%, P = .0002; median titer 1.403 vs 0.545, P = .003). There were no differences in IgG antibodies between the 2 groups. The hs-CRP values (in milligrams per liter) in ACS group were significantly higher than in non-ACS group (median 2.8 vs 1.2, P = .0019). Serum IgA titers in patients with at least 5 Cpn+ cells/mm2 in the specimens were significantly higher than in patients with fewer Cpn+ cells (median 1.52 vs 0.86, P = .026). There was no difference in serum hs-CRP values in patients with more Cpn+ cells but a trend to an increase. CONCLUSION: Immunohistology frequently detected Cpn in coronary plaques; Cpn+ cells were more prevalent in plaques associated with ACS, and Cpn IgA but not IgG titers were increased with ACS and with high densities of Cpn+ cells within plaque.

Acute Disease↗

Comparison of pharmacokinetics of the sirolimus-eluting stent in Japanese patients with those in American patients.

The aim of this study was to evaluate the pharmacokinetics of the sirolimus-eluting stent (SES) implanted in 20 Japanese patients with angina pectoris and compare it with that in US study. Bx VELOCITY stent loaded with a total sirolimus dose of 150 mug was used in this study. Ten patients were treated by single-SES (group 1) and 10 patients were treated by double-SES (group 2). Sirolimus levels in whole blood were serially measured in the 2 groups after the SES implantation and compared with the pharmacokinetics in US study. We also evaluated the side effect of sirolimus, major adverse clinical events, and binary angiographic restenosis at 8 months after the SES implantation. Peak concentrations were observed approximately 4 hours after the SES implantation, and sirolimus half-lives were approximately 120 hours in each group. Mean peak sirolimus levels were 0.86 and 2.00 ng/mL for the group 1 and group 2, respectively. The peak concentrations of sirolimus in this study were twice higher in Japanese than in Americans, but they were much lower than effective concentration of sirolimus when orally administrated as an immunosuppressive agent. There were no side effects of sirolimus and no binary angiographic restenosis in any patients. One patient had target vessel revascularization at 8 months after the SES implantation. Although blood concentrations of sirolimus in Japanese patients after SES implantation are somewhat higher than those in American patients, its level is extremely low compared with the systemic administration, indicating the same clinical benefits by the SES could be safely expected in Japanese patients.

Adult↗

Angiographic and clinical outcomes of a pharmacokinetic study of sirolimus-eluting stents: lesson from restenosis cases.

BACKGROUND: A pharmacokinetic (PK) study was conducted to evaluate sirolimus-eluting stents (SES) in Japanese people, representing the first clinical trial of the use of drug-eluting stents in Japan. METHODS AND RESULTS: The PK study was conducted in 20 patients with 30 lesions treated with sirolimus-coated BX Velocity stents. All lesions were treated with a single SES (3 x 18 mm). Angiographic follow-up was performed at 8 months after SES implantation, and the clinical outcomes were evaluated at 1 year in all cases. All procedures were successful, and all patients were discharged without any adverse cardiac events. The total restenosis rate was 10% (3 lesions) and target vessel revascularization was performed in those 3 cases (15%). Restenoses occurred at the proximal and distal stent margins. Intravascular ultrasound examination of restenosis cases revealed abundant plaque burden at the stent edges even though the luminal area was preserved. CONCLUSIONS: The sirolimus-eluting BX Velocity stent is safe and useful for Japanese patients with coronary artery disease. However, restenosis at proximal stent edge seems to be a problem.

Aged↗

Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.

Vascular endothelial growth factor A (VEGF-A) has two kinds of isoforms depending on cellular binding domains. VEGF189 is the largest molecule with the strongest cellular binding ability, and is thought to be most potent for vascularization in various cancers. This study aims to clear the clinicopathological characteristics of VEGF189 in the pulmonary adenocarcinoma. We finely and quantitatively examined the expression of VEGF-A isoforms (VEGF121, VEGF165 and VEGF189) by real-time polymerase chain reaction in a total of 100 pulmonary adenocarcinomas resected by surgical operation. The VEGF isoform expression status was analyzed on clinicopathological features including stromal vascularization, vascular involvement, distant metastasis, lymph nodal metastasis, postoperative relapse time and prognosis of long-term observation periods. All the pulmonary adenocarcinomas showed significant expression of VEGF-A. Twenty-two cases with the adenocarcinomas overexpressing VEGF-A significantly showed earlier postoperative relapse and poorer prognosis between 5- to 15-year periods (p = 0.0093 and p = 0.0240, Kaplan Meier, log-rank test). The expression levels of VEGF189 increased in 13% of the pulmonary adenocarcinoma. These 13 cases with increased VEGF189 expression significantly showed higher distant metastases, earlier postoperative relapse, and poorer prognosis (p = 0.0006, Fisher's test; p = 0.0016 and p = 0.0084, Kaplan Meier, log-rank test) than the other 87 cases. The 13 lung cancers with VEGF189 overexpression also showed increased vessel counts, areas (p = 0.0091 and p < 0.0001, Mann-Whitney U test) and enhanced venous involvement (p = 0.0056, Fisher's test). The cellular binding isoform VEGF189 confers pulmonary adenocarcinoma patients with poorer prognosis with distant metastasis via blood flow.

Adenocarcinoma↗

Bcl-2 overexpression enhances in vitro sensitivity against docetaxel in non-small cell lung cancer.

Taxanes (docetaxel and paclitaxel) as well as cisplatin (CDDP) are key chemotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC). Although some indicators of taxane resistance, such as beta-tubulin mutations, P-glycoprotein (P-gp) and Bcl-2, have been reported in malignant cells, the mechanisms of taxane resistance in NSCLCs have yet to be fully elucidated. We evaluated in vitro chemosensitivity to docetaxel (DOC) and CDDP in 87 surgically-resected specimens of NSCLC by collagen gel-droplet embedded culture drug sensitivity test (CD-DST). Bcl-2 and P-gp expression in these specimens were also investigated by immunohistochemistry. We examined the association between Bcl-2 and P-gp expression and in vitro chemosensitivity to DOC and CDDP. Out of the 87 NSCLCs that were examined, Bcl-2 and P-gp were expressed in 32 (36.8%) and 28 (32.2%) of the tumors, respectively. Positive Bcl-2 expression was significantly associated with enhanced DOC sensitivity in NSCLCs (p=0.007) while no apparent association was observed between DOC sensitivity and P-gp expression. Interestingly, although DOC, but not CDDP has been reported to be a substrate of P-gp, P-gp expression was significantly inversely correlated with CDDP sensitivity in pulmonary adenocarcinomas (p=0.03). Positive Bcl-2 expression may be a promising indicator in determining in vitro taxane sensitivity in NSCLCs. On the other hand, positive P-gp expression may be an indicator of enhanced in vitro resistance to CDDP in pulmonary adenocarcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts.

Certain pulmonary adenocarcinomas show gastrointestinal differentiation with the expression of various mucins. The CDX homeobox gene, an intestine-specific transcription factor, is related to gastric carcinogenesis with MUC2 and MUC6 expression. The intestinal mucin MUC2 is expressed in the normal lung, while the gastric mucin MUC6 is not. Previously, we have reported that the expressions of MUC2 and MUC6 were related to a poor prognosis in small adenocarcinomas of the lung. We estimated the expressions of the mucin (MUC2 and MUC6) and CDX (CDX1 and CDX2) to examine how CDX relates to the gastrointestinal mucin production in the pulmonary adenocarcinoma. Thirty-nine human non-small cell lung cancer (NSCLC) xenografts were examined (13 adenocarcinoma, 18 squamous cell carcinoma and 8 large cell carcinoma). Significant expression of the MUC6 gene was observed in 7 out of 39 (17.9%) NSCLC xenografts. The expressions of the MUC6 genes were noted in 6 out of 13 (46.2%) adenocarcinoma xenografts, but only in 1 of 18 (0.06%) squamous cell carcinoma xenografts. The adenocarcinoma xenografts significantly showed higher expression of the MUC6 gene than squamous cell carcinoma xenografts (t-test, p=0.0343). Four adenocarcinoma-xenografts co-expressed both the MUC2 and MUC6 genes, and the residual 2 adenocarcinoma-xenografts expressed only the MUC6 gene. One MUC6 overexpressing squamous cell carcinoma focally contained an adenocarcinoma component. The expression patterns of the gastrointestinal mucins were analogous to gastric cancer. The cellular morphology of these carcinoma xenografts was of the gastric cancer type. The proteins of the MUC2 and MUC6 were immunohistochemically confirmed in the xenografts. The expression of the MUC6 gene was significantly correlated with the expressions of the CDX1 and CDX2 genes in the xenografts (Fisher's test, p<0.0001 and p=0.0005, respectively), while there was no significant association between the expression of the MUC2 and CDX genes. These results suggest that the expression of CDX molecules in the pulmonary carcinogenesis pathway relates to gastric cancerous features of aberrant MUC6 expression.

Adenocarcinoma↗

Hepatocellular carcinoma with metastasis to the pharynx: report of a case.

Hepatocellular carcinoma (HCC) is rarely metastasized to the pharyngeal region. We report the case of a 59-year-old man admitted to our hospital with a complaint of hematemesis. An endoscopic examination revealed a tumor located in the left piriform sinus. Histological examination showed metastasis from HCC. Subsequent abdominal examinations demonstrated mild liver cirrhosis due to chronic HCV infection and primary nodules in the lateral segment of the liver. The pharyngeal tumor was completely removed by endoscopic polypectomy after radical hepatectomy for HCC. The patient died of recurrence of HCC 8 months after the first admission. With the presentation of this case, we review the literature reported so far.

Carcinoma, Hepatocellular↗

The modifier subunit of glutamate cysteine ligase relates to cisplatin resistance in human small cell lung cancer xenografts in vivo.

Glutamate cysteine ligase (GCL) plays an important role in the intracellular detoxification of cisplatin (CDDP). GCL is composed of a modifier or light chain subunit (GCLM) and a catalytic or heavy chain subunit (GCLC). Previously, we showed that the GCL subunits enhanced CDDP-resistance in non-small cell lung cancer (NSCLC) xenografts. In small cell lung cancer (SCLC), it is unclear whether the GCL subunits are essential to CDDP-resistance. We examined the gene expression of GCLM and GCLC in four human SCLC xenografts with the real-time polymerase chain reaction (PCR). An in vivo drug sensitivity test with CDDP was performed on the SCLC xenografts. CDDP-resistance was examined as the growth ratio of the relative volume of the treated xenografts to the controls (T/C%). The expression level of GCLM gene in SCLC was significantly lower than that in NSCLC (p=0.0026, Welch's t-test). One of four SCLC xenografts showed 62% of T/C and this was evaluated as CDDP-resistance, while the other three xenografts were sensitive to CDDP in vivo (Mann-Whitney U-test, p<0.01, one-sided). The expression level of the GCLM gene was significantly correlated to T/C% (Fisher's test, p=0.0289, correlations = 0.975), while the GCLC gene expression level was not associated with T/C%. These results suggest that the overexpression of GCLM is correlated with CDDP-resistance in SCLC xenografts in vivo.

Animals↗

S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in the NOD/SCID/gammaCnull (NOG) mouse model.

Tumor xenografts in immune-deficient mice (athymic nude mice and SCID mice) are well-established animal models for the study of human cancer. Several human melanoma cell lines were reported to metastasize in the immune-deficient mice models. However, metastatic rates were extremely low in spite of large numbers of injections of cancer cells, more than 1 x 10(6) cells/mouse. The NOD/SCID/gamma(C)(null) (NOG) mouse shows multiple immunological dysfunctions, including cytokine production capability, in addition to the functional incompetence of T, B and natural killer (NK) cells. However, the immune-deficient mice, with preserved NK cell activity, might interfere with engraftment efficiency. We examined the distant metastasis of the human melanoma cell lines (A2058, A375, G361 and HMY-1, 1 x 10(4) cells/mouse) in the 6 weeks after intravenous inoculation. All four melanoma cell lines showed metastasis in the NOG mice, while no metastatic lesions were observed in the NOD/SCID mice. Metastatic lesions were noted in the liver and lung of 6/6 (100%) mice at A2058, 8/9 (89%) at A375, 2/6 (33%) at G361 and 2/8 (25%) at HMY-1. A2058 and A375 cell lines with high metastatic potentials show increased gene expression of S100A4. Western blot assay confirmed the increased protein levels of S100A4 in the A2058 and A375 cell lines. E-cadherin gene expression was conversely inhibited in these cell lines. The increased expression of S100A4 combined with inhibited E-cadherin expression resulted in high metastatic potentials of the human melanoma cell lines in vivo.

Animals↗

[A case of HCC with inferior caval vein tumor thrombus and multiple pulmonary metastases that remarkably responded to combination therapy of TS-1 and interferon-alpha].

A 56-year-old male was admitted to our hospital for hepatoma with portal vein thrombus and multiple intrahepatic metastases. He underwent an extended left lobectomy and a partial resection of the liver in May 2002. After two weeks from the surgery, he received intra arterial 5-FU infusion chemotherapy combined with subcutaneous interferon-alpha injection to treat the lesions in the residual liver. Four months after the surgery, hepatic vein tumor thrombus appeared in the remnant liver and it extended to the inferior caval vein. And another 4 months later, multiple pulmonary metastases were detected with computed tomography and they grew rapidly in the view of their sizes and numbers. Because the combined therapy of 5-FU/interferon-alpha was not effective to distant metastases, we started a new regimen of oral administration of TS-1 and a subcutaneous interferon-alpha injection. After 1 treatment cool, hepatic vein thrombus was markedly reduced the size and vascularity in the CT. Multiple pulmonary metastases also decreased in their sizes and numbers. No adverse effect was seen during this treatment. It was suggested that a combination therapy of TS-1 and interferon-alpha may be one of the most effective treatment modalities against advanced HCC with distant metastasis.

Administration, Oral↗

[A successful surgical treatment for solitary pulmonary and adrenal metastases after hepatic resection to hepatocellular carcinoma--a case report].

We report a 65-year-old man who received a successful surgical treatment for both pulmonary and adrenal metastases after curative resection to hepatocellular carcinoma (HCC). He received a partial hepatic resection for HCC of the right hepatic lobe. Thirty-eight months after the first hepatic resection, a metastatic lesion of the right pulmonary lobe was detected by computed tomography (CT). He was orally administered of UFT (600 mg/day). After 6 months of the chemotherapy, a metastatic lesion of lung became decreased in size. However, a metastatic lesion of the right adrenal gland was detected by abdominal CT scan. Fifty six months after the first operation, we performed right adrenalectomy. A further 4 months later, we performed partial resection of the right pulmonary lobe. Eight months after the pulmonary resection, intrahepatic recurrence was detected and he received transcatheter arterial embolization (TAE) twice. Eighty one months after the first operation, he died of liver failure due to tumor progression. Surgical resection for metastases from HCC resulted in long-term survival even if there were extrahepatic metastases in two different sites.

Adrenal Gland Neoplasms↗

[Successful treatment of combined intraarterial (5-fluorouracil and adriamycin and cisplatin) infusion chemotherapy for advanced hepatocellular carcinoma with multiple intrahepatic metastases and/or portal vein thrombosis--two case reports].

Hepatic arterial infusion chemotherapy has been often selected as a therapeutic option for advanced hepatocellular carcinoma with multiple intrahepatic metastases and/or portal vein thrombosis. We successfully treated and obtained CR in the 2 cases of far advanced hepatocellular carcinoma with intraarterial infusion chemotherapy (FAP). Case 1 was a 71-year-old male who had advanced hepatocellular carcinoma with intrahepatic metastasis (IM3) which was recurrent after two surgeries. He received hepatic arterial infusion chemotherapy (FAP: 5-fluorouracil 500 mg/day: continuous infusion, day 1-5, adriamycin 10 mg/day, day 1, CDDP 10 mg/day, day 1). After 10 courses, abdominal CT revealed that the viable lesions had completely disappeared (CR). This patient is still alive with no recurrence after 21 months from the beginning of this treatment. Case 2 was a 74-year-old male who had advanced hepatocellular carcinoma with portal vein thrombi (Vp4) and intrahepatic metastasis (IM3). He received FAP arterial infusion chemotherapy with the same protocol as case 1. After 8 courses of this therapy, CT revealed that these lesions had disappeared (CR). This patient is still alive with no recurrence after 9 months from the beginning of this treatment. For 15 patients with advanced hepatocellular carcinoma using a same protocol, the response rate of this therapy was 33.3% (CR & PR). These findings suggested that combined arterial infusion chemotherapy of FAP may be feasible and a promising modality for the advanced HCC with intrahepatic metastases and/or portal vein thrombosis.

Aged↗

[Health-related quality of life in Japanese patients with ischemic heart disease: a multicenter cooperative investigation assessed using SF-36].

OBJECTIVES: To investigate the quality of life (QOL) of Japanese patients with ischemic heart disease. METHODS: The QOL data of 753 patients with chronic and stable ischemic heart disease was assessed using SF-36 Japanese version 1.2 and compared with Japanese national norms. Physical (PCS) and Mental Component Summary (MCS) scores were calculated to examine the correlation with patient background. Patients were also asked about subjective symptoms during the QOL investigation. RESULTS: Mean age was 63.6 +/- 7.5 years old and the male/female ratio was 85.7/14.3. About one third (30.7%) of the patients were symptomatic and about half (52.6%) had a history of myocardial infarction. Compared to Japanese national norms, physical functioning, role-physical, social functioning, general health and role-emotional were lower, and body pain, vitality and mental health were higher. PCS was significantly lower and MCS was significantly higher in aged patients than in younger patients (p < 0.0001, p < 0.0001). PCS and MCS were significantly lower in the symptom (+) group than in the symptom (-) group (p = 0.0009, p < 0.0001). PCS decreased as the number of anti-angina medications for the patients increased (p = 0.0002). PCS was significantly lower and MCS was significantly higher in the beta blocker (+) group than in the beta blocker (-) group (p < 0.0001, p < 0.03). Multivariate logistic regression analysis showed that age ( > or = 63 years old), symptom (+), duration of disease (> or = 3 years) and beta blocker (+) influenced the QOL. CONCLUSIONS: The QOL level of patients with ischemic heart disease was found to depend on the clinical condition and treatment, so the optimal treatment for ischemic heart disease must be established to improve QOL.

Adrenergic beta-Antagonists↗

Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma.

PURPOSE: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNalpha and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNalpha, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNalpha-induced cytotoxic effects of PBMC on HCC cell lines were examined by (51)Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. RESULTS: HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNalpha induced TRAIL on CD4(+) T cells, CD14(+) monocytes, and CD56(+) NK cells. Treatment of effector cells by IFNalpha and target HCC cells by 5-FU enhanced the cytotoxicity of CD14(+) monocytes and CD56(+) NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNalpha/5-FU combination therapy, and TRAIL(+) mononuclear cells were found in cancer tissue of a responder. CONCLUSION: Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNalpha and 5-FU combination therapy.

Adult↗

Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists.

Novel group II metabotropic glutamate receptor (mGluR) antagonists, 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives 11 and 12, were discovered by the incorporation of a hydroxy or alkoxyl group onto the C-3 portion of selective and potent group II mGluR agonist 5, (1R,2S,5R,6R)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid. Among these compounds, (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (-)-11be (MGS0039) was a highly selective and potent group II mGluR antagonist with the best pharmacokinetic profile. Compound (-)-11be exhibited high affinities for mGlu 2 (Ki = 2.38 +/- 0.40 nM) and mGlu 3 (4.46 +/- 0.31 nM) but low affinity for mGluR 7 (Ki = 664 +/- 106 nM), and potent antagonist activities for mGlu 2 (IC50 = 20.0 +/- 3.67 nM) and mGluR 3 (IC50 = 24.0 +/- 3.54 nM) but much less potent antagonist activities for mGlu 4 (IC50 = 1740 +/- 1080 nM), mGlu 6 (IC50 = 2060 +/- 1270 nM), mGlu 1 (IC50 = 93300 +/- 14600 nM), and mGluR 5 (IC(50) = 117000 +/- 38600 nM). No significant agonist activities of (-)-11be were found for mGluRs 2, 3, 4, 6, 1, and 5 (EC50 > 100,000 nM). Furthermore, (-)-11be exhibited dose-dependent oral absorption (plasma C(max): 214 +/- 56.7, 932 +/- 235, and 2960 +/- 1150 ng/mL for 3 mg/kg, 10 mg/kg, and 30 mg/kg, po, respectively) and acceptable blood-brain barrier penetration (brain C(max): 13.2 ng/mL for 10 mg/kg, p.o. 6 h). In this paper, we report the synthesis, in vitro pharmacological profile, and structure-activity relationships (SARs) of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives 11 and 12, and pharmacokinetic profiles of several typical compounds.

Administration, Oral↗

Prognostic value of stress myocardial perfusion imaging using adenosine triphosphate at the beginning of haemodialysis treatment in patients with end-stage renal disease.

BACKGROUND: Non-invasive detection of coronary artery disease (CAD) remains difficult in patients with end-stage renal disease (ESRD). This study evaluated the ability of pharmacologic stress myocardial perfusion imaging to predict cardiac events in patients with ESRD. METHODS: A prospective study was carried out in 49 consecutive patients with ESRD. Thallium-201 single photon emission computed tomography (SPECT) using high-dose adenosine triphosphate (ATP) was performed within 1 month of the beginning of haemodialysis. The study end-point was a cardiac event or the 1-year anniversary of the SPECT study. RESULTS: Twenty-four patients (17 diabetics, 57% and seven non-diabetics, 37%) had myocardial perfusion defects. The remaining 25 patients had normal perfusion images. Fifteen patients had non-fatal cardiac events and two patients died of a cardiac cause. All patients who had non-fatal cardiac events underwent myocardial revascularization and survived until the end of follow-up. The 1-year cardiac event-free survival rate was 34% among patients with perfusion defects and 96% among patients without perfusion defects (P<0.001). The presence of a myocardial perfusion defect was the only independent predictor of 1-year cardiac events both in overall (HR, 49.91; 95% CI, 5.15-484.00; P<0.001) and in diabetic patients (HR, 33.72; 95% CI, 2.96-383.5; P = 0.005). Diabetes and an increased C-reactive protein were associated with the progression of CAD. CONCLUSIONS: Normal myocardial perfusion imaging by stress thallium-201 SPECT using high-dose ATP performed within 1 month after the beginning of haemodialysis treatment is a powerful predictor of cardiac event-free survival in patients with ESRD.

Cardiovascular Diseases↗