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A scintigraphic technique using indium-111 labelled platelets to detect left atrial thrombi was used in 28 patients, 14 of whom had mitral valve disease and 14 combined valve disease. Imaging was performed in the anterior, right anterior oblique (45 degrees), and left lateral views on the day of injection and thereafter at one or two day intervals for a maximum of four days. When scintiphotos obtained in two or three views 72 or 96 hours after the platelet injection showed "hot spot areas" within the left atrial pool and indium-111 activity in these areas did not decrease with time they were interpreted as positive for thrombi. Of 28 patients, seven had positive platelet images by this criterion; of these, three underwent surgery and were found to have left atrial thrombi. One patient died, and a thrombus was found at necropsy. The remaining 21 patients had normal scintiphotos; of these, seven had no thrombi at operation and one had false negative images. The diagnostic accuracy of platelet scintigraphy by this criterion of positivity in the 12 patients in whom surgical or postmortem confirmation of thrombi could be obtained was 92%. These results indicate that this technique is a promising method for detecting active left atrial thrombi. [ABSTRACT FROM PUBLISHER]

Objectives: We evaluated the efficacy and safety of cyanoacrylate closure (CAC) for endovascular treatment of varicose veins with cyanoacrylate adhesive (VenaSeal® closure system) in Japan., Methods: A multicenter prospective consecutive registry study was conducted at 12 centers in Japan on 125 patients with primary varicose veins who underwent CAC. The patients were evaluated on target vein occlusion, postoperative complications, Visual Analogue Scale (VAS) for pain, revised Venous Clinical Severity Score (rVCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and EuroQol 5 dimensions 5-level (EQ-5D-5L) for 1-year after the surgery., Results: The closure rate was 92.6% at 1 year postoperatively, and 95.0% and 90.2% for GSV and SSV respectively with little difference ( p = .491). The mean VAS in the immediate postoperative period was 18.9 ± 23.4. Postoperative complications were observed in 20 patients (16%). Hypersensitivity-type phlebitis occurred in 7 patients (5.6%). Infection of the treated vein resulted in resection of GSV. The rVCSS and AVVQ improved significantly after 90 days and 1 year postoperatively ( p < .001), while the EQ-5D-5L have not changed., Conclusion: Cyanoacrylate Closure was considered generally a safe and minimally invasive treatment with good mid-term outcomes including SSV. However further study is required for some CAC specific complications., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HM is consultant of Integral Co. Tokyo Japan. The other authors have no conflict of interest in relation to the contents of this manuscript.

Bejel, caused by Treponema pallidum subsp. Endemicum (TEN), is a locally transmitted disease among children and juveniles in hot and dry regions. The number of adult cases of TEN infection outside of endemic areas has recently increased. We clinically examined five cases of TEN infection among adult cases previously reported in Japan. TEN infection mainly developed among young to middle-aged men who have sex with men (MSM). The clinical features of cases of TEN infection were similar to those of primary- and secondary-stage T. pallidum subsp. pallidum (TPA) infection. Genital lesions were common as the primary lesion. The clinical features and laboratory parameters of cases of TEN infection were similar to those of TPA infection. Most of the isolated strains had the A2058G mutation in 23S rDNA, which is responsible for resistance to macrolides. We also performed the systemic literature review of the TEN cases outside the endemic countries. The recent reported cases diagnosed with molecular methods shared the clinical features, occurred in young-to middle-aged sexually active persons in urban areas of developed countries and often accompanied with genital lesions, which were distinct from the classic description of bejel. This case series and the literature review provides important clinical insights and will contribute to the clinical detection of this rarely identified disease in developed countries. The surveillance of treponematoses, including TEN infection, using molecular diagnostic techniques is also warranted in developed countries, for the purpose of grasping the epidemic situation and control the local transmission., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Abstract: We identified and characterized the first 2 Neisseria gonorrhoeae strains with high-level azithromycin resistance isolated in Japan. These were in the clade of ceftriaxone- and azithromycin-resistant strains isolated in Australia and the United Kingdom. The multilocus sequence typing, N. gonorrhoeae multiantigen sequence typing, and N. gonorrhoeae sequence typing for antimicrobial resistance types of these strains were found in gonococci from eastern Asia., Competing Interests: Conflict of Interest and Sources of Funding: This work was partly supported by Japan Agency for Medical Research and Development (grant number 18fk0108062), JSPS KAKENHI (grant number JP18K09163), and the Ministry of Health, Labour, and Welfare of Japan (grant H30-Shinkou-Ippan-004). The authors declare no conflicts of interest directly relevant to the content of this article., (Copyright © 2020 American Sexually Transmitted Diseases Association. All rights reserved.)

We developed a rapid multiplex PCR assay available in bedside for the simultaneous detection of Neisseria gonorrhoeae and Chlamydia trachomatis, which enables diagnosis in less than 30 minutes. In this study, we validated the clinical utility of this assay including its sensitivity and specificity for NG and CT detection., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction. Human adenovirus (HAdV) has been reported as a potential cause of sexually transmitted urethritis. Aim. We aimed to investigate HAdVs associated with urethritis in Osaka, Japan through molecular characterization. Methodology. Urine samples were obtained from male patients with urethritis from 2015 to 2018. Molecular analysis of the isolated strains and follow-up real-time polymerase chain reaction analyses of the clinical samples were performed. Results. The isolates were classified into five types belonging to species D (18 cases) or E (one case). HAdV-85 (species D) was detected for the first time in a urethritis case. Follow-up examination demonstrated that HAdV was isolated from urine samples half a month after the first sampling in four cases, and that viral DNA could be detected after 1 month in two cases. Conclusion. The HAdV types detected from urethritis cases were related to respiratory and ocular HAdV infections, while a novel HAdV type identified as a cause of conjunctivitis also causes urethritis. Sexual contact should be avoided for 1 month after HAdV genital infection.

Bejel, an endemic treponematosis caused by infection with Treponema pallidum subspecies endemicum, has not been reported in eastern Asia and the Pacific region. We report local spread of bejel among men who have sex with men in Japan. Spread was complicated by venereal syphilis.

Human treponematosis is caused by various pathogenic Treponema pallidum subspecies, including T. pallidum subsp. pallidum , T. pallidum subsp. pertenue , T. pallidum subsp. endemicum , and Treponema carateum The global prevalence of syphilis has been increasing since the 2000s. Men account for more than 90% of the cases, with the majority being men who have sex with men (MSM). In Japan, the increase in the number of syphilis patients began in 2011, a 10-year delay from the global trend. In 2017, a total of 5,829 syphilis cases (3,934 men and 1,895 women) were reported, with an outstanding increase in cases among young adult women; the number reported for women age 15 to 20 years was 1,100. Hence, a molecular epidemiological study was conducted on circulating T. pallidum strains using two strain typing methods, the enhanced CDC method and sequencing-based molecular typing. Clinical specimens from 95 adults suspected of syphilis were collected from September 2013 to August 2017 in Osaka, Japan. T. pallidum DNA was detected in specimens from 25 males and 11 females, including seven MSM. The majority of the heterosexual patients (66.7% and 90.9% of males and females, respectively) were positive for 14d/f-SSR8. In contrast, the genotypes identified in the MSM group were significantly divergent. T. pallidum subsp. endemicum was notably identified in two MSM patients. Macrolide-sensitive or Nichols-like strains were significantly associated with the MSM group. These data suggest that distinct T. pallidum strains were circulating in the heterosexual and MSM groups. Our findings imply that independent factors may contribute to the increased syphilis prevalence in heterosexual and MSM populations., (Copyright © 2019 American Society for Microbiology.)

Macrolide or fluoroquinolone-resistant Mycoplasma genitalium is spreading worldwide. We aimed to determine the influence of single nucleotide polymorphisms (SNPs) in the quinolone resistance determining regions (QRDR) of parC and gyrA in cultured M. genitalium strains. In addition, we examined the prevalence of macrolide- and fluoroquinolone resistance mediating mutations in specimens collected from Japanese male patients with urethritis in two time-periods between 2005-2009 and 2010-2017, respectively, by sequencing the QRDR of parC and gyrA and domain V of the 23S rRNA gene. The minimum inhibitory concentrations (MIC) of moxifloxacin, sitafloxacin, ciprofloxacin, levofloxacin, doxycycline, minocycline, azithromycin and clarithromycin were determined in 23 M. genitalium strains. Three cultured strains had elevated MICs for moxifloxacin at 16, 4 and 2 mg/L and had SNPs with the amino-acid change Ser83→Ile in ParC (p<0.001) and 3 kinds of SNPs with amino-acid changes Asp99→Asn, Gly93→Cys and Met95→Ile in GyrA, respectively. Among a total of 148 M. genitalium positive urine specimens, the prevalence of A2058G and A2059G SNPs in the 23S rRNA gene and any SNPs in ParC increased from 4.8% and 22.6% in 2005-2009 to 42.2% and 53.1% in 2010-2017, respectively. If M. genitalium is considered multi-drug resistant in clinical specimens carrying SNPs in the 23S rRNA gene and Ser83→Ile in ParC, the prevalence of multi-drug resistance is 12.5% in 2010-2017 in Japan. In conclusion, the SNP resulting in Ser83→Ile in ParC is closely related to moxifloxacin resistance even though other factors may also affect treatment outcomes by moxifloxacin. The prevalence of circulating multi-drug resistant M. genitalium strains with macrolide- and fluoroquinolone-resistance is dramatically increasing in Japan., Competing Interests: The authors have read the journal’s policy and have declared that no competing interests exist.

Objectives: To investigate the presence of microorganisms related to urethritis in the oral cavity of male patients with urethritis and the efficacies of antimicrobials for urethritis on microorganisms in the oral cavity., Methods: Ninety-two male patients with urethritis and 17 male controls participated to this study at 12 urology clinics in Japan between March 2014 and March 2015. The first voided urine (FVU) and oral wash fluid (OWF) specimens were collected from the participants. The microorganisms in both FVU and OWF specimens were detected by nucleic acid amplification tests at the first and follow-up visit. The efficacies of antimicrobials were evaluated after 1-4 weeks treatment completion., Results: In a total of 92 male patients with urethritis, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, Ureaplasma parvum, Trichomonas vaginalis and Gardnerella vaginalis were detected from OWF specimens of 12%, 3%, 9%, 0%, 12%, 3%, 3% and 15% patients, respectively. From control males, no microorganism was detected from OWF specimens. Among 46 patients who could be evaluated for antimicrobial efficacies at the follow-up visit, 5 in FVU specimens failed by azithromycin (AZM), and 10 failed in OWF specimens (7 by AZM, 2 by tetracycline, 1 by spectinomycin; p = 0.002). Especially, a high prevalence of G. vaginalis remained positive after treatment for urethritis in the oral cavity., Conclusion: Microorganisms related to urethritis were detected in the oral cavity of male patients with urethritis. Antimicrobials that focused on urethritis, especially AZM regimen seem to be less effective for microorganisms in the oral cavity., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We have characterized in detail a new ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain (FC428) isolated in Japan in 2015. FC428 differed from previous ceftriaxone-resistant strains and contained a novel mosaic penA allele encoding a new mosaic penicillin-binding protein 2 (PBP 2). However, the resistance-determining 3'-terminal region of penA was almost identical to the regions of two previously reported ceftriaxone-resistant strains from Australia and Japan, indicating that both ceftriaxone-resistant strains and conserved ceftriaxone resistance-determining PBP 2 regions might spread., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The rare hepatitis B virus (HBV) genotype G (HBV/G) coinfects HIV-1-positive individuals along with HBV/A and generates recombinants. However, the circulation of HBV A/G recombinants remains poorly understood. This molecular epidemiologic study examined HBV A/G recombinants in Japanese HIV-1-positive men who have sex with men (MSM). Initially, blood specimens submitted for confirmatory tests of HIV infection in Osaka and Tokyo, Japan, from 2006 to 2013 were examined for HIV-1, and HIV-1-positive specimens were screened for HBV. Among 817 specimens from HIV-1-positive individuals, HBsAg was detected in 59 specimens; of these, HBV/Ae (alternatively A2), a subgenotype of HBV/A prevalent in Europe and North America, was identified in 70.2%, HBV/C in 17.5%, and HBV/G in 10.5%, and HBV/E in 1.8% according to the core gene sequence. The full-length genome analysis of HBV was performed on HBV/G-positive specimens because some HBV A/G recombinants were historically overlooked by genotyping based on a partial genome analysis. It revealed that five of the specimens contained novel Ae/G recombinants, the core gene of which had a high sequence similarity to HBV/G. Detailed analyses showed that novel recombinants were coinfected with HBV/Ae in a recombinant-dominant fashion. No major drug-resistant mutations were found in the newly identified HBV Ae/G recombinants. Some of the individuals asymptomatically coinfected with HIV/HBV suffered mild liver injury. This study demonstrated that novel Ae/G HBV recombinants were identified in Japanese HIV-1-positive MSM. The pathogenicity of novel HBV Ae/G recombinants should be examined in a future longitudinal study. Surveillance of such viruses in HIV-1-positive individuals should be emphasized.

Objectives: To evaluate the feasibility and safety of a virtual 3-Fr system [5-Fr sheathless-guiding catheter (GC)] for percutaneous coronary intervention (PCI)., Background: The use of miniaturized devices for PCI is gaining popularity because of increased patient comfort and decreased risk of access site complications., Methods: From July 2010 to December 2012, consecutive patients who underwent elective PCI (planned or ad hoc PCI) at our hospital were enrolled. PCI using the virtual 3-Fr system was attempted as our initial strategy, unless a 6-Fr or larger GC was considered to be suitable [lesions with heavy calcification, large (>2 mm) side branches, or chronic total occlusion]., Results: Five hundred sixty-six patients underwent elective PCI during the study period, and 132 patients who met the criteria underwent PCI using the virtual 3-Fr system. Procedures using the virtual 3-Fr system were successful in 126 patients (95%); 111 (84%) were performed using the transradial approach, 110 (83%) were ad hoc procedures, and 45 (31%) were complex coronary lesions (type B2 or C). Six patients required conversion to a conventional 5- or 6-Fr sheath and catheter system. No intraoperative complications occurred, and radial artery patency was achieved in all patients who underwent transradial procedures., Conclusions: PCI using the virtual 3-Fr system is a feasible and viable alternative to conventional procedures that use a sheath and GC in appropriately selected patients. This small-caliber system may minimize endovascular trauma, particularly during transradial coronary procedures., (© 2014 Wiley Periodicals, Inc.)

This study was performed to determine the associations between human papillomavirus (HPV) infection and cytological changes in the male glans and urethral samples. Two rubbed samples of the glans and distal urethra were collected from 160 patients with urethritis, and the collected cells were placed into preservative solution for liquid-based cytology. DNA was extracted from all samples, and β-globin gene amplification, HPV-DNA test, and HPV genotyping were performed. After papanicolaou staining of each sample, cytological findings were assessed based on nine non-classic signs, and compared with the results of HPV-DNA test. Among the β-globin positive samples, HPV (any type) was detected in 33 and 25% of the glans and urethra samples, respectively. High-risk HPV-DNA was detected in 25 and 15% of the glans and urethra samples, respectively. In the glans samples, cytological signs of HPV infection were observed in 17% of low-risk HPV-positive samples and in 58% of high-risk HPV-positive samples. Cytological atypia suspected to indicate penile intraepithelial neoplasia were observed in 17 and 33%, respectively. On the other hand, abnormal cells were observed in 29% of low-risk HPV-positive and 83% of high-risk HPV-positive urethral samples. Cytological atypia suspected to be urethral intraepithelial neoplasia was observed in 29 and 65%, respectively. In situ hybridization demonstrated the presence of HPV-DNA in the morphologically abnormal cells in 31 and 35% of high-risk HPV-positive glans and urethral samples, respectively. Cytological changes similar to cervical intraepithelial neoplasia in females could be detected in the HPV-positive glans and urethral samples., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To describe a novel technique using an antegrade wire in a retrograde microcatheter advanced through a transcollateral vessel for recanalization of challenging infrapopliteal chronic total occlusions., Technique: A 75-year-old diabetic man presented with critical limb ischemia manifested as nonhealing ulcers on the toes. Baseline angiography revealed a blunt, long, total occlusion of the anterior tibial artery. A retrograde microcatheter was advanced over a guidewire tracking the collateral channel from the planter artery. Antegrade and retrograde microcatheters were aligned inside the occluded lesion. An antegrade wire was then advanced further down through the retrograde microcatheter. Final angiography of the anterior tibial artery following balloon dilation demonstrated a satisfactory result, without evidence of significant residual stenoses or flow-limiting dissections. Complete wound healing was achieved at 3 weeks., Conclusion: This alternative wire method may be useful when traditional interventional approaches are unfeasible.

Addition of O(2) enables the liquid-phase hydrogenation of phenol using H(2) at low temperatures under atmospheric pressure with an unexpected selectivity towards 2-cyclohexene-1-one rather than cyclohexanone. As a catalyst, as-synthesized Pd/MCM-41 including the residual templates within the mesoporous channels exhibits a prominent positive effect on the catalytic performance.

Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by in situ hybridization (ISH). The β-globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (P < 0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except Ureaplasma parvum) were significantly higher in urethritis cases than controls (P < 0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and Ureaplasma. HPV infection occurs in urothelial cells, especially in gonococcal urethritis.

To analyze the risk factors for HPV infection in the urethra, we examined the prevalence of various microorganisms, for example Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, Gardnerella vaginalis, and human papillomavirus (HPV) in Japanese male patients with urethritis, and investigated their sexual backgrounds. Rubbed samples obtained from the distal urethra and questionnaires regarding sexual activity and demographic information were collected from 176 participants. N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis, U. urealyticum, U. parvum, G. vaginalis, and HPV were detected in 19, 26, 18, 12, 12, 8.5, 14, and 20%, respectively, of all cases in this study. Multivariate logistic regression analysis indicated that more than 4 sexual partners within the last year and presence of N. gonorrhoeae and/or C. trachomatis and/or M. genitalium infections were independent risk factors for urethral HPV infection, with odds ratios of 3.85 (95% CI 1.49-9.94) and 2.41 (95% CI 1.03-5.61), respectively. It is likely that urethral HPV detection is associated with current sexual activity and the presence of N. gonorrhoeae, C. trachomatis, and/or M. genitalium infections.

Objectives: To investigate the prevalence of human papillomavirus (HPV) in the genital and urinary tract of men with urethritis., Methods: Cell samples were collected from the penis, urethra and urine of 142 men with urethritis. A HPV test was performed on the samples using the modified GP5+/6+ polymerase chain reaction method, and the HPV genotype was determined using a HPV GenoArray test., Results: Out of 142 urethritis patients, HPV was detected in 48% (68 cases), and high-risk HPV was found in 32% (46 cases) of patients, on their penis or in the urinary tract (urethra or urine). HPV was detected in 31% in the penis, 20% in the urethra and 24% in the urine, while high-risk HPV was identified in 23% in the penis, 12% in the urethra and 11% in the urine. Among the HPV-positive men, 66% had HPV infection in the urinary tract where the most common HPV types were HPV6, HPV16, HPV18 and HPV58. Single HPV-type infection was more frequently found in the urinary tract (89%) than in the penis (65%) (P < 0.05)., Conclusions: Similar to the penis, the urinary tract represents a common HPV infection site in men with urethritis.

In Japan, the incidence of syphilis has decreased, and clinicians might be more likely to overlook syphilis than before. We show typical clinical manifestations and treatment of syphilis for clinicians unfamiliar with the disease and emphasize that two types of serologic test, non treponemal tests and specific treponemal tests, are essential for diagnosis of syphilis. Recent automated serologic tests for syphilis are useful to examine patients' progress after they are treated. The early stage of syphilis is gradually spreading among men in Japan, and HIV coinfections are often caused by homosexual contacts. We present a sample figure in the classic medical book, "Atlas of syphilis and the venereal diseases".

Chymase is an important enzyme for the generation of angiotensin (Ang) II and in the activation of transforming growth factor (TGF)-beta1. Therefore, chymase may be involved in the hemodialysis access dysfunction, which is caused by intimal hyperplasia that occurs after polytetrafluoroethylene (PTFE) graft implantations. Bilateral U-shaped PTFE grafts were placed between the femoral vein and artery in dogs. Chymase inhibitor (NK3201, 1 mg/kg per day, p.o.) treatments were initiated 3 days before the operation. After the implantation, the stenosis by neointima proliferation was most frequently observed in the venous side of the PTFE grafts. In the hyperplastic neointima, myofibroblasts were the main cellular components. On the other hand, fibroblasts only occupied cellular components in a much smaller proportion in the neointima. However, these cells seem to be rich in the properties of proliferation and migration. After PTFE graft implantations, extensive accumulations of chymase-positive mast cells were found mainly in the tissue surrounding the grafts. The Ang II- and TGF-beta-positive cells were found in an adjacent section that was in close proximity to the chymase-positive cells. In contrast, the AT(1) receptors, as well as TGF-beta type II receptors, were expressed either in the neointima or in the outside adventitia of the PTFE grafts. Chymase inhibitor treatment resulted in a reduction of chymase, Ang II and TGF-beta1 expression, leading to a significant inhibition of neointimal formation. These findings indicating that an increase of chymase via promoting Ang II and TGF-beta1 generation plays a pivotal role in the neointimal formation after the implantation of PTFE grafts and also suggesting that chymase inhibition may be a new strategy that can be used to prevent PTFE graft dysfunctions in clinical settings.

We investigated whether an angiotensin-converting enzyme (ACE) inhibitor could inhibit matrix metalloproteinase (MMP) activities in cerebral infarct lesions after middle cerebral artery occlusion (MCAO) in rats. After placebo or trandolapril (5 mg/kg per day) was administered orally for 7 days, we permanently occluded the right middle cerebral artery. ACE activity in extracts from the infarct side of placebo-treated rats was significantly higher than that in extracts from the non-infarct side from 5 days after MCAO, though they did not differ at 1 day. ACE activities in extracts from both hemispheric segments in the trandolapril-treated group were significantly decreased compared with those in the placebo-treated group before MCAO, and this significant reduction persisted even at 7 days after MCAO. In the placebo-treated group, MMP-9 and MMP-2 activities in the infarct side were significantly increased at 12 h and at 1 day after MCAO, respectively. Trandolapril treatment significantly reduced MMP-9 and MMP-2 activities to 68.5% and 53.2%, respectively. Seven days after MCAO, the ratios of infarct areas to the hemispheric sectional areas in placebo- and trandolapril-treated rats were 55.4+/-2.1% and 30.9+/-2.9%, respectively, and this difference was significant. Neurological severity scores were significantly improved from 1 to 7 days after MCAO in trandolapril-treated rats. Cumulative survival in trandolapril-treated rats was significantly increased compared with that in placebo-treated rats. Thus, the inhibition of MMP-9 by trandolapril might be part of the mechanism that prevents cerebral damage after cerebral ischemia.

In this study, we investigated the effect of a specific chymase inhibitor, NK3201, in the progression of abdominal aortic aneurysm in a dog experimental model. Abdominal aortic aneurysms were induced in dogs by injecting elastase into the abdominal aorta. NK3201 (1 mg/kg per day, p.o.) or a placebo was started 3 days before elastase injection and continued for 8 weeks after the injection. On abdominal ultrasound, the aortic diameter was seen to gradually expand in the placebo-treated group, but not in the NK3201-treated group. Eight weeks after elastase injection, the ratio of the medial area to the total area in the placebo-treated group was significantly smaller than that in the normal group, but it was significantly larger than that in the NK3201-treated group. In addition to chymase activity, angiotensin II-forming and matrix metalloproteinase-9 activities were significantly higher in the placebo-treated group than in the normal group; in the NK3201-treated group, all of these activities were significantly decreased. On immunohistochemical analyses, there was a significantly greater number of chymase-positive cells in the placebo-treated group than in the normal group, but the number was significantly smaller in the NK3201-treated group than in the placebo-treated group. Thus, chymase inhibition may become a useful strategy for preventing abdominal aortic aneurysms.

Chymase is known to generate angiotensin II in the vascular wall. In this study we investigated a novel role for chymase other than angiotensin II production in vascular proliferation after balloon injury. Chymase promoted the migration of vascular smooth muscle cells in the matrix-coated invasion chambers and activated promatrix metalloproteinase-2 obtained from the culture medium of vascular smooth muscle cells. Two weeks after balloon injury, significant neointimal formation was found in dog carotid arteries. After injury, active matrix metalloproteinase-2 was increased in parallel with the augmentation of chymase activity that was seen in the proliferating region of the vascular wall. The oral administration of NK3201 (1 mg/kg per day), a chymase inhibitor, prevented neointimal formation and significantly suppressed both active matrix metalloproteinase-2 and chymase activities 2 weeks after injury. These results suggest that chymase inhibitors can prevent the development of intimal hyperplasia via the inhibition of matrix metalloproteinase-2 activation in balloon-injured arteries.

Objectives: Traumatic aortic rupture is highly lethal and an ongoing therapeutic challenge. We review our 7-year experience with traumatic aortic disruption., Methods: We treated 12 cases of traumatic rupture of the thoracic aorta (TRTA) from December 1994 to June 2001 at our institution. Of these, 9 were male, and the average age 26 years. Injuries were caused by traffic accidents in 9 cases and falls in 3. Contrast-enhanced helical computed tomography was used to diagnose10 cases and digital subtraction angiography to diagnose 2 at other hospitals. Six of 12 (50%) disruptions were located in the aortic isthms. All surgery was conducted under cardiopulmonary bypass. A percutaneous cardiopulmonary support system (heparin-bonded artificial lung and centrifugal pump) was used in 6 cases since 1998., Results: Among the 12 patients, 6 had early surgical repair within 2 days after the accident, and all survived free of neurological problems. Six other had repair delayed more than 2 days and all were doing well., Conclusion: Immediate repair of aortic lesions should be the rule because the majority of deaths from TRTA occur within 24 hours. We believe, however, that immediate surgery may not be necessary for some patients with severe, multiple associated lesions who survive initial traumatic aortic disruption of the aorta.

We report herein the case of a 78-year-old man found to have abdominal aortic aneurysm (AAA) with an isolated left-sided inferior vena cava (IVC). The patient was admitted to our hospital to undergo surgery for the AAA. The computed tomography revealed the sacular aneurysm of the infrarenal abdominal aorta (60 x 40 mm) and right common iliac aneurysm (30 x 30 mm). At the same time the left sided IVC was found by the CT. This IVC (13 mm wide) ascended 76 mm, dorsally to the ureter, the left side of the AAA from the right common iliac artery to the left renal artery. We performed aneurysmectomy and 20 mm knitted Dacron bifurcating graft replacement by the right retroperitoneal approach without manipulating the left-sided IVC. The procedure was completed without incident and the patient has continued to do well.

To evaluate the effect of contrast material on left ventricular (LV) function, LV pressure and its first derivative were continuously monitored during and after LV cineangiography with Mikro-tip angiocatheters in 15 normal subjects (Group 1) and patients with coronary artery disease (CAD) without LV asynergy (Group 2, n = 10), with mild asynergy (Group 3, n = 12) and severe asynergy (Group 4, n = 13). In all 4 groups, systolic hypotension, decrease of negative dP/dt, and prolonged time constant of LV pressure fall (T) were observed in 30 seconds after dye injection, and all these parameters returned to the control value in 2 minutes. LV end-diastolic pressure (EDP) began to elevate at one minute, reached its peak at 2 minutes, and stayed elevated for 7 minutes. Although significant decrease in LV systolic pressure was seen, indexes of LV contractility, peak positive dP/dt and (dP/dt)/DP40, showed increase in all groups. No different directional changes of these parameters were observed among 4 groups. The degree of LVEDP elevation was parallel to the diastolic elastic stiffness constant (K) in Group 1 (r = 0.64, (p less than 0.05). It is concluded that systolic hypotension and prolonged relaxation are only transient, and elevation of LVEDP after the contrast material injection seems to be the effect of only acute volume overload.

To elucidate the hemodynamics and mechanical properties of the myocardium in hypertrophic (HCM) and congestive cardiomyopathies (CCM), preload (end-diastolic stress), afterload (mid-systolic stress), contractility (peak positive dp/dt, (dp/dt)/DP40, ejection fraction), relaxation (peak negative dp/dt, time constant T), compliance (elastic stiffness constant, end-diastolic elastic stiffness), and performance (left ventricular minute work, left ventricular minute work/muscle mass) were determined in 19 patients with HCM, 11 with CCM, and 15 normal subjects. Preload was in the normal range in HCM even with elevated left ventricular end-diastolic pressure. In cases of CCM it was high only when congestive heart failure was present. Afterload was mildly elevated in CCM with heart failure, but only half the normal value in patients with HCM. The three indices of contractility were in the normal range in patients with HCM, and markedly reduced in those with CCM. Relaxation abnormalities were demonstrated in both HCM and CCM. The elastic stiffness constant was high in HCM and normal in CCM. End-diastolic stiffness was normal in HCM and high in CCM with heart failure. These observations suggest that chamber stiffness is markedly elevated in HCM, and stiffness of unit muscle is elevated in CCM when heart failure appears. Although left ventricular minute work was normal in HCM, minute work of unit muscle (left ventricular minute work/muscle mass) was markedly reduced. These observations indicate that the chief problem in CCM is contractile failure and that elevation of preload and muscle stiffness is associated with congestive heart failure in this disease. Although the conventional indices of contractility are in the normal range in HCM, the contractility of unit muscle is reduced, and hypertrophy seems to be a compensatory mechanism when the relations between afterload and ejection fraction and between preload and performance are considered.

A precise assessment of left ventricular function was performed in 20 patients with hypertrophic nonobstructive cardiomyopathy to elucidate the basic pathophysiology, and the data were compared with those in 22 normal subjects. Whereas end-diastolic pressure was high in those with cardiomyopathy, a more accurate index of preload, end-diastolic stress, did not differ from normal value. Afterload was about half the normal value. Both isovolumic indexes [peak positive dP/dt and (dP/dt)/DP40] and ejection phase indexes of contractility (ejection fraction) were in the normal range; however, the end-systolic stress volume ratio was significantly reduced (43% of the normal value). Although the left ventricular minute work index was in the normal range, the unit muscle performance (minute work/mass) was very low (49%). An abnormality of left ventricular relaxation was demonstrated by low peak negative dP/dt (56%) and prolonged time constant T (191%), and a stiff left ventricle was demonstrated by a high diastolic elastic stiffness constant (129%). These observations suggest that the contraction of a unit muscle is inappropriate to produce an adequate contraction of the whole ventricle, and that hypertrophy might be an adaptive process to maintain normal systolic function by increasing mass and reducing afterload.

A precise assessment of left ventricular (LV) function was performed in 20 patients with hypertrophic cardiomyopathy (HCM) and 14 patients with congestive cardiomyopathy (CCM) to elucidate the pathophysiology of these diseases, expecting to establish a fundamental therapeutic approach of them. Twenty-two patients who underwent cardiac catheterization and were found to have normal LV function served as normal control. LV preload, defined as LV end-diastolic stress, was normal in HCM, and it was elevated in patients with CCM and congestive heart failure (CHF). While an index of afterload, defined as mid-systolic stress, was markedly reduced in HCM, it was elevated in CCM and CHF. Although three indices of LV contractility including the rate of LV pressure rise divided by developed pressure of 40 mmHg ((dp/dt)/DP40), ejection fraction (EF) and LV minute work index, were all in a normal range in HCM, they were very low in CCM. This observation indicates that the systolic function of HCM is normal as a pump, and that it is markedly reduced in CCM. One index of LV relaxation, which was the peak rate of LV pressure fall (peak negative dp/dt) was reduced in both HCM and CCM, and the other index, which was the time constant of LV pressure fall (the time constant T) was prolonged in both of these diseases. An index of compliance, defined as diastolic elastic stiffness constant (K) was high in HCM and normal in CCM, and the other index, defined as end-diastolic elastic stiffness was normal in HCM and high in patients with CCM and CHF. This observation suggests that chamber compliance is low in HCM, and that muscle compliance begins to decline with the appearance of CHF in CCM. Although poor systolic function is evident in CCM, poor contractility or inadequate contraction of a unit muscle is also suspected in HCM since 1) normal EF was maintained with very low afterload, 2) LV end-systolic volume index was normal with very low end-systolic stress, and 3) LV unit muscle minute work about one half of normal value with normal preload. Several important therapeutic guidelines can be derived from this study: As CCM is a disease of reduced LV contractility, the main therapy for this disease is to enhance the contractility. Elevation of preload and afterload are associated with the appearance of CHF, and this coincides with New York Heart Association functional class III. Therefore, the indication of preload and/or afterload reducing agents, such as diuretics and vasodilators, is considered for such patients. Although preload and/or afterload reducing agents are well known to be contraindicated in obstructive type of HCM, since they increase the intracardiac pressure gradient, these agents must be used with great precaution in nonobstructive type, as they reduce preload suddenly, and life-threatening low cardiac output might take place. For the same reason, strenuous exercise must be prohibited in HCM...