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This study aimed to update cost-effectiveness and public health impact estimates of the two-dose recombinant zoster vaccine (RZV) compared with no vaccination against herpes zoster (HZ) in the Japanese population aged 65 years. List price of the vaccine and latest RZV efficacy and waning estimates were incorporated.A multicohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of one million people aged 65 years over their remaining lifetime (base case). Age-stratified vaccine efficacy and waning rates were updated on the basis of the latest clinical trial data (interim ZOE-LTFU; NCT02723773). First-dose coverage was assumed at 40%, and second-dose compliance was assumed at 95%. Costs and outcomes were discounted at 2% annually, and the incremental cost-effectiveness ratio (ICER) was calculated from payer and societal perspectives. The societal perspective considered productivity loss due to suffering HZ, or due to suffering HZ and time required for vaccination. Sensitivity analyses explored the overall uncertainties in the model. Scenario analyses for Japanese adults aged 50, 60, 70, 80, ≥ 50, and ≥ 65 years (main scenario) were conducted. An ICER below ¥5-6 million/quality-adjusted life-year (QALY) was considered cost-effective.RZV was estimated to prevent 71,423 HZ cases and 15,858 post-herpetic neuralgia (PHN) cases per million people aged 65 years compared with no vaccine in Japan. The ICER was ¥4,205,515 from a payer perspective and was most sensitive to assumptions regarding vaccine efficacy waning, proportion of patients with HZ developing PHN, and HZ incidence. From societal perspectives, ICERs were ¥3,854,192 (productivity loss from suffering HZ only) and ¥4,622,212 (productivity loss from suffering HZ and time required for vaccination). Overall, the results were considered robust under extensive sensitivity and scenario analyses.Vaccination against HZ with RZV is cost-effective compared with no vaccination in Japanese adults aged 65 years.

Adjuvanted vaccines are recommended for administration through an intramuscular route. The Centers for Disease Control and Prevention (CDC) has recommended the anterolateral thigh using a 22 - 25-G 25-mm (1 inch) needle for infants, injected at a 90° into the skin surface, and using a 16 mm (5/8 inch) for newborns. Appropriate needle lengths may differ depending on racial backgrounds. In the present study, the thickness of the epidermis and lengths from the skin surface to the muscle fascia and bone were measured using ultrasonic echograms in order to determine suitable needle lengths for Japanese infants aged 2, 3, 4, 5, 6, and 12 - 15 months old. The thickness of the epidermis was 1.44 - 1.54 mm (95% CI), and the lengths from the skin surface to the muscle fascia and bone were 11.52 - 12.28 mm (95% CI), and 25.66 - 26.93 mm (95% CI), respectively, at the anterolateral thigh. At the center of the deltoid muscle, skin thickness was similar to that at the thigh, furthermore the lengths from the skin surface to the muscle fascia and bone were 8.49 - 9.10 mm (95% CI), and 17.38 - 18.31 mm (95% CI), respectively. The lengths from the skin surface to the muscle fascia and bone were 1 - 2 mm shorter in 2-month-old infants than those in older generations. Therefore, the appropriate needle length for intramuscular injections in Japanese infants was 16 mm (5/8 inch) at any age and sites, and with 25 mm (1 inch) needles at a 90° angle being associated with the risk of over-penetration.

Objective To investigate the effects of wearing complete dentures on pharyngeal shape for swallowing in edentulous older people. Background In the absence of complete dentures, edentulous older people often lose the occlusal support necessary to position the mandible, which leads to an anterosuperior shift of the mandible during swallowing. This may result in pharyngeal shape changes effecting swallowing function in older people. However, the details of this phenomenon are currently unclear. Materials and methods Participants were 17 older edentulous volunteers. Cone-beam computed tomography imaging was performed with the participant in the seated position and wearing (i) both maxillary and mandibular dentures, (ii) maxillary dentures only and (iii) no dentures. During imaging, participants were instructed to keep their mouth closed to the mandibular position determined in advance during swallowing for each denture-wearing condition. The volume, height and average cross-sectional area of the velopharynx and oropharynx were measured, and the positions of the epiglottis and mandible were recorded. Results While the vertical height of the oral cavity and pharynx significantly decreased, the volume and average cross-sectional area of the oropharynx significantly increased when dentures were not worn (p

This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.

We encountered an 83-year-old man with 3-repeat dominant grain-like tau deposition. Tau-positive lesions exhibited apparent similarity to argyrophilic grains in terms of their distribution in the ambient gyrus, amygdala, and dorsomedial temporal tip and the characteristic comma-like morphology. The abundant oligodendroglial tau immunoreactivities were 3-repeat dominant. Tuft-shaped astrocytes showed partial 3-repeat tau immnoreactivities. These grain-like structures, as well as tuft-shaped astrocytes and oligodendroglia, exhibited predominant 3-repeat tau immunoreactivity, suggesting that grain-like structures and their characteristic distribution are mutually linked and not unique to 4-repeat tau deposition. pTDP immunoreactivity, extensive macrophage infiltration, and spongiosis were associated with these 3-repeat tau deposits.

A 65-year-old woman presented with pain in her throat and neck. Thin-section computed tomography (CT) revealed an air-filled lesion at the right paratracheal region and two narrow connections to the trachea. Flexible bronchoscopy showed four diverticula 4-5 cm below the vocal cords in the right lateral part of the trachea. Consistent with the CT findings, two of the diverticula were deep. A radiological barium swallow study and an esopagogastroduodenal endoscopic examination revealed no abnormalities. We therefore believe that her right paratracheal air cyst is an extension of a tracheal diverticulum. Right-sided paratracheal air cysts at the level of the thoracic inlet are a common finding on CT and should not be confused with pneumomediastinum in order to avoid unnecessary examinations or treatments.

Background. Pulmonary spindle cell carcinoma is a rare lung cancer which was first classified in 1999 by the World Health Organization (WHO). Case. A 70-year-old man was admitted to our hospital because of bloody sputum, right-side chest and back pain, and an abnormal lung shadow. He was originally given a diagnosis of poorly differentiated non-small cell lung carcinoma based on cytology. The tumor had invaded the bones, and the patient received radiotherapy and chemotherapy, both of which were ineffective. The cancer progressed and he died 5 months later. An autopsy revealed that the cancer was sarcomatoid carcinoma (subgroup, spindle cell carcinoma) according to the 2004 WHO classification of tumors. It was difficult to distinguish the carcinoma from sarcomatoid mesothelioma by pathological examination alone. Initial chest computed tomography had showed a lung mass that led to the diagnosis of sarcomatoid carcinoma. The cause directly leading to his death was respiratory failure caused by diffuse alveolar damage. Conclusion. Pulmonary spindle cell carcinoma is believed to have a poor prognosis and is sometimes difficult to distinguish from sarcomatoid mesothelioma. Additional study of cases is needed to confirm this disease entity and to develop better treatments.

A 39-year-old man with dyspnea was revealed to have severe pneumothorax and received partial resection of the left upper lobe after unsuccessful drainage. Necrotizing epitheloid granuloma was found in the resected lung and Mycobacterium fortuitum was detected from the lesion. Chemotherapy with levofloxacin and clarithromycin was started one year after surgery because of the newly found nodular shadow near the lesion. The case experienced pyothorax due to pulmonary tuberculosis three years before and Mycobacterium avium pleuritis one year before this episode. Three-time mycobacterial pleural infection in three years seems to be uncommon. Furthermore this is the first report of pneumothorax associated with pulmonary Mycobacterium fortuitum infection.

Heme oxygenase-1 (HO-1) is an inducible form of heme oxygenase that catabolizes heme to carbon monoxide, biliverdin, and ferrous iron. We have investigated whether HO-1 can induce angiogenic effects in vivo. Rats were subjected to a bolus injection of either wild type adenovirus (ad-wt) or adenovirus encoding HO-1 (ad-HO-1) through the right femoral artery, which was then removed immediately. HO-1 gene transfer resulted in about a sixfold increase in HO-1 protein levels as compared to the non-treated animals. The increase in both blood flow and capillary density was significantly greater in the ischemic hindlimbs that had been injected with ad-HO-1 than in those injected with ad-wt. These angiogenic effects of ad-HO-1 infection could be completely abolished by treating the animals with the HO inhibitor, zinc protoporphyrin, indicating that they were specifically due to the expression of HO-1. Thus, HO-1 gene transfer improves the blood flow in ischemic hindlimb, at least in part, via angiogenesis facilitated by the induction of this molecule.

We report a 17-year-old man with destructive pulmonary embolism caused by Staphylococcus aureus bacteremia. The patient was not immunocompromised and had neither underlying diseases nor risk factors, such as concomitant influenza viral infection, which exacerbate staphylococcal infections. The rapid and extensive progression of pulmonary involvement in all lung fields make this a rare case; there have been few reports in the literature describing a similar radiographic appearance in patients with community-acquired staphylococcal bacteremia. In-vitro studies did not demonstrate the production of enterotoxins or toxic shock syndrome toxin 1 (TSST-1) by the isolated strain, but genetic analysis detected Panton-Valentine leukocidine gene from the strain. Subsequent empyema with bilateral pneumothorax was prolonged because of superinfection with both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Optional surgical treatments, including thoracostomy and thoracopneumoplasty, finally improved his condition.

Significant evidence has been provided for the pathophysiological involvement of the β 2 -adrenergic receptor ( ADRB2 ) in hypertension. Among ADRB2 polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and Gln27Glu, and a promoter variant, T-47C, are considered functionally important. In particular, Arg16Gly was shown to be associated with hypertension in black and white subjects. To investigate the relevance of ADRB2 polymorphisms to hypertension, we undertook an extensive association study in a Japanese population. An association was tested in 2 ways. First, a case-control study was conducted in 842 hypertensive and 633 normotensive subjects. In addition to the overall comparison between case and control groups, each was stratified by body mass index and compared with an independent panel of 525 diabetic subjects. Second, ANOVA and multivariate analyses were performed to test the significance of an association between ADRB2 genotype and the level of blood pressure within the entire population except for 395 subjects who had been under treatment for hypertension. Although no significant association was observed for Arg16Gly and T-47C, 2 analytical methods indicated a marginal association ( P =0.01 to 0.04) between the Glu27 variant and lower blood pressure levels. Given such a normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99) reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no apparent confounding influences of obesity and diabetes on the postulated association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to confer principal genetic susceptibility for hypertension in the Japanese population. However, further investigation is warranted to clarify the relevance of ADRB2 polymorphisms to blood pressure regulation.

The study investigated whether patients hospitalized for unstable angina pectoris (UAP), who subsequently develop complete coronary thrombosis (acute transmural myocardial infarction (AMI)) despite medical treatment, exhibit platelet hyperaggregability in an assay system that does not employ agonist stimulation. The study comprised 89 patients with UAP (Braunwald type B). Unfractionated heparin and nitrate were administered to all patients via continuous intravenous drip together with aspirin taken orally. Citrated platelet-rich plasma (230-250 × 103/μl) was obtained on admission and again, in some patients, following the AMI. Platelet aggregability was measured in an optically modified cone-plate viscometer that enables the detection of platelet aggregation without agonist stimulation. A continuous shear rate of 1,200/s was employed. Of the 89 patients, 85 were finally stabilized, while 4 developed an AMI accompanied by persistent ST-segment elevation with increased levels of plasma creatine kinase within 3 h after starting the treatment. The extent of platelet aggregation on admission was significantly greater in these 4 patients compared with the 85 who were stabilized (87.8±6.8%, n=4 vs 26.8±9.1%, n=85; mean ± SD). These data suggest that platelet hyperaggregability mediated mainly by fibrinogen binding to the activated glycoprotein IIb/IIIa complex occurs before a complete thrombotic occlusion and this evaluation may provide important information before the onset of myocardial infarction. (Jpn Circ J 2001; 65: 279 - 282)

Anatomic variations of the radial artery and their effect on the use of the radial artery as a route for transradial coronary intervention (TRI) were studied. Ultrasonography of the radial artery was performed prospectively in 115 patients selected to undergo elective TRI. Anatomic variations were observed in 11 of 115 patients (9.6%). Variations included six tortuous configurations (5. 2%), two stenoses (1.7%), two hypoplasias (1.7%), and one radioulnar loop (0.9%). The hypoplastic radial arteries and the radioulnar loop were inaccessible for catheterization, and coronary intervention was planned via the femoral artery. The transradial approach was attempted in the remaining 112 patients (97.4%) with only one instance of access failure, in a patient who had a stenotic vessel. These findings indicate that anatomic variations of the radial artery is not rare, and that preoperative ultrasound examination may help to exclude patients with inaccessible arteries and those at high risk for access failure.

New long-tip catheters, one for the left and the other for the right coronary artery, were designed specifically for right transradial intervention. We utilized the overbending principle to achieve more precise control of the catheters. We also analyzed principal factors involved to determine guiding catheter support considering the anatomy of the innominate artery, ascending aorta, left and right coronary arteries. Catheter shapes were designed to exploit favorable factors to compensate for mechanically disadvantageous anatomy. The catheter for the left coronary artery has an initial loop to make use of the angle between the innominate artery and the ascending aorta to introduce the catheter to the correct position to provide strong backup support. The catheter for the right coronary artery has a unique three-dimensional curve that provides sufficient backup support and compensates for the angles between the innominate artery and the proximal portion of right coronary artery to achieve coaxial engagement. The distal portions of these catheters include long tips aiming to minimize the loss of transmitted force. The performance of these catheters was studied in 143 patients with 161 lesions. Successful engagement was achieved in 138 patients with 156 lesions (97%) and coronary intervention was successful in 136 patients with 154 lesions (99%). No major complications or coronary artery dissection occurred due to use of these catheters. This study showed the present long-tip catheters to be safe and highly effective for right transradial coronary intervention. Cathet. Cardiovasc. Intervent. 49:218-224, 2000.

Automated 3-dimensional intravascular ultrasound (IVUS) analysis was used to assess status of the treated coronary artery immediately and 6 months after placement of a self-expanding Radius stent in 15 patients. Serial 3-dimensional IVUS analysis demonstrated gradual stent expansion that countered neointimal proliferation and preserved the lumen.

A 76-year-old HTLV-I-positive male with acute cerebellar ataxia was suffering from dyspnea on exertion. Chest CT suggested interstitial pneumonitis. Methylprednisolone pulse therapy improved his symptoms and chest CT findings. Twelve months after discharge, when the prednisolone dose was tapered to 5 mg every other day, his lung lesion recurred. The lesion responded initially to steroid therapy. However, hypoxemia intractable to steroid pulse therapy developed and the patient died of respiratory failure. The autopsy revealed diffuse alveolar hemorrhage with no finding of vasculitis. This is the first case report of diffuse alveolar hemorrhage in an HTLV-I carrier.

Immunoglobulin (Ig) production by human B cells in thymus-independent (TI) and -dependent (TD) immune response against Staphylococcus aureus was investigated in vitro. Highly purified human peripheral B cells were cultured either in the presence of formalinized Cowan I strain Staphylococcus aureus (SAC) or with anti-CD3 stimulated T cells, and Ig content in supernatants was analyzed after 10 days of culture by specific sandwich ELISA. When activated with SAC in the absence of T cells, B cells produced minimal amounts of Ig. In the presence of interleukin-2 (IL-2) or supplemental recombinant CD40 ligand plus IL-2, Ig production by SAC-induced B cells was dramatically enhanced. When cultured with T cells stimulated with low concentrations of anti-CD3 or when cultured with smaller numbers of T cells, B cells produced large amounts of Ig, whereas T cells stimulated with higher concentrations of anti-CD3 or large numbers of T cells failed to induce effective Ig secretion by B cells. These findings suggest that TI immune response against Staphylococcus aureus is strongly enhanced in the presence of activated T cells in an antigen non-specific manner, indicating its critical role in the local humoral immune defense. Moreover, it is indicated that the secretion of Ig induced by TD antigens participates in the immune defense against Staphyloccocus aureus dependent on activated T cell/B cell ratio or an impact of CD3 stimulation on T cells.

Local inflammation within the coronary arteries is involved in the pathogenesis of acute coronary syndrome. However, the contribution of a systemic inflammatory response to the pathogenesis of this syndrome has not been well characterized. Accordingly, we investigated systemic inflammatory responses in patients with acute coronary syndrome.A total of 83 patients with ischemic heart disease (15 with stable exertional angina and 68 with acute coronary syndrome) were studied. The luminol-dependent chemiluminescence (CL) response of polymorphonuclear leukocytes (PMNs), which reflects their ability to generate oxygen species, was used as a marker for PMN activation. Soluble interleukin-2 receptor (sIL-2R) levels were measured to assess T-lymphocyte activation.CL counts of whole blood from patients with acute coronary syndrome were twice those of patients with stable angina (2.38 +/- 0.22 vs 1.10 +/- 0.17 x 10(6) counts, P0.05). A comparison of CL counts between patients with unstable angina and those with acute myocardial infarction revealed no significant differences. T-lymphocyte activity, measured by serum sIL-2R, was significantly lower in patients with acute coronary syndrome than those with stable angina (214.3 +/- 11.5 vs. 358.3 +/- 115.7 U/ml, P0.05).This investigation shows that there is a systemic increase in PMN activity and a decrease in T-lymphocyte activity in patients with acute coronary syndrome. This contrasts with the pattern of cellular activation seen at sites of local inflammation within atherosclerotic plaques, suggesting that two independent inflammatory processes (local and systemic) may be involved in the pathogenesis of this syndrome.

Background Current methods of angiography cannot provide images of arteries measuring Methods and Results Microangiography was performed in the normal and the ischemic limb 4 weeks after the excision of the femoral artery. In the normal limb, up to the fourth branches of the iliac and/or femoral arteries (diameter Conclusions The small collateral artery network was angiographically visualized with a resolution limit

The relationship between ST reelevation at reperfusion and the occurrence of late potentials (LPS) in 35 patients with a first anterior infarction who had single vessel disease was investigated. All patients underwent a successful primary angioplasty and had a patent infarct related artery confirmed angiographically 4 weeks later. Patients were classified into groups based on changes in the ST level at reperfusion: patients with ST reelevation (group A, n = 22) and patients without ST reelevation (group B, n = 13). Signal-averaged ECG was performed 4 weeks after primary angioplasty to detect LPS. Cineventriculography was performed to measure left ventricular ejection fraction (LVEF) and evaluate regional wall motion of the infarct area (SD/chords). LPS were present in eight of the 22 group A patients (36%) and in none of the 13 group B patients (P < 0.05). Left ventricular function was impaired in patients in group A compared with patients in group B (LVEF: 5 1 +/- 12 vs 63 +/- 10, P < 0.01; SD/chords: -2.7 +/- 0.9 vs -1.9 +/- 1.1, P < 0.05). These data suggest that ST reelevation and myocardial damage at reperfusion are associated with the occurrence of LPS in patients with successfully recanalized infarct related arteries after acute anterior infarction.

A 53-year-old man developed bilateral pleural effusion with respiratory failure. The amylase level in the pleural effusion was elevated. He had neither abdominal symptoms nor abdominal physical findings. Abdominal computed tomography (CT) also showed no abnormalities. Magnetic resonance cholangiopancreatography (MRCP) was non-diagnostic, but endoscopic retrograde cholangiopancreatography (ERCP) and subsequent CT showed a fistula connecting the pancreatic duct with the right pleural cavity. The pleural effusion was refractory to drug therapy, leading to the need for surgical intervention. The pathological findings revealed chronic pancreatitis without pseudocysts. The elevated pancreatic amylase in the pleural effusion offered an important clue to the correct diagnosis.

Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, 156-8506 Tokyo, Japan Department of Medicine, Nakano General Hospital, 4-59-16 Chuo, Nakano-ku, 164-8607 Tokyo, Japan Department of Neurology, Nakano General Hospital, 4-59-16 Chuo, Nakano-ku, 164-8607 Tokyo, Japan Department of Pathology, Nakano General Hospital, 4-59-16 Chuo, Nakano-ku, 164-8607 Tokyo, Japan Department of Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8510 Tokyo, Japan Department of Neurology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666 Tokyo, Japan

慢性心不全の治療上ジギタリスと利尿薬はアンジオテンシン変換酵素阻害薬とともに現在標準的な薬物である.通常,これらを併用することが多い.ジギタリスは頻脈型心房細動を伴う慢性心不全に,利尿薬はうっ血症状を改善するためにきわめて有用である.本稿では,ジギタリスの新しい作用機序,ジギタリスの再評価,両薬の投与法と投与上の注意点,さらに両薬の限界など最近の進歩と問題点に的をしぼり解説を行った.

The case of a symptomatic fifty-four-year-old woman with a huge, solitary aneurysm of the right coronary artery is presented. A coronary angiogram did not visualize the aneurysm because of tightly packed thrombi in it, but it was definitely diagnosed intraoperatively after the mass was opened. Excision of the aneusymal wall, removal of thrombi, closure of coronary ostium, and plication of the aneurysmal wall were performed without revascularization. Histologic ex aminations demonstrated cystic medial necrosis with deposition of acid- mucopolysaccharides, suggesting that pathogenesis might be a dissecting aneurysm.

Cilostazol, an antiplatelet drug that also may inhibit smooth muscle proliferation, was given together with aspirin after primary stenting to treat patients with acute myocardial infarction. In a randomized controlled trials of 50 patients, clinical and angiographic outcome at 6 months was significantly improved with cilostazol, depicting a significantly smaller late loss and/or loss index.

We analyzed clinical features of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with underlying chronic respiratory disease, and evaluated the efficacy and tolerability of voriconazole against CNPA in those patients. Voriconazole therapy was indicated in 45 CNPA patients between October 2005 and September 2007, in 23 patients as first-line treatment and in 22 after lack of response to or intolerance of prior antifungal agent. The most common underlying respiratory disease was sequelae of tuberculosis (n = 23) followed by COPD (n = 13). Cavitary lesions were found in 32 patients. Galactomannan antigen test was positive in 29 patients while 28 patients out of 36 were positive for anti-Aspergillus serum antibody. The antibody-negative group had significantly higher levels of galactomannan antigen than the antibody-positive group. Mycological culture or hyphae were positive in 15 patients. Beta-D glucan level was within the normal limit in 27 patients. Clinical, radiological improvement, or both was obtained in 30 patients after an average voriconazole treatment of 4.8 months, with the main adverse effects being visual disturbance and hepatotoxicity. During the observation period 14 patients died due to CNPA or other causes. Although voriconazole demonstrated good efficacy against CNPA, the outcome is still unsatisfactory.

We report 4 cases of pulmonary infection due to Mycobacterium szulgai with review of 23 cases previously reported in Japan. All 4 patients were male and two of them in their 20's were found to have abnormal chest X-ray findings recognized on a health checkup without any symptoms. One case had no previous history of illness and had never smoked. Radiographic study showed thick-walled cavities in 3 cases and multiple small nodules in 2, indicating the difficulty of distinguishing M. szulgai infection from pulmonary tuberculosis or M. kansasii infection. Three cases were treated as pulmonary tuberculosis at first, and later we changed the medication referring to the drug susceptibility. In most cases, rifampicin, ethionamide and ethanbutol were used and the medication regimen was successfully completed in all cases. Considering that the detected M. szulgai could be regarded as pathogen in almost all cases, it is important to evaluate the risk factor of patients and not to delay diagnosis and treatment with adhering to usual diagnostic criteria.

We analyzed clinical and microbiological features of six cases involving Mycobacterium fortuitum isolated from sputum or surgical lung specimen. Patients were five men and one woman with an average age of 59. Four cases had a history of pulmonary tuberculosis and three had nontuberculous mycobacterial lung disease. Three out of six cases had underlying chronic obstructive pulmonary disease. Diabetes mellitus was complicated in five cases. All diseases were in the upper lobes of either lung. Clinical symptoms were mainly cough and sputum, while two cases developed pneumothorax. Although all strains showed low sensitivity to standard anti-tuberculous agents, chemotherapy including those drugs or fluoroquinolones and macrolides were successful in all treated cases.

A 71-year-old man presented with a thin-walled cavity in his left lung in November 2006. A previous chest CT in 2003 showed a small thin-walled cavity in his left lingula. Although no obvious change was observed in 2004, the cavity increased its size from 11mm to 14mm in diameter and the wall became thicker in June 2006. On the first visit to our hospital in November 2006, the diameter of the cavity was 30mm and some part of the wall was thinner than on the previous CT. The patient developed pneumothorax one month later and underwent segmentectomy of the left lingula after unsuccessful thoracic drainage. Poorly differentiated adenocarcinoma was identified in both the pleura and the inner wall around the cavity. Lung adenocarcinoma with gradual enlargement of a thin-walled cavity causing pneumothorax has never been reported before. We report here the natural course of lung adenocarcinoma with a thin-walled cavity.

Immunohistochemical and biochemical analyses of several tissues were performed in two unusual cases of Fabry's disease which showed accumulation of globotriaosylceramide (Gal alpha 1-4Gal beta 1-4 Glc-Cer, Gb3Cer) only in the hearts, but no clinical signs of the disease. Immunohistochemical study revealed that the hearts from our cases (cases no. 1 and 2) contained large amounts of anti-Gb3Cer antibody-positive granules in cytoplasms as in typical Fabry's disease. The contents of accumulated Gb3Cer in the hearts from case no. 1, case no. 2, and a typical Fabry's disease case were approximately 100, 340, and 100 times higher than those from normal controls, respectively. While typical Fabry's diseased kidney and liver contained approximately 40 and 50 times higher amounts of Gb3Cer than did controls, no accumulation of Gb3Cer was observed in kidney and liver of our cases. The only exception was a slight increase of Gb3Cer in kidney of case no. 2 (about two times higher than controls), in which epithelial cells of the glomeruli but not of other types of cells were positively stained by anti-Gb3Cer antibody. Case no. 1 kidney and liver were not stained by the antibody. The glomerular endothelium and epithelium, tubular epithelium, smooth muscle of renal arteries, and several hepatocytes were Gb3Cer-positive in the typical Fabry's disease case. The involvements of our cases differed distinctly from the typical Fabry's disease case.

Objectives: Natural angiogenesis has been shown to be impaired in spontaneously hypertensive rats (SHR). The purpose of this study was to determine whether pathological angiogenesis in the setting of tissue ischemia is also impaired in SHR, and to what extent it is modified by angiotensin-converting enzyme (ACE) inhibition. Methods: Ischemia was induced in the hindlimb of SHR by excision of the femoral artery, after which the animals were randomly assigned to receive low-dose perindopril (sub-antihypertensive, 0.2 mg/kg/day), high-dose perindopril (antihypertensive, 2.0 mg/kg/day), or vehicle for 3 weeks. Wistar–Kyoto rats (WKY) with femoral artery excision served as a control group. Results: Tissue ACE activity in SHR was significantly increased compared to WKY (49.4±6.2 vs. 34.0±14.2 IU/mg, P

Background Components of the renin–angiotensin (R–A) system have been repeatedly investigated as candidate genes for essential hypertension. In particular, suggestive or significant association has been detected in some studies for the angiotensinogen M235T, angiotensin I-converting enzyme I/D, angiotensin II type 1 receptor A1166C, and aldosterone synthase C-344T polymorphisms, although the results remain inconclusive. Objective and Methods To evaluate the importance of these candidate genes for hypertension, we undertook an extensive association study in the Japanese. This case–control study was conducted in a total of 1476 individuals using the four R–A gene polymorphisms. In the assessment of genotyping data, 843 hypertensive subjects were divided into three case subgroups according to severity of hypertension, while 633 normotensive subjects divided into two control subgroups by the age of enrollment. Each subgroup was further divided by sex. Subsequently, the presence of synergy (or gene–gene interaction) was evaluated among four R–A gene polymorphisms. Results No significant association was observed between the individual R–A gene polymorphisms and hypertension status in our case–control study. The results were almost unchanged when severity of hypertension, sex-specificity, and synergy were taken into account. Conclusions Despite a relatively large number of subjects, we did not find significant evidence for disease association in the Japanese population. Given confounding factors in the case–control strategy, the lack of association does not exclude the relevance of the R–A genes to hypertension. Further investigation needs to be performed in large-scale populations, where the use of not only hypertension status, but also ‘intermediate’ phenotypes would be useful.

P studies have established the feasibility of using the radial artery as an access route for percutaneous coronary interventions.1–3 This strategy, transradial coronary intervention (TCI), has several advantages over the conventional transfemoral and/or transbrachial interventions.4 In TCI, hemostasis is achieved easily by local compression because the radial artery is superficially located. Furthermore, because no major veins or nerves exist near the radial artery, risk of injury to such structures is negligible. These anatomic features significantly lower the risk of access site-related complications, and thus constitute the basis for considering the transradial route over the conventional transfemoral and/or transbrachial routes. The major drawback of TCI is the radial artery occlusion. Because radial artery occlusion can result in serious hand ischemia, it is necessary to ensure that collateral circulation from the ulnar artery is adequate to support the hand in the event of the radial artery thrombosis. The modified Allen’s test (AT) is often used to assess collateral blood supply to the hand.5–12 The results of this test are dependent on the change in hand color, the assessment of which is highly subjective and may seriously overestimate collateral blood supply. The present study investigated the feasibility of using color Doppler ultrasonography as an alternative to AT to assess the collateral supply to the hand before performing TCI. • • • The study cohort included 102 patients who were scheduled to undergo elective coronary interventions via the radial artery; 77 (76%) were men. The mean age was 65 6 10 years (range 41 to 84). Sixty-five patients (64%) had a history of myocardial infarction, and 11 (11%) had undergone coronary bypass surgery. Sixty-six patients (65%) had 1-vessel disease, and 36 (35%) had multivessel disease (Table I). When not contraindicated, patients received oral vasodilators including calcium channel blockers and nitrates at the time of AT and ultrasonographic assessment according to our institutional angioplasty protocol. Written informed consent was obtained from all patients before enrollment, and the institutional ethics committee approved the study protocol. All patients had a palpable radial artery pulse, and underwent the modified AT. Briefly, the patient was asked to repeatedly clench his or her fist to exsanguinate the hand while the examiner compressed both the ulnar and radial arteries. The fist was relaxed, and ulnar compression was released. The test was considered positive (normal) if an erythematous blush developed over the entire palm and the fingers within 10 seconds. This sign suggested adequate collateral blood supply from the ulnar artery to the area originally perfused by the radial artery. If the hand was not reperfused within 10 seconds, the test was considered negative, indicating that collaterals did not completely supply the area perfused by the radial artery. Ultrasonographic assessment of collateral blood supply to the hand was performed using a Sequoia 512 (Acuson, Mountain View, California) with an 8-MHz linear transducer. A consensus reading was reached by at least 2 investigators. With the patient at rest in the supine position, the Doppler probe was placed on the dorsal surface of the hand in the area between the thumb and forefinger (Figure 1A, left panel). The distal radial artery was visualized as it gave off branches to form the palmar arch (Figure 1B, upper left panel). While visualizing flow in the distal radial artery, the examiner compressed the radial artery at the level of the wrist (Figure 1A, right panel). When From the Departments of Medicine (Cardiology) and Clinical Laboratory, Teikyo University School of Medicine, Tokyo, Japan. Dr. Takeshita’s addrress is: Department of Medicine, Teikyo University School of Medicine, 2–11–1 Kaga, Itabashi, Tokyo 173–8605, Japan. E-mail: stake@blue.ocn.ne.jp. Manuscript received November 30, 1999; revised manuscript received and accepted February 8, 2000. TABLE I Demographics and Clinical Characteristics of Patients Evaluated for Transradial Coronary Intervention

A-75-year old woman with agammaglobulinemia developed Moraxella catarrhalis bacteremic pneumonia. M. catarrhalis pneumonia is rarely associated with bacteremia, and neutrophils have been reported as a significant factor in the host defense system against this bacteria. This case suggests that immunoglobulin also plays a key role in the host defense system against M. catarrhalis.

Abstract —The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm 2 ) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 μg/mL AJvW-2. Under low-shear conditions (12 dyne/cm 2 ), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.

We conducted a prospective observational study to assess the effectiveness of "transradial primary stenting" in 33 patients with acute myocardial infarction, along with acute risk stratification and accelerated patient care. With use of adequate inclusion and exclusion criteria, the radial artery can be used as an access site for catheterization, and transradial primary stenting can be performed rapidly and successfully by trained coronary interventionalists.

Objective: Platelet aggregation has been implicated in the pathogenesis of acute coronary syndromes. Small aggregates consisting of ≤100 platelets cannot be quantified with a conventional aggregometer employing optical density. Using a recently developed aggregometer based on laser light scattering, we studied platelet aggregability in patients with acute coronary syndromes. Methods: Peripheral blood samples were obtained from 39 patients with acute myocardial infarction or unstable angina who had received no prior antiplatelet or anticoagulant therapy, to be assayed immediately using a PA-100 platelet aggregometer. Blood samples from 14 healthy volunteers were used as controls. Results: Spontaneous formation of platelet aggregates was observed only in patients with acute coronary syndromes. The size of these aggregates was small, consisting of ≤100 platelets (primary aggregation). Agonist-induced aggregation consisted of two phases. In the first few minutes, the number of small aggregates increased markedly (primary aggregation), followed by an increase in larger aggregates (secondary aggregation). The EC50 of epinephrine for primary aggregation was nearly 50 times lower in acute coronary patients than in controls ( P

Background —Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. Methods and Results —Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 μg of a plasmid encoding VEGF or β-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 μm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dilation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6±17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.1±8.4% in VEGF-treated animals ( P Conclusions —These results demonstrate in vivo that the use of VEGF restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation after therapeutic angiogenesis with VEGF.

We classified 33 patients with a first anterior infarction and single-vessel disease who had undergone successful primary angioplasty and had a patent infarct-related artery into groups based on the development of late potentials. Left ventricular function improved between 1 and 3 months after angioplasty only in patients without late potentials; the development of late potentials after acute anterior infarction was associated with prolonged left ventricular dysfunction despite successful revascularization with primary angioplasty.

Objective: The development of collateral microvessels following therapeutic angiogenesis with vascular endothelial growth factor (VEGF) was investigated using a new system of microangiography that employs monochromatic synchrotron radiation (SR) and a high definition video system to visualize arteries with a spatial resolution of 30 μm. Methods: Ischemia was induced in the hindlimb of 20 rats by excision of the femoral artery, followed by transfection of the plasmid (400 μg) encoding VEGF or β-galactosidase (control) into limb muscles. Microangiography was used to assess the development of collaterals in the ischemic limb four weeks after treatment. Results: Gene transfer of VEGF produced morphologically similar, but significantly more extensive, collateral networks at the microvascular level as compared with the naturally occurring collateral arteries in the control animals (angiographic score: 0.88±0.08 versus 0.54±0.05, p

We evaluated the therapeutic efficacy of cilostazol, a novel potent inhibitor of phosphodiesterase, for the prevention of stent thrombosis following implantation of a Palmaz-Schatz stent guided by angiographic visual estimation alone in 71 patients with 84 lesions. Patients received 81 mg of aspirin 3 times daily and 100 mg of cilostozol twice daily after angiographic confirmation of optimal Palmaz-Schatz stent implantation. Of the 84 vessels stented, 65 (77%) were classified as type B2 or C lesions according to the modified American Heart Association/American College of Cardiology classification, and 51 (61%) were3.0 mm in diameter. Multiple stents were used in 26 patients (31%). The final balloon inflation pressure was 18.3 +/- 1.5 atm. The balloon-to-vessel ratio was 1.18 +/- 0.16. No patient received heparin or warfarin after the procedure. There were no deaths, Q-wave myocardial infarctions, in- or out-of-hospital stent thrombosis, coronary bypass surgery, or serious side effects such as neutropenia and/or liver dysfunction during the 1-month follow-up period. These results indicate that cilostazol was a safe and effective antiplatelet agent with minimum side effects after Palmaz-Schatz stent implantation.

The purpose of this study was to investigate the significance of ST re-elevation at reperfusion using strict criteria for patient inclusion and exclusion. Twenty-nine patients who had a first anterior infarction with single-vessel disease, successful recanalization by intracoronary thrombolysis (ICT) with urokinase, and an angiographically confirmed patent infarct-related artery after 4 weeks, were divided into three groups according to the deviation of the ST segment at reperfusion: Group A, 10 patients with sustained ST re-elevation; Group B, 10 patients with transient ST re-elevation; and Group C, 9 patients with ST reduction. Left ventricular (LV) function was evaluated from cineventriculograms performed in the 30 degrees right anterior projection 4 weeks after ICT. LV ejection fraction and regional wall motion of the infarct area, evaluated by the centerline method (SD/chords), were significantly lower in Group A (44 +/- 10%, -3.2 +/- 0.4) than in Group B (61 +/- 9%, -1.9 +/- 0.7) and Group C (60 +/- 5%, -2.0 +/- 0.4) (p0.01). Peak creatine kinase (CK) activity was significantly higher in Group A (5848 +/- 2112 IU) than in Group B (2485 +/- 1254 IU) and Group C (1889 +/- 1525 IU) (p0.05). These data suggest that a sustained ST re-elevation at reperfusion was strongly associated with marked LV dysfunction and higher peak CK activity. It was concluded that sustained, not transient, ST re-elevation associated with successful reperfusion indicates extensive myocardial damage.

The purpose of this study was to determine whether computed tomography (CT) can detect hemorrhagic infarction occurring after intracoronary thrombolytic therapy (ICT) for acute myocardial infarction (AMI). In an experimental study, 12 dogs underwent 2-4 h of left anterior descending artery (LAD) occlusion, followed by reperfusion, and infusion of contrast material into the LAD. After CT examination, the heart was cut into transverse sections. A good correlation was obtained between the CT-enhanced area and the hemorrhagic area in the sliced heart section (r = 0.895, p less than 0.001). In a clinical study, we applied CT immediately after ICT in 25 patients with AMI. In 13 of 25 patients, the CT showed post-ICT myocardial enhancement areas. To evaluate the relationship of the enhancement areas shown by CT to the viability of the myocardium, we compared enhancement areas by CT with the corresponding perfusion defect areas of Thallium-201 imaging (SPECT) one month later. There was no significant correlation between the enhancement areas and perfusion defect areas (r = 0.38, p greater than 0.1). The SPECT defect areas were consistently smaller than the CT enhancement areas. These results indicate that CT can detect hemorrhage into the myocardium after ICT, and that after ICT half the AMI patients showed hemorrhagic infarction. However, hemorrhage did not cause complete deterioration of the myocardium.

Recently a new β 2 stimulant “Dopexamine” has been developed and is expected to be effective in the treatment of congestive heart failure (CHF). We used it in a case of severe CHF in ventricular septal rupture due to anterior myocardial infarction and saw excellent improvement. The usefulness of this drug in severely reduced cardiac function is discussed in this paper.