Operative Results and Clinical Features of Chronic Stanford Type B Aortic Dissection: Examination of 234 Patients Over 6 Years.

OBJECTIVE/BACKGROUND: Recently, the indications for thoracic endovascular aortic repair (TEVAR) have been expanding, and the applicability of TEVAR for acute type B aortic dissection (TBAD) is proposed with regard to the high mortality of open surgery for chronic TBAD. TEVAR in the acute phase may lead to remodeling of the false lumen (FL), but it is controversial whether it completely resolves the aortic expansion in the chronic phase. In this study, operative results and the relationship between FL status and the time before surgical intervention were retrospectively analyzed. METHODS: From January 2008 to September 2013, 234 patients underwent open surgery for chronic TBAD. Most patients were on left heart bypass. By considering Japanese aortic disease treatment guidelines and the smaller physique of Japanese patients, operative indications were aneurysm >50 mm in diameter or rapid aneurysm enlargement of >5 mm in a 6 month period. RESULTS: In 180 cases, the FL was patent. The mean interval between onset of TBAD and operation was 61 ± 54 months. There was no significant difference between patients in the patent FL group and those in the thrombosed FL group (p = .44). Mean ratio of FL diameter to maximum aortic diameter (FL/AD) was 0.64 ± 0.21. There was no correlation between FL and AD before the operation (r = .12). Descending thoracic aortic replacement (DTAR) was performed in 127 cases and thoracic ascending aortic replacement (TAAR) in 107 cases (Crawford type I, n = 9; Crawford type II, n = 65; Crawford type III and IV, n = 22, respectively; Safi type V, n = 11). The overall operative mortality was 6.8%: 3.9% (5/127) for DTAR and 10.3% (11/107) for TAAR. The three year survival was 86.7, and the freedom from re-intervention rate was 97.0%. CONCLUSION: Enlargement of uncomplicated TBAD in the chronic phase was poorly related to FL status and the results of open repair have improved. However, further prospective study is necessary.

Regional Inequalities in Oral Frailty and Social Capital.

INTRODUCTION: Oral frailty leads to poor nutritional status, which, in turn, leads to frailty. This cross-sectional study aimed to determine regional differences in the prevalence of oral frailty and to identify factors associated with oral frailty using 3-level multilevel models. METHODS: This study comprised 165,164 participants aged ≥65 y without long-term care requirements in the Japan Gerontological Evaluation Study. The dependent variable was oral frailty, which was calculated based on age, number of teeth, difficulty in eating tough foods, and choking. The individual-level independent variables included sociodemographics, present illness, social participation, frequency of meeting friends, and social capital. The local district-level independent variable was social capital (n = 1,008) derived from exploratory factor analyses. The municipality-level independent variable was population density (n = 62). Three-level multilevel Poisson regression analysis was performed to calculate the prevalence ratios (PRs). RESULTS: The prevalence of oral frailty in municipalities ranged from 39.9% to 77.6%. Regarding district-level factors, higher civic participation was significantly associated with a lower probability of oral frailty. At the municipality level, the PR of the rural-agricultural area was 1.17 (95% confidence interval, 1.11-1.23) (reference: metropolitan). CONCLUSION: These results highlight the usefulness of oral frailty prevention measures in encouraging social participation in rural areas. KNOWLEDGE TRANSFER STATEMENT: The results of the present study showed regional differences in oral frailty. In particular, rural-agricultural areas show higher prevalence rates of oral frailty than those in metropolitan cities. Promoting measures of social participation among older adults may help prevent oral frailty in rural areas.

Simultaneous evaluation of long-lasting knee synovitis in patients undergoing arthroplasty by power Doppler ultrasonography and contrast-enhanced MRI in comparison with histopathology.

OBJECTIVES: We simultaneously assessed ultrasonography (US) and magnetic resonance imaging (MRI) in comparison with histopathological changes in the knee joints of long-lasting arthritis patients. METHODS: We studied 15 patients with rheumatoid arthritis and 5 patients with osteoarthritis, who underwent total knee arthroplasty. On the day before surgery, the joints were examined by US and contrast-enhanced MRI. In US, synovitis was graded with 0-3 grey scale (GSUS) and power Doppler (PDUS). In MRI, synovitis was graded according to OMERACT-RAMRIS (grade 0-3). Synovial tissue samples were obtained during arthroplasty and evaluated on the basis of inflammatory cell infiltrates (grade 0-3), synovial lining layer thickness (grade 0-3) and vascularity (grade 0-3). RESULTS: Positive findings of PDUS and contrast-enhanced MRI were 45% and 85% of 20 operated joints, respectively. GSUS, PDUS and MRI synovitis were well correlated with overall histopathological grades of synovitis (Spearman correlation coefficients 0.48, 0.84 and 0.48, p<0.05, p<0.01 and p<0.05, respectively). Moreover, positive PDUS findings were closely associated with all pathological comportments of synovitis including inflammatory cell infiltrates, synovial lining layer thickness and vascularity. CONCLUSIONS: The present study revealed that positive PDUS findings more faithfully illustrated active synovitis than MRI, whereas contrast-enhanced MRI was more sensitive in detecting synovitis in patients with long-lasting arthritis. It is important to understand distinct features of the both modalities for clinical assessment of chronic joint diseases.

Navigated opening wedge high tibial osteotomy improves intraoperative correction angle compared with conventional method.

PURPOSE: The correction angle after high tibial osteotomy (HTO) depends on an accurate preoperative planning and an accurate intraoperative technique. We hypothesized that the use of a navigation system in opening wedge HTO would improve the intraoperative target angles in the coronal and sagittal planes. METHODS: Postoperative femoro-tibial angle (FTA) and tibial posterior slope (TPS) in 28 knees with navigated opening wedge HTO were compared to those in 31 knees with the conventional method. Intraoperative correction angle was determined by the predicted medial opening width in the conventional group, and by the change of hip-knee-ankle angle in the navigated group. We defined lateral unstable knee as the knees with lateral cortex breakage or lateral tibial plateau fracture. RESULTS: Mean postoperative FTA was higher in the conventional group than in the navigated group (P < 0.037). In the conventional group, 4 lateral unstable knees were corrected to 174.6°. In the navigated group, 5 lateral unstable knees were corrected to 170.3° and no knees showed FTA > 173°. Mean change in TPS was greater in the conventional group than in the navigated group (P = 0.001). CONCLUSION: The navigation system in opening wedge HTO might reduce undercorrection in the knees with lateral cortex breakage or lateral tibial plateau fracture, and provide the better intraoperative FTA and TPS. LEVEL OF EVIDENCE: III.

Role of glycosaminoglycans of biglycan in BMP-2 signaling.

Recently we have reported that biglycan (BGN) promotes osteoblast differentiation and that this function is due in part to its ability to positively modulate bone morphogenetic protein (BMP) functions. In this study we investigated the role of glycosaminoglycans (GAGs) of BGN in this function using in vitro and in vivo models. C2C12 myogenic cells were treated or untreated with BMP-2 alone or in combination with glycanated, partially glycanated or de-glycanated BGN, and the effects on BMP signaling and function were assessed by Smad1/5/8 phosphorylation and alkaline phosphatase (ALP) activity. Furthermore, the effect of de-glycanation of BGN on BMP-2 induced osteogenesis was investigated employing a rat mandible defect model. The defects were filled with collagen scaffolds loaded with glycanated or de-glycanated BGN alone or in combination with a sub-optimal dose of BMP-2 (subBMP). In in vitro experiments, BMP signaling and function were the greatest when BMP-2 was combined with de-glycanated BGN among the groups tested. In the rat mandible experiments, µCT analyses revealed that the newly formed bone was significantly increased only when subBMP was combined with de-glycanated BGN. The data indicate that the GAG component of BGN functions as a suppressor for the BGN-assisted BMP function.

Remarkable Improvement of Cardiac Function After Pre-emptive Kidney Transplant in a Patient With Severe Mitral Regurgitation Accompanied by Low Cardiac Function: A Case Report.

Patients with end-stage renal disease are at a high risk for cardiovascular diseases. It is controversial whether end-stage renal disease patients with low cardiac function can safely accept kidney transplant. Here, we present a 42-year-old kidney transplant recipient with severe mitral regurgitation accompanied by low cardiac function. He wanted to undergo a pre-emptive kidney transplant from his uncle. We decided to perform living kidney transplant prior to cardiac surgery. Despite adequate ultrafiltration and hemodiafiltration before operation, the patient's ejection fraction still remained 35% 1 day before transplant. He showed complete recovery of cardiac function in only 2 days after pre-emptive kidney transplant, although his body weight did not change before and after the operation. Early removal of the uremic toxin or inflammatory cytokines may play a role in rapid improvement of the cardiac function. Increase of vasoactive substances by improvement of kidney function may lead to reduction of afterload and amelioration of cardiac microcirculation. This report also suggests that optimal timing for operation might be important.

Loss of Function of Evc2 in Dental Mesenchyme Leads to Hypomorphic Enamel.

Ellis-van Creveld (EvC) syndrome is an autosomal-recessive skeletal dysplasia, characterized by short stature and postaxial polydactyly. A series of dental abnormalities, including hypomorphic enamel formation, has been reported in patients with EvC. Despite previous studies that attempted to uncover the mechanism leading to abnormal tooth development, little is known regarding how hypomorphic enamel is formed in patients with EvC. In the current study, using Evc2/ Limbin mutant mice we recently generated, we analyzed enamel formation in the mouse incisor. Consistent with symptoms in human patients, we observed that Evc2 mutant mice had smaller incisors with enamel hypoplasia. Histologic observations coupled with ameloblast marker analyses suggested that Evc2 mutant preameloblasts were capable of differentiating to secretory ameloblasts; this process, however, was apparently delayed, due to delayed odontoblast differentiation, mediated by a limited number of dental mesenchymal stem cells in Evc2 mutant mice. This concept was further supported by the observation that dental mesenchymal-specific deletion of Evc2 phenocopied the tooth abnormalities in Evc2 mutants. Overall, our findings suggest that mutations in Evc2 affect dental mesenchymal stem cell homeostasis, which further leads to hypomorphic enamel formation.

Angiotensin-converting enzyme gene polymorphism adds risk for the severity of coronary atherosclerosis in smokers.

To investigate the relation between the angiotensin-converting enzyme (ACE) gene polymorphism and acute coronary syndromes with respect to environmental factors, we analyzed the association of genotype with the coronary angiographic findings of patients with acute myocardial infarction or unstable angina pectoris, and we examined the linkage of each genotype with established risk factors for coronary artery disease. We determined the ACE genotype in 152 Japanese patients with acute coronary syndromes and 399 healthy individuals. The genotype distributions were not different between the two groups (P=.74, chi2 test). In the former group, coronary angiograms were evaluated by criteria based on the number of diseased vessels, the number of stenotic lesions (> or = 50%), and the relative abnormal arterial portion (extent index). Although the number of stenotic lesions was higher in patients with the DD genotype than in those with the ID or II genotype (P=.006), there were no differences in the number of diseased vessels or the extent index. When only smokers were analyzed, the number of diseased vessels (P=.032), number of stenotic lesions (P=.003), and extent index (P=.019) were all higher in patients with the DD genotype than in those with the ID or II genotype. In contrast, these differences in the respective parameters did not exist in nonsmokers. The results indicate smoking-associated effects of the ACE genotype on the severity of coronary atherosclerosis.

New electrocardiographic criteria for predicting the site of coronary artery occlusion in inferior wall acute myocardial infarction.

In patients with inferior wall acute myocardial infarction (AMI), the site of the culprit lesion is an important determinant of outcome. Patients with right ventricular infarction have a poor prognosis, whereas those with occlusion of the left circumflex coronary artery (LCx) have a good prognosis. Therefore, we assessed whether standard 12-lead electrocardiograms obtained on admission could identify the site of coronary artery occlusion, (i.e., a site proximal to the origin of the right ventricular branch of the right coronary artery [RCA], a site distal to the origin of the right ventricular branch of the RCA, or a site in the LCx). The ratio of ST depression in lead V3 to ST elevation in lead III (V3/III ratio) was evaluated immediately before coronary angiography in 152 patients with a first inferior wall AMI confirmed by coronary angiography within 12 hours after the onset of symptoms. For occlusion of the proximal RCA, distal RCA, and LCx, V3/III ratio was 0.2+/-0.3, 0.8+/-0.5, and 2.5+/-2.5 (p = 0.0001), respectively. The V3/III ratio <0.5 identified proximal RCA occlusion, 0.5

Rapid detection cytomegalovirus pneumonia in recipients of bone marrow transplant: evaluation and comparison of five survey methods for bronchoalveolar lavage fluid.

To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in recipients of BMT in its earliest stage, five CMV methods were assessed for their usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43 cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight, culture in eight and cytology in three. There were no positive cases in in situ hybridization. Based on this result, the 43 cases were classified into four groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2, five cases: positive in PCR and shell vial; Group 3, four cases: positive only in PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were judged as having the highest risk of overt CMV-IP. They were successfully treated with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as having active CMV infection and ganciclovir monotherapy was effective for these patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from CMV-related manifestations throughout the study. The sensitivity and specificity of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in cytology. Similarly, the positive and negative predictive values were 0.67 and 1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88 in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful in detecting post BMT CMV-IP in its earliest stage.

Comparison of cytomegalovirus (CMV) antigenemia and CMV in bronchoalveolar lavage fluid for diagnosis of CMV pulmonary infection after bone marrow transplantation.

A comparative cytomegalovirus (CMV) diagnostic study was carried out on 30 bone marrow transplant patients. Forty-three bronchoalveolar lavage fluid (BALF) samples from these patients were examined for CMV by viral culture, polymerase chain reaction (PCR), shell vial and cytology. In parallel, peripheral blood samples were subjected to CMV antigenemia assay. CMV was detected in 12 (27.9%) of the 43 BALF samples (10 samples in viral culture, 10 samples in PCR, eight samples in shell vial and three samples in cytology). The CMV antigenemia assay yielded a positive result for six samples. The rates of agreement between results of the CMV antigenemia assay and results of each of the BALF tests were as follows: 81.4% with viral culture, 76.7% with PCR, 86.0% with shell vial, and 88.4% with cytology. Although the sensitivity of the CMV antigenemia assay was inferior to the sensitive tests of BALF samples, statistically significant correlations were demonstrated between the CMV antigenemia assay, viral culture, shell vial and cytology. Although the CMV antigenemia assay was shown to be useful for detection of CMV, it may be necessary to confirm not only the sensitivity but also the specificity of this method for prevention of CMV disease after BMT.

Difficulties of molecular dissociation of Clostridium botulinum type G progenitor toxin.

Clostridium botulinum type G progenitor toxin was chromatographed on DEAE-Sephadex and Q-Sepharose equilibrated with 0.05 M Tris-HCl buffer, pH 8.0, containing 0.2 M urea. The toxin was eluted in a single protein peak from DEAE-Sephadex, but it was eluted in four protein peaks from Q-Sepharose; the third peak was toxic and the others were nontoxic. The third peak, appearing to be the toxic component, had a molecular mass of 150,000. In SDS-polyacrylamide gel electrophoresis, purified type G progenitor toxin migrated in six bands, with molecular masses of 150,000, 140,000, 58,000, 10,800, 10,600, and 10,400. Type G progenitor toxin may be composed of a toxin component with a molecular mass of 150,000 and a nontoxic component in a manner similar to progenitor toxins of other types. Type G toxic component, whether it was reduced or not, migrated in a single band to the same relative positions in SDS-PAGE; type A toxic component reduced with 2-mercaptoethanol migrated in two bands.

Wear debris from two different alumina-on-alumina total hip arthroplasties.

We compared wear particles from two different designs of total hip arthroplasty with polycrystalline alumina-ceramic bearings of different production periods (group 1, before ISO 6474: group 2, according to ISO 6474). The neocapsules and interfacial connective tissue membranes were retrieved after mean implantation times of 131 months and 38 months, respectively. Specimen blocks were freed from embedding media, either methylmethacrylate or paraffin and digested in concentrated nitric acid. Particles were then counted and their sizes and composition determined by SEM and energy-dispersive x-ray analysis (EDXA). The mean numbers and sizes of most alumina wear particles did not differ for both production periods, but the larger sizes of particle in group 1 point to more severe surface destruction. The increased metal wear in group 2 was apparently due to alumina-induced abrasion of the stems. In this study the concentrations of particles in the periprosthetic tissues were 2 to 22 times lower than those observed previously with polyethylene and alumina/polyethylene wear couples.

Malignant proliferating trichilemmal tumor in the skin over the breast: a case report.

A proliferating trichilemmal tumor is relatively uncommon. It is composed of multiple cysts consisting of squamous epithelium with trichilemmal keratinization without granular layer interposition. This lesion usually occurs in the scalp of elderly women. We describe a 67-year-old woman with a malignant proliferating trichilemmal tumor in the skin over the breast. We first misdiagnosed the disease as a primary squamous cell carcinoma of the breast with a metastatic lymph node in the axilla because of the disease site and our unfamiliarity with the disease. The patient underwent radical mastectomy with axillary dissection. Eight months postoperatively, a tumor appeared in her right axilla and progressively enlarged. We subsequently excised the tumor. She is healthy as of 8 months postoperatively. To the best of our knowledge, only one case of a proliferating trichilemmal tumor occurring in the skin over the breast has been reported.

Treatment of disseminated hepatoblastoma involving bilateral lobes.

A 30-month-old boy was investigated because of a huge abdominal mass in the right upper abdomen. A computed tomography scan and celiac angiography showed that the tumor involved bilateral lobes of the liver. At first, for this disseminated and "unresectable" tumor we did liver biopsy and hepatic arterial catheterization. Through this catheter we started chemotherapy using THP-Adriamycin and cis-platinum. After three courses of chemotherapy, a second-look operation was performed and trisegmentectomy was done to remove the main tumor and metastases, including the left lobe and the right anterior segment. The trisegmentectomy was performed with success, and the boy's serum alpha-fetoprotein (AFP) remains normal 37 months after the start of treatment, indicating a probable permanent cure. Such cases have rarely been reported in the literature. Our experience in treating this patient would seem to encourage aggressive management of advanced hepatoblastoma in other patients.

Determination of plasma total renin level by RIA with a monoclonal antibody: value as a marker for nephroblastoma.

Plasma total renin is a new, useful marker for nephroblastoma, but the conventional method for determining its level is sophisticated and requires large blood samples. To develop a simpler technique, a monoclonal antibody specific for both inactive and active renin (inactive + active = total) was raised, and a radioimmunoassay (RIA) system was established. This monoclonal antibody stains only the juxtaglomerular apparatus; values determined by this RIA did not change before and after activation. So far, the RIA system has been applied to 136 samples from 92 patients. Plasma total renin levels were also determined with the conventional method: samples were activated, then renin activity was assayed by measuring angiotensin I. The coefficient of the data obtained by these two different techniques was 0.921 (P less than .01). Plasma total renin levels in patients with nephroblastoma were significantly increased (546.5 +/- 297.8 pg/mL) over those in patients with neuroblastoma (218.6 +/- 46.5 pg/mL) and in controls (165.8 +/- 67.5 pg/mL, P less than .01). After removal of Wilms' tumors, the levels decreased to normal when sampled every 2 weeks. It was concluded that a newly developed RIA system is more useful in determining plasma total renin levels in patients with nephroblastoma.

Primary cardiac leiomyosarcoma growing rapidly and causing right ventricular outflow obstruction.

Leiomyosarcomas are extremely rare primary cardiac tumors. We report a rapidly growing primary leiomyosarcoma of the right ventricle, which obstructed the right ventricular outflow tract within one month after symptom onset in a 68-year-old man. Two-dimensional echocardiography was useful in diagnosing the extent and progression of the tumor. The tumor was surgically resected on an emergency basis, and the right ventricle and pulmonary artery were successfully reconstructed. Recurrence of the tumor on the right ventricle was observed, and the patient was overcome by sudden dyspnea and died three months after surgery.

[The effect of long-term group education for obese women in a public health center].

In order to improve maintenance of weight reduction, a long-term (5 month) weight reduction class for obese women consisting of repeated group learning three times a month in areas of dietary regimen and practice of physical exercise, and self-help group activities was conducted at a health center. Maintenance of achieved weight reduction was studied six months and one year after completion of the class. The results are as follows. 1) Among 30 alumni, percentages of rebound, regaining weight of more than half of reduction during the class, were 18% at six months and 48% at one year after the class. These results appear to indicate the difficulty in maintaining weight loss. 2) However, when changes were studied in terms of fat mass and lean body mass, rebound of fat mass, regaining fat mass of more than half of reduction, was very small--only 5%, through the follow-up periods--while lean body mass increased gradually. These results indicate very good maintenance of fat mass reduction, and from the view point of the objective of weight reduction which is principally fat mass reduction, this objective was supported. 3) The attendees were divided into two groups, diet group and exercise group. There were almost no differences in the follow-up results for weight maintenance between the two groups. This can be attributed to the fact that since the combination of dieting and exercise was emphasized in both groups, with moderate energy restriction and balanced food intake in the dietary regimen and aerobic walking for exercise in addition to the classroom learning, instructions for lifestyle changes were rather similar for both groups.

[Functional analysis of apoptosis signal-regulating kinase 1 (ASK 1)-binding proteins].

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are pleiotropic cytokines that activate two transcription factors, Activator Protein-1 (AP-1) and Nuclear Factor-kappa B (NF-kappa B). Apoptosis signal-regulating kinase 1 (ASK 1) is a mitogen-activated protein (MAP) kinase kinase kinase (MAPKKK) that is activated by TNF and IL-1, and stimulates c-Jun N-terminal kinase (JNK also known as SAPK; stress-activated protein kinase) and p38 activation. Through genetic screening for ASK 1-binding proteins, Transforming Growth Factor beta (TGF-beta)-activated kinase (TAK 1), another MAPKKK family protein, was identified. Here we report that ASK 1 binds to TAK 1 and dissociates TAK 1 from TNF receptor-associated factor 6 (TRAF 6), and inhibits TAK 1- and TRAF 6-, but not NF-kappa B-inducing kinase (NIK)-induced NF-kappa B activation.

Selective intracellular delivery of proteasome inhibitors through pH-sensitive polymeric micelles directed to efficient antitumor therapy.

The ubiquitin-proteasome system is central in the regulation of cellular proteins controlling cell cycle progression and apoptosis, drawing much interest for developing effective targeted cancer therapies. Herein, we developed a novel pH-responsive polymeric-micelle-based carrier system to effectively deliver the proteasome inhibitor MG132 into cancer cells. MG132 is covalently bound to the block copolymer composed of polyethylene glycol (PEG) and polyaspartate through an acid-labile hydrazone bond. This bond is stable at physiological condition, but hydrolytically degradable in acidic compartments in the cell, such as late-endosomes and lysosomes, and thus, it was used for controlled release of MG132 after EPR-mediated preferential accumulation of the micelles into the tumor. MG132-loaded micelles have monodispersed size distribution with an average diameter of 45nm, and critical micelle concentration is well below 10(-7)M. In vitro studies against several cancer cell lines confirmed that MG132-loaded micelles retained the cytotoxic effect, and this activity was indeed due to the inhibition of proteasome by released MG132 from the micelles. Real-time in vitro confocal-microscopy experiments clearly indicated that MG132-conjugated micelles disintegrated only inside the target cells. By intravital confocal micro-videography, we also confirmed the prolonged circulation of MG132 loaded micelles in the bloodstream, which lead to tumor specific accumulation of micelles, as confirmed by in vivo imaging 24h after injection. These micelles showed significantly lower in vivo toxicity than free MG132, while achieving remarkable antitumor effect against a subcutaneous HeLa-luc tumor model. Our findings create a paradigm for future development of polymeric-micelle-based carrier system for other peptide aldehyde type proteasome inhibitors to make them effective cohort of the existing cancer therapeutic regiments.