Pathological Study on the Expression of Vasohibins in Peripheral Artery Disease.

Vasohibin-2 (VASH2) is a gene that promotes local angiogenesis. The tubulin carboxypeptidase activity of vasohibin causes detyrosination of alpha-tubulin and may play an important role in the regulation of various phenomena. Pathological and therapeutic angiogenesis are involved in atherosclerotic lesions. This study aimed to investigate whether the expression of VASH2 is associated with peripheral artery disease (PAD) in relation to angiogenesis, tubulin detyrosination, and severity of atherosclerotic lesions. An analysis of femoral and tibial arteries obtained from 86 patients with PAD or abdominal aortic aneurysm (AAA) was performed. The expressions of cluster of differentiation 31, VASH1, VASH2, and detyrosinated alpha-tubulin (DT-tubulin) were examined by immunohistochemistry, and their association with PAD was analyzed. The counts of VASH2 in the tunica media and adventitia in the tibial artery were significantly higher than those in the femoral artery in the PAD (P = 0.005 and P = 0.008, respectively) and AAA (P = 0.002 and P < 0.001, respectively) groups. In the tunica media and adventitia, VASH2 was significantly correlated with DT-tubulin. There was no significant difference in the expression of VASH2 and DT-tubulin in medial smooth muscle cells (McNemar test, P > 0.999). This study revealed the possible involvements of VASH2 in atherosclerosis by two methods-one maybe related to the progression of atherosclerosis by inducing angiogenesis and the second may be related to the decrease in arterial elasticity by increasing DT-tubulin in medial smooth muscle cells.

Total Debranching Plus Antegrade Thoracic Endovascular Aortic Repair without Side Clamping in a Patient with Arch Aneurysm and Ascending Aorta Calcification.

A high-risk patient with aortic arch aneurysm, associated with severe calcification of the ascending aorta and iliac arteries, was treated with total debranching and antegrade thoracic endovascular aortic repair (TEVAR) via the ascending aorta. Proximal anastomosis for a triple-branched graft to the ascending aorta was performed without side clamping using the "real chimney technique." After bypassing the supra-aortic branches, a TEVAR was performed in an antegrade fashion through the ascending aorta. This case suggests that the approaches mentioned above should be considered in patients with arch aneurysms and severe calcified degeneration.

Bioelectrical impedance analysis for perioperative water management in adult cardiovascular valve disease surgery.

PURPOSE: Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients. METHODS: We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the "preoperative EI" and the maximum as the "peak EI". RESULTS: A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p < 0.001). Positive correlations were found between the peak EI and the ICU stay (R = 0.625, p < 0.001), the peak EI and the ventilation time (R = 0.366, p < 0.01), and the preoperative EI and the ICU stay (R = 0.464, p = 0.026). CONCLUSION: The EI is possibly a predictive marker for perioperative water management in cardiac surgery.

Balloon-expandable stent graft for coral reef aorta.

Coral reef aorta (CRA) is a rare aortic occlusive disease with calcified intraluminal lesions. We report the case of a patient with CRA who underwent endovascular treatment (EVT). A 78-year-old woman presented with intermittent claudication. A computed tomography scan showed a preocclusive calcified lesion in the infrarenal aorta. EVT with a balloon-expandable stent graft was successfully performed, and her intermittent claudication improved. Compared with the conventional surgical treatments for CRA, EVT with a balloon-expandable stent graft is less invasive. This procedure is an effective option for the treatment of CRA.

Iatrogenic femoral vein pseudoaneurysm.

Femoral vein pseudoaneurysm is a rare complication during percutaneous interventions. We report the case of a patient with common femoral vein pseudoaneurysm caused by unsuccessful manual compression. A 68-year-old woman underwent catheter ablation for atrial fibrillation at another institution. Postoperatively, she experienced right groin pain and leg edema. Doppler ultrasound examination revealed a 2-cm venous pseudoaneurysm as a compressible and hypoechoic lesion. We successfully performed venous aneurysmectomy after failed ultrasound-guided compression therapy. Appropriate procedures must be selected for patients with femoral pseudoaneurysm. The efficacy of hemostatic techniques for preventing vascular complications after venous sheath removal should not be underestimated.

The influence of a noisy environment on hearing impairment and tinnitus: The hearing outcomes of 50-year-old male Japan ground self-defense force personnel.

OBJECTIVES: Hearing loss is one of the biggest health problems in the world and occupational noise-induced hearing loss is recognized as the most common work-related illness. However, many factors that result in hearing loss make it difficult to define the specific factor that induces noise-induced hearing loss. To access the exact effect of occupational noise exposure on hearing, we conducted a cross-sectional cohort study of the relationship between noise exposure and hearing impairment in 50-year-old male Japanese Self-Defense Force (JSDF) personnel who work in a noisy environment. This population is ideal for the detection of noise-induced hearing impairments due to the homogeneity of genetic and social backgrounds. METHODS: The data utilized in this study were collected from a "50-year-old milestone health examination" of the JSDF from July 2013 to October 2015. One thousand sixty-seven male personnel were enrolled in the study. Pure-tone audiometry was conducted with an audiometer. A survey questionnaire asked participants to self-report occupational noise exposure. RESULTS: This cohort revealed that noise-exposed personnel had a higher hearing threshold and a higher odds ratio in 1) the average threshold of 4 frequencies (500 + 1000 + 2000 + 4000 Hz / 4), 2) the average threshold of higher 3 frequencies (2000 + 4000 + 8000 Hz / 3), and 3) the threshold of 4 kHz compared to no noise-exposed control personnel. The prevalence of tinnitus was also significantly higher in the noise-exposed group. CONCLUSIONS: This study provides specific evidence for the relationship between noise exposure and noise-induced hearing impairments.

A Case of Birt-Hogg-Dubé (BHD) Syndrome Harboring a Novel Folliculin (FLCN) Gene Mutation.

BACKGROUND Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder clinically characterized by pulmonary cysts, spontaneous pneumothorax, renal cell cancer, and skin fibrofolliculomas. The disorder is caused by germline mutations in the FLCN gene. CASE REPORT A 56-year-old female was admitted to our hospital with a diagnosis of bilateral spontaneous pneumothorax. A computed tomography (CT) scan of the chest revealed bilateral multiple bullae predominantly located in the subpleural and mediastinal areas in the bilateral upper and lower lobes. Although she was cured by thoracic cavity drainage, she underwent resection of bilateral lung bullae because she had a prior history of right pneumothorax at 37- and 45-years of age. She had no signs of renal tumor but had fibrofolliculoma in her face and a family history of pneumothorax, we therefore suspected BHD syndrome. DNA sequence analyses determined that there was a two base pair deletion in exon 4 of the FLCN gene, confirming the diagnosis of BHD syndrome. CONCLUSIONS Here we report a case of BHD syndrome with a previously unreported FLCN mutation.

A long-living case of carotid aneurysm caused by inflammatory leiomyosarcoma.

We report here on a long-surviving patient with a vascular leiomyosarcoma arising in the right common carotid artery, and some possible reasons for the long-term survival. The patient was a 40-year-old woman who was diagnosed with a right common carotid aneurysm and underwent aneurysmectomy with graft replacement. Two years and nine months after her surgery, she developed a cerebral infarction and left hemiparesis due to graft occlusion, but later achieved functional recovery through physical rehabilitation. She has been alive for 20 years since her surgery.

NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea.

Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2(-/-) mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2(-/-) mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2(-/-) mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention.

Ankle-Brachial Index, Toe-Brachial Index, and Pulse Volume Recording in Healthy Young Adults.

OBJECTIVE: To clarify the characteristics of ankle-brachial index (ABI), toe-brachial index (TBI), and pulse volume recording (PVR) of the ankle with brachial-ankle pulse wave velocity (baPWV) in healthy young adults. MATERIAL AND METHODS: We analyzed ABI, TBI, baPWV, and PVR in the ankle of healthy adults aged 20 to 25 years (median, 20 years) using an automatic oscillometric device between 2002 and 2013. The ABI, baPWV, and PVR in 1282 legs of 641 subjects (301 men and 340 women) and the TBI in 474 toes of 237 subjects (117 men and 120 women) were evaluated. RESULTS: The measured values showed no bilateral differences. ABI and baPWV were higher in men than in women, but TBI was similar in both sexes. ABI <1.0 was observed in 18.1% of the legs in men and in 25.6% in women. TBI <0.7 was observed in 16.2% of the toes in men and 19.1% in women. For ankle PVR, the % mean arterial pressure was higher in women than in men. The upstroke time was <180 ms in most subjects. CONCLUSIONS: For young people, ABI <1.0 or TBI <0.7 may not always indicate vascular abnormalities. When evaluating circulatory indexes, age and sex should be considered.

A case of autoimmune pulmonary alveolar proteinosis appearing as a localized ground-glass opacity.

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease caused by abnormal intra-alveolar surfactant accumulation; it commonly appears as a "crazy-paving" pattern on high-resolution computed tomography. Here, we report a rare case of autoimmune PAP appearing as localized ground-glass opacity. An 82-year-old woman underwent chest computed tomography (CT) at another facility for cough, and a 2-cm localized ground-glass opacity was detected at the bottom of the right upper lung lobe. When she presented for follow-up at our hospital 6 months later, she was asymptomatic. The CT examinations performed at that point and 2 months thereafter did not reveal any changes. However, a CT examination performed after 5 months revealed slight increases in size and concentration. Adenocarcinoma in situ or minimally invasive adenocarcinoma was suspected. Incomplete lobulation between the upper and middle lobes of the right lung was detected, and video-assisted thoracoscopic lobectomy of the upper lobe and partial resection of the middle lobe of the right lung were performed. Histological examination revealed alveoli and terminal bronchioles filled with eosinophilic proteinaceous material positive for periodic acid-Schiff stain. The histopathological diagnosis was PAP and positive serum anti-GM-CSF antibody findings confirmed autoimmune PAP.

A case of acute superior mesenteric artery embolism with severe ischemic liver injury successfully treated by endovascular treatment.

We describe an interesting clinical course of a patient who developed severe ischemic liver injury due to acute embolism of the superior mesenteric artery (SMA) and celiac artery. A 70-year-old man was hospitalized for abdominal pain and diarrhea. Abdominal computed tomography demonstrated a variant common hepatic artery arising from the SMA and multiple thromboembolic occlusions of visceral arteries, including the SMA and celiac artery. Laboratory data showed markedly elevated hepatic enzymes, which increased after admission despite the initiation of systemic anticoagulant and thrombolytic therapy. The patient was successfully treated by endovascular recanalization of the SMA occlusion via transcatheter embolus aspiration, thrombolysis, balloon angioplasty, and stent placement. Severe ischemic liver injury may occur in the setting of synchronous embolism of the SMA and celiac artery, and these phenomena may have a critical impact on the choice of treatment strategies and prognosis. Endovascular treatment appears to an effective treatment option.

Targeting KRAS mutation-bearing lung cancer in vivo by pulmonary surfactant-adenovirus-mediated gene transfer.

Pulmonary surfactant has been used as a carrier to deliver a therapeutic virus to dysfunctional lung cells that reside within an intricate lung structure. To investigate whether pulmonary surfactant enhances the efficacy of intratracheal instillation of a therapeutic virus to target KRAS mutation-bearing lung cancer in vivo, we developed a recombinant adenovirus that induces cell death only in lung cancer cells and injected the adenovirus into a mouse model of KRAS mutation-positive lung cancer intratracheally with and without surfactant. A therapeutic adenovirus that induces cell death only in lung cancer cells was constructed by combining a cancer-specific human telomerase reverse transcriptase (hTERT) promoter fused to CCAAT/enhancer-binding protein alpha (CEBPα) with a modified lung-specific Clara cell-specific 10-kDa protein (CC10) promoter fused to cytotoxic adenovirus type 5 early region 1A (E1A). CEBPα is induced only in cancer cells and activates the CC10 promoter, which in turn induces cytotoxic E1A, and causes cell death only in lung cancer cells in vitro. This adenovirus was intratracheally administered to the model mice (CCSP-rtTA/Tet-op-K-Ras4bG12D bitransgenic mice) in the presence and absence of pulmonary surfactant. Intratracheally administered therapeutic adenovirus with pulmonary surfactant spread to airways, as well as to the alveolar region of the lung, and caused a reduction of lung tumors developed. The therapeutic adenovirus without pulmonary surfactant spread only to airways and was ten-fold less effective in tumor reduction. Here, we demonstrate that pulmonary surfactant is an efficient tool to intratracheally deliver a therapeutic virus to treat KRAS mutation-positive lung cancer in vivo.

Inhibition of Myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc.

Myc is an oncogenic transcription factor that promotes tumorigenesis. Recently, a dominant negative form of Myc (Omomyc) was shown to cause regression of lung tumors in a mouse model of lung cancer caused by KRAS mutation, suggesting that Myc might be a potential therapeutic target to treat the KRAS lung cancer. However, it is not yet known whether Omomyc can also inhibit the growth of human lung tumors that carry a similar KRAS mutation. In the present study, we demonstrate that Omomyc induces cell death of KRAS-mutated human lung adenocarcinoma A549 cells in vitro and in vivo. However, Omomyc does not induce cell death in human lung adenocarcinoma H441 cells that also carry the KRAS mutation. Interestingly, A549 cells express high levels of Myc, while H441 cells do not. Co-expression of exogenous Myc with Omomyc in H441 cells induces cell death, indicating that Omomyc requires high levels of Myc to induce cell death in KRAS mutation-positive lung adenocarcinoma. Here, we show for the first time that KRAS mutation-positive lung cancer displaying high levels of Myc could be treated by inhibiting Myc transactivation function.

[Dexmedetomidine for sedation during voice monitoring surgery in a patient with an episode of seizure].

We present a rare case of 26-year-old male patient without a history of epilepsy, who underwent a voice monitoring surgery under local anesthesia plus sedation using modified neuroleptanalgesia. As he developed generalized tonic-clonic seizure probably due to pentazocine, the operation was cancelled. Later, the same surgery was rescheduled. After a premedication with intramuscular phenobarbital, the patient was sedated with dexmedetomidine and locally anesthetized, showing sedation of high quality with no respiratory depression and no seizure. Dexmedetomidine was used succesfully for voice monitoring surgery.

Comparison of the health condition between the 8020 achievers and the 8020 non-achievers.

AIM: To review of the difference in the health condition between 8020 achievers and 8020 non-achievers covering 25 papers which were published mainly in Japan. BACKGROUND: A campaign targeting the elderly to retain at least 20 teeth by the time they reach the age of 80 years (8020) has been in place since 1991 in Japan. RESULTS: The percentage of 8020 achievers increased from 10.9% in 1993, 15.3% in 1999 and 24.1% in 2005. The 8020 achievers had a tendency towards a strict upbringing and were not fond of sweets in their childhood. Physical indices such as height, weight, BMI score, bone mineral density, balance ability, grip strength, and exercise function in the 8020 achievers were better than the 8020 non-achievers. A close inverse relationship between the number of teeth and heart rate was recognised. The food intake survey showed that 8020 achievers ate many kinds of food. However, these foods were those with less kilocalories and lower levels of carbohydrate. The 8020 achievers had good activity in daily life (ADL) level, were satisfied with life, and had a higher cumulative survival rate. Oral health conditions including periodontal condition, masticatory ability, occlusal force, occlusal and maxillofacial forms in the 8020 achievers were better than the 8020 non-achievers.

Extramedullary plasmacytoma of the tonsil diagnosed by fine-needle aspiration cytology.

A case of tonsillar extramedullary plasmacytoma in a 53-year-old man with a complaint of lump sensation in the throat is presented. Examination of the oral cavity showed enlargement of the left tonsil. Magnetic resonance imaging demonstrated a solid mass, measuring 3.2 x 2.0 x 3.8 cm, in the left tonsil. Cytologic smear obtained by fine-needle aspiration biopsy appeared highly cellular and was composed of clusters of plasma cells with varying maturity. Atypical plasma cells had prominent eccentric nuclei with nucleoli and finely granular cytoplasm. Binucleated cells and mitotic figures were also identified. The cytoplasm of mature-looking small plasma cells was also finely granular without a perinuclear halo. A cytologic diagnosis of plasmacytoma was made. Excisional biopsy showed sheets of plasmacytoid cells with abundant eosinophilic granular cytoplasm. Occasional binucleated and pleomorphic cells with giant nuclei and prominent nucleoli were observed. These plasmacytoid cells were diffusely immunoreactive for lambda light chain and IgG, partially positive for epithelial membrane antigen. Metastatic examination finding was negative for multiple myeloma, and the patient was diagnosed as having extramedullary plasmacytoma. Although the diagnosis of plasmacytoma on cytologic smear may be difficult, in the current case, fine-needle aspiration cytology provided a rapid and accurate diagnosis.

Recurrent hearing loss after myelography treated with epidural blood patch.

Transient hearing impairment is a known sequel after various procedures that result in loss of cerebrospinal fluid, such as lumbar puncture, spinal anesthesia and myelography. But persistent or recurrent hearing loss after dural puncture is a rare entity. We present a case with recurrent low-frequency sensorineural hearing loss after myelography. The patient was treated successfully by means of an epidural blood patch, although the conservative treatment was ineffective.

Long-term prognosis of patients with type a aortic intramural hematoma.

BACKGROUND: Recent studies have shown an favorable short-term prognosis of patients with type A acute aortic intramural hematoma (IMH). The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to elucidate clinical features and long-term prognosis of patients with type A IMH. METHODS AND RESULTS: Clinical data were compared retrospectively between 30 patients with acute type A IMH (IMH group) and 101 patients with acute type A AD (AD group) who were admitted to our institutions from 1988 to 1998. In AD group, 72 patients underwent surgical repair and 29 patients were treated medically. All patients in IMH group were treated initially with supportive medical therapy. Thirteen patients who demonstrated progression to AD or increase in size of hematoma underwent timed surgical repair except for 1 patient. The overall in-hospital mortality rate in IMH group was significantly lower than that in AD group (7% and 34%, P=0.004). Follow-up periods were 56+/-37 (IMH group) and 60+/-42 months (AD group), which revealed 1 and 6 late deaths, respectively. The actuarial survival rates in IMH group were all 90% at 1, 2, and 5 years, which were significantly higher than those in AD group (67%, 66%, and 62%, respectively; P=0.004). CONCLUSIONS: Patients with type A IMH have better long-term prognosis than patients with AD.

[Clinical investigation of acute sensorineural hearing impairment due to rifles].

This study examined 53 patients (74 ears) with acute sensorineural hearing impairment due to rifles. After patients were admitted, 16 were treated by steroid alone and 37 by steroid and PGE1 through intravenous drip injection. The therapeutic ratio was 19% and the recovery ratio 66% with no significant difference seen between treatment types in hearing improvement. Forty-two patients were treated within 7 days of injury and 32 8 or more days after injury. The therapeutic ratio was 21% and the recovery ratio 78% among patients treated sooner and a significant difference was seen between in hearing improvement early and later (8 or more days) treatment. We studied average hearing improvement between pre- and post treatment across the frequency spectrum. The average hearing improvement of 500 Hz and 1 kHz was significantly high compared to that of 8 kHz. This suggests that impairment of middle-pitched tones is improved more easily than high-pitch tones in hearing injuries due to rifles, and that early treatment after injury is extremely important.