A double bifurcated graft for abdominal aorta and bilateral iliac artery reconstruction

Revascularization of the hypogastric artery often tends to be neglected in aortoiliac reconstructive surgery; however, its incomplete revascularization can result in unfavorable complications such as buttock claudication or necrosis, vascular impotence, and colonic ischemia. Multiple vascular lesions in the abdominal aorta and bilateral iliac arteries were reconstructed using a newly designed double bifurcated graft in five male patients. All five patients demonstrated excellent graft limb patency and postoperative improvement of the ankle-brachial pressure index without any clinical signs of ischemia in regions of the hypogastric artery. Thus, we conclude that an aggressive approach toward hypogastric circulation maintenance is essential in aortoiliac reconstructive surgery. By using this double bifurcated graft, rapid and safe revascularization of the bilateral hypogastric arteries concomitant with the external iliac or femoral arteries can be performed.     

Isolation of two distinct prion strains from a scrapie-affected sheep

We performed a transmission study using mice to clarify the characteristics of the most recent case of scrapie in Japan. The mice that were inoculated with the brain homogenate from a scrapie-affected sheep developed progressive neurological disease, and one of the scrapie-affected mice showed unique clinical signs during primary transmission. This mouse developed obesity, polydipsia, and polyuria. In contrast, the other affected mice exhibited weight loss and hypokinesia. In subsequent passages, the mice showed distinct characteristic scrapie phenotypes. This finding may prove that different prion strains coexist in a naturally affected sheep with scrapie.     

Anesthetic management for cleft palate plasty in a patient with Pierre-Robin syndrome

A girl (15 months-old) with Pierre-Robin Syndrome was scheduled for cleft palate plasty. She had a past history of difficulty feeding, mild airway obstruction during sleeping and mental retardation. After induction of anesthesia with an inhalational anesthetic technique, conventional tracheal intubation was impossible. We introduced a laryngeal mask airway (LMA) and successfully intubated through the LMA. After extubation of the tracheal tube, she developed upper airway obstruction with arterial desaturation. We ventilated her lungs in the lateral position with an inhalation of epinephrine and injection of methylprednisolone. Airway obstruction then improved gradually. In this case, LMA was a valuable device as a guide for the tracheal intubation. Because airway obstruction after extubation is a common complication in a patient with Pierre-Robin syndrome, we need to observe the patient closely.     

Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues

We recently reported the intraspecies transmission of L-type atypical bovine spongiform encephalopathy (BSE). To clarify the peripheral pathogenesis of L-type BSE, we studied prion distribution in nerve and lymphoid tissues obtained from experimentally challenged cattle. As with classical BSE prions, L-type BSE prions accumulated in central and peripheral nerve tissues.     

Successful repair for a giant coronary artery aneurysm with coronary arteriovenous fistula complicated by both right- and left-sided infective endocarditis

We report a rare case of a 65-year-old woman who underwent an emergent lifesaving heart operation for an undiagnosed right coronary artery aneurysm with a coronary arteriovenous fistula complicated by active infective endocarditis, which affected the aortic valve, mitral valve, and coronary sinus. We performed direct closure of the coronary arteriovenous fistula, ligation of the right coronary artery aneurysm, double coronary artery bypass grafting, and double valvular replacement. Five years after the operation, she had no sign of congestive heart failure or infection, and was not receiving antibiotics.     

Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells

The mammalian target of rapamycin (mTOR) plays a central role in regulating the proliferation of malignant glioma cells, and mTOR-specific inhibitors such as rapamycin analogs are considered as promising therapy for malignant gliomas. However, the efficacy of mTOR inhibitors alone in the treatment of patients with malignant gliomas is only modest, potentially because these agents rather than acting as mTOR kinase inhibitors instead interfere with the function of only mTOR/raptor (regulatory-associated protein of mTOR) complex and thus do not perturb all mTOR functions. The purpose of this study was to determine whether global inhibition of the mTOR molecule enhances the antitumor effect of rapamycin on malignant glioma cells. We showed that rapamycin induced autophagy and that inhibition of autophagy by small interfering RNA (siRNA) directed against autophagy-related gene Beclin 1 attenuated the cytotoxicity of rapamycin in rapamycin-sensitive tumor cells, indicating that the autophagy was a primary mediator of rapamycin's antitumor effect rather than a protective response. Exogenous expression of an mTOR mutant interfering with its kinase activity markedly enhanced the incidence of rapamycin-induced autophagy. Moreover, silencing of mTOR with siRNA augmented the inhibitory effect of rapamycin on tumor cell viability by stimulating autophagy. Importantly, not only rapamycin-sensitive malignant glioma cells with PTEN mutations but also rapamycin-resistant malignant glioma cells with wild-type PTEN were sensitized to rapamycin by mTOR siRNA. These results indicate that rapamycin-induced autophagy is one of the agent's antitumor effects and that silencing or inhibiting mTOR kinase activity could enhance the effectiveness of rapamycin.     

Tumor suppressor 101F6 and ascorbate synergistically and selectively inhibit non-small cell lung cancer growth by caspase-independent apoptosis and autophagy

101F6 is a candidate tumor suppressor gene harbored on chromosome 3p21.3, a region with frequent and early allele loss and genetic alterations in many human cancers. We previously showed that enforced expression of wild-type 101F6 by adenoviral vector-mediated gene transfer significantly inhibited tumor cell growth in 3p21.3-deficient non-small cell lung cancer (NSCLC) cells in vitro and in vivo. The molecular mechanism of 101F6-mediated tumor suppression is largely unknown. A computer-aided structural and functional model predicts the 101F6 protein to be a member of the cytochrome b561 protein family that is involved in the regeneration of the antioxidant ascorbate. 101F6 protein is expressed in normal lung bronchial epithelial cells and fibroblasts but is lost in most lung cancers. Treatment with 101F6 nanoparticle-mediated gene transfer in combination with a subpharmacologic dose (200-500 micromol/L) of ascorbate synergistically and selectively inhibited lung cancer cell growth in vitro. Systemic injection of 101F6 nanoparticles plus the i.p. injection of ascorbate synergistically inhibited both tumor formation and growth in human NSCLC H322 orthotopic lung cancer mouse models (P<0.001). Furthermore, exogenous expression of 101F6 enhanced intracellular uptake of ascorbate, leading to an accumulation of cytotoxic H(2)O(2) and a synergistic killing of tumor cells through caspase-independent apoptotic and autophagic pathways. The antitumor synergism showed by the combination treatment with systemic administration of 101F6 nanoparticles and ascorbate on lung cancer offers an attractive therapeutic strategy for future clinical trials in cancer prevention and treatment.     

Pre-dinner administration increases the efficacy of proton pump inhibitors on refractory GERD symptoms in connective tissue disease patients

Background

A significant proportion of patients with connective tissue disease (CTD) have gastric esophageal reflux disease (GERD) symptoms despite receiving proton pump inhibitors (PPIs). Although pre-meal administration of PPIs is recommended in Western countries, the benefit of this administration timing in Japanese CTD patients with refractory GERD symptoms has not been proven.

Objective

To determine whether pre-dinner administration of PPIs is more efficacious for refractory GERD symptoms in Japanese CTD patients.

Methods

CTD patients receiving oral PPIs were instructed to take PPIs 1 h before dinner. Gastrointestinal symptoms were evaluated with frequency scale for the symptoms of GERD (FSSG) and gastrointestinal symptom rating scale (GSRS) before and after the intervention.

Results

Pre-dinner administration of PPIs significantly improved FSSG total score, from a median of 8 to 6.5 (P = 0.005). Pre-dinner administration was more effective in patients with overt GERD symptoms (from median 18 to 10, P < 0.001) than in those with mild GERD symptoms (from median 2 to 2, P = 0.201). In addition to reflux syndrome, pre-dinner administration of PPIs significantly decreased abdominal pain syndrome and constipation syndrome of GSRS.

Conclusion

Pre-dinner administration of PPIs may increase their efficacy in Japanese CTD patients with GERD, especially those with overt symptoms.