Correlation between Cranial Nerve Microstructural Characteristics and Vestibular Schwannoma Tumor Volume.

BACKGROUND AND PURPOSE: Vestibular schwannomas are common cerebellopontine angle tumors arising from the vestibulocochlear nerve and can result in cranial nerve dysfunction. Conventional MR imaging does not provide information that could correlate with cranial nerve compression symptoms of hearing loss or imbalance. We used multitensor tractography to evaluate the relationship between the WM microstructural properties of cranial nerves and tumor volume in a cohort of patients with vestibular schwannomas. MATERIALS AND METHODS: A retrospective study was performed in 258 patients with vestibular schwannomas treated at the Gamma Knife clinic at Toronto Western Hospital between 2014 and 2018. 3T MR images were analyzed in 160 surgically naïve patients with unilateral vestibular schwannomas. Multitensor tractography was used to extract DTI-derived metrics (fractional anisotropy and radial, axial, and mean diffusivities of the bilateral facial and vestibulocochlear nerves [cranial nerves VII/VIII]). ROIs were placed in the transition between cisternal and intracanalicular segments, and images were analyzed using the eXtended Streamline Tractography reconstruction method. Diffusion metrics were correlated with 3D tumor volume derived from the Gamma Knife clinic. RESULTS: DTI analyses revealed significantly higher fractional anisotropy values and a reduction in axial diffusivity, radial diffusivity, and mean diffusivity (all P < .001) within the affected cranial nerves VII and VIII compared with unaffected side. All specific diffusivities (axial, radial, and mean diffusivity) demonstrated an inverse correlation with tumor volume (axial, radial, and mean diffusivity, P < .01). CONCLUSIONS: Multitensor tractography allows the quantification of cranial nerve VII and VIII WM microstructural alterations in patients with vestibular schwannomas. Our findings support the hypothesis that tumor volume may cause microstructural alterations of the affected cranial nerves VII and VIII. This type of advanced imaging may represent a possible avenue to correlate diffusivities with cranial nerve function.

A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis.

Sepsis is a common and frequently fatal condition and there is an urgent need for new therapies that will further reduce sepsis-induced mortality. Macrophage migration inhibitory (MIF) factor is important in the regulation of innate and adaptive immunity and is believed to play a key regulatory role in sepsis and autoimmune disease. As MIF deficiency or immunoneutralization protects mice or rats from fatal endotoxic shock or other inflammatory diseases, we examined whether DNA vaccination against this molecule would also be protective. DNA vaccines can stimulate both humoral and cellular immunity simultaneously and have been shown to be effective against a variety of pathogens or cytokine-driven pathologies. Mice were immunized with a MIF/tetanus toxin (TTX) DNA vaccine and sepsis was then induced by lipopolysaccharide or cecal ligation and puncture. The MIF/TTX DNA-vaccinated mice were protected from the lethal effect of sepsis compared with control-vaccinated mice in both models. Compared with the control-vaccinated mice, the MIF/TTX DNA-vaccinated mice also showed significantly lower serum tumor necrosis factor (TNF)-alpha protein levels and reduced mRNA expression of TNF-alpha, interleukin (IL)-1beta, IL-6, macrophage inflammatory protein-2 and Toll-like receptor-4 in the lungs. Thus, the MIF/TTX DNA vaccine may be useful for the prophylaxis of septic shock.

Enhancing Survival of Human Hepatocytes by Neonatal Thymectomy and Partial Hepatectomy in Micro-miniature Pigs.

BACKGROUND: With the goal of in vivo cultivation of human hepatocytes that have not been sufficient in full differentiation in vitro, the advantage of neonatal thymectomy was verified on expansion of xenogeneic human hepatocyte in the micro-miniature pig (MMP). METHODS: The thymus was excised immediately after the birth of the MMPs via cesarean section. Newborns were fed by artificial feeding under specific pathogen-free conditions. The thymectomized and nonthymectomized littermates were transplanted with human hepatocytes via a portal vein with or without partial hepatectomy at the MMP adult stage. RESULTS: The growth of thymectomized MMPs and the sham operated littermates was not significantly different; the former weighed 1.98 ± 0.30 kg (average ± standard deviation, n = 4) and the latter weighed 2.28 ± 0.39 kg (n = 4) at 1 month of age, and 17.48 ± 1.92 kg and 16.75 ± 2.68 kg at 12 months of age. Blood thymosin α1 concentrations in the thymectomy group were significantly lower than in the control group (0.22 ± 0.05 ng/mL vs 0.46 ± 0.16 ng/mL; n = 4, 12 months old, P = .029). After human hepatocyte transplantation, human albumin levels were detectable on day 28 in the peripheral blood of the thymectomy plus hepatectomy group (14.3 ± 4.9 ng/mL [± range, n = 2]) but were not detectable even on day 21 in the control group. CONCLUSIONS: Neonatal thymectomy was successfully achieved in infantile MMPs born via cesarean section. These pigs were considered to be an ideal in vivo bioreactor for human hepatocytes.

Tissue-engineered vascular autograft: inferior vena cava replacement in a dog model.

Tissue-engineered vascular autografts (TEVAs) were made by seeding 4-6 x 10(6) of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolid acid (PGA) nonwoven fabric sheet and a copolymer of L-lactide and caprolactone (n = 4). After 7 days, the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5, and 6 months, angiographies were performed, and the dogs were sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance similar to that of native IVCs. Immunohistological staining revealed the presence of factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where alpha-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA. These results strongly suggest that "ideal" venous grafts with antithrombogenicity can be produced.

Subjective symptoms acquisition system in a health promotion system for the elderly. Committee of System Development, Council of Japan AMHTS Institutions.

A previous report was concerned with the evaluation of quality of life using a Health Promotion System for the Elderly. In the present report, we describe one part of that system: a subjective symptoms acquisition and reporting system. The main purpose of this system is to permit any physician or nurse to uniformly employ questionnaires to acquire accurate subjective symptoms. This system is applied in three steps. First, the subjective answers to 21 questions displayed on a personal computer are obtained. These answers correspond to the basic subjective symptoms. Second, if a basic subjective symptom is "positive", more detailed questions are automatically generated. Finally, clear sentences regarding subjective symptoms are generated and output as a "finding report". This information is helpful to physicians and nurses in their health-counseling work. An artificial intelligence (AI) program based on "XpertRule" produces detailed questions which are generated by an interactive questionnaire using branching logical rules.

Development of a health guidance support system for lifestyle improvement. Committee of Health Evaluation Support System Council of Japan AMHTS Institutions.

OBJECTIVE: To provide automated advice for lifestyle adjustment based on an assessment of the results of a questionnaire and medical examination or health checkup data. METHODS: A system was developed that gathers data based on questions regarding weight gain, exercise, smoking, sleep, eating habits, salt intake, animal fat intake, snacks, alcohol, and oral hygiene; body mass index, resting blood pressure, fasting blood sugar, total cholesterol, triglycerides, uric acid and liver function tests. Based on the relationships between the lifestyle data and the health checkup data, a health assessment sheet was generated for persons being allocated to a multiple-risk-factor syndrome group. RESULTS: Health assessment and useful advice for lifestyle improvement were automatically extracted with the system, toward the high risk group for lifestyle related diseases. The system is operational. CONCLUSIONS: We developed a health guidance support system for lifestyle improvement. In comparison with conventional, limited advice methods, we developed a practical system that defined the necessity for lifestyle improvement more clearly, and made giving advice easier.

[A case of chronic recurrent pulmonary embolism complicated with effort angina pectoris].

A 50-year-old man was admitted to our hospital because of shortness of breath and an oppressive feeling in his chest on exertion. As a result of examinations including pulmonary-angiography, pulmonary perfusion scan and phlebogram, we diagnosed the case as chronic recurrent pulmonary embolism due to deep vein thrombosis. Later on, the patient showed an abnormal reaction on treadmill exercise test, and revealed redistribution at the anteroseptal and the inferior wall on thallium exercise test. We performed coronary angiography and diagnosed the case as angina pectoris (seg. 1 was total occlusion, segs. 2 and 3 were filled with bridge collateral, seg. 7 was 75% stenotic lesion). We evaluated the acute effect of vasodilators on pulmonary and systemic hemodynamics. The effect was beneficial in that it improved the hemodynamics. On account of this we thought a reversible condition was presented, and we administered these drugs to this patient.

Desulfovirga adipica gen. nov., sp. nov., an adipate-degrading, gram-negative, sulfate-reducing bacterium.

A novel, mesophilic, Gram-negative bacterium was isolated from an anaerobic digestor for municipal wastewater. The bacterium degraded adipate in the presence of sulfate, sulfite, thiosulfate and elemental sulfur. (E)-2-Hexenedioate accumulated transiently in the degradation of adipate. (E)-2-Hexenedioate, (E)-3-hexenedioate, pyruvate, lactate, C1-C12 straight-chain fatty acids and C2-C10 straight-chain primary alcohols were also utilized as electron donors. 3-Phenylpropionate was oxidized to benzoate. The G + C content of the DNA was 60 mol%. 16S rDNA sequence analysis revealed that the new isolate clustered with species of the genus Syntrophobacter and Desulforhabdus amnigenus. Strain TsuAS1T resembles Desulforhabdus amnigenus DSM 10338T with respect to the ability to utilize acetate as an electron donor and the inability to utilize propionate without sulfate in co-culture with Methanospirillum hungatei DSM 864. Strains TsuAS1T and DSM 10338T form a 'non-syntrophic subcluster' within the genus Syntrophobacter. Desulfovirga adipica gen. nov., sp. nov. is proposed for the newly isolated bacterium, with strain TsuAS1T (= DSM 12016T) as the type strain.

[Risk of side branch occlusion after coronary Palmaz-Schatz stenting].

The immediate and long-term patency of lesion-associated side branches after Palmaz-Schatz stent implantation was assessed by coronary angiography in 78 patients (83 lesions) at baseline, before and immediately after Palmaz-Schatz stent placement, and at 6 months. The patency of side branches was then analyzed. Of 83 lesions stented, 48 stent placements spanned 53 side branches with a diameter > or = 0.5 mm. Ten (19%) side branches were occluded before and 14 (26%) after stenting, and 4 (8%) at 6 months. Side branch ostial stenosis (> or = 50%) was present in 17 side branches; 5 (29%) with ostial stenosis became occluded before and 12 (71%) after stenting. Four of nine (44%) side branches arising from stenosis became occluded after predilatation and five (56%) after stenting. These findings demonstrate that both ostial stenosis and the location of side branches are associated with side branch occlusion.

Low-dose tissue plasminogen activator followed by planned rescue angioplasty reduces time to reperfusion for acute myocardial infarction treated at community hospitals.

The time from admission to reperfusion in patients with acute myocardial infarction (AMI) was compared according to the type of hospital and treatment strategy. A total of 164 patients with a first AMI within 12h of onset were enrolled at one tertiary emergency center (TEC) and 6 community hospitals (CHs). The subjects were randomly assigned to receive either primary percutaneous transluminal coronary angioplasty (PTCA) (TEC-primary PTCA and CHs-primary PTCA groups) or 800,000 units of intravenous monteplase, half the standard dose of a mutant tissue plasminogen activator (t-PA), followed by rescue PTCA if the Thrombolysis in Myocardial Infarction (TIMI) flow grade was 2 or less (TEC-monteplase and CHs-monteplase groups) on the first coronary angiogram. Sixty minutes after admission, TIMI flow grade 3 rates of the study groups were as follows, in descending order: TEC-monteplase group, CHs-monteplase group, TEC-primary PTCA group, and CHs-primary PTCA group (56%, 41%, 36%, and 8%, respectively; p<0.01). However, there was no significant difference in the final TIMI flow grade 3 rate among the 4 groups. In the CHs, the peak creatine kinase tended to be lower in the monteplase group than in the primary PTCA group. The results suggest that low-dose monteplase followed by rescue PTCA is an effective strategy for promoting early reperfusion in patients with AMI, especially those who are treated at CHs.

Development of a health promotion system for the elderly: Committee of Health Evaluation for Elderly Persons Council of Japan AMHTS Institutions.

A new health promotion approach for elderly persons is required which maintains not only their physical health but also their quality of life. We are developing a health promotion system which makes use of questionnaires dealing with physical conditions and quality of life, and makes health reports. Health evaluation is carried out in three steps. First, detailed information about the physical health of each client is collected. Second, quality of life is evaluated according to five health indicators. Last, health recommendations are generated. An artificial intelligence (AI) program produces detailed questions to collect necessary information for the evaluation of a client's health. The information related to quality of life is converted into five health indicators and presented as a radar-chart in documents and displays. The knowledge-based AI program automatically generates the health recommendation documents. This information is available for physicians and nurses for health counseling.

[Efficacy of low-dose mutant tissue-type plasminogen activator followed by planned rescue percutaneous transluminal coronary angioplasty as reperfusion therapy for acute myocardial infarction].

OBJECTIVES: The efficacy of injection of a low-dose mutant tissue-type plasminogen activator (mt-PA), monteplase, followed by planned rescue percutaneous transluminal coronary angioplasty (PTCA) was compared with that of primary PTCA. METHODS: A total of 164 patients with acute myocardial infarction within 12 hr from onset were randomly assigned to a treatment with 80 x 10(4) U bolus of monteplase (Group M) or no administration (Group P) by the envelope method, followed by immediate angiography with angioplasty in patients with Thombolysis in Myocardial Infarction (TIMI) flow grade 0, 1 or 2. RESULTS: There were no differences in baseline characteristics between the two groups. Initial angiography showed a higher reperfusion rate (TIMI 2 + 3: 21% + 38% vs 13% + 9%, p < 0.001) and the median time to TIMI 3 was shorter (63 vs 78 min, p < 0.005) in Group M than in Group P, but the final TIMI 3 rate was similar (93% vs 96%). Peak creatine kinase was lower, and predischarge left ventricular ejection fraction measured in 70% of all patients was higher (59 +/- 9% vs 54 +/- 14%, p = 0.02) in Group M than in Group P. Recurrent ischemia with ST elevation occurred in three patients in Group M, but death, re-acute myocardial infarction or stroke did not occur in either group and the rate of bleeding complication was similar (4.9% vs 3.7%). PTCA was performed less frequently in Group M, but medical expenses were comparable in both groups. CONCLUSIONS: Low-dose mt-PA followed by rescue PTCA is effective for early recanalization and preservation of left ventricular function without increases in bleeding complications or medical expenses. These results suggest that low-dose mt-PA should be given to all patients with acute myocardial infarction who are scheduled to undergo primary PTCA.