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Funding Acknowledgements Ministry of Health, Labor and Welfare (MHLW) Geriatrics and Gelontorogy sponsored research funds Background & purpose: Recently, many longitudinal studies have shown that heart failure with reduced ejection fraction (HFrEF) is associated with various types of brain abnormalities: cerebral micro-bleeding, atrophy, or pathologic degeneration (white matter hyperintensity; WMH). These brain abnormalities are known to increase with aging and to be closely associated with cognitive impairment. Heart failure with preserved ejection fraction (HFpEF) also increases with aging, but there have been few longitudinal studies to address the relationship between HFpEF and brain abnormalities. Thus, this longitudinal study aimed to clarify this relationship by focusing on WMH volume. METHODS The participants were 111 well-controlled hypertensive patients aged between 65 and 75 years with normal LV contraction and no history of symptomatic heart failure, ischemic heart disease, atrial fibrillation, stroke, or cognitive dysfunction. The participants were classified into 3 groups: Low E/e", E/e" < 8; Middle E/e", 8≤ E/e" ≤ 15; and High E/e", E/e" > 15. WMH volume was quantified on brain magnetic resonance imaging using analytical software. RESULTS During the mean 2.6 ± 1.0-year follow-up period, the rate of increase of WMH volume was significantly higher in the high E/e" group (1.1 ± 1.2 mL/year) than in the low E/e" group (0.30 ± 0.78 mL/year; P = 0.0238). Linear regression analysis including other confounders showed that the only positive association was between the rate of increase of WMH volume and the E/e" ratio (beta- coefficient = 0.225, P = 0.018). CONCLUSION The severity of LV diastolic dysfunction is positively correlated with increasing WMH volume. Abstract P103 Figure. The rates of increase of WMH volumes

Introduction Frailty is a syndrome associated with aging that produces subclinical dysfunction across multiple organ systems and leads to increased risk of mortality. The Kihon Checklist (KCL) was developed by the Japanese Ministry of Health, Labor and Welfare to identify older persons in need of care; it is a reliable tool for predicting general frailty in older adults. There is little information about the relationship between frailty status and exercise capacity. Purpose To investigate whether cardiopulmonary exercise testing (CPX) parameters are associated with frailty in stable elderly patients with heart failure (HF). Methods Ninety-two stable elderly patients with HF were evaluated by using CPX and the total KCL (t-KCL). A t-KCL score of 0–3 was classified as robust, 4–7 as pre-frail, and ≥8 as frail. Diagnostic performance (DP) -plot analysis was used to assess the utility of CPX parameters to distinguish between the presence and absence of frailty. Results Mean age, left ventricular ejection fraction, plasma brain natriuretic peptide, peak work rate (WR), peak VO2, and t-KCL score were 81.7 years, 57.8%, 182 pg/mL, 49.6 W, 13.2 mL/kg/min, and 10.7, respectively. t-KCL score was significantly correlated with peak VO2 (r=−0.53, p Cut-off value for peak WR Conclusions Frailty status was significantly associated with peak WR in stable elderly patients with HF. CPX may be useful for assessing frailty status in stable elderly patients with HF.

The therapeutic effects of human IgM and IgG with exogenous complement (fresh guinea pig serum) on experimental infections were compared in mice. Purified IgM and IgG were injected intraperitoneally to mice challenged with Escherichia coli or Pseudomonas aeruginosa , and the protective effects of IgM and IgG were evaluated. However, it was found that the additional administration of fresh guinea pig serum greatly enhanced the protective effect of the immunoglobulins, and that the enhancement was greater with IgM treatment. The results suggested that IgM has a higher protective activity than IgG, and that this activity of IgM is not fully expressed in native mice because of their intrinsically low level of complement activity. In vivo evaluation of immunoglobulins in mice should be carefully examined by co-administering exogenous complement.

A series of 241 consecutive autogenous vein bypasses for chronic lower-limb ischaemia performed by two surgeons since 1980 was reviewed. After 1985, in situ vein bypass was employed preferentially and was compared with reversed vein bypass. The two groups of patients had similar risk factors, indications and outflow. Of the 241 bypasses, 157 were to the below-knee popliteal artery and 84 to infrapopliteal arteries. The utilization rates of a single ipsilateral saphenous vein were 57.5% for reversed and 71.9% for in situ vein bypass. However, in situ vein bypass was impossible in 43 procedures and these were changed to the reversed operation with contralateral vein. The primary 5-year patency rates of reversed and in situ vein bypass grafts to the popliteal artery were 82.5 versus 74.5%, and the primary 4-year patency rates for infrapopliteal bypass 68.5 versus 80.0%. The respective secondary patency rates were 94.2 versus 92.1% and 85.7 versus 91.1%. The main cause of graft failure was vein graft stenosis (reversed vein bypass, 13.0%; in situ, 11.1%), which usually occurred in the first 2 years after surgery. Of 23 grafts revised for stenosis. 21 were salvaged and restenosis rarely occurred. Both reversed and in situ vein bypass grafts were equally effective, but careful surveillance for 2 years and aggressive revision were extremely important after either type of reconstruction.

This study proposes methods for the support of radiotherapy planning for dynamic tumor-tracking irradiation for lung tumors. It aims to simulate the deformation of the lung caused by respiration and to visualize the result as DRRs (Digitally Reconstructed Radiographs) in real time. Our lung- deformation model treats the lung as an elastic object and analyzes the deformation based on linear FEM (the Finite Element Method). The simulation models the lung using CT volume data and generates a model with boundary conditions with freely adjustable regions, displacements, and phases. The doctor planning the radiotherapy can reproduce the movement of the lung tumor by freely adjusting the regions, displacements, and phases of the boundary conditions while comparing the position of the lung tumor in an X-ray photograph. For highspeed display we propose a method for rapid-generation DRRs by slice-based volume rendering. The result of several functional evaluations and trials of simulation established that the proposed method can describe the movement of the lung tumor with adequate precision. The developed system is expected to be useful for radiotherapy planning for real-time tumor-pursuing irradiation.

Insulin-like growth factor I (IGF-I) is a useful therapeutic agent in insulin resistant diabetes mellitus due to insulin receptor disease because of its hypoglycaemic effects through the IGF-I receptor. A girl with typical type A insulin resistant syndrome was treated with IGF-I for two years and the treatment was effective in ameliorating hyperglycaemia. Overproduction of testosterone in polycystic ovaries was aggravated with this treatment, however. Therefore, IGF-I treatment may be used for glycaemic control but with caution because of its possible side effect of aggravating hyperandrogenism in these patients.

Aim To examine whether Cycrobilirubin Formation Capacity (CFC) could be clinically relevant in the treatment of neonatal hyperbilirubinemia. Study design CFC is a sum of irradiances multiplied by the wavelength-specific bilirubin photoisomerization rate, calculated at 40 nm intervals between the ranges 400–520 nm, measured using a novel spectroradiometer. After evaluating CFC and footprints of light emitting diode (LED) device and fluorescent tube (FT) device, we performed a randomised controlled trial (RCT) to test whether phototherapies provided with different light spectra using the same CFC are equally effective. Thirty-two babies were enrolled without any exclusion criteria. Total serum bilirubin (TSB) levels before and after phototherapies were compared. Result Seventeen babies were assigned to FT and fifteen to LED group. Birth characteristics were similar. Changes in TSB levels before and after phototherapy in LED and FT group were not different. Conclusion Under the same CFC evaluated by the spectroradiometer, LED was as effective as FT. This supports the idea that CFC could be relevant in phototherapy for the treatment of hyperbilirubinemia in otherwise healthy newborns.

A musical hallucination is defined as a type of auditory hallucination characterised by the perception of music without an external source.1 Reports in the literature state that musical hallucinations are common in women, and are associated with ageing, deafness,2,3 brain diseases (epilepsy, tumour, stroke, meningitis and neurosyphilis),3,4 psychiatric diseases (schizophrenia and manic depression),3,4 toxic states (alcohol)2 and drugs (antidepressants,1 salicylate,5 quinine and aspirin4). Some authors proposed that, when listening to music, the auditory input is processed by three stages, operating in a hierarchical fashion: perception of individual sounds, perception or imagery of pattern in segmented sound, and encoding or recognition of patterned segmented sound.6 It is supposed that musical hallucinations are caused by abnormal autonomous activity in the auditory brain systems responsible for normal musical imagery.7 It seems reasonable to say that, in acquired peripheral deafness, there is impoverished auditory input that allows spontaneous activity between perception or imagery and encoding or recognition of pattern in segmented sound.6 Regarding lesions in the central nervous system, these lesions may alter the threshold of spontaneous activity within the network for the perception and imagery of music.6 We describe a patient with musical hallucination who experienced an increase in the repertoire of musical hallucinations as she sang various songs, and discuss some of the undetermined problems related to cognitive processing of music: melody, accompaniment and timbre. In July 2002, a 75-year-old, right-handed woman was visiting a hospital on a daily …

7-Substituted 5-methyl-2-isopropylamino-4H-3,1-benzoxazin-4-ones (BOZNs) were prepared and tested as inhibitors of human sputum elastase (HSE). The BOZNs with certain amino acid residues at the 7-position proved to be potent inhibitors of HSE. Some of the compounds also showed a high selectivity for HSE versus chymotrypsin. In a hamster model in which acute injury was induced by intratracheal administration of HSE (1.0 mg/kg), these compounds, when administered intratracheally (1.0 mg/kg) either 30 or even 240 min before challenge with HSE, significantly suppressed pulmonary hemorrhage. These findings suggest that 7-substitution of BOZN by amino acid residues can produce strong and HSE-specific inhibitors, with potential use in elastase-mediated disorders.

Purpose: The purpose of this study was to estimate skin dose from real‐time X‐ray fluoroscopyimaging to do clinical trials for real‐time tumor irradiation in MHI‐TM2000 system (Vero). Methods: First, exposure dose with backscatter was measured using a single set of kilovoltage X‐ray tube and a flat panel detector; a cylindrical ionization chamber (DC300, IBA); and a water‐equivalent plate phantom. The chamber was rigidly attached on the plate phantom of 200 mm in thickness. Then, the chamber was positioned to 150 mm upper from the isocenter. Subsequently, exposure dose to an irradiation field of 171 mm × 226 mm was measured at a speed of 5 fps with 200 mA of the X‐ray tube current; and 40∼120 kVp of the X‐ray tube voltage, respectively. The nominal exposure time was set to 5 ms. Next, half‐value layer of aluminum was measured using a spherical ionization chamber (A4, Exradin) to calculate the effective energy and absorbed dose conversion factors of soft tissue. Then, the skin dose was calculated from the exposure dose and absorbed dose conversion factors. Results: There were good liner correlations between the X‐ray tube current and skin doses; and therefore, estimated skin dose from the X‐ray fluoroscopy with 1 mAs and 100 kV was 140 μGy. Furthermore, estimated skin dose for one successive minute exposure at a speed of 5 fps with 0.1 mAs and 100 kV was 4 mGy. The skin doses in the MHI‐TM2000 were greater by a factor of 1.4∼1.6 than those in Elekta Synergy system with the tube voltage of 100 or 120 kV. Conclusions: We have observed that the skin dose is a little larger than in the Synergy system while the filtration to the X‐ray source has not been applied to the MHI‐TM2000. To perform real‐time tumor tracking, further investigation may be required. This research was in part sponsored by Mitsubishi Heavy Industries, Ltd., Japan.

e12057 Background: Vulvar Paget's disease is difficult to diagnose early because this is a rare disease with an incidence of 10 patients per one million females per year and often ocurrs in elderly women aged 60-70 years old. A randomized controlled trial, meta-analysis and evidence-based medicine are not suitable methods of improving the prognosis of this disease. Vulvar Paget's disease is an adenocarcinoma in situ and a malignant disease. Since early diagnosis and treatment is necessary to improve prognosis, we extracted the causes of late diagnosis and proposals to improve prognosis from the literature. Methods: Literature review was performed through Japana Centra Revuo Medicina and PubMed. Ten articles including our study on 283 Asian women and seven articles on 363 Caucasian women were collected and examined according to patient age, interval between the initial symptom and the start of therapy, reason for delay in treatment and measures to prevent delay. Results: The mean age was 69.2 years (min∼ma...

Immunohistochemical localization of ornithine aminotransferase (L-ornithine: 2-oxo-acid aminotransferase, EC 2.6.1.13), a mitochondrial enzyme whose hereditary absence induces gyrate atrophy of the choroid and retina, was elucidated by a direct immunoperoxidase method using Fab'-horseradish peroxidase conjugates. In immunodiffusion studies, the antibodies raised with the re-crystallized enzyme were highly specific to ornithine aminotransferase. To show localization of ornithine aminotransferase in normal rat tissues, clear immunohistochemical staining of this enzyme through the inner mitochondrial membrane in paraffin sections was achieved with Fab'-horseradish peroxidase conjugates. Strong immunoreactivity was present in cerebral neurons, hepatocytes, and epithelial cells of renal tubuli, gut mucous membranes, and ocular tissues. Specific distribution of ornithine aminotransferase was found in ependymal cell groups: namely, epithelial cells of the choroid plexus, pigmented and nonpigmented epithelial cells of the ciliary body. and Müller cells and pigment epithelium of the retina.

Premature rabbit neonates (gestational age 27 days) were treated at birth with natural surfactant purified from chloroform extracts of porcine lung lipids either by acetone precipitation (Surfactant CK, n=10) or liquid gel chromatography (Curosurf, n=22). Another group of animals received artificial surfactant “reconstituted” from isolated low molecular weight (≤15 K) apoproteins and synthetic dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) (Aposurf, n=10). The phospholipid concentrations of the preparations were adjusted to provide the same individual dose of DPPC for each group of treated animals (3 or 4 mg). In comparison with untreated controls from the same litters, there was a 4–7-fold enhancement of lungthorax compliance in all groups of surfactant-treated animals during a 3-h period of artificial ventilation. The average initial (20 min) compliance value was lower in the Aposurf-treated group than in animals receiving natural surfactant preparations, but the difference between the groups gradually diminished and was no longer statistically significant during the 2nd and 3rd h of artificial ventilation. Judged from the fall in tidal volume during ventilation with a short expiration phase (0.17 instead of 0.75s), the apoprotein-based artificial surfactant was also less effective in stabilizing the lungs. A similar conclusion could be drawn from data on alveolar expansion in histological sections, evaluated by automated image analysis. Alveolar volume density was improved only moderately in the Aposurf-treated group (0.24 vs. 0.14; P=0.05), whereas the expected, prominent increase in this parameter was observed in both groups of natural surfactant-treated animals (0.48–0.62 vs. 0.14; P

By using adult rabbits in which the lung surfactant had been reduced by repeated whole-lung lavage, we examined the effects of surfactant supplement and positive end-expiratory pressure (PEEP). The rabbits were anesthetized with pentobarbital sodium and mechanically ventilated with pure O2. Surfactant that was extracted from pigs' lungs was supplemented to the rabbits through the trachea. The PEEP was set at 4 cmH2O. The seven rabbits that were ventilated without the supplement and without the PEEP all died of hypoxia, hypercapnia, and reduction of lung compliance within 2 h. The 18 rabbits that were ventilated with either the supplement or the PEEP showed some elevations of arterial O2 tension, but 9 of them died within 4 h. After application of both the surfactant supplement and the PEEP, six out of the eight rabbits survived for more than 11 h with nearly normal values of blood gases and compliance. We concluded that the combination of the transtracheal surfactant supplement and ventilation with PEEP has favorable therapeutic effects on surfactant deficiency.