Usefulness of an artificial neural network for a beginner to achieve similar interpretations to an expert when examining myocardial perfusion images.

This study examined whether using an artificial neural network (ANN) helps beginners in diagnostic cardiac imaging to achieve similar results to experts when interpreting stress myocardial perfusion imaging (MPI). One hundred and thirty-eight patients underwent stress MPI with Tc-labeled agents. An expert and a beginner interpreted stress/rest MPI with or without the ANN and the results were compared. The myocardium was divided into 5 regions (the apex; septum; anterior; lateral, and inferior regions), and the defect score of myocardial blood flow was evaluated from 0 to 4, and SSS, SRS, and SDS were calculated. The ANN effect, defined as the difference in each of these scores between with and without the ANN, was calculated to investigate the influence of ANN on the interpreters' performance. We classified 2 groups (insignificant perfusion group and significant perfusion group) and compared them. In the same way, classified 2 groups (insignificant ischemia group and significant ischemia group) and compared them. Besides, we classified 2 groups (normal vessels group and multi-vessels group) and compared them. The ANN effect was smaller for the expert than for the beginner. Besides, the ANN effect for insignificant perfusion group, insignificant ischemia group and multi-vessels group were smaller for the expert than for the beginner. On the other hand, the ANN effect for significant perfusion group, significant ischemia group and normal vessels group were no significant. When interpreting MPI, beginners may achieve similar results to experts by using an ANN. Thus, interpreting MPI with ANN may be useful for beginners. Furthermore, when beginners interpret insignificant perfusion group, insignificant ischemia group and multi-vessel group, beginners may achieve similar results to experts by using an ANN.

High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma.

AIM: To evaluate the high-resolution computed tomography (CT) findings of primary lung cancer with cavitation and compare the findings in adenocarcinoma and squamous cell carcinoma. MATERIALS AND METHODS: The high-resolution CT findings of tumours with cavitation were retrospectively evaluated in 60 patients. Forty-seven of the lesions were diagnosed as adenocarcinomas; 13 were diagnosed as squamous cell carcinomas. The diameters of the tumour and cavity, the maximum thickness of the cavity wall, shape of the cavity wall, the number of cavities, and the presence of ground-glass opacity, bronchial obstruction, intratumoural bronchiectasis, emphysema, and honeycombing were evaluated. The mechanisms of cavity formation were examined according to the pathological features. RESULTS: The maximum thickness of the cavity wall was significantly greater in squamous cell carcinomas than in adenocarcinomas (p=0.002). Ground-glass opacity and intratumoural bronchiectasis were significantly more common in adenocarcinomas than in squamous cell carcinomas (p<0.001 and p=0.040, respectively). Regarding the pathological findings, intratumoural bronchiectasis with or without alveolar wall destruction contributed to a significant difference between adenocarcinoma and squamous cell carcinoma (p<0.001; odds ratio [OR], 20.35; 95% confidence interval [CI], 3.87-107.10). CONCLUSION: The cavity wall tends to be thicker in squamous cell carcinomas than in adenocarcinomas. The presence of ground-glass opacity and intratumoural bronchiectasis is strongly suggestive of adenocarcinoma.

Efficacy of pre-operative computed tomography evaluation of the tympanic cavity for hearing improvement after stapes surgery for tympanosclerosis with stapes fixation.

OBJECTIVE: Our aim was to determine if stapes surgery is useful for treating inflammatory ear diseases. MATERIALS AND METHODS: Thirteen patients underwent single-stage or staged surgery for stapes fixation due to tympanosclerosis alone or with cholesteatoma. Operative criteria were: no tympanic membrane retraction, perforation or adhesion; middle-ear cavity with aeration >1 year; a fixed stapes. Computed tomography was used to analyse the relation between operative success and pre-operative pneumatisation. RESULTS: Success rate at six months was 75 per cent. Hearing results were stable with little deterioration and no complications. Patients with poor pneumatisation had good results (with improved air-bone gap) only after staged surgery. Well-aerated ears heard better even with single-stage surgery. CONCLUSIONS: Pre-operative computed tomography and intra-operative findings are necessary to determine the pneumatisation status of tympanic mastoid cavities. If criteria approved, poorly pneumatised patients underwent staged surgery. Stapedectomy achieved good hearing results for inflammatory middle-ear disease with stapes fixation.

Antiemetic efficacy of combined aprepitant and dexamethasone in patients at high-risk of postoperative nausea and vomiting from epidural fentanyl analgesia.

BACKGROUND: Postoperative opioid analgesia increases the incidence of postoperative nausea and vomiting (PONV). We investigated whether a combination of the neurokinin-1 antagonist aprepitant and dexamethasone decreases PONV incidence compared with dexamethasone alone in high-risk patients receiving continuous epidural fentanyl. METHODS: Sixty nonsmoking female patients scheduled for elective knee osteoarthritis surgery were randomly allocated to receive oral aprepitant 80 mg (aprepitant+dexamethasone group, N.=30) 2 h before anesthesia induction or no oral aprepitant (dexamethasone group, N.=30). All patients received intravenous dexamethasone 8 mg immediately before anesthesia induction. Anesthesia was maintained with remifentanil and sevoflurane. Continuous infusion of epidural analgesia, including fentanyl, was provided during and after surgery. We assessed complete response (no PONV and no rescue antiemetic use), incidence of nausea and vomiting, nausea severity scale, vomiting frequency, rescue antiemetic use, and postoperative pain at 2 and 24 h after surgery. RESULTS: The cumulative incidence of vomiting at 24 h was 3% in the aprepitant+dexamethasone group and 27% in the dexamethasone group (P=0.011). The incidence and frequency of vomiting in the late postoperative period was also significantly lower in the aprepitant+dexamethasone group than in the dexamethasone group. However, there were no significant group differences in the proportion of patients who experienced a complete response, the incidence and severity of nausea, and rescue antiemetic use at 24 h. CONCLUSION: The combination of aprepitant and dexamethasone was more effective in preventing postoperative vomiting compared with dexamethasone alone in patients at high-risk of PONV from continuous epidural fentanyl analgesia.

Short-term low carbohydrate/high-fat diet intake increases postprandial plasma glucose and glucagon-like peptide-1 levels during an oral glucose tolerance test in healthy men.

BACKGROUND/OBJECTIVES: Postprandial hyperglycemia increases the risks of development of type 2 diabetes and cardiovascular diseases. The purpose of this study was to determine whether a 3-day low-carbohydrate/high-fat diet (LC/HFD) alters postprandial plasma glucose and incretin levels during oral glucose tolerance test (OGTT) in healthy men. SUBJECTS/METHODS: Nine healthy young men (age (mean ± s.e.), 27 ± 1 years; body mass index, 22 ± 1 kg/m(2)) consumed either a normal diet (ND: energy from ∼22% fat) or a LC/HFD (energy from ∼69% fat) for 3 days each. The total energy intake from each diet was similar. An OGTT was performed after each 3-day dietary intervention. Postprandial plasma glucose, insulin, free fatty acid and glucagon-like peptide-1 (GLP-1) levels were determined at rest and during the OGTT. RESULTS: Plasma glucose levels and incremental area under the curve during the OGTT were significantly higher in the LC/HFD trial than in the ND trial (P=0.024). In addition, increase in GLP-1 levels was significantly higher in the LC/HFD trial than in the ND trial (P=0.025). The first-phase insulin secretion indexes were significantly lower in the LC/HFD trial than in the ND trial (P<0.041). CONCLUSIONS: These results demonstrate that even short-term LC/HFD increased postprandial plasma glucose and GLP-1 levels in healthy young men. A decrease in first-phase insulin secretion may partially contribute to the short-term LC/HFD-induced increase in postprandial plasma glucose levels.

Adverse effects of coexistence of sarcopenia and metabolic syndrome in Japanese women.

BACKGROUND/OBJECTIVES: Little information is available regarding the interactions of sarcopenia and metabolic syndrome (MetS) in the risks of these age-associated diseases in women. The present cross-sectional study was performed to investigate whether the coexistence of sarcopenia and MetS further increases the risks of lifestyle-related diseases in Japanese women. SUBJECTS/METHODS: Healthy Japanese women (n=533) aged 30-84 participated in this study. MetS was defined as higher body mass index, fasting plasma glucose, systolic or diastolic blood pressure and blood lipid abnormalities. Appendicular muscle mass and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. The criterion of low muscle mass and strength defined median skeletal muscle index (appendicular muscle mass/height², kg/m²) and handgrip strength. RESULTS: Two-way ANCOVA with adjustment for age, body fat percentage and whole-body lean tissue mass indicated that sarcopenia and MetS interacted to produce a significant effect on HbA1c, systolic blood pressure, triglycerides and brachial-ankle pulse wave velocity in Japanese women. The systolic blood pressure, triglycerides and brachial-ankle pulse wave velocity were significantly higher in women with coexisting sarcopenia and MetS than in healthy controls or in those with sarcopenia or MetS alone. The HbA1c in the coexisting sarcopenia and MetS group was higher than in healthy controls and sarcopenia subjects. CONCLUSIONS: The coexistence of sarcopenia and MetS further increases the risks of cardiovascular diseases, such as type 2 diabetes mellitus, hypertension, arterial stiffness and hyperlipidemia even adjustment of age and body composition in adult Japanese women.

Anaesthesia for a patient with paraneoplastic limbic encephalitis with ovarian teratoma: relationship to anti-N-methyl-D-aspartate receptor antibodies.

Paraneoplastic limbic encephalitis associated with ovarian teratoma has recently been related to the development of antibodies to specific heteromers of the N-methyl-d-aspartate receptor and exhibits various manifestations including psychiatric symptoms, hypoventilation, seizures and derangement of autonomic nervous system function. Although recovery can sometimes occur spontaneously, early tumour resection with immunotherapy facilitates earlier recovery. Herein, we describe anaesthetic management of a 20-year-old woman who developed general convulsions and decreased level of consciousness, whom we suspected of having paraneoplastic limbic encephalitis and was scheduled for left ovarian tumour resection. Anaesthetic management was successful with no complications but the case acts as focus of discussion for the potential interaction of N-methyl-D-aspartate receptors and anaesthetic sensitivity.

A new cell-based reporter system for sensitive screening of nuclear export inhibitors.

Nucleocytoplasmic transport of proteins across the nuclear pore complex (NPC), mediated by the nuclear localization signal (NLS) and the nuclear export signal (NES), is a vital homeostatic process in eukaryotic cells and also in mitogen-activated protein kinase (MEK) signaling molecule in tumor cell proliferation. Some viruses, including the influenza virus and HIV-1, also employ this nuclear export mechanism during their life cycle. Hence, drugs that control nucleocytoplasmic transport of proteins are putative candidate antivirals or anti-cancer agents. Thus, we previously developed a GFP/NES-MDCK reporter cell system for screening novel nuclear export inhibitors. NES signal-conjugated GFP accumulates in the nucleus in the presence of the nuclear export inhibitor leptomycin B (LMB). In this study, a stable GFP/NLS/NES fusion protein-expressing cell line was established, and its potential as a reporter was evaluated. The GFP/NLS/NES-MDCK cell line demonstrates improved nuclear accumulation of GFP in a time-course treatment with LMB. In addition, the dose-response data demonstrated superior sensitivity of GFP/NLS/NES-MDCK over GFP/NES-MDCK cells. As low as 0.01 ng/mL LMB is sufficient to cause accumulation of the GFP fusion protein in the nucleus in GFP/NLS/NES-MDCK cells, while at least 1 ng/mL of LMB is needed for the accumulation of GFP fusion protein in the nucleus of GFP/NES-MDCK cells. These results indicate that the newly established GFP/NLS/NES-MDCK cell line is a potentially powerful tool to screen for novel nuclear export inhibitors.

Region-specific projections from the subfornical organ to the paraventricular hypothalamic nucleus in the rat.

Neurons in the subfornical organ (SFO) project to the paraventricular hypothalamic nucleus (PVN) and there, in response to osmolar and blood pressure changes, regulate vasopressin neurons in the magnocellular part (mPVN) or neurons in the parvocellular part (pPVN) projecting to the cardiovascular center. The SFO is functionally classified in two parts, the dorsolateral peripheral (pSFO) and ventromedial core parts (cSFO). We investigated the possibility that neurons in each part of the SFO project region-specifically to each part of the PVN, using anterograde and retrograde tracing methods. Following injection of an anterograde tracer, biotinylated dextran amine (BDX) in the SFO, the respective numbers of BDX-uptake neurons in the pSFO and cSFO were counted and the ratio of the former to the latter was obtained. In addition, the respective areas occupied by BDX-labeled axons per unit area of the mPVN and pPVN were measured and the ratio of the former to the latter was obtained. Similarly, following injection of the retrograde tracer in the PVN, the respective areas occupied by tracer per unit area of the mPVN and pPVN were measured and the ratio of the former to the latter was obtained. The respective numbers of retrogradely labeled neurons in the pSFO and cSFO were also counted and the ratio of the former to the latter was obtained. It became clear by statistical analyses that there are strong positive correlations between the ratio of BDX-uptake neuron number in the SFO and the ratio of BDX-axon area in the PVN in anterograde experiment (correlation coefficient: 0.787) and between the ratio of retrograde neuron number in the SFO and the ratio of tracer area in the PVN in retrograde experiment (correlation coefficient: 0.929). The result suggests that the SFO projects region-specifically to the PVN, the pSFO to the mPVN and the cSFO to the pPVN.

Age and cardiorespiratory fitness are associated with arterial stiffening and left ventricular remodelling.

Arterial stiffening, hypertension and left ventricular (LV) remodelling are associated with increased risk of cardiovascular disease. Cardiorespiratory fitness is associated with cardiovascular function and reduced risk of cardiovascular disease. This cross-sectional study was carried out to determine the relationships between cardiorespiratory fitness, arterial stiffness, blood pressure (BP) and LV remodelling in women. On the basis of peak oxygen uptake, a total of 159 premenopausal (young) and postmenopausal (older) women were categorized into either low (unfit) or high (fit) cardiorespiratory fitness groups. The arterial stiffness and LV remodelling were measured by brachial-ankle pulse wave velocity (baPWV) and carotid augmentation index (AI) and LV relative wall thickness (RWT). Two-way analysis of variance indicated a significant interaction between age and cardiorespiratory fitness in baPWV, carotid AI, BP and RWT. In the older group, arterial stiffness (baPWV; 1401+/-231 vs 1250+/-125 cm s(-1), P<0.01, AI; 32.9+/-9.9 vs 24.8+/-10.1%, P<0.01), systolic blood pressure (SBP) (130+/-22 vs 117+/-15 mm Hg, P<0.01) and RWT (0.47+/-0.08 vs 0.42+/-0.04, P<0.05) in fit women were lower than in unfit women. In older women, RWT was significantly related to baPWV (r=0.46, P<0.01), carotid AI (r=0.29, P<0.05), SBP (r=0.57, P<0.01) \[V(2peak) (r=-0.32, P<0.05). In young women, they were not significant correlations, except for a weak correlation between RWT and SBP (r=0.21, P<0.05). These results suggest that higher cardiorespiratory fitness is associated with lower arterial stiffness, BP and RWT in older women.

Extended mycophenolate mofetil administration beyond day 30 in allogeneic hematopoietic stem cell transplantation as preemptive therapy for severe graft-versus-host disease.

To prevent acute graft-versus-host disease (GVHD), mycophenolate mofetil (MMF) combined with calcineurin inhibitors have been used in allogeneic hematopoietic stem cell transplantation (allo-SCT). Previous studies commonly utilize MMF treatment until day 30 after allo-SCT. However, the feasibility of continuous administration after day 30 has not been well evaluated. We retrospectively assessed the safety and efficacy of extended drug administration. Twenty-five patients ceased MMF at day 30 (group A); whereas, 16 patients (group B) received extended regimens depending on individual risk factors for GVHD. No severe adverse events were observed in either group. Although the cumulative incidence (CI) of grade I to IV GVHD at day 100 was comparable between the 2 groups, the CI of grade II to IV GVHD was less among group B (12.5%) compared with group A (42.3%). Extended MMF administration may be safe and beneficial as preemptive therapy to reduce the development of moderate-to-severe acute GVHD.

Muscle mass and bone mineral indices: does the normalized bone mineral content differ with age?

OBJECTIVE: To investigate the relationships between regional skeletal muscle mass (SM mass) and bone mineral indices and to examine whether bone mineral content (BMC) normalized to SM mass shows a similar decrease with age in young through old age. SUBJECTS/METHODS: One hundred and thirty-eight young and postmenopausal women aged 20-76 years participated in this study and were divided into three groups: 61 young women, 49 middle-aged postmenopausal women and 28 older postmenopausal women. Muscle thickness (MTH) was determined by ultrasound, and regional SM mass (arm, trunk and leg) was estimated based on nine sites of MTH. Whole-body and regional lean soft tissue mass (LSTM), bone mineral density (BMD) and BMC (whole body, arms, legs and lumbar spine) were measured using dual-energy X-ray absorptiometry. RESULTS: Ultrasound spectroscopy indicated that SM mass is significantly correlated with site-matched regional bone mineral indices and these relationships correspond to LSTM. The BMC and BMD in older women were significantly lower than those in middle-aged women. When BMC was normalized to site-matched regional SM mass, BMC normalized to SM mass in arm and trunk region were significantly different with age; however, whole-body and leg BMC normalized to SM mass showed no significant difference between middle-aged and older postmenopausal women. CONCLUSIONS: The age-related differences in BMC were found to be independent of the ageing of SM mass in the arm and trunk region. However, differences in BMC measures of the leg and whole body were found to correspond to age-related decline of SM mass in postmenopausal women.

Chronic expanding hematoma in combination with a pseudoaneurysm: a case report.

After bleeding from trauma or surgery, most of the hematomas undergo spontaneous reabsorption. But, in some rare cases, hematomas persist for long periods as slowly expanding masses for months or years. These hematomas were termed as chronic expanding hematomas. In this report, we describe a case of chronic expanding hematoma with a pseudoaneurysm that underwent surgical biopsy, which led to an increase in its expansion speed.

Induction of murine AA amyloidosis by various homogeneous amyloid fibrils and amyloid-like synthetic peptides.

We investigated amyloid-enhancing factor (AEF) activity of amyloid fibrils extracted from amyloid-laden livers of mice, cow, cheetah, cat and swan. All amyloid fibrils were confirmed to be amyloid protein A (AA) by an immunohistochemical analysis. We found that these fibrils accelerated the deposition of amyloid in an experimental mouse model of AA amyloidosis. Furthermore, the degree of deposition was dependent on the concentration of fibrils. When we compared the minimal concentration of amyloid fibrils needed to induce deposition, we found that these fibrils showed different efficiencies. Murine amyloid fibril induced amyloid deposition more efficiently than cow, cat, cheetah or swan amyloid fibrils. These data suggest that amyloid deposition is preferentially induced by amyloid fibrils with the same primary sequence as the endogenous amyloid protein. We then analysed the AEF activity of synthetic peptides, synthesized corresponding to amino acids 1-15 of mouse SAA (mSAA), 2-15 of cow SAA (bSAA), 1-15 of cat SAA (cSAA), which was the same as cheetah, and the common amino acids 33-45 of these four SAA (aSAA). We found that mSAA, bSAA and cSAA formed amyloid-like fibrils in morphology and showed similar AEF properties to those of native amyloid fibrils. Although aSAA also formed highly ordered amyloid-like fibrils, it showed weaker AEF activity than the other synthetic fibrils. Our results indicate that amyloidosis is transmissible between species under certain conditions; however, the efficiency of amyloid deposition is species-specific and appears to be related to the primary amino acid sequence, especially the N-terminal segment of the amyloid protein.

Pancreatic B-cell function is altered by oxidative stress induced by acute hyperglycaemia.

AIMS: Type 2 diabetes is preceded by a symptom-free period of impaired glucose tolerance (IGT). Pancreatic B-cell function decreases as glucose intolerance develops. In many patients with IGT, fasting blood glucose is within normal limits and hyperglycaemia occurs only postprandially. We examined whether pancreatic B-cell function changes during acute hyperglycaemia induced by oral glucose loading. METHODS: We calculated the insulinogenic index (I.I.) as an indicator of pancreatic B-cell function and measured serum levels of thioredoxin, a marker of cellular redox state, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, during a 75-g oral glucose tolerance test (OGTT) in 45 subjects [24 patients with normal glucose tolerance (NGT), 14 with IGT and seven with Type 2 diabetes]. RESULTS: Thioredoxin levels decreased after glucose loading [66.1 +/- 23.7, *59.3 +/- 22.4, *49.3 +/- 21.2 and *37.7 +/- 18.0 ng/ml, fasting (0 min) and at 30, 60 and 120 min, respectively; *P < 0.001 vs. fasting]. In contrast, concentrations of 8-OHdG peaked at 30 min and then gradually decreased (0.402 +/- 0.123, *0.440 +/- 0.120, 0.362 +/- 0.119 and 0.355 +/- 0.131 ng/ml, *P < 0.05 vs. fasting, P < 0.01 vs. 30 min). The insulinogenic index correlated with the change in thioredoxin levels (r = 0.34, P < 0.05). However, there was no relationship with the change in 8-OHdG levels from 0 to 30 min. CONCLUSIONS: Hyperglycaemia in response to oral glucose impairs pancreatic B-cell function with decreasing thioredoxin levels. The augmented oxidative stress induced by hyperglycaemia may affect the cellular redox state. These findings strongly suggest that repeated postprandial hyperglycaemia may play an important role in the development and progression of diabetes mellitus.

Galanin inhibits neural activity in the subfornical organ in rat slice preparation.

The activation of the subfornical organ (SFO), a circumventricular organ, induces water intake and vasopressin release. Since central administrations of galanin (GAL) suppress water intake and vasopressin release, GAL may inhibit the neural activity of SFO neurons. In the present study, we investigated effects of GAL on the SFO using molecular biological, electrophysiological and anatomical techniques. Reverse transcription-polymerase chain reaction analysis demonstrated the presence in the SFO of rats of the mRNAs for each of the three known GAL receptor subtypes (GalR1, GalR2 and GalR3). In extracellular recordings in SFO slice preparations, GAL dose-dependently inhibited the neural activity of cells from a number of recording sites. Many GAL-sensitive SFO neurons showed excitatory responses to angiotensin II (ANGII). The GalR1 agonist M617 inhibited the activity of SFO neurons, whereas the GalR2 and GalR3 agonist GAL(2-11) had almost no effect. In patch-clamp recordings, GAL induced an outward current in SFO neurons without influencing synaptic currents. An immunoelectron microscopic study revealed the existence of GAL-containing synaptic vesicles in the SFO. These results suggest that the SFO has neural inputs involving GAL. The response to GAL is inhibitory, mediated at least in part by GalR1 and provides a plausible explanation for the opposite effects of ANGII and GAL seen in vivo on water intake and vasopressin release.