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Jun Hirai,1,2 Hiroyuki Suzuki,3 Daisuke Sakanashi,2 Yuji Kuge,4 Takaaki Kishino,4 Nobuhiro Asai,1,2 Mao Hagihara,5 Hiroshige Mikamo1,2 1Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 2Department of Infection Control and Prevention, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 3Department of Neurology, Aichi Medical University, Nagakute, Aichi, Japan; 4Department of Emergency and Critical Care Medicine, Aichi Medical University Hospital, Nagakute, Aichi, Japan; 5Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute, Aichi, JapanCorrespondence: Jun Hirai, Department of Clinical Infectious Diseases, Aichi Medical University Hospital, 1-1, Yazako-karimata, Nagakute, Aichi, 480-1195, Japan, Tel +81-561-62-3311, Fax +81-561-76-2673, Email hiraichimed@gmail.comAbstract: Staphylococcus argenteus is a new species classified as part of the Staphylococcus aureus-related complex in 2015 and has been recognized to be as pathogenic as S. aureus. We describe the first case of endocarditis caused by S. argenteus. A 51-year-old man presented with chief complaints of fever and headaches. On admission, he showed a slight decrease in consciousness level (Glasgow Coma Scale, E4V4M6). Careful physical examination and imaging revealed a systolic heart murmur, Janeway lesions, and complicating convexity subarachnoid hemorrhage (cSAH) of the left frontal lobe. Ceftriaxone 4 g/day was administered immediately after blood cultures were obtained. The next day, all blood cultures grew Gram-positive cocci, identified as Staphylococcus aureus or Staphylococcus argenteus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). However, the version of MALDI-TOF MS used could not distinguish these bacteria. Although we could not find valvular vegetation, he was clinically diagnosed with infective endocarditis according to the modified Duke’s criteria. Meropenem 6 g/day and linezolid 1.2 g/day were started to cover S. aureus and methicillin-resistant S. aureus. Finally, ampicillin was selected based on drug susceptibility, and the patient was treated for 8 weeks and recovered without permanent damage. The isolated strain formed white colonies on blood agar plates, characteristic of S. argenteus, and differs from golden colony-forming S. aureus. Genetic analysis revealed the isolated strain as S. argenteus (sequence type 1223). Although distinguishing S. argenteus from S. aureus using routine conventional laboratory tests is difficult, the updated library version of MALDI-TOF MS is useful in identifying S. argenteus. Interestingly, all published cases of infection caused by ST1223 have been reported in Japan. Therefore, the trend of infections from the ST1223 strain should be carefully monitored, particularly in Japan. Further investigation is needed to clarify the epidemiology and clinical characteristics of S. argenteus infection, as there are few studies regarding this pathogen.Keywords: Staphylococcus argenteus, sequence type 1223, infective endocarditis, convexity subarachnoid hemorrhage, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Japan

Jun Hirai,1,2 Tessei Kuruma,3 Daisuke Sakanashi,2 Yuji Kuge,4 Takaaki Kishino,4 Yuuichi Shibata,5 Nobuhiro Asai,1,2 Mao Hagihara,6 Hiroshige Mikamo1,2 1Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 2Department of Infection Control and Prevention, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 3Department of Otolaryngology, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 4Department of Emergency and Critical Care Medicine, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 5Department of Pharmacy, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan; 6Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute, Aichi, 480-1195, JapanCorrespondence: Jun Hirai, Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Aichi, 480-1195, Japan, Tel +81-561-62-3311, Fax +81-561-76-2673, Email hiraichimed@gmail.comAbstract: Although Dialister pneumosintes is a commensal microorganism of the oral cavity, it may sometimes cause severe systemic infections. We report a case of Lemierre syndrome (LS), which developed after D. pneumosintes infection, in a 73-year-old Japanese woman who was admitted to the hospital for throat pain, neck swelling, and fever for 3 days. She had a 3-month history of neglected dental caries, gingivitis, and periodontitis. Physical examination revealed right tonsillar erythema and swelling, and computed tomography (CT) showed peritonsillar and retropharyngeal abscesses. Ampicillin/sulbactam was promptly administered after collecting two sets of blood cultures. Surgical drainage for peritonsillar and retropharyngeal abscesses was also conducted on the second hospital day. Although only commensal oral microflora grew in the culture from the drained pus, Gram-negative bacilli were confirmed in the anaerobic blood cultures. Metronidazole was administered intravenously; however, the fever and neck swelling persisted. Repeat CT performed on the fifth hospital day revealed right internal jugular vein thrombosis, a known complication of tonsillitis and pharyngitis once the infection extends beyond the oropharynx. We diagnosed she had coexisting LS, and anticoagulant therapy was added to her treatment regimen. Her condition improved, and she was discharged after completing 3 weeks of antibiotics. Conventional methods failed to identify the isolated bacterium, and 16S rRNA sequencing ultimately identified it as D. pneumosintes. In a literature review of bacteremia due to D. pneumosintes, poor oral hygiene was considered a probable risk factor for invasive D. pneumosintes infection. We consider this to be the case in our patient who presented with dental caries, gingivitis, and periodontitis. In addition, all cases revealed that the 16S rRNA gene sequencing is useful for identifying this species. Although the diagnosis of LS by physical examination is difficult, physicians should always consider it as a potential complication of infections in the pharyngeal area.Keywords: Dialister pneumosintes, Lemierre syndrome, tonsillar abscess, retropharyngeal abscess, oral hygiene, anticoagulation

BACKGROUND - Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurological function when transplanted into animal model of central nervous system (CNS) disorders. However, there still exist several questions to solved prior to clinical application. In this study, therefore, we aimed to clarify the optimal delivery route of BMSC transplantation over a reasonable time window.MATERIALS AND METHODS - The rats were subjected to permanent middle cerebral artery occlusion. The BMSC were labeled with quantum dot (QD) 800. The labeled BMSC were transplanted into the infarct brain directly or intravenously at 7 days after the insult. Motor function was serially assessed. The BMSC were also tracked using near infrared (NIR) fluorescence imaging technique every week. The fate of the transplanted BMSC was examined at 5 weeks after transplantation, using Immunohistochemistry. RESULTS - Direct, but not intravenous, transplantation of BMSC significantly enhanced functional recovery. NIR fluorescence imaging could visualize their migration towards cerebral infarct in directly, but not intravenously, injected animals. The findings were supported on histological analysis. Thus, the BMSC were widely engrafted in the infarct brain in the directly injected animals, but few BMSC were observed in the intravenously injected ones. CONCLUSION - This study strongly suggests that direct transplantation of BMSC may be more beneficial in treating patients with ischemic stroke than their intravenous transplantation. Therapeutic time window must be called into account when considering the route of BMSC transplantation.

Background and Purpose: Much interest is currently being focused on the anti-nociceptive effects mediated by nicotinic acetylcholine (nACh) receptors, including their location and mechanism of action. The purpose of this study was to elucidate these issues using 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA), a nACh receptor agonist, and [(125)I]5IA.Experimental Approach: We partially ligated the sciatic nerve of Sprague-Dawley rat to induce neuropathic pain [Seltzer's partial sciatic nerve ligation (PSL) model]. We then examined the changes in nACh receptor density in the CNS using [(125)I]5IA autoradiography and the involvement of nACh receptors in anti-nociceptive effects in the region where changes occurred.Key Results: Autoradiographic studies showed that the accumulation of [(125)I]5IA and the number of nACh receptors in the thalamus of PSL rats were increased about twofold compared with those in the sham-operated rats. No change was observed in other brain regions. Rats injected in the ventral posterolateral thalamic nucleus (VPL) with 5IA demonstrated a significant and dose-dependent anti-allodynic effect and this effect was completely antagonized by mecamylamine, injected with 5IA, into the VPL. The blockade of nACh receptors in the VPL by mecamylamine decreased by 70% the anti-allodynic effect of 5IA, given i.c.v. Moreover, mecamylamine given intra-VPL by itself, induced significant hyperalgesia.Conclusions and Implications: Our findings suggest that the nACh receptors expressed in the VPL play an important role in the anti-allodynic effects produced by exogenous and endogenous agonists. [ABSTRACT FROM AUTHOR]

Background and purpose: Annexin V (AV), a human protein with a high affinity for membrane-bound phospholipid (phosphatidylserine, PS), has been labeled with 99mTc and shown to be useful for detecting apoptosis in vivo. We assessed the potential of 99mTc-AV for detecting apoptotic tumor response and examined the change of radioactivity to chemotherapy in an experimental model. Methods: HYNIC-annexin V was labeled with 99mTc (99mTc-AV). Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. Eleven days after tumor inoculation, rats were randomized to receive a single dose of cyclophosphamide (CP; 150 mg/kg, ip) or to serve as control. 99mTc-AV was injected 4, 12 and 20 h following the chemotherapy. Radioactivity in tissues was determined 6 h after injection of 99mTc-AV by means of ex vivo tissue counting. TUNEL and caspase-3 staining was performed to detect apoptosis in the tumor. We measured tumor blood flow by 14C-iodoantipyrine (IAP) on both treated and control rats (n=4, respectively). Results: Cyclophosphamide treatment significantly increased the tumor uptake of 99mTc-AV at 20 h but not at earlier phases, coinciding with an increased number of immunohistological positive cells. There was no significant change in tumor blood flow by a cyclophosphamide. Conclusions: In vivo detection of apoptosis with 99mTc-Annexin V can be used as a non-invasive means to assess tumor response to chemotherapy without the influence of blood flow. Effective detection required approximately 20 h, not 4 h, for the best timing of annexin V imaging after the start of chemotherapy in a clinical setting. [Copyright &y& Elsevier]

Objectives: Brain distributions of [123I]iomazenil ([123I]IMZ) and [1-14C]octanoate were compared with CBF and histopathologic findings in a rat model of focal cerebral ischemia, in order to characterize [123I]IMZ and [1-11C]octanoate as markers of neuronal and astroglial functions, respectively. Methods: (1) Brain distributions of [123I]IMZ and [125I]IMP were determined by dual-tracer autoradiography. Microtubule-associated protein-2 (MAP-2) was immunostained. In situ DNA polymerase-I-dependent dUTP incorporation into damaged DNA was used as an indicator of DNA fragmentation. (2) Brain distributions of [1-14C]octanoate and [123I]IMP (or [123I]IMZ) were determined by dual-tracer autoradiography. HE stain was performed to evaluate histologic changes. Results: (1) Neither DNA fragmentation nor MAP-2 denaturation was detected in the ischemic regions with preserved [123I]IMZ accumulation. [123I]IMZ accumulation was significantly impaired in the regions with damaged DNA. (2) Uptake of [1-14C]octanoate and [123I]IMZ was decreased in the peri-infarct regions where necrotic cells were occasionally observed, while [1-14C]octanoate uptake was significantly higher than that of [123I]IMZ in the peri-infarct regions without morphological changes. Conclusion: Impairment of [123I] IMZ accumulation precedes DNA fragmentation. [1-14C]octanoate uptake was relatively preserved in the regions without morphological changes despite the reduced CBF and [123I]IMZ uptake. Our results provide the molecular basis for analyzing neuronal and glial functions with [123I]IMZ and [1-11C]octanoate. [Copyright &y& Elsevier]

In the synthesis of 18F-FDG by the nucleophilic substitution method, 18O-H2O is usually used as target water. The target water should be recovered after synthesis and reused, because it is expensive, but recovered water contains impurities such as organic substances, and it must be purified before reuse. For this reason Sumitomo Heavy Industries, Ltd. developed an O-18 water purifier for elimination of organic substances in recovered water. This instrument consists of a UV irradiation unit and low-temperature distillation unit. Our institution had an opportunity to test use this instrument and evaluated its performance. The concentrations of organic substances after UV irradiation was greatly reduced, and recovery efficiency after distillation by the low-temperature distillation unit was very satisfactory at 99.3 +/- 0.5%. Furthermore, the yield of 18F-FDG from 18O-H20 purified with this instrument was sufficient for the clinical use. [ABSTRACT FROM AUTHOR]

Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the TCA cycle after beta-oxidation. We speculate that [1-11C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1-11C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [15O]H2O measured 1-2 h and 5-6 h after insult was compared with that of [1-11C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [15O]H2O were lower than those determined with [1-11C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1-11C]octanoate was observed in the ischemic regions. The uptake of [1-11C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1-11C]octanoate provides functional information different from CBF. In conclusion, we found that [1-11C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia. [ABSTRACT FROM AUTHOR]

Encephalitis is generally diagnosed by clinical symptoms, cerebrospinal fluid examination, and imaging studies including CT, magnetic resonance imaging (MRI), and perfusion single photon emission tomography (SPECT). However, the role of positron emission tomography (PET) in diagnosis of encephalitis remains unclear. A 49-year-old woman presenting with coma and elevated inflammatory reaction was diagnosed as having encephalitis according to slow activity on electroencephalogram, broad cortical lesion in MR fluid attenuated inversion recovery image, and increased blood flow demonstrated by SPECT. PET revealed increased accumulation of (11)C-methionine (MET) in the affected brain tissues. After the symptom had improved 2 months later, the accumulation of MET as well as the abnormal findings of MR imaging and SPECT was normalized. This case indicated that MET PET may monitor the activity of encephalitis. [ABSTRACT FROM AUTHOR]

Purpose: The impact of a new type of positron emission tomography (New PET) with semiconductor detectors using 18F-labeled fluoromisonidazole (FMISO)-guided intensity modulated radiation therapy (IMRT) was compared with a state-of-the-art PET/computed tomography (PET/CT) system in nasopharyngeal cancer (NPC) patients. Methods and Materials: Twenty-four patients with non-NPC malignant tumors (control group) and 16 patients with NPC were subjected to FMISO-PET. The threshold of the tumor-to-muscle (T/M) ratio in each PET scan was calculated. The hypoxic volume within the gross tumor volume (GTVh) was determined using each PET (NewPETGTVh and PET/CTGTVh, respectively). Dose escalation IMRT plans prescribing 84 Gy to each GTVh were carried out. Results: The threshold of the T/M ratio was 1.35 for New PET and 1.23 for PET/CT. The mean volume of NewPETGTVh was significantly smaller than that of PET/CTGTVh (1.5±1.6 cc vs 4.7±4.6 cc, respectively; P=.0020). The dose escalation IMRT plans using New PET were superior in dose distribution to those using PET/CT. Dose escalation was possible in all 10 New PET-guided plans but not in 1 PET/CT-guided plan, because the threshold dose to the brainstem was exceeded. Conclusions: New PET was found to be useful for accurate dose escalation in FMISO-guided IMRT for patients with NPC. [ABSTRACT FROM AUTHOR]