Crossed raised arm position improves the flow of contrast medium in torso contrast-enhanced computed Tomography.

INTRODUCTION: This retrospective cohort study examined the effects of the crossed raised arm (CRA) position in contrast-enhanced computed tomography (CECT) on contrast medium influx and image quality relative to the conventional position. METHODS: Contrast medium influx into the collateral veins on CECT images was evaluated in 92 participants. The CT values of the pulmonary artery, descending aorta, and spleen were obtained in both positions and compared. Anatomical changes in the diameters and area of the subclavian vein and costoclavicular distance were also analyzed. RESULTS: Contras 27 and 6 patients in the conventional and CRA positions, respectively. The influx risk ratio in the CRA position versus that in the conventional position was 0.22 (95% confidence interval, 0.10-0.51). Elevations in the median CT value of the pulmonary artery, descending aorta, and spleen in the CRA position were 7.0% (p < .001), 7.4% (p < .001), and 9.8% (p < .001), respectively. Enlargements in the major and minor diameters of the subclavian vein, subclavian vein area, and costoclavicular distance in the CRA position versus those in the conventional position were 19.3% (p < .001), 28.1% (p < .001), 53.6%, and 30.0% (p < .001), respectively. CONCLUSION: The CRA position effectively prevented contrast medium influx into the collateral veins due to SVS and increased CT values in the target organs in CECT. The diameters and area of the subclavian vein and costoclavicular distance were enlarged at the thoracic outlet, which improved the flow of the contrast medium into the targeted organs. IMPLICATIONS FOR PRACTICE: The CRA position can contribute to obtaining better CECT images during common clinical assessments at no additional cost.

Urinary biomarkers of kidney tubule injury, risk of acute kidney injury, and mortality in patients with acute ischaemic stroke treated at a stroke care unit.

BACKGROUND AND PURPOSE: Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). The aim of this study was to investigate whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischaemic stroke. METHODS: Acute ischaemic stroke patients hospitalized in the stroke care unit (SCU) within 24 h after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured on admission. We evaluated the associations among urinary L-FABP, incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria and other potentially predictive variables, using multivariable analysis. RESULTS: In total, 527 acute ischaemic stroke patients (342 men, median age 74 years) were enrolled in the study. Twenty-seven patients (5.1%) experienced AKI within 7 days of admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI [53.8 µg/g creatinine (Cr) vs. 3.9 µg/g Cr; P < 0.001] and 90-day mortality (15.5 µg/g Cr vs. 4.0 µg/g Cr; P < 0.001). In the multivariate analysis, elevated urinary L-FABP level (per 10-µg/g Cr increase) was independently associated with AKI (odds ratio 1.225, 95% confidence interval (CI) 1.083-1.454; P = 0.003) and 90-day mortality (hazard ratio 1.091, 95% CI 1.045-1.138; P < 0.001). CONCLUSION: Urinary biomarkers of kidney tubule injury are independently associated with the development of AKI and 90-day mortality in patients with acute ischaemic stroke treated at the SCU.

Erratum for Mirhendi et al., the first case of onychomycosis in a koala (Phascolarctos cinereus) due to atypical isolates of Microsporum gypseum, a diagnostic challenge.

[This corrects the article DOI: 10.18869/acadpub.cmm.2.2.2.].

Effectiveness of Cardiac Rehabilitation for Prevention and Treatment of Sarcopenia in Patients with Cardiovascular Disease - A Retrospective Cross-Sectional Analysis.

OBJECTIVE: Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, with the risk of frailty and poor quality of life. This study aimed to clarify the clinical characteristics of sarcopenia and to investigate the effects of comprehensive cardiac rehabilitation (CCR), including nutrition, physical exercise and medication, in patients with cardiovascular disease (CVD). METHODS: We retrospectively studied 322 inpatients with CVD (age 72±12 years). Muscle mass, muscle strength and physical performance were assessed before and after exercise training in patients with and without sarcopenia, which was defined as either a gait speed of <0.8 m/s or reduced handgrip strength (<26 kg in males and <18 kg in females), together with lower skeletal muscle index (SMI) (<7.0 kg/m2 in males and <5.7 kg/m2 in females). The actual daily total calorie and nutrient intake was also calculated. RESULTS: Sarcopenia was identified in 28% of patients with CVD, these patients having a higher prevalence of symptomatic chronic heart failure and chronic kidney disease. SMI was significantly associated with protein intake and statin treatment. The ratio of peak VO2 and SMI was significantly higher in the statin treatment group. Handgrip strength, gait speed, leg weight bearing index, and nutritional intake improved after exercise training in patients both with and without sarcopenia. CONCLUSIONS: The present findings suggest that CCR is a promising strategy for prevention and treatment of sarcopenia in patients with CVD.

Effects of behavioural activation on the neural basis of other perspective self-referential processing in subthreshold depression: a functional magnetic resonance imaging study.

BACKGROUND: It has been demonstrated that negatively distorted self-referential processing, in which individuals evaluate one's own self, is a pathogenic mechanism in subthreshold depression that has a considerable impact on the quality of life and carries an elevated risk of developing major depression. Behavioural activation (BA) is an effective intervention for depression, including subthreshold depression. However, brain mechanisms underlying BA are not fully understood. We sought to examine the effect of BA on neural activation during other perspective self-referential processing in subthreshold depression. METHOD: A total of 56 subjects underwent functional magnetic resonance imaging scans during a self-referential task with two viewpoints (self/other) and two emotional valences (positive/negative) on two occasions. Between scans, while the intervention group (n = 27) received BA therapy, the control group (n = 29) did not. RESULTS: The intervention group showed improvement in depressive symptoms, increased activation in the dorsal medial prefrontal cortex (dmPFC), and increased reaction times during other perspective self-referential processing for positive words after the intervention. Also, there was a positive correlation between increased activation in the dmPFC and improvement of depressive symptoms. Additionally, there was a positive correlation between improvement of depressive symptoms and increased reaction times. CONCLUSIONS: BA increased dmPFC activation during other perspective self-referential processing with improvement of depressive symptoms and increased reaction times which were associated with improvement of self-monitoring function. Our results suggest that BA improved depressive symptoms and objective monitoring function for subthreshold depression.

The first case of onychomycosis in a koala (Phascolarctos cinereus) due to atypical isolates of Microsporum gypseum, a diagnostic challenge.

BACKGROUND AND PURPOSE: Superficial mycotic infections have been only poorly described in koalas and there are no reliable mycologically confirmed data regarding clinical isolation of dermatophytes in this animal. We report an 11-year-old female koala, kept in a zoo in Tokyo, Japan, and presenting with hyperkeratotic lesions and scaly plaques on forepaw claws and pads reminiscent of fungal infection. CASE REPORT: Direct microscopy of the scrapings was indicative of a dermatophyte infection. By culture and subsequent repeated subculturing of clinical specimens on Sabouraud dextrose agar, Mycobiotic agar, and potato dextrose agar, two distinct strains with different colony morphotypes (designed as types I and II) were identified. Macroscopic and microscopic characteristics of the strains were suggestive of three different species, i.e. Microsporum canis, M. gypseum, and M. fulvum. However, partial sequencing of internal transcribed spacer (ITS) region of rDNA, translation elongation factor-1α (Tef-1α), and beta-tubulin (BT2) genes confirmed the identity of both isolates as M. gypseum. The animal was treated with a continuous terbinafine regimen (250 mg/kg) once daily for 12 weeks. CONCLUSION: To the best of our knowledge, the present report is the first confirmed case of dermatophytosis in a koala. The genetics underlying a variety of phenotypic traits in most classical dermatophyte species are unknown, and further studies are needed to understand this phenomenon.

Accurate NMR determination of C-H or N-H distances for unlabeled molecules.

Cross-Polarization with Variable Contact-time (CP-VC) is very efficient at ultra-fast MAS (νR ≥ 60 kHz) to measure accurately the dipolar interactions corresponding to C-H or N-H short distances, which are very useful for resonance assignment and for analysis of dynamics. Here, we demonstrate the CP-VC experiment with (1)H detection. In the case of C-H distances, we compare the CP-VC signals with direct ((13)C) and indirect ((1)H) detection and find that the latter allows a S/N gain of ca. 2.5, which means a gain of ca. 6 in experimental time. The main powerful characteristics of CP-VC methods are related to the ultra-fast spinning speed and to the fact that most of the time only the value of the dipolar peak separation has to be used to obtain the information. As a result, CP-VC methods are: (i) easy to set up and to use, and robust with respect to (ii) rf-inhomogeneity thus allowing the use of full rotor samples, (iii) rf mismatch, and (iv) offsets and chemical shift anisotropies. It must be noted that the CP-VC 2D method with indirect (1)H detection requires the proton resolution and is thus mainly applicable to small or perdeuterated molecules. We also show that an analysis of the dynamics can even be performed, with a reasonable experimental time, on unlabeled samples with (13)C or even (15)N natural abundance.

Studies of minute quantities of natural abundance molecules using 2D heteronuclear correlation spectroscopy under 100 kHz MAS.

Two-dimensional (1)H{(13)C} heteronuclear correlation solid-state NMR spectra of naturally abundant solid materials are presented, acquired using the 0.75-mm magic angle spinning (MAS) probe at spinning rates up to 100 kHz. In spite of the miniscule sample volume (290 nL), high-quality HSQC-type spectra of bulk samples as well as surface-bound molecules can be obtained within hours of experimental time. The experiments are compared with those carried out at 40 kHz MAS using a 1.6-mm probe, which offered higher overall sensitivity due to a larger rotor volume. The benefits of ultrafast MAS in such experiments include superior resolution in (1)H dimension without resorting to (1)H-(1)H homonuclear RF decoupling, easy optimization, and applicability to mass-limited samples. The HMQC spectra of surface-bound species can be also acquired under 100 kHz MAS, although the dephasing of transverse magnetization has significant effect on the efficiency transfer under MAS alone.

Theoretical study of CP-VC: a simple, robust and accurate MAS NMR method for analysis of dipolar C-H interactions under rotation speeds faster than ca. 60 kHz.

We show that Cross-Polarization with Variable Contact-time (CP-VC) allows an accurate determination of C-H dipolar interactions, which permits an easy detailed analysis of bond lengths and local dynamics, e.g. in biomolecules. The method presents a large dipolar scaling factor of 1/√2, leading to a better determination of dipolar interactions, especially for long C-H distances, and it allows the observation of very small local details such as those related either to CH(2) three spin systems, or even to hydrogen bonds. CP-VC is very simple to set up and very robust with respect to most experimental parameters, such as: rf-offsets, chemical-shift anisotropies, imperfect Hartmann-Hahn setting, and rf-inhomogeneity. The only required condition is the use of a sufficiently fast MAS spinning speed of at least ca. 60 kHz.

Suppression of streptozotocin-induced type-1 diabetes in mice by radon inhalation.

We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas.

Preventive and curative effects of radon inhalation on chronic constriction injury-induced neuropathic pain in mice.

BACKGROUND: Radon therapy is clinically useful for the treatment of pain-related diseases. However, there have been no studies regarding the effects of radon inhalation on neuropathic pain. In this study, we aimed to determine whether radon inhalation actually induced a remission of neuropathic pain and improved the quality of life. METHODS: First, we investigated the antinociceptive effects of radon inhalation in the chronic constriction injury (CCI) model of neuropathic pain. We evaluated pain behaviour in mice before and after CCI surgery, using von Frey test. Pretreated mice received CCI surgery immediately after 24-h inhalation of radon at background (BG) concentration (c. 19 Bq/m(3) ), or at a concentration of 1000 or 2000 Bq/m(3) , and post-treated mice inhaled similar levels of radon 2 days after CCI surgery. RESULTS: CCI surgery induced mechanical allodynia and hyperalgesia on a plantar surface of mice, as assessed using von Frey test, and 2000 Bq/m(3) radon inhalation alleviated hyperalgesic conditions 22-37% compared to BG level concentration. Concurrently, CCI surgery increased norepinephrine (NE), tumour necrosis factor-alpha (TNF-α) and nitric oxide (NO) concentrations in plasma, and leukocyte migration in paws. Furthermore, CCI-induced neuropathy reduced superoxide dismutase (SOD) activity. Treatment with radon inhalation, specifically at a concentration of 2000 Bq/m(3) , produced antinociceptive effects, i.e., lowered plasma TNF-α, NE and NO levels and restored SOD activity, as well as pain-related behaviour. CONCLUSIONS: This study showed that inhalation of 2000 Bq/m(3) radon prevented and alleviated CCI-induced neuropathic pain in mice.

Cerebral blood flow and metabolism measurement using positron emission tomography before and during internal carotid artery test occlusions: feasibility of rapid quantitative measurement of CBF and OEF/CMRO(2).

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study is a sensitive test for predicting the outcome of permanent ICA occlusion. However, false negative results sometimes occur using single photon emission tomography (SPECT). We have recently developed a rapid positron emission tomography (PET) protocol that measures not only the CBF but also the cerebral oxygen metabolism before and during BTO in succession. We measured acute changes in regional CBF and OEF/CMRO(2) before and during BTO in three cases with large or giant cerebral aneurysms using the rapid PET protocol. Although no patients showed ischemic symptoms during BTO, PET studies exhibited mildly to moderately decreased CBF (9∼34%) compared to the values obtained before BTO in all cases. The average OEF during BTO was significantly increased (21% and 43%) than that of before BTO in two cases. The two cases were considered to be non-tolerant for permanent ICA occlusion and treated without ICA sacrifice. Measurement of the CBF and OEF/CMRO(2) using a rapid PET protocol before and during BTO is feasible and can be used for accurate assessment of tolerance prediction in ICA occlusion.

Symptomatic middle cerebral artery stenosis treated by percutaneous transluminal angioplasty: improvement of cerebrovascular reserves.

This study evaluated the recoveries of cerebrovascular reserves (CVR) after applying percutaneous transluminal angioplasty (PTA) to patients with symptomatic middle cerebral artery (MCA) stenosis of varying severity. The patients were submitted to single photon emission computed tomography (SPECT) to obtain their regional cerebral blood flows at resting stage (rCBF(rest)) and acetazolamide-challenged CBF in five regions of interest (ROIs), including the MCA, on the ipsilateral and contralateral sides of the hemisphere. rCVR values were then calculated from these CBF data to evaluate the CVR recoveries after PTA treatment. When the PTA effects were statistically analyzed of the patients dichotomized into more severe (n=9) and less severe (n=5) groups, distinctly significant ROI-specific PTA effectiveness was observed for CVR rather than CBF values in the patients of the severer group.

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer.

Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P=0.016). Angiogenesis was significantly higher in treatment group (P=0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P=0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.

Radiation pneumonitis in patients with lung and mediastinal tumours: a retrospective study of risk factors focused on pulmonary emphysema.

OBJECTIVES: To evaluate the impact of pulmonary emphysema (PE) on the incidence and severity of radiation pneumonitis (RP) in patients with lung and mediastinal tumours. METHODS: 92 patients were enrolled. Involved-field radiation therapy (non-small cell carcinoma or mediastinal tumours in 69 patients; median 70 Gy) and accelerated hyperfractionation (limited disease small cell carcinoma in 23 patients; median 45 Gy) were performed. Common Terminology Criteria for Adverse Events v.3.0 was used to evaluate RP and the relationship with the percentage of pulmonary volume irradiated to >20 Gy (V20) and PE. PE was diagnosed by the presence of low-attenuation areas (LAAs) on CT scans and was classified into Grades 0-4 according to the extent of the LAAs. RESULTS: The median follow-up time was 16 months. The 6-month cumulative incidence of RP at Grade 3 or greater was 7.7% and 34.1% in patients with a V20 of <25% and ≥25%, respectively (p=0.017). In patients with PE Grades 0, 1, 2 and 3 or greater, the incidence of RP was 16.5%, 9.1%, 8.6% and 54.0%, respectively. As the PE Grade increased, the incidence of RP also increased significantly. CONCLUSION: The incidence and severity of RP are significantly higher in patients with a high V20 value as well as in those with severe PE.

Hepatocyte growth factor incorporated into herpes simplex virus vector accelerates facial nerve regeneration after crush injury.

Hepatocyte growth factor (HGF) promotes regeneration of the central nervous system, but its effects on the peripheral nervous system remain unclear. This study was conducted to elucidate the effect of HGF on regeneration of the murine facial nerve after crush injury. To do so, a replication-defective herpes simplex virus vector that incorporated HGF was prepared (HSV-HGF). The main trunk of the facial nerve was compressed by mosquito hemostats, and HSV-HGF, control vector or medium was then applied to the compressed nerve. We found that mice in the HGF group required significantly fewer days for complete recovery from nerve compression. Furthermore, the amplitude of the evoked buccinator muscle compound action potential increased following HSV-HGF application. HGF expression in and around the compressed nerve was demonstrated by enzyme-linked immunoassay and immunohistochemistry. In addition, HSV-HGF introduction around the damaged nerve significantly accelerated recovery of function of the facial nerve. These data suggest a possible role of HGF in promoting facial nerve regeneration after nerve damage. Furthermore, this viral delivery method may be applied clinically for many types of severe facial palsy during facial nerve decompression surgery.

A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer.

In 2005, we initiated a clinical trial that examined the efficacy of the oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to have a high mortality rate, despite multimodal treatments for patients, and new therapeutic methods are greatly needed. The current mainstream methods for cancer treatment include biological therapeutics such as trastuzumab (Herceptin) for breast cancer or erlotinib (Tarceva) for non-small cell lung cancer. Oncolytic virus therapy is a new and promising treatment strategy for cancer. Oncolytic viruses are novel biological therapeutics for advanced cancer that appear to have a wide spectrum of anticancer activity with minimal human toxicity. To examine the efficacy of oncolytic virus therapy for pancreatic cancer, we initiated pilot studies by injecting six patients with non-resectable pancreatic cancer with three doses of HF10. All patients were monitored for 30 days for local and systemic adverse effects and were not administered any other therapeutics during this period. There were no adverse side-effects, and we observed some therapeutic potential based on tumor marker levels, survival, pathological findings and diagnostic radiography. The tumors were classified as stable disease in three patients, partial response in one patient and progressive disease in two patients.