Underwater polypectomy without submucosal injection for colorectal lesions ≤ 20 mm in size-a multicenter retrospective observational study.

BACKGROUND: Underwater polypectomy (UWP) of large (≥ 20 mm) colorectal lesions is well described, but reports of UWP for lesions ≤ 20 mm in size, which account for > 95% of polyps encountered in routine clinical practice, are limited. We assessed the feasibility of UWP in routine practice across various sites for colorectal lesions ≤ 20 mm in size. METHODS: A multicenter retrospective study was performed on pooled data from nine colonoscopists at 3 U.S., 1 Taiwanese and 2 Italian sites. Outcomes related to UWP on lesions ≤ 20 mm in size were analyzed. RESULTS: In 117 patients, UWP netted 169 lesions. Polypectomy by hot (HSP, 54%) or cold (CSP, 41%) snare, and cold forceps (CFP, 5%) were performed successfully without endoscopic evidence of residual neoplasia or immediate clinically significant adverse events. The majority (74.6%) were tubular adenomas; 60.9% were from the proximal colon. Histopathologic margins were positive in 4 and unavailable in 26 CSP and 24 HSP specimens. The remainder had negative resection margins on pathologic reports. CONCLUSION: UWP for colorectal lesions ≤ 20 mm in routine practice across multiple sites confirms the feasibility and acceptability of this technique. Improvement of resection outcomes by UWP in routine practice deserves further evaluation in a randomized controlled trial.

Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (ß=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (ß=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (ß=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.

Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.

Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underpinnings may elucidate etiological mechanisms. We therefore conducted a genome-wide association study (GWAS) of monoamine metabolite (MM) levels in cerebrospinal fluid (CSF) of 414 human subjects from the general population. In a linear model correcting for covariates, we identified one locus associated with MMs at a genome-wide significant level (standardized ß=0.32, P=4.92 × 10(-8)), located 20 kb from SSTR1, a gene involved with brain signal transduction and glutamate receptor signaling. By subsequent whole-genome expression quantitative trait locus (eQTL) analysis, we provide evidence that this variant controls expression of PDE9A (ß=0.21; P unadjusted=5.6 × 10(-7); P corrected=0.014), a gene previously implicated in monoaminergic transmission, major depressive disorder and antidepressant response. A post hoc analysis of loci significantly associated with psychiatric disorders suggested that genetic variation at CSMD1, a schizophrenia susceptibility locus, plays a role in the ratio between dopamine and serotonin metabolites in CSF. The presented DNA and mRNA analyses yielded genome-wide and suggestive associations in biologically plausible genes, two of which encode proteins involved with glutamate receptor functionality. These findings will hopefully contribute to an exploration of the functional impact of the highlighted genes on monoaminergic transmission and neuropsychiatric phenotypes.

A multicenter, randomized, controlled trial testing the effects of acupuncture on allergic rhinitis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of acupuncture in the treatment for allergic rhinitis. METHODS: This study was a multicenter, randomized, parallel-controlled study. Participants were randomized to either the active acupuncture, sham acupuncture, or waitlist groups. The active and sham acupuncture groups received acupuncture treatment three times per week for 4 weeks. In the sham group, minimal acupuncture at nonacupuncture points was used. The waitlist group did not receive any acupuncture treatment. RESULTS: Of the 238 participants, 97, 94, and 47 individuals were assigned to the active acupuncture, sham acupuncture, and waitlist group, respectively. After the treatment, the difference in the total nasal symptom score (TNSS) was significantly reduced in the active acupuncture group compared with the sham acupuncture (difference: -1.03, 95% confidence interval [CI]: -1.96, -0.09, P = 0.03) and waitlist (difference: -2.49, 95% CI: -3.68, -1.29, P < 0.0001). The active acupuncture group exhibited a significant change in the total non-nasal symptom score (TNNSS) compared with the waitlist (difference: -0.78, 95% CI: -1.22, -0.34, P = 0.0002), but not the sham acupuncture group (difference; 0.15, 95% CI: -0.21, 0.5, P = 0.56). Both active and sham acupuncture treatments resulted in significant improvements in TNSS and TNNSS compared to baseline. CONCLUSION: Active acupuncture showed a significantly greater effect on symptoms of allergic rhinitis than either sham acupuncture or no active treatment. The symptoms of allergic rhinitis decreased significantly after treatment in the both acupuncture and sham acupuncture groups. Acupuncture appears to be an effective and safe treatment for allergic rhinitis.

The time-dependent alteration of anti-diuretic hormone system in hindlimb unloaded rats.

It is important to understand the mechanism on the fluid shift and volume regulation occurring in astronauts after spaceflight for future life in space. In the present study, we examined the time-dependent alteration of anti-diuretic hormone (ADH) concentrating on the water reabsorption system in hindlimb unloaded rats. Male Sprague-Dawley rats were hindlimb unloaded for 1 (HU1), 7(HU7), 14 days (HU14) or rested in the ground for 3 days after HU14 (HU14+3). The plasma ADH and angiotensin II level showed peak value at HU7, and the alterations were restored at HU14. However, several serum electrolytes (Na, K, Cl) were not changed regardless of HU period. In the immunohistochemical study, we examined that ADH and c-Fos immunoreactivities (IR) were maximized at HU7 in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). Aquaporin 2 (AQP2) IR also was increased in the renal collecting duct for water re-absorption at HU7 showing a similar pattern with ADH. These results present a series of physiological ADH system alteration following to period of hindlimb unloading stimulus, indicating that ADH system is activated significantly at HU7. In addition, our results suggest that ADH system activation may be involved in anti-diuretic phenomenon in early spaceflight period. Furthermore, it is speculated that ADH system may require 14 days for adaptation to microgravity.

Esophageal capsule endoscopy for evaluation of patients with chronic gastroesophageal reflux symptoms: findings and its image quality.

Esophageal capsule endoscopy (ECE) may offer an alternative approach to visualize esophageal lesions associated with gastroesophageal reflux (GER) disease. The objective of this study was to report the ECE findings in patients with GER symptoms and validate a new scoring system to assess ECE video quality. Five hundred two ECE were performed in patients with GER symptoms. We devised a new grading scale called ECE Utility score to assess the quality of images using five different parameters: anatomic landmarks visualized, esophageal transit time, image quality, illumination, and artifacts. The ECE cases were independently scored by two interpreters in a randomized, blinded fashion. Reflux esophagitis was diagnosed via ECE in 254 patients (50.5%). We identified 12 cases (2.4%) with suspected Barrett's esophagus and all of them had endoscopic evidence of Barrett's esophagus on esophagogastroduodenoscopy. Histologic confirmation Barrett's esophagus was found in six patients and dysplasia was found in one patient. From the 502 cases, mean ± standard deviation total ECE Utility score was 8.89 ± 0.96 for interpreter 1 and 8.96 ± 0.93 for interpreter 2. The concordance rate between the two interpreters for the ECE Utility score ranged from 75.9-96.8% across the parameters and the Pearson correlation rate of the total score was 0.81. ECE is shown to be a simple noninvasive valuable technique for evaluating esophageal mucosa and producing high quality images in patients with GER symptoms. ECE can help as an alternative screening tool for diagnosing Barrett's esophagus.

Implanted bone marrow-derived mesenchymal stem cells fail to metabolically stabilize or recover electromechanical function in infarcted hearts.

Mesenchymal stem cells (MSCs) have been used with success in several clinical applications for clinical treatment of ischemic hearts. However, the reported effects of MSC-based therapy on myocardial infarction (MI) are inconsistent. In particular, the preventive effects of MSC-based therapy on arrhythmic sudden death and metabolic disorders after infarction remain controversial. Here, we investigated the effects of MSCs on reverse remodeling in an infarcted myocardium, and found that MSC-therapy failed to achieve the complete regeneration of infarcted myocardium. Histological analyses showed that although infarct size and interstitial fibrosis induced by MI recovered significantly after MSC treatment, these improvements were marginal, indicating that a significant amount of damaged tissue was still present. Furthermore, transplanted MSCs had slight anti-apoptotic and anti-inflammatory effects in MSC-implanted regions and no significant improvements in cardiac function were observed, suggesting that naïve MSCs might not be the right cell type to treat myocardial infarction. Furthermore, small ion profiling using ToF-SIMS revealed that the metabolic stabilization provided by the MSCs implantation was not significant compared to the sham group. Together, these results indicate that pretreatment of MSCs is needed to enhance the benefits of MSCs, particularly when MSCs are used to treat arrhythmogenicity and metabolically stabilize infarcted myocardium.

Novel external sensor array for capsule endoscopy.

Capsule endoscopy (CE) requires placement of an eight-lead sensor array over the abdomen that receives image and localization data transmitted from the capsule. The current process of applying this array to the skin has several disadvantages: firstly, it is time-consuming; secondly, it can be cumbersome for the patient; and thirdly, it is often difficult to place the leads consistently. A new external sensor array system designed to improve this process was tested. It was hypothesized that the new method would be able to receive the transmitted data adequately during CE. The new method and device were tested on an in-patient who had two sets of sensor arrays, batteries, and data recorders placed on her simultaneously. One set was placed in the standard fashion, which served as the control, while the other set was placed using the novel external method. The data provided by the two recorders were compared and the patient's preferences were noted. The quality of the CE images provided by the two methods was identical, but the CE localization tracings were different, presumably due to movement of the gown and leads during the recording period. No signal interference was noted. The patient preferred the external device. A prepositioned external sensor array is capable of transmitting CE data without any loss in image quality, but the localization tracing differs due to movement of the external array. This new method will require testing with a larger sample size in an outpatient setting to allow full assessment of the clinical value of the new approach.

The effects of weight load and joint immobilization on reorganization of postural tremor.

To investigate change in coordinative strategies due to wrist immobilization and index loading, postural tremors from the index, hand, and forearm were recorded during different postural holding tasks. The wrist joint was immobilized with a thermoplastic splint in the constrained condition, and a copper mass of 100 grams was applied to the index finger in the loaded condition. The structures of the postural tremors of all upper limb segments among the unloaded-unconstrained, unloaded-constrained, loaded-unconstrained, and loaded-constrained conditions were compared. Index loading exaggerated index/forearm postural tremor, while the load-induced tremor enhancement was no longer evident for wrist immobilization. In the unloaded condition, wrist immobilization resulted specifically in enhancement of carpal postural tremor, rather than in the index and forearm. Index loading induced a marked tremor peak and relative power in the range of 5-8 Hz. Wrist immobilization potentiated the carpal tremor peak of 1-4 Hz in association with enhancement of carpal-forearm mechanical coupling. In light of structural changes in postural tremor, our data suggest that (1) a wrist splint is effective to counteract load-induced enhancement of postural tremor, and (2) freezing of the wrist joint might facilitate compensatory strategies to minimize passive fluctuation transmission from the carpal to index.

Elk-1 associates with the mitochondrial permeability transition pore complex in neurons.

The nuclear transcription factor E-26-like protein 1 (Elk-1) is thought to impact neuronal differentiation [Sharrocks, A. D. (2001) Nat. Rev. Mol. Cell Biol. 2, 827-837], cell proliferation [Sharrocks, A. D. (2002) Biochem. Soc. Trans. 30, 1-9], tumorigenesis [Chai, Y. L., Chipitsyna, G., Cui, J., Liao, B., Liu, S., Aysola, K., Yezdani, M., Reddy, E. S. P. & Rao, V. N. (2001) Oncogene 20, 1357-1367], and apoptosis [Shao, N., Chai, Y., Cui, J., Wang, N., Aysola, K., Reddy, E. S. P. & Rao, V. N. (1998) Oncogene 17, 527-532]. In addition to its nuclear localization, Elk-1 is found throughout the cytoplasm, including localization in neuronal dendrites [Sgambato, V., Vanhoutte, P., Pages, C., Rogard, M., Hipskind, R., Besson, M. J. & Caboche, J. (1998) J. Neurosci. 18, 214-226], raising the possibility that Elk-1 may have alternative extranuclear functions in neurons. Using coimmunoprecipitation and reciprocal coimmunoprecipitation from adult rat brain, we found an association between Elk-1 protein and the mitochondrial permeability transition pore complex (PTP), a structure involved in both apoptotic and necrotic cell death. Electron microscopy in adult rat brain sections confirmed this association with mitochondria. Elk-1 was also identified from purified mitochondrial fractions by using Western blotting, and Elk-1 increased its association with mitochondria following proapoptotic stimuli. Consistent with a role for Elk-1 in neuron viability, overexpression of Elk-1 in primary neurons decreased cell viability, whereas Elk-1 siRNA-mediated knockdown increased cell viability. This decrease in viability induced by Elk-1 overexpression was blocked with application of a PTP inhibitor. These results show an association of the nuclear transcription factor Elk-1 with the mitochondrial PTP and suggest an additional extranuclear function for Elk-1 in neurons.

RNA splicing capability of live neuronal dendrites.

Dendrites are specialized extensions of the neuronal soma that contain components of the cellular machinery involved in RNA and protein metabolism. Several dendritically localized proteins are associated with the precursor-mRNA (pre-mRNA) splicing complex, or spliceosome. Although some spliceosome-related, RNA-binding proteins are known to subserve separate cytoplasmic functions when moving between the nucleus and cytoplasm, little is known about the pre-mRNA splicing capacity of intact dendrites. Here, we demonstrate the presence and functionality of pre-mRNA-splicing components in dendrites. When isolated dendrites are transfected with a chicken delta-crystallin pre-mRNA or luciferase reporter pre-mRNA, splicing junctions clustered at or near expected splice sites are observed. Additionally, in vitro synaptoneurosome experiments show that this subcellular fraction contains a similar complement of splicing factors that is capable of splicing chicken delta-crystallin pre-mRNA. These observations suggest that pre-mRNA-splicing factors found in the dendroplasm retain the potential to promote pre-mRNA splicing.

Glutamate on demand: astrocytes as a ready source.

The past decade of studies has changed our view of the integrative capacities and roles of glia. A picture is emerging in which neurons and astrocytes, a subtype of glial cell, are in a continuous regulatory dialogue. Initial studies demonstrated that chemical transmitters, which are released from neurons, induce elevations of astrocytic calcium. Furthermore, stimulation of neuronal afferents at modest frequencies induces a calcium response in astrocytes that is graded with stimulation frequency. The consequence of this astrocytic calcium response is now beginning to be appreciated in that changes in calcium level can induce the release of the chemical transmitter glutamate from this nonneuronal cell. During the past few years, it has been shown that by releasing glutamate, astrocytes can regulate synaptic transmission and contribute to certain forms of synaptic plasticity. The roles played in information processing by this glial feedback loop remain to be determined. However, it is likely that the results of these recent studies will signal a new way of thinking about the nervous system, in which the glial cell comes to the forefront of our attention.

Efficacy of MRI in complicated congenital heart disease with visceral heterotaxy syndrome.

PURPOSE: The authors' goal was to assess the diagnostic accuracy and clinical effect of MRI compared with echocardiography and catheterization in the evaluation of cardiac defects with situs ambiguous. METHOD: Twenty-two patients with visceral heterotaxy syndrome were included. RESULTS: Because situs determined by the relation between the pulmonary artery and bronchi showed most predominantly a tendency toward lateralization, this was regarded as the standard reference of situs determination. For the purpose of this study, patients were classified as having right isomerism (n = 13) or left isomerism groups (n = 9). MRI has several advantages compared with echocardiography or cardiac angiography for examining patients with situs ambiguous. (1) The bronchial, pulmonary arterial, and splenic situs can be readily determined, and discrepancies (n = 2) can be assessed easily. (2) Venoatrial connections are adequately imaged. In particular, all types of total and partial anomalous pulmonary venous return are delineated, regardless of whether restrictions of pulmonary blood flow or pulmonary venous obstructions are involved (n = 4). The courses of vertical veins were easily identified, and the prearterial position was revealed in only one of seven right isomerisms with total anomalous pulmonary venous return. The drain pattern of the hepatic vein can be visualized using three-dimensional spatial information and is useful for total cavopulmonary connection design. (3) Associated complicated cardiac anomalies, particularly the size or peripheral stenosis of the pulmonary arteries, may be evaluated, and this information is useful for palliative shunt operations. CONCLUSION: Because of its wide field of view and imaging, which is not restricted by associated anomalies, a thorough understanding of the cardiovascular anatomy of the situs ambiguous can be achieved using MRI, which is of considerable value in the surgical correction of this complicated anomaly. MRI can obviate or facilitate catheterization in these critically ill patients.

Magnetic resonance imaging of unroofed coronary sinus: three cases.

Unroofed coronary sinus is a rare cardiac anomaly in which communication occurs between the coronary sinus and the left atrium due to the partial or complete absence of the roof of the coronary sinus. It is usually associated with other cardiovascular anomalies, especially persistent left superior vena cava. It is often not discovered during cardiac catheterization without clinical suspicion. We report three cases of unroofed coronary sinus which were incidentally detected by magnetic resonance imaging.

Albumin elicits calcium signals from astrocytes in brain slices from neonatal rat cortex.

1. Albumin causes calcium signals and mitosis in cultured astrocytes, but it has not been established whether astrocytes in intact brain also respond to albumin. The effect of albumin on intracellular calcium concentration ([Ca2+]i) in single cells was therefore studied in acutely isolated cortical brain slices from the neonatal rat. 2. Physiological concentrations of albumin from plasma and from serum produced an increase in [Ca2+]i in a subpopulation of cortical cells. Trains of transient elevations in [Ca2+]i (Ca2+ spikes) were seen in 41 % of these cells. 3. The cells responding to albumin are identified as astrocytes because the neurone-specific agonist NMDA caused much smaller and slower responses in these cells. On the other hand NMDA-responsive cells, which are probably neurones, exhibited only small and slow responses to albumin. The residual responses of astrocytes to NMDA and neurones to albumin are likely to be due to crosstalk with adjacent neurones and astrocytes, respectively. 4. Methanol extraction of albumin removes a polar lipid and abolishes the ability of albumin to increase intracellular calcium. 5. Astrocyte calcium signalling caused by albumin may have important physiological consequences when the blood-brain barrier breaks down and allows albumin to enter the CNS.

Computing system for pediatric cardiology (CathEcho 2.5).

CathEcho version 2.5 (CathEcho 2.0) was developed as database system of clinical data for pediatric cardiology patients including X-ray and echocardiogram picture for a scientific purpose. We classified congenital heart defects and combined these data to meet any diagnosis or syndrome and any diagnostic coding system. Anatomical data was saved systematically along the anatomical hierarchy of heart. Laboratory data were calculated automatically after the validation. All congenital defects were revised and diagnosis was made automatically. In this system the determination of operation can be suggested according to the cardiac indexes and data can be reported as clinical charts. We can monitor the statistics of patient data and obtain information about patient clinical data easily even at emergency state. This system can make physician to have complete examination about congenital heart disease as well as other heart state. The followings are the main constitutions of the CathEcho version 2.5. BASIC INFORMATION RECORDS. In this part, the unique number is given to any patient. The basic patient informations are checked and stored as clinical data for the management of patients and for the research purposes. CARDIAC CATHETERIZATION RECORDS. Cardiac catheterization data are recorded in this part. The cardiac anatomical data are recorded in according to the segmental steps and the anatomical relationships. Laboratory data are recorded and the cardiac indexes are calculated automatically. This system can recommend the therapeutic plans on operation. Final diagnosis can be automatically arranged by a complete revision of anatomical and laboratory data. CARDIAC ECHOCARDIOGRAM RECORDS. Echocardiogram data are recorded systematically and the cardiac indexes can be calculated automatically. This system also can recommend the necessity of the operation. Full anatomical and laboratory data are completely revised and diagnosis can be made automatically. ELECTROCARDIOGRAPHY (EKG) RECORDS. EKG data are stored systematically and reported with catheterization data, echo data and X-ray data. X-RAY RECORDS. X-ray data of patients also are stored for the complete clinical data. With CathEcho 2.5 we are now storing the formatted clinical data for the expert systems which are now being developed to assist the therapeutic planning and updated to link to cardiac electrophysiology.

Takayasu arteritis in Korean children: clinical report of seventy cases.

Seventy cases of Takayasu arteritis in Korean children are reported. There were 57 females and 13 males (male-to-female ratio; 1:4.4). The youngest patient was a 3-year-old female. Family history was positive in one patient. The most common chief complaints on admission were dyspnea, headache, palpitation, and edema which were due to hypertension and congestive heart failure. Hypertension was seen in 65 out of 70 patients (92.8%). The abdominal aorta, thoracic aorta, and renal arteries were the most commonly involved sites in these children. Two patients had nephrotic syndrome. The frequency of positive tuberculin reaction was much higher in children with Takayasu arteritis compared with the general population, and the intensity of the reaction was also stronger. The majority of the patients required immediate medical treatment to control congestive heart failure due to hypertension at initial presentation. When ESR was elevated, corticosteroid was administered. Surgical treatment showed good results in six out of ten cases. Percutaneous intraluminal angioplasty was effective for lowering the blood pressure in six out of nine cases. In three cases, restenosis occurred and angioplasty was repeated in two cases.