A GABAergic depolarizing potential in the hippocampus disclosed by the convulsant 4-aminopyridine

Intracellular recordings from hippocampal pyramidal cells in the CA1 subfield of the 'in vitro' slice in the presence of 4-aminopyridine (4-AP, 5-50 microM) revealed a long-lasting (up to 1.5 s) depolarizing potential which occurred either spontaneously or following orthodromic stimulation. This potential was: capable of blocking both direct and synaptic activation of the cell; sensitive to bath application of low concentrations of bicuculline methiodide; and associated to an extracellular current sink in the dendrites as suggested by the extracellular field potentials recorded at different levels along an axis perpendicular to the stratum pyramidale. It is concluded that the long-lasting depolarizing potential evoked by 4-AP is caused by the activation of GABA receptors localized in the dendritic region of the CA1 subfield.     

Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria"

New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.     

Socio-demographic and clinical features associated with demoralization in medically ill in-patients

Introduction In the present study we tried to identify which socio-demographic and clinical characteristics are associated with demoralization in medically ill in-patients. Method Patients (n. 296), consecutively admitted to medical wards in a 120 day period, were evaluated with the Demoralization Scale of the Psychiatric Epidemiological Research Interview (PERI-D) to assess demoralization , with the Mini International Neuropsychiatric Interview (MINI) to assess mental disorders (DSM-IV), with the Brief Disability Questionnaire for the evaluation of the functional disability, with the Duke Severity of Illness to assess severity of the medical illness. Moreover, the family support and threatening life events were also evaluated. Results A significant effect in increasing the demoralization score was observed for presence of Major Depression or Adjustment Disorder, poor family support, severity of functional disability, number of threatening life events in the past year and female gender. Conclusion Major Depression needs to be recognized in demoralized medically ill in-patients, because it is one of the most important conditions associated with demoralization, which successfully responds to adequate treatment.     

Evolution of clinical,electrophysiological, and radiological aspects of the carpal tunnel syndrome before and after surgery

The aim of the study was to analyze the evolution of the clinical, electrophysiological, and ultrasound aspects of carpal tunnel syndrome (CTS) before and 4 and 8 weeks after surgery. A Boston Carpal Tunnel Questionnaire, an ultrasound scan, and an electrophysiological exam were performed in 14 patients the day of surgery, 4 and 8 weeks after. The nerve conduction study included: median nerve sensory conduction stimulating digit 3 and 4, median motor conduction from the abductor pollicis brevis, ulnar nerve sensory, and motor conduction. A significant improvement of the symptoms and a significant decrease of the median nerve proximal cross-sectional area on the ultrasound scan were observed 4 weeks after surgery. Distal motor latency (DML) was > 4.2 ms in six patients and decreased along the three visits. DML was ≤ 4.2 ms in the eight others and stayed stable after surgery. We observed a significant increase of the sensory median nerve amplitude response at the wrist stimulating the third digit 8 weeks after surgery. When operated patients are referred for control, we recommend to perform: (1) 4 weeks after surgery, an ultrasonography, and a measure of the DML of the median nerve; (2) 8 weeks after surgery, a measure of the sensory conduction velocity of the median nerve.     

Integrative genetic, epigenetic and pathological analysis of paraganglioma reveals complex dysregulation of NOTCH signaling

Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The “NOTCH signaling pathway” was the most significantly enriched term in the list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunohistochemistry in 47 head and neck paraganglioma cases. There were no relationships between level and pattern of NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes, implicated in paraganglioma predisposition, or the presence/absence of immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly, NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of this pathway. To address this issue we performed microarray-based microRNA expression analyses. Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most downregulated in the tumors, correlated to NOTCH signaling and directly targeted NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore, lentiviral transduction of miR-200s and miR-34s in patient-derived primary tympano-jugular paraganglioma cell cultures was associated with NOTCH1 downregulation and increased levels of markers of cell toxicity and cell death. Taken together, our results provide an integrated view of common molecular alterations associated with head and neck paraganglioma and reveal an essential role of NOTCH pathway deregulation in this tumor type.     

Surveillance study for creating the national clinical database relating to ECG-gated myocardial perfusion SPECT of asymptomatic ischemic heart disease in patients with type-2 diabetes mellitus: J-ACCESS 2 study design

Objective Diabetes mellitus is an independent risk factor for acute myocardial infarction. Thus, a surveillance study was conducted as part of studies to create a national database related to electrocardiogram (ECG)-gated myocardial perfusion single-photon emission computed tomography (SPECT) of ischemic heart disease. Methods Single-photon emission computed tomography was conducted in patients with type 2 diabetes mellitus and their prognoses will be followed for 3 years, stratified by patients’ clinical background and SPECT findings. Results A total of 513 patients from 50 institutions were enrolled in this study, 297 of whom were men (age 66.2 ± 0.4 years, mean ± SEM) and 261 women (age 67.8 ± 0.5 years). They have a history of retinopathy (25.3%), neuropathy (19.9%), cerebrovascular disorder, chronic obstructive pulmonary disease, and photocoagulation. Major risk factors for present disease were hypertension (82.3%) and hyperlipidemia (79.7%). In 244 patients (129 men and 115 women), body mass index (BMI) was 25 or more. Fifty-two of them (10.1%) underwent coronary angiography; of these, 26 (50.0%) had no coronary artery lesions with 75% or more stenosis, and only 1 (1.9%) had a left main trunk with 50% or more stenosis. An overwhelming majority of patients (94.3%) underwent SPECT imaging by a 1-day stress-followed-by-rest procedure. Stress procedure was exercise in most (70.8%) patients, followed by dipyridamole infusion in 14.6%, adenosine infusion in 6.6%, and adenosine triphosphate infusion in 5.7%. Endpoint of stress examination was most often fatigue in lower limbs (40.7%), followed by completion of pharmacological stress protocol (28.7%), and achievement of target heart rate (26.3%). The largest number of patients (198, 38.6%) received ^99mTc-tetrofosmin at an initial dosage of 200–300 MBq (mean 331 ± 3 MBq) followed by a second dosage of 700–800 MBq (mean 748 ± 8 MBq). Among them, 491 (95.7%) received some kind of therapeutic drug: hypoglycemic drugs were used by the largest number (83.2%), followed by hypotensive (66.7%), hypolipidemic (40.7%), and antiplatelet drugs (27.7%), vasodilators (5.5%), and antioxidants and others (2.3%). Conclusions This study was designed to clarify the correlation between coronary artery disease and diabetes mellitus as its risk factor based on the clinical and imaging findings. Patient enrollment was closed on September 30, 2005, and follow-up is now under way.     

Development of laminar organization of the fetal cerebrum at 3.0T and 7.0T: a postmortem MRI study

Introduction  

The purpose of this study is to show the condition of laminar organization on 3.0T and 7.0T postmortem magnetic resonance imaging (MRI) and analyze developmental changes.     

Evaluation of a decision support system for interpretation of myocardial perfusion gated SPECT

PURPOSE: We have recently presented a decision support system for interpreting myocardial perfusion scintigraphy (MPS). In this study, we wanted to evaluate the system in a separate hospital from where it was trained and to compare it with a quantification software package. METHODS: A completely automated method based on neural networks was trained for the interpretation of MPS regarding myocardial ischaemia and infarction using 418 MPS from one hospital. Features from each examination describing rest and stress perfusion, regional and global function were used as inputs to different neural networks. After the training session, the system was evaluated using 532 MPS from another hospital. The test images were also processed with the quantification software package Emory Cardiac Toolbox (ECTb). The images were interpreted by experienced clinicians at both the training and the test hospital, regarding the presence or absence of myocardial ischaemia and/or infarction and these interpretations were used as gold standard. RESULTS: The neural network showed a sensitivity of 90% and a specificity of 85% for myocardial ischaemia. The specificity for the ECTb was 46% (p < 0.001), measured at the same sensitivity. The neural network sensitivity for myocardial infarction was 89% and the specificity 96%. The corresponding specificity for the ECTb was 54% (p < 0.001). CONCLUSION: A decision support system based on neural networks presents interpretations more similar to experienced clinicians compared to a conventional automated quantification software package. This study shows the feasibility of disseminating the expertise of experienced clinicians to less experienced physicians by the use of neural networks.