Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A

Evidence that febrile seizures have a strong genetic predisposition has been well documented. In families of probands with multiple febrile convulsions, an autosomal dominant inheritance with reduced penetrance is suspected. Four candidate loci for febrile seizures have been suggested to date; FEB1 on 8q13-q21, FEB2 on 19p, FEB3 on 2q23-q24, and FEB4 on 5q14-15. A missense mutation was identified in the voltage-gated sodium (Na(+))-channel beta 1 subunit gene, SCN1B at chromosome 19p13.1 in generalized epilepsy with the febrile seizures plus type 1 (GEFS+1) family. Several missense mutations of the (Na(+))-channel alpha 1 subunit (Nav1.1) gene, SCN1A were also identified in GEFS+2 families at chromosome 2q23-q24.3. The aim of this report is precisely to describe the phenotypes of Japanese patients with novel SCN1A mutations and to reevaluate the entity of GEFS+. Four family members over three generations and one isolated (phenotypically sporadic) case with SCN1A mutations were clinically investigated. The common seizure type in these patients was febrile and afebrile generalized tonic-clonic seizures (FS+). In addition to FS+, partial epilepsy phenotypes were suspected in all affected family members and electroencephalographically confirmed in three patients of two families. GEFS+ is genetically and clinically heterogeneous, and associated with generalized epilepsy and partial epilepsy as well. The spectrum of GEFS+ should be expanded to include partial epilepsies and better to be termed autosomal dominant epilepsy with febrile seizures plus (ADEFS+).     

Long-term changes of hemodynamics and metabolism after carotid artery occlusion

OBJECTIVE: To investigate whether in selected patients with internal carotid artery (ICA) occlusion and initially normal oxygen extraction fraction (OEF) measured with PET, subsequent changes of cerebral hemodynamics and metabolism occur during long-term follow-up and, if so, whether the changes are associated with atrophy of the corpus callosum or subsequent ischemic strokes. BACKGROUND: The course of the changes in cerebral hemodynamics and metabolism after ICA occlusion remain unclear. After ICA occlusion, an increase in OEF may increase the risk of cerebral ischemia, and an increase in cortical ischemia would cause progression of callosal atrophy. METHODS: The authors used PET and MRI to examine twice seven medically treated patients with unilateral ICA occlusion and initially normal OEF at intervals ranging from 24 to 64 (mean +/- SD, 42 +/- 17) months. No intervening ischemic attacks occurred between the two examinations. RESULTS: In the hemisphere with ICA occlusion, OEF increased and blood flow decreased during follow-up. At the follow-up evaluation, abnormally increased OEF values were found in three patients, in whom ipsilateral ischemic strokes occurred during subsequent follow-up (18 +/- 6 months). A decrease in oxygen metabolism also occurred and was significantly correlated with the decrease of callosal size. CONCLUSIONS: These preliminary findings in a small, selected patient sample suggest that in patients with ICA occlusion and initially normal OEF, deteriorations of cerebral hemodynamics and metabolism during long-term follow-up may be associated with callosal atrophy or subsequent ischemic strokes.     

Left Diaphragmatic Hernia Complicated by Perforation of an Intrathoracic Gastric Ulcer into the Aorta: Report of a Case

(Received for publication on Apr. 6, 1998; accepted on May 27, 1999)     

Change in digital blood flow with simultaneous reduction in plasma endothelin induced by hand-arm vibration

Involvement of endothelium-derived relaxing factor (EDRF) or endothelium-derived constricting factor (EDCF) has been proposed as the pathophysiologic mechanism of vibration-induced white finger (VWF). Recent evidence that endothelin is a potent vasoconstrictor peptide indicates that it may play a role in vasoregulation during vibration exposure through the local actions of EDRF or EDCF. Therefore, we examined the effects of grasping (50 N) and hand-arm vibration (50 m/s² rms, 120 Hz, x-axis) on digital blood flow (DBF) and on the level of plasma endothelin in seven healthy male office workers. Grasping decreased DBF without affecting endothelin, and vibration increased DBF with a simultaneous reduction in endothelin. The grasping-induced decrease in DBF seemed to be due to mechanical compression of the vessels. The negative correlation between DBF and endothelin during vibration exposure suggests that a reduction in release of endothelin from smooth muscle into the vessel cavity during vibration leads to vasodilatation, possibly attributable to the local axon reflex.     

Computerized intermittent scanning system for automated treatment in intensive care unit

Conclusion The computerized intermittent scanning system for intensive care unit has been described in detail. This system scans over eight patients consecutively, makes diagnosis, and performs automated treatment through the automatic injectiors. With the introduction of the scanning system with a mini-computer, the entire system cost approximately 100,000 dollars which, we believe, would encourage a widespread use of those based on the similar principle in the future.     

Effects of Epidural Saline Injection on Cerebrospinal Fluid Volume and Velocity Waveform: A Magnetic Resonance Imaging Study

Background: The phenomenon of epidural "top-up" (increased spread of local anesthetic due to epidural fluid injection) is explained partly by an epidural volume effect. This study was designed to investigate the change in cerebrospinal fluid (CSF) volume and velocity waveform induced by epidural saline injection.

Methods: (1) Lumbar epidural catheters were placed in 28 patients. Magnetic resonance images were obtained for measurements of lumbosacral CSF volume and velocity waveform. Saline was injected into the epidural space through the catheter to three groups of randomly assigned patients: 5-ml saline (n = 10), 10-ml saline (n = 9), and 15-ml saline (n = 9) groups. A repeat image series was performed after epidural injection to compare CSF volume and velocity waveform before and after epidural injection. (2) We also examined the time course of dural sac compression after epidural saline injection in a separate series. Seven axial images at disk levels from T11-T12 to L5-S1 were obtained before injection and 1, 3, 5, 10, 15, 20, 25, and 30 min after 10-ml saline injection to compare each dural area before and after injection.

Results: (1) Saline injected through the epidural catheter compressed the dural sac with variability of the extent of compression, resulting in a significantly decreased CSF volume in all patients (P [less than over equal to] 0.001). The mean reductions in CSF volume were 2.0 +/- 1.0 ml in the 5-ml group, 4.4 +/- 1.4 in the 10-ml group, and 7.2 +/- 2.6 in the 15-ml group. There were significant differences among the three groups (P < 0.05~0.001). After the saline injection, the synchronization between the CSF velocity waveform and the cardiac cycle disappeared in significantly more patients in the 10-ml group (7 of 9 patients) than in the other groups (P < 0.05). However, there was no significant relation between measures of CSF velocity waveform and dural area in any patient. (2) The maximum reduction of the sum of the total of seven disk areas occurred 5 min after epidural saline injection; thereafter, dural compression was gradually restored but did not return to the value before injection for 30 min.     

TRPM8 protein localization in trigeminal ganglion and taste papillae

TRPM8 is a TRP family cation channel which can be activated by cold stimuli or l-menthol. However, TRPM8 protein localization of nerve terminals in sensory organs remains unknown. Here we generated an antibody against TRPM8 and analyzed TRPM8 protein localization in trigeminal ganglia (TG) and in sensory nerve fibers in the tongue. TRPM8 immunoreactivity was detected in a subset of neurons with a small diameter in TG and in nerve fibers in the tongue. TRPM8-immunoreactive nerve fibers were rich in fungiform papillae, but sparse in foliate and circumvallate papillae. The TRPM8-immunoreactive nerve fibers reached the outer epithelial layer in each papilla, while no TRPM8-immunoreactive nerve fibers penetrated into taste buds. Double labeling analysis revealed that TRPM8 immunoreactivity was co-expressed with a part of TRPV1 or CGRP-immunoreactive neurons in TG. However, TRPM8 immunoreactivity was not observed in TRPV1- or CGRP-positive nerve fibers in fungiform, foliate, and circumvallate papillae. These results suggest that TRPM8 protein is present in sensory lingual nerve fibers mainly projected from TG and might work as cold and l-menthol receptors on tongue.     

Incremental benefits of FDG positron emission tomography over CT alone for the preoperative staging of ovarian cancer

OBJECTIVE: The purpose of this study was to determine whether the addition of positron emission tomography (PET) with the radiotracer FDG to cross-sectional imaging, such as CT, increases accuracy in the detection of tumor spread. SUBJECTS AND METHODS. Fifteen patients who were thought to have ovarian cancer on the basis of the results of physical examination, sonography findings, and level of serum cancer antigen 125 were enrolled over an 11-month period. After screening, patients underwent two imaging examinations-abdominopelvic CT and whole-body FDG PET- within 2 weeks before surgery. Also before surgery, staging accuracy was assessed separately using CT with or without FDG PET (which was based on modifications of the International Federation of Gynecology and Obstetrics [FIGO] criteria). The results of the histology and surgery findings were used to assess the accuracy of the scanning findings. RESULTS: Staging revealed stage III disease in seven patients (IIIC, n = 6; IIIB, n = 1), stage II in three (IIC, n = 2; IIB, n = 1), and stage I in five (IC, n = 3; IA, n = 2), according to the FIGO criteria. Although CT staging correlated with postoperative staging in eight (53%) of 15 patients, consensus evaluation of CT with FDG PET staging improved correlation with postoperative staging in 13 (87%) of 15 patients. CONCLUSION: The addition of FDG PET to CT increases accuracy in staging of ovarian cancer.     

Effects of metabolite correction for arterial input function on quantitative receptor images with 11C-flumazenil in clinical positron emission tomography studies

OBJECTIVE: To evaluate the effect of inputs estimated from different methods for metabolite correction on binding potential (BP) of C-flumazenil (FMZ). METHODS: Five healthy volunteers underwent C-FMZ positron emission tomography. Arterial blood was sampled to obtain plasma radioactivity and metabolite fraction, followed by estimation of input functions with several methods. Binding potential images for different input functions and that using the noninvasive graphic method were calculated. Images of standardized uptake value (SUV) with different acquisition times were also compared. RESULTS: Binding potential images calculated from arterial inputs were almost equivalent, and regional values were not significantly different irrespective of methods for metabolite correction as well as the noninvasive graphic plot method. Standardized uptake value images showed less contrast compared with quantitative BP images, and the regional values varied depending on scan time. Statistical parametric mapping analysis showed significant regional differences between BP and SUV images. CONCLUSION: Binding potential images were equivalent irrespective of calculation methods; however, SUV was not appropriate for quantitative evaluation.