Diagnosis of nasopharyngeal carcinoma metastatic to mediastinal lymph nodes by endoscopic ultrasonography-guided fine-needle aspiration biopsy

We report the case of a patient with nasopharyngeal carcinoma who was diagnosed as having metastasis in mediastinal lymph nodes and successfully underwent systemic chemotherapy without surgery. A 61-year-old male with a history of nasopharyngeal carcinoma presented with odynophagia. Examination revealed two palpable lymph nodes in the right neck. Pharyngoscopy showed a mass in the left inferior pharyngeal mucosa, and upper gastrointestinal endoscopy showed only chronic gastritis, with no sign of esophageal disease. Chest CT confirmed the presence of a non-enhancing 20-mm soft tissue mass in the paraesophageal area, with increased attenuation compared with the adjacent esophagus. To evaluate this lesion we applied endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA). Two passes were made with a 21-gauge fine needle and the patient tolerated the procedure well, without complications. Cytological findings were compatible with metastatic squamous cell carcinoma from a nasopharyngeal tumor, and the clinical stage was determined as T3N2bM1 (stage IVC) because of mediastinal lymph node metastasis. We thus determined the nodal status of a head and neck tumor by means of EUS-FNA. In conclusion, EUS-FNA is a safe and reliable technique for evaluation of mediastinal lymphadenopathy, and is especially valuable for head and neck tumors with suspected metastasis.     

Voice restoration by primary insertion of indwelling voice prosthesis following circumferential pharyngolaryngectomy with free jejunal graft

BACKGROUND: Voice restoration after circumferential pharyngolaryngectomy (CPL) with free jejunal graft remains a difficult problem to solve. Few reports have analyzed the success rate and complications following primary insertion of indwelling voice prostheses during CPL with free jejunal graft. PATIENTS AND METHODS: Eight patients who underwent CPL with free jejunal graft had a Groningen voice prosthesis inserted as a tracheoesophageal (TE) shunt at the time of oncological surgery. A 10-point scale was used to assess each patient's speech intelligibility. Complications following the voice prosthesis insertion were also analyzed. RESULTS: Six of the eight patients (75%) achieved excellent speech intelligibility and the remaining two patients (25%) were judged as moderate. Six of the eight patients (75%) used the TE shunt as their major means of daily communication. Leakage through or around the prosthesis, which occurred in six (75%) patients, was the most frequent prosthesis-related complication. CONCLUSIONS: This safe and reliable technique can be effective in improving the quality of life in selected patients undergoing CPL.     

Side-to-side linking of myocardial cells in hypertrophic cardiomyopathy: whole heart microscopic observation with tangential sections

By cross-section or longitudinal section, it is difficult to investigate longitudinal features of myocardial cells in the whole heart. Here, introducing the use of tangential sections to obtain longitudinal aspect of myocardial cells in any part of myocardium, the authors evaluated myocardium in the left ventricle in 10 normal hearts and four hearts with hypertrophic cardiomyopathy (HCM). Tangential sections were obtained by peeling the superficial layer of myocardium. After peeling the whole surface, secondary deep layer was peeled. These procedures were repeated more than five times through the wall. Intercalated discs (ICD) were observed immunohistochemically with anti-N-cadherin and antidesmoplakin. In normal hearts, myocardial cells were cut longitudinally and ran parallel in tangential sections. They linked end-to-end with simple and regular ICD with average lengths of 120-130 microm and average sarcomere numbers of 56-65. In HCM hearts, many myocardial cells were cut almost longitudinally running approximately parallel in tangential sections. Myocardial cells frequently showed side-to-side linking characterized by skewed ICD, indistinct ICD counterparts, and longitudinally arranged ICD. Two young HCM hearts had circle-shaped ICD and vacuole-like structures highlighted by immunostaining for N-cadherin, which were actually extracellular structures comparable with irregular side-to-side linking. It is considered that side-to-side linking of myocardial cells is a characteristic microscopic feature in HCM rather than myocardial disarray.     

Uroplakin III is not a major candidate gene for primary vesicoureteral reflux

Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the ureter and towards the kidneys. VUR is the most common cause of end stage renal failure in both children and adults and it is a major cause of severe hypertension in children. VUR is seen in approximately 1-2% of newborn Caucasians. Substantial evidence exists that VUR is a genetic disorder. Uroplakins are integral membrane proteins found in the bladder wall. Knockout studies in mice have suggested uroplakin III (UPK3) as a candidate gene for VUR. We have used parametric and nonparametric linkage analysis and tests for association, to investigate this possibility in a cohort of 126 sibling pairs affected with primary VUR. None of the analyses showed any substantial evidence for linkage or association of markers at the UPK3 locus to VUR. Our results do not support a role for UPK3 in primary VUR.     

Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex

Gamma-aminobutyric acid (GABA)ergic neurons in the neocortex have been mainly regarded as interneurons and thought to provide local interactions. Recently, however, glutamate decarboxylase (GAD) immunocytochemistry combined with retrograde labeling experiments revealed the existence of GABAergic projection neurons in the neocortex. We further studied the network of GABAergic projection neurons in the neocortex by using GAD67-green fluorescent protein (GFP) knock-in mice for retrograde labeling and a novel neocortical GABAergic neuron labeling method for axon tracing. Many GFP-positive neurons were retrogradely labeled after Fast Blue injection into the primary somatosensory, motor and visual cortices. These neurons were labeled not only around the injection site, but also at a long distance from the injection site. Of the retrogradely labeled GABAergic neurons remote from the injection sites, the vast majority (91%) exhibited somatostatin immunoreactivity, and were preferentially distributed in layer II, layer VI and in the white matter. In addition, most of GABAergic projection neurons were positive for neuropeptide Y (82%) and neuronal nitric oxide synthase (71%). We confirmed the long-range projections by tracing GFP-labeled GABAergic neurons with axon branches traveled rostro-caudally and medio-laterally. Axon branches could be traced up to 2 mm. Some (n = 2 of 4) were shown to cross the areal boundaries. The GABAergic projection neurons preferentially received neocortical inputs. From these results, we conclude that GABAergic projection neurons are distributed throughout the neocortex and are part of a corticocortical network.     

Bi-directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity

Abstract Cortactin is an F-actin-associated protein which interacts with the postsynaptic scaffolding protein Shank at the SH3 domain and is localized within the dendritic spine in the mouse neuron. Green fluorescent protein (GFP)-based time-lapse imaging revealed cortactin redistribution from dendritic cytoplasm to postsynaptic sites by application of brain-derived neurotrophic factor (BDNF). This response was mediated by mitogen-activated protein (MAP) kinase activation and was dependent on the C-terminal SH3 domain. In contrast, activation of N-methyl-D-aspartate (NMDA) receptors induced loss of cortactin from postsynaptic sites. This NMDA-dependent redistribution was blocked by an Src family kinase inhibitor. Conversely, increasing Src family kinase activity induced cortactin phosphorylation and loss of cortactin from the postsynaptic sites. Finally, blocking of endogenous BDNF reduced the amount of cortactin at the postsynaptic sites and an NMDA receptor antagonist prevented this reduction. These results indicate the importance of counterbalance between BDNF and NMDA receptor-mediated signalling in the reorganization of the postsynaptic actin cytoskeleton during neuronal development.     

An open trial of outpatient group therapy for bulimic disorders: combination program of cognitive behavioral therapy with assertive training and self-esteem enhancement

The purposes of this study were to examine the therapeutic efficacy of combined group cognitive behavioral therapy (CGCBT) and to explore the characteristics of the patients who failed to complete it. Our group cognitive behavioral therapy combined with assertiveness training for alexithymia and self-esteem enhancement therapy were attended over a 10-week period. Twenty-five participants were enrolled in the study. The clinical symptoms were assessed before and after treatment, using rating scales including the Eating Disorder Inventory-2, the Bulimic Investigatory Test, Edinburgh, the Toronto Alexithymia Scale, the Rosenberg Self-Esteem Scale, and Global Assessment of Functioning. Sixteen participants (64%) completed the CGCBT program. Completion of the CGCBT resulted in significant improvements in reducing binge-eating behavior and improving social functioning. Eight patients (32%) significantly improved using the Clinical Global Impression Change (CGI-C). Stepwise logistic regression analysis of the results indicated that a lower age (P=0.04) and psychiatric comorbidity (P=0.06) were predictors of dropout from the CGCBT program. Our CGCBT program is a promising first-line treatment for bulimic outpatients. Lower age and the presence of comorbidity had effects on dropout rates.     

Linkage disequilibrium in aquaporin 4 gene and association study with schizophrenia

Aquaporin 4 (AQP4) has an important role in water homeostasis of human brain and a dysfunction of AQP4 could induce pathological conditions in neuronal activity. Several genome scan studies for schizophrenia found a suggestive linkage on 18q, where human AQP4 (18q11.2-12.1) is located nearby. A case-control study was performed which comprised 261 schizophrenia subjects and 278 controls from the Japanese population with four SNP markers. We found strong linkage disequilibrium (LD) and an LD block in the AQP4 gene but found no association between AQP4 and schizophrenia, both single SNP and haplotype analyses. The present study shows that AQP4 is not directly associated with schizophrenia in these Japanese patients.     

Association between abdominal wall fat index on ultrasonography and carotid atherosclerosis in non-obese men

We tried to investigate whether accumulation of visceral fat, assessed by a simple but widely used ultrasonographic method, was associated with common carotid atherosclerosis in non-obese men ranging from 16 to 79 years old. The subjects were consecutive 297 male in-patients whose body mass index ranged from 18.5 kg/m(2) to 25 kg/m(2). An ultrasonographic evaluation using a 7.5 MHz linear type B-mode probe was performed by a specialist to determine the intima-media thickness (IMT) of the common carotid artery and the maximal thickness of peritoneal fat (Pmax) at the anterior surface of the liver and the minimal thickness of subcutaneous fat (Smin) of the abdomen. The Pmax/Smin ratio, which was termed the abdominal wall fat index (AFI), was then calculated. The mean age +/- standard deviation in this series was 65 +/- 13 (range, 15-79) years. Multiple regression analysis using IMT as an objective variable, adjusted by various risk factors as explanatory variables, showed that AFI [beta, 0.0538; 95% confidence interval (CI), 0.0116-0.0960] was a significant independent contributing factor along with known risk factors such as age, smoking status, systolic blood pressure, HDL-cholesterol and LDL-cholesterol. We found that AFI was useful in evaluating disorders of metabolism and atherosclerosis in non-obese men.