Three-dimensional reversed fast imaging with steady-state precession diffusion-weighted imaging for the detection of middle ear cholesteatoma.

AIM: To determine the usefulness of three-dimensional reversed fast imaging with steady-state precession diffusion-weighted imaging (3D-PSIF DWI) for the detection of middle ear cholesteatoma. MATERIALS AND METHODS: The study population consisted of 81 patients who underwent 3D-PSIF-DWI at 3 T. They included cholesteatoma in 73 cases, otitis media in five, and cholesterol granuloma in three. Two observers independently performed qualitative evaluations for the detection of cholesteatoma and measured apparent diffusion coefficient (ADC) values and ADC ratios of the lesions. Kappa (κ) statistics, the intraclass correlation coefficient (ICC), the independent t-test, and receiver operating characteristic (ROC) analysis were used for statistical analysis. Pair-wise comparison of the ROC curves was performed using the area under the ROC curve (AUC). RESULTS: Interobserver agreement and ICC for the qualitative and quantitative evaluations were excellent (κ=0.92 and ICC=0.90-0.92, respectively). The ADC value and the ADC ratio were significantly lower for cholesteatoma than non-cholesteatoma lesions (p<0.0001). In <5 mm cholesteatoma group, the diagnostic performance of the ADC value (AUC=0.97) and the ADC ratio (AUC=1) was significantly superior to qualitative 3D-PSIF-DWI (AUC=0.76; p=0.0001 and <0.0001, respectively). For ≥5 mm cholesteatoma group, there were no significant differences in diagnostic performance among the three parameters. CONCLUSION: 3D-PSIF-DWI sequence is useful for the detection of middle ear cholesteatomas, especially <5 mm lesions.

Topical erythritol combined with L-ascorbyl-2-phosphate inhibits staphylococcal growth and alleviates staphylococcal overgrowth in skin lesions of canine superficial pyoderma.

Erythritol (ERT) and L-ascorbyl-2-phosphate (APS) are bacteriostatic, but their effects on staphylococcal skin infections remain unknown. We aimed to determine whether ERT combined with APS inhibits the growth of staphylococci that are commonly isolated from pyoderma skin lesions in dogs. We investigated the individual and combined effects of ERT and APS on the growth of Staphylococcus pseudintermedius, S. schleiferi, and S. aureus using turbidity assays in vitro. Skin lesions from 10 dogs with superficial pyoderma were topically treated with 5% ERT and 0.1% APS for 28 days, and swabbed skin samples were then analyzed using 16S rRNA amplicon sequencing and quantitative real-time PCR (qPCR). Results showed that ERT inhibited S. pseudintermedius growth regardless of harboring the mecA gene, and APS increased the inhibitory effects of ERT against S. pseudintermedius, S. schleiferi, and S. aureus in vitro. Moreover, combined ERT and APS decreased the prevalence of staphylococci on canine skin lesions at the genus level. The combination slightly increased the α-diversity but did not affect the ß-diversity of the microbiota. The qPCR results revealed that the combination significantly decreased S. pseudintermedius and S. schleiferi in skin lesions. Topical administration of EPS combined with APS can prevent staphylococcal colonization on the surface of mammalian skin. The results of this study may provide an alternative to systemic antibiotics for treating superficial pyoderma on mammalian skin surfaces.

[Thoracic surgery in patients with autoimmune diseases].

Autoimmune diseases arise from an inappropriate immune response against substances and tissues normally present in the body. Although the pathogenesis are still unclear, several autoimmune diseases, such as dermatomyositis, systemic sclerosis, have a higher incidence of thoracic neoplasm. Also in the mediastinum several autoimmune diseases are known to associate thymoma. While the manifestations of the disease diverse, administration of immunosuppressant are commonly used for the management of aberrant immune response. Immunosuppressive therapies likely to increase susceptibility to infections and associate other side-effects, which could increase the risk of surgery and complicate the perioperative management. In this article we discuss the autoimmune diseases which are known to associate with thoracic and mediastinal neoplasms, and the perioperative management of thoracic surgery in patients with autoimmune diseases.

The bacteriostatic effect of erythritol on canine periodontal disease-related bacteria.

Erythritol helps both prevent and improve periodontal disease and is therefore widely used for dental care in humans. However, only a few studies have investigated the effects of erythritol on periodontal disease in animals. We hypothesized that erythritol could be used to prevent and improve periodontal disease also in canines and investigated the effects of erythritol on canine periodontal disease-related pathogenic bacteria using both in vitro and in vivo methods. The effect of erythritol on the proliferation of Porphyromonas gulae, which is reportedly associated with canine periodontal disease, was investigated in vitro. In addition, a 4-week intervention trial using an external gel preparation containing 5% erythritol was performed in canines with mild periodontal disease; changes in the microbiota around periodontal lesions were investigated using next-generation sequencing and bioinformatics analysis. The growth of P. gulae was significantly suppressed by erythritol in vitro. In the intervention study, the Shannon index, an indicator of the species distribution α-diversity, and the occupancy of several canine periodontal disease - related bacteria ( P. gulae, P. cangingivalis) were significantly decreased in periodontal lesions. Based on the results of in vitro and in vivo studies, we conclude that, as in humans, erythritol has bacteriostatic effects against periodontal disease - related bacteria in canines.

Reduced heart rate variability predicts poor sleep quality in a case-control study of chronic fatigue syndrome.

Parasympathetic function is important in the induction and maintenance of sleep. We examined whether nocturnal vagal modulation of heart rate is related to the poor sleep quality commonly reported in chronic fatigue syndrome (CFS). Heart rate (HR, as R-R intervals) was continuously monitored during sleep in 20 patients with CFS and 20 matched control subjects. Questionnaires assessed demographic information, symptoms, functional impairment, and subjective sleep quality. CFS was associated with more sleep problems in general and poorer subjective sleep quality on the study night (all p < 0.003), and reports of repeated awakening during the night were 7 times more likely compared to healthy subjects (p = 0.017). Time and frequency-domain parameters of HR variability during sleep were significantly lower in patients with CFS (all p < 0.006). Multiple regression analyses revealed that heart rate variability (HRV) parameters were the best predictors of subjective sleep measures. This study identified significant reductions in vagal modulation of heart rate during sleep in CFS. Low HRV strongly predicted sleep quality-suggesting a pervasive state of nocturnal sympathetic hypervigilance in CFS.

[Outcomes of bronchoplasty procedures for lung cancer].

A sleeve lobectomy is an established general thoracic surgical procedure. To improve clinical outcomes following the procedure, we reviewed the records of 60 patients who underwent a bronchoplasty procedure in our department from 1992 to 2007. Induction chemotherapy was performed for 20, of whom 10 underwent radiotherapy as well. For all subjects, the postoperative mortality and morbidity rates were 1.7% and 33.3%, respectively. Induction therapy did not significantly affect those rates, though complications related to bronchial anastomoses occurred exclusively in subjects who received that therapy. The overall 5-year survival rate was 51.0%, while subjects with pN0 (67.9%) and pN1 (60.0%) disease, and those in stage I (79.1%) and stage II (59.9%) had better survival as compared with patients with pN2 (16.9%) disease, and those in stage III (21.8%) and stage IV (0%). Furthermore, the survival rate of yp-stage I and II patients was significantly greater than that of those in yp-stage III and IV (59.9% vs. 14.3%, p = 0.0158). We concluded that patients in stages I, II or with pN0-1 disease are good candidates for a bronchoplasty procedure, though induction therapy should be considered thereafter. In addition, due diligence for postoperative complications is necessary.

Clinical and functional significance of WHO classification on human thymic epithelial neoplasms: a study of 146 consecutive tumors.

We examined the clinical and functional significance of histologic classification of thymic epithelial neoplasms proposed by the World Health Organization (WHO), based on an analysis of 146 consecutive tumors derived from 141 patients and 47 normal thymuses derived from children ranging in age from 1 to 9 years. Invasive tumors were seen in 12.5%, 38.6%, 40.0%, 69.4%, 80.0%, and 100% of type A, AB, B1, B2, B3, and C primary tumors, respectively. All of six recurrent or metastatic lesions were type B2 tumors. Myasthenia gravis was associated in 0%, 6.8%, 40.0%, 55.6%, 10.0%, and 0% in patients with type A, AB, B1, B2, B3, and C tumors, respectively. The average number (x10(6)) of tumor-associated CD4+CD8+ cells present in 1 g of tumor tissue was 1.5, 391.1, 1041.7, 333.9, 24.5, and 0.2 in type A, AB, B1, B2, B3, and C, respectively, and it was 1168.2 in the normal thymuses. Thus, type B1 tumor retained the function to induce CD4+CD8+ double-positive cells at a level comparable to that of the normal thymic cortical epithelial cells, followed by type AB and type B2 tumors. Type A and B3 tumors had this function at a barely detectable level, and type C tumor was nonfunctional. WHO histologic classification was shown to reflect the clinical features and the T-cell-inducing function of thymic epithelial tumors.

A newly identified membrane protein localized exclusively in intracellular organelles of neurons.

We report here cloning of the cDNA of a novel membrane protein, termed p24, which, of the eight mouse tissues tested, was found only in brain where it is localized exclusively in neurons. The cDNA encodes 196 amino acids with a molecular weight of approximately 24000. P24 contains two putative membrane spanning domains and a sequence in the hydrophilic tail homologous to the microtubule-binding domain of microtubule-associated proteins, such as TAU and MAP-2. We prepared antibodies to p24 and demonstrated that the protein is rich in nerve fibers of the cerebral cortex, anterior cerebral nuclei and hypothalamus. When neuroblastoma Neuro 2a cells were treated with retinoic acid to induce differentiation, p24 mRNA increased but the p24 protein was not detected. The protein expressed from the p24 cDNA in non-neuronal Cos-7 cells was 24 kDa in size and were localized only in lysosomes. These findings indicate that p24 is a neuron-specific membrane protein localized in intracellular organelles of highly differentiated neural cells and suggest that it may play a role in the neural organelle transport system.

Observations on the blood and perineurial permeability barriers of surviving nerve allografts in immunodeficient and immunosuppressed rats.

The authors investigate whether there are any permeability changes in the endoneurial blood-nerve barrier and the perineurium-nerve barrier of surviving nerve allografts. In a normal nerve, the blood-nerve barrier regulates the passage of substances from endoneurial blood vessels into the endoneurium, whereas the perineurium-nerve barrier protects the endoneurium from agents that escape from permeable epineurial vessels and accumulate around the nerve. Nerves from ACI rats were transplanted into immunologically deficient nude rats or normal Fischer rats immunosuppressed with cyclosporin A. None of the nerve allografts was rejected. The blood-nerve barrier of nerve allografts at 2 and 6 weeks postoperatively was permeable to intravenously injected horseradish peroxidase, which spread into endoneurial tissue. Electron microscopy revealed that horseradish peroxidase escaped from endoneurial vessels through intercellular junctions between endothelial cells. At 24 weeks, the blood-nerve barrier of nerve allografts had recovered and the endoneurial vessels, like those in normal nerves, were impermeable to horseradish peroxidase. The perineurium-nerve barrier of nerve allografts remained impermeable to horseradish peroxidase at all times. Axons were grouped into numerous minifascicles at nerve anastomosis zones at 24 weeks. Each nerve fascicle was surrounded by an impermeable perineurium. These results demonstrate that regenerated axons in long-term surviving nerve allografts and at anastomosis zones are protected by permeability barriers. It is concluded that permeability barriers of nerve allografts are not permanently altered by a foreign environment (grafts to nude rats) even when immunosuppression with cyclosporin A is required to prevent allograft rejection (grafts to Fischer rats).

Melanotic neuroectodermal tumor of infancy: a molecular approach to diagnosis. Case report.

A case of melanotic neuroectodermal tumor of infancy arising from the transverse sinus is presented. The tumor was located on the outer surface of the dura and extended extracranially through the occipitomastoid suture. Two cell populations were observed: pigmented melanocyte-like cells and small neuroblast-like cells. Ultrastructural analysis revealed epithelial tumor cells and melanosomes at various stages. Expression of melanotransferrin messenger RNA transcripts within the tumor tissue was observed using a reverse transcriptase-polymerase chain reaction method in addition to immunohistological studies. The positive expression of melanotransferrin confirmed that this melanotic neuroectodermal tumor was derived from neural crest cells.

Induction of peripheral-type benzodiazepine receptors in mouse brain following thioacetamide-induced acute liver failure.

To investigate the possible role of peripheral-type benzodiazepine receptors (PBR) in hepatic encephalopathy, we examined expression of PBR in mouse brain following thioacetamide (TAA)-induced acute liver failure. Treatment of mice with TAA resulted in an increase in the number of binding sites of the PBR ligand [3H] Ro5-4864 to brain homogenates, with no significant change in affinity of the ligand. The order of potency of different ligands to compete against [3H] Ro5-4864 binding in the brain of TAA-treated mice was Ro5-4864 > PK11195 > diazepam > protoporphyrin IX, findings similar to those in the control. Northern blot analysis revealed an increase in PBR/isoquinoline binding protein (PBR/IBP) mRNA in mouse brain following TAA treatment, in a time- and dose-dependent manner. These results indicate that the increased number of PBR in the brains of TAA-treated mice relates to the induction of PBR/IBP expression and suggest that the induction of PBR in brain may contribute to pathogenesis of hepatic encephalopathy.

Quantitative evaluation of the effects of thyroarytenoid muscle activity upon pliability of vocal fold mucosa in an in vivo canine model.

Stiffness of the vocal fold is a significant factor in determining mucosal wave propagation and in the control of the fundamental frequency of phonation. We measured pliability of the vocal fold mucosa in an in vivo canine model as an index of stiffness while the histological layer-by-layer structure of the vocal fold was not disrupted. The point 1 mm below the free edge showed a maximal pliability that gradually diminished toward the tracheal side and reached a minimum. When the thyroarytenoid (TA) muscle contracted, pliability of the mucosa was significantly increased (P < 0.001). Mucosal pliability of the excised larynx was significantly increased compared with that in vivo (P < 0.001). The point of minimal pliability in the absence of TA muscle contraction did not shift after excision of the larynx, while TA muscle contraction caused a downward shift of the point of minimal pliability. Mucosal pliability can thus be used to quantitatively assess the effects of TA muscle contraction on stiffness of the vocal fold mucosa.

Pliability of the vocal fold mucosa in relation to the mucosal upheaval during phonation.

OBJECTIVES: To quantitatively evaluate the effect of vocal fold lengthening on pliability of the mucosa measured along the superior-inferior axis and to examine the relation of the location of mucosal upheaval (MU) during phonation to the changes in pliability pattern of the mucosa when the vocal fold was lengthened. DESIGN: Investigation of mechanical characteristics of the vocal fold in relation to the MU during phonation. MATERIALS: Five excised canine larynges. INTERVENTIONS: Vibrations with and without vocal fold lengthening were recorded from the tracheal side via high-speed photography or video recording combined with stroboscopic illumination. Tattooed marks on the lower surface of the vocal fold were used to locate the MU. Pliability was defined as the maximal distance elevated in response to a constant focal negative pressure. RESULTS: Pliability decreased significantly (P=.05) when the vocal fold was lengthened. The point of minimal pliability and MU without vocal fold lengthening were located slightly above the area where the muscular layer approached the epithelial layer. They were located closer to the free edge of the vocal fold when it was lengthened than when it was not. Discrepancy of their locations when the vocal fold was lengthened was suggested. CONCLUSIONS: The MU occurs around the point of minimal pliability when the vocal fold is not lengthened, whereas the MU occurs slightly more laterally than the point of minimal pliability when the vocal fold is lengthened. Although further study is necessary to explain this discrepancy, the presence of the sparse deep layer of the lamina propria seems to be essential in the generation of the mucosal wave.

Tracheal view of vocal fold vibration in excised canine larynxes.

The mucosal upheaval where the mucosal wave starts and propagates upward appears on the lower surface of the vocal fold during vibration. We investigated the location of the mucosal upheaval in response to variations in vocal fold tension and mean air flow rate. Twelve excised canine larynxes were used in the experiment. The lower surfaces of the vocal folds were marked with india ink. After cinematography was performed, a small cut wound was made at the mark. This wound served to relate cinematographic findings with the histologically observed position of the mark. The larynx was then fixed, sectioned in the frontal plane, and stained for histologic examination. Horizontal movements of the free edge, mucosal wave, mucosal upheaval, and marks were analyzed. Under a fixed vocal fold tension, the mucosal upheaval appeared more laterally to a limited extent as mean air flow rate increased, but its location on the vocal fold mucosa did not change from its position before the increase of mean air flow rate. The mucosal upheaval appeared more medially when vocal fold tension increased. The position of the mucosal upheaval actually changed medially compared with its original position before the tension increase. Histologic examination indicated that the mucosal upheaval arose on the lower surface of the vocal fold between the free edge and the area where the muscular layer comes in close proximity to the epithelial layer.

Thyroarytenoid muscle activity and infraglottic aspect of canine vocal fold vibration.

OBJECTIVES: To investigate the effect of contraction of the thyroarytenoid (TA) muscle on the location of the mucosal upheaval (MU) and to estimate the location of the MU in relation to the histologic structure of the vocal fold. BACKGROUND: The MU is a small mucosal ridge arising on the lower surface of the vocal fold during phonation and is thought to be the lower border of the vibrating structure. METHODS: Vibrations were elicited under three conditions: during bilateral TA muscle contraction, without TA muscle stimulation, and during vocal fold lengthening. The vibrations were recorded from the tracheal side by high-speed cinematography or videotape recording combined with stroboscopic illumination. The larynx was prepared for histologic observation in the frontal plane. Tattooed marks on the lower surface of the vocal fold were used to locate macroscopically observed landmarks with reference to microscopic structures. RESULTS: The MU shifted laterally toward the tracheal side during TA muscle contraction. When the vocal fold was lengthened, the MU shifted medially toward the free edge. Histologic examination showed that the MU in the absence of TA muscle contraction arose slightly above the area where the muscular layer approached the epithelial layer. CONCLUSION: When the TA muscle contracts, the vibrating area expands toward the tracheal side, and a more dynamic mucosal wave occurs in the vertical direction. We believe that a part of the body and the cover are probably involved in the vibratory movement of the vocal fold.

T-cell development in human thymoma.

Human thymoma is derived from thymic epithelial cells and often associated with a large number of cortical thymocytes. Since thymic epithelial cells play key roles in T-cell development in the normal thymus, we hypothesized that the neoplastic epithelial cells of thymoma may support T-cell differentiation. We attempted to reconstitute the T-cell development in vitro by using neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on a proportion of CD4-CD8- cells in thymoma. These CD34+CD4-CD8- cells also expressed both IL-7R alpha-chain and common gamma-chain. Purified CD4-CD8- cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. The CD34+CD4-CD8- cells purified from a normal thymus also differentiated to CD4+CD8+ cells in an allogeneic co-culture with the neoplastic epithelial cells of thymoma. In addition, a pleural dissemination from thymoma contained a large amount of cortical thymocytes. These results suggest that the neoplastic epithelial cells retain the function of thymic epithelium and can support T-cell development in thymomas.

Vocal fold vibration viewed from the tracheal side in living human beings.

The mucosal upheaval where the mucosal wave starts and propagates upward appears on the lower surface of the canine vocal fold during vibration. We investigated the vibratory behavior of the in vivo human vocal fold viewed from the tracheal side. Subjects consisted of 14 men and 6 women who had undergone tracheostomy for various head and neck diseases; their ages ranged from 22 to 70 years, with a mean of 53.9 years. The inferior aspect of the vocal fold during phonation was observed with the aid of a rigid oblique-view endoscope inserted through a tracheostoma (inferior glottoscopy). Each subject was asked to sustain the vowel /a/ at a comfortable pitch and loudness (easy phonation) and then at a higher pitch. Inferior glottoscopy could be performed during easy phonation in 19 subjects and during high-pitched phonation in 10 subjects. During easy phonation, the mucosal upheaval appeared on the lower surface of the vocal fold between the anterior commissure and the vocal process in all 19 subjects. During high-pitched phonation, the vocal fold became longer, and the subglottic vault surrounded by the bilateral mucosal upheavals became narrower compared with those during easy phonation. Use of a dilated blood vessel as a landmark in one subject showed the location of the mucosal upheaval on the vocal fold mucosa to actually shift medially toward the oral side during high-pitched phonation. Despite structural differences between the human and canine vocal folds, the infraglottic aspect of the vocal fold vibration observed in the living human larynx was quite similar to that observed in the excised canine larynx.

Skull base reconstruction in cases of intracranial teratoma extending into the extracranial structures.

Recently experienced were two cases of postnatally diagnosed intracranial teratoma, one a mature teratoma and the other an immature teratoma, both extending into the extracranial structures. In each case, tumor resection was performed in which a barrier was created between the intracranial and extracranial spaces with a temporalis muscle flap. The technical aspect of skull base reconstruction is described, and previously reported cases of intracranial teratoma involving the skull base are reviewed.

Quantitative measurement of mucosal wave by high-speed photography in excised larynges.

The movement characteristics of mucosal waves of the vocal fold are important components in normal phonation. Quantitative studies of the mucosal wave have used stroboscopic techniques from a supraglottic view. The current study measured displacement of mucosal epithelium during experimental phonation by using high-speed photography from an infraglottic view. Effects of thyroarytenoid contraction, increased mean airflow rate, and variation of vocal fold length were examined in canine larynges. Top and bottom vocal fold "lip" amplitude, fundamental frequency, and phase difference were the dependent variables examined. Thyroarytenoid contraction increased the amplitude of the top and bottom lips, decreased the fundamental frequency, and increased the phase difference. Increase in airflow through the glottis decreased the top lip amplitude and phase difference and appeared to increase the fundamental frequency and to decrease the bottom lip amplitude. Vocal fold lengthening decreased the bottom lip amplitude and increased the fundamental frequency and appeared to decrease the top lip amplitude and phase difference.

Infraglottic aspect of canine vocal fold vibration: effect of increase of mean airflow rate and lengthening of vocal fold.

The mucosal upheaval (MU), where the mucosal wave starts and propagates upward, appears only when the vocal fold vibrates. The location of the MU histologically and the effect of changes in mean air flow rate (MFR) and vocal fold length on occurrence of the MU were studied in twelve excised canine larynges. The lower surface of the vocal fold was marked to serve as a landmark for subsequent study. Cricothyroid approximation was performed to lengthen the vocal fold. After taking high-speed pictures or recording stroboscopic images from the tracheal side, a small cut wound was made at the mark. This wound served to compare the position of the MU with the histologically identified location of the mark. The larynx was then sectioned in the frontal plane. Before lengthening the vocal fold, the MU occurred on the area where the lamina propria became thinner and where the muscular layer neared the epithelial layer. After lengthening the vocal fold, the MU actually shifted medially compared with its original position. The subglottic area surrounded by the bilateral MUs became longer and thinner. Whether or not complete glottal closure during a vibratory cycle was achieved did not alter these findings. In contrast, with a fixed vocal fold length the MU appeared more laterally as MFR increased, but, based on the relation with the mark, its location on the vocal fold did not change from its original position before increase of MFR.