Tracking of Prosaposin, a Saposin Precursor, in Rat Testis.

We tracked prosaposin (PSAP), a trophic factor, using an antibody specific to its proteolytic portion and an antibody to sortilin that traffics PSAP only to the lysosome. Immunostaining revealed that PSAP was distributed mainly on the basal side of seminiferous tubules, where many Sertoli cells and pachytene spermatocytes contained PSAP and its distribution differed depending on the stage of the spermatogenic cycle. The PSAP-sortilin complex was sorted to large lysosomes in the basal cytoplasm of Sertoli cells, where it may be processed into saposins. In contrast, in the thinner apical cytoplasm of Sertoli cells, PSAP in small lysosomes was transported to the apical side around sperm heads or into the lumen for secretion. The results of in situ hybridization analyses suggested that immature tubular cells in young animals produce PSAP to self-stimulate proliferation. However, in adults, not only Sertoli cells but also pachytene spermatocytes produce and secrete PSAP around germ cells or into the tubular lumen to stimulate cell proliferation or differentiation in a paracrine or autocrine manner. In summary, PSAP is not only a precursor of lysosomal enzymes but also a pivotal trophic factor in organogenesis in the immature testis and spermatogenesis in the mature testis.

Comparison of the Signal Intensity of Vestibular Schwannoma Between Growing and Nongrowing Tumors.

OBJECTIVES/HYPOTHESIS: To determine the relationship between signal intensity on gadolinium (Gd)-enhanced magnetic resonance images and growth of vestibular schwannomas (VSs). STUDY DESIGN: Cross-sectional study. METHODS: In this cross-sectional study, we retrospectively reviewed the data of 31 patients with VSs who underwent magnetic resonance imaging (MRI). The mean signal intensities within the regions of interest in the tumor, pons, and temporal muscles were measured on Gd-enhanced T1-weighted MRI. Relative intensity ratios were calculated as follows: T/N pons ratio (T/Np) is the tumor signal intensity/pons signal intensity and T/N muscle ratio (T/Nm) is the tumor signal intensity/temporal muscle signal intensity. Volume measurements were used to assess the tumor size. Growth rate was determined by assessing previous imaging studies. Growing VS was defined as a tumor with a growth rate >100 mm3 /year. RESULTS: The mean (standard deviation) T/Np and T/Nm were 1.47 (0.27) and 1.50 (0.24), respectively, in nongrowing tumors and 1.78 (0.17) and 1.90 (0.12), respectively, in growing tumors. The T/Np and T/Nm differed significantly between the two groups (T/Np, P < .001; T/Nm, P < .001). Receiver operating characteristic curve analysis showed that cutoffs of 1.56 and 1.76 for T/Np (93.33% sensitivity, 75.00% specificity) and T/Nm (100.00% sensitivity, 93.75% specificity), respectively, could be used to diagnose a growth rate of >100 mm3 /year. The area under the curve was 0.85 (95% confidence interval, 0.70-1.00) for T/Np and 0.94 (0.82-1.00) for T/Nm. CONCLUSION: Growing VSs show higher signal intensities on Gd-enhanced MRI. Thus, measuring the signal intensity of VS on Gd-enhanced MRI may aid in predicting VS growth. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:198-203, 2022.

The expression of prosaposin and its receptors, GRP37 and GPR37L1, are increased in the developing dorsal root ganglion.

Prosaposin (PSAP), a highly conserved glycoprotein, is a precursor of saposins A-D. Accumulating evidence suggests that PSAP is a neurotrophic factor, as well as a regulator of lysosomal enzymes. Recently, the orphan G-protein-coupled receptors GPR37 and GPR37L1 were recognized as PSAP receptors, but their functions have not yet been clarified. In this study, we examined the distribution of PSAP and its receptors in the dorsal root ganglion (DRG) during development using specific antibodies, and showed that PSAP accumulates primarily in lysosomes and is dispersed throughout the cytoplasm of satellite cells. Later, PSAP colocalized with two receptors in satellite cells, and formed a characteristic ring shape approximately 8 weeks after birth, during a period of rapid DRG development. This ring shape, which was only observed around larger neurons, is evidence that several satellite cells are synchronously activated. We found that sortilin, a transporter of a wide variety of intracellular proteins containing PSAP, is strongly localized to the inner side of satellite cells, which contact the neuronal surface. These findings suggest that PSAP and GPR37/GPR37L1 play a role in activating both satellite and nerve cells.

Intratympanic Insulin-like Growth Factor-1 Administration Via the Otic Bulla in a Severe Facial Paralysis Model.

HYPOTHESIS: We investigated the treatment effect of intratympanic insulin-like growth factor-1 (IGF-1) on severe facial paralysis in guinea pigs. BACKGROUND: The use of regenerative medicine involving growth factors has been reported in the treatment of peripheral nerve diseases. IGF-1 plays a crucial role in nerve regeneration. METHODS: We performed the following procedures on guinea pigs. In the normal group (n = 7), no procedure was performed. In the saline (n = 7) and IGF-1 (n = 7) groups, facial paralysis was induced by freezing of the facial canal. Subsequently, in the saline and IGF-1 groups, a gelatin hydrogel impregnated with 100 µL saline and 400 µg/100 µL IGF-1, respectively, was placed in the facial canal. Facial nerve functions were evaluated using three test batteries: facial movement observation, electrophysiological testing, and histological assessment. RESULTS: At 10 weeks postoperatively, the facial movement scores for the IGF-1 group were improved compared to those in the saline group. The conductive velocity was significantly faster in the IGF-1 group than in the saline group. There was a significant between-group difference in the nerve fiber number and myelin thickness. CONCLUSION: Intratympanic IGF-1 administration improved facial nerve regeneration. This novel method could provide prompt ambulatory regenerative treatment and reduce the incidence of poor recovery in patients with severe facial paralysis.

Verbalization, Categorization, and Evaluation of Fundamental Surgical Skills: An Expert Consensus in Open Head and Neck Surgery.

Objective: This study aimed to verbalize fundamental surgical skills required for open head and neck surgery (OHNS), to organize them by categorization, and to establish a consensus among surgeons regarding the importance and difficulty of each skill. Summary Background Data: Improvement of fundamental surgical skills is the core of surgical education; however, surgical skills are not yet organized, and consensus in any surgical field remains uncertain. Methods: Fundamental surgical skills during OHNS were collected from surgical textbooks, real surgeries, and expert interviews. The items were analyzed to calculate the frequency of words and were categorized by 2 expert surgeons. After consensus on the importance and difficulty of each item was established by 15 expert surgeons using a Delphi survey, principal component (PC) analysis was performed to integrate importance and difficulty into a single parameter. Results: Sixty skills were verbalized and categorized into 7 categories: "skin flap elevation (n = 6)," "vessel management (n = 9)," "nerve preservation (n = 8)," "instrument handling (n = 11)," "counter traction (n = 7)," "tissue exposure (n = 9)," and "flow and planning (n = 10)." In the Delphi survey, expert consensus was established after 2 voting rounds (Cronbach's α ≥ 0.80). The "counter traction" and "flow and planning" categories had high PC scores, which indicate priority in surgical education. Conclusion: Fundamental OHNS skills were verbalized, categorized, and evaluated via expert consensus. Assessment of surgeons' skills by the structured items hereby developed will help standardize the quality of OHNS and improve patient outcomes.

Prosaposin in the rat oviductal epithelial cells.

Prosaposin (PSAP) has two forms: a precursor and a secreted form. The secreted form has neurotrophic, myelinotrophic, and myotrophic properties. The precursor form is a precursor protein of saposins A-D. Although the distribution of PSAP in male reproductive organs is well known, its distribution in female reproductive organs, especially in the oviduct, is unclear. Immunoblots and immunohistochemistry of oviducts showed that oviductal tissues contain PSAP proteins, and a significant increase in PSAP was observed in the estrus-metestrus phase compared to the diestrus-proestrus phase in the ampulla. To identify PSAP trafficking in cells, double-immunostaining was performed with antibodies against PSAP in combination with sortilin, mannose 6 phosphate receptor (M6PR), or low-density lipoprotein receptor-related protein 1 (LRP1). PSAP and sortilin double-positive reactions were observed near the nuclei, as well as in the apical portion of microvillous epithelial cells, whereas these reactions were only observed near the nuclei of ciliated epithelial cells. PSAP and M6PR double-positive reactions were observed near the nuclei of microvillous and ciliated epithelial cells. PSAP and M6PR double-positive reactions were also observed in the apical portion of microvillous epithelial cells. PSAP and LRP1 double-positive reactions were observed in the plasma membrane and apical portion of both microvillous and ciliated epithelial cells. Immunoelectron staining revealed PSAP immunoreactive small vesicles with exocytotic features at the apical portion of microvillous epithelial cells. These findings suggest that PSAP is present in the oviductal epithelium and has a pivotal role during pregnancy in providing an optimal environment for gametes and/or sperm in the ampulla.

Prosaposin and its receptors GRP37 and GPR37L1 show increased immunoreactivity in the facial nucleus following facial nerve transection.

Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.

Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: a case report and literature review.

BACKGROUND: The most common sites of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be the liver, lung, bone, and adrenal glands, but there have also been many reports of cases of multiple recurrence. The prognosis after recurrence is poor, with reported median survival after recurrence of HCC ranging from 9 to 19 months. Here, we report a case of long-term survival after recurrence of pharyngeal metastasis following living-donor liver transplantation (LDLT) for HCC within the Milan criteria, by resection of the metastatic region and cervical lymph node dissection. CASE PRESENTATION: A 47-year-old man with a Model End-stage Liver Disease (MELD) score of 11 underwent LDLT for HCC within the Milan criteria for liver cirrhosis associated with hepatitis B virus infection, with his 48-year-old elder brother as the living donor. One year and 10 months after liver transplantation, he visited a nearby hospital with a chief complaint of discomfort on swallowing. A pedunculated polyp was found in the hypopharynx, and biopsy revealed HCC metastasis. We performed pharyngeal polypectomy. Two years later, cervical lymph node metastasis appeared, and neck lymph node dissection was performed. Although recurrence subsequently occurred three times in the grafted liver, the patient is still alive 12 years and 10 months after recurrence of pharyngeal metastasis. He is now a tumor-free outpatient taking sorafenib. CONCLUSION: It is necessary to recognize that the nasopharyngeal region is a potential site of HCC metastasis. Prognostic improvement can be expected with close follow-up, early detection, and multidisciplinary treatment, including radical resection.

A prosaposin-derived Peptide alleviates kainic Acid-induced brain injury.

Four sphingolipid activator proteins (i.e., saposins A-D) are synthesized from a single precursor protein, prosaposin (PS), which exerts exogenous neurotrophic effects in vivo and in vitro. Kainic acid (KA) injection in rodents is a good model in which to study neurotrophic factor elevation; PS and its mRNA are increased in neurons and the choroid plexus in this animal model. An 18-mer peptide (LSELIINNATEELLIKGL; PS18) derived from the PS neurotrophic region prevents neuronal damage after ischemia, and PS18 is a potent candidate molecule for use in alleviating ischemia-induced learning disabilities and neuronal loss. KA is a glutamate analog that stimulates excitatory neurotransmitter release and induces ischemia-like neuronal degeneration; it has been used to define mechanisms involved in neurodegeneration and neuroprotection. In the present study, we demonstrate that a subcutaneous injection of 0.2 and 2.0 mg/kg PS18 significantly improved behavioral deficits of Wistar rats (n = 6 per group), and enhanced the survival of hippocampal and cortical neurons against neurotoxicity induced by 12 mg/kg KA compared with control animals. PS18 significantly protected hippocampal synapses against KA-induced destruction. To evaluate the extent of PS18- and KA-induced effects in these hippocampal regions, we performed histological evaluations using semithin sections stained with toluidine blue, as well as ordinal sections stained with hematoxylin and eosin. We revealed a distinctive feature of KA-induced brain injury, which reportedly mimics ischemia, but affects a much wider area than ischemia-induced injury: KA induced neuronal degeneration not only in the CA1 region, where neurons degenerate following ischemia, but also in the CA2, CA3, and CA4 hippocampal regions.

[A retrospective study on parotid carcinoma].

We retrospectively analyzed the clinicopathological factors affecting survival in patients with previously untreated parotid carcinoma. The subjects were 50 patients treated in our department from 1987 through 2011. The T stage was T1, T2, T3, and T4 in 4 patients, 11 patients, 9 patients, and 26 patients, respectively. The N stage was N0, N1, and N2 in 36 patients, 3 patients, and 11 patients, respectively. The clinical stage was I, II, III, and IV in 4 patients, 10 patients, 7 patients, and 29 patients, respectively. Histopathologically, eleven tumor types were observed; mucoepidermoid carcinoma was the most common. The overall 5-year survival rate was 72.1%, and the disease-specific 5-year survival rate was 74.0% in 42 patients who received radical surgery. Twelve patients relapsed; the site of relapse was the primary site alone in 2, in the neck alone in 3 patients, in the neck with distant metastases in 2 patients, and in distant metastatic site (s) alone in 5 patients. Univariate analysis showed that significant prognostic factors for overall survival rates were the T stage, cervical lymph node metastasis, clinical stage, grade, facial nerve palsy, and tumor size. We concluded that patients at high risk of recurrence should receive adjuvant therapy to improve the therapeutic outcomes.

Distribution of prosaposin in rat lymphatic tissues.

Prosaposin (PSAP) is as a trophic factor and an activator protein for sphingolipid hydrolase in lysosomes. We generated a specific antibody to PSAP and examined the spatiotemporal distribution of PSAP-immunoreactive (PSAP-IR) cells in the lymphatic tissues of Wistar rats. Immunoblots of tissue homogenates separated electrophoretically showed a single band for PSAP in brain but two bands in spleen. PSAP-IR cells were distributed in both the red and white pulp of the spleen, in both the cortex and medulla of the thymus and in mesenteric lymph nodes. Many PSAP-IR cells were found in the dome portion of Peyer's patches and the number of PSAP-IR cells increased with the age of the rat. To identify the PSAP-IR cells, double- and triple-immunostainings were performed with antibodies against PSAP, CD68 and CD1d. The large number of double- and triple-positive cells suggested that antigen-presenting cells contained much PSAP in these lymphatic tissues. Intense expression of PSAP mRNA, examined by in situ hybridisation, was observed in the red pulp and corona of the spleen. In rats, the PSAP gene generates two alternative splicing forms of mRNA: Pro+9 containing a 9-base insertion and Pro+0 without the insertion. We examined the expression patterns of the alternative splicing forms of PSAP mRNA in the spleen. The presence of both types of mRNA (Pro+9 and Pro+0) indicated that the spleen contains various types of prosaposin-producing and/or secreting cells. These findings suggest diverse functions for PSAP in the immune system.

Prosaposin-derived peptide alleviates ischaemia-induced hearing loss.

CONCLUSION: An 18-mer peptide derived from the neurotrophic region of prosaposin (PS-pep) prevents hearing loss and cochlear damage due to transient cochlear ischaemia by activating an anti-apoptotic pathway. PS-pep is a potent candidate molecule for alleviating ischaemia-induced hearing loss. OBJECTIVE: PS-pep was investigated for its protective effects against ischaemia-induced hearing loss and cochlear damage. METHODS: Ischaemia was induced in both cochleae in Mongolian gerbils by pulling the ligatures around both vertebral arteries in an anterior direction using 5 g weights for 15 min. PS-pep was synthesized artificially and administered subcutaneously four times after the induction of transient cochlear ischaemia. RESULTS: An increase in the auditory brainstem response threshold was alleviated in animals treated with 2.0 mg/kg PS-pep. Histological examinations conducted on day 7 showed that the loss of inner hair cells (IHCs) was more prominent than that of outer hair cells. Higher doses of PS-pep significantly alleviated IHC loss. An increase in the anti-apoptotic factor bcl-2 was also noted in the IHCs treated with PS-pep.

One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma.

OBJECTIVES: Lymph node stage is an important prognostic factor in head and neck squamous cell carcinoma (HNSCC). We previously reported the clinical usefulness of sentinel lymph node biopsy diagnosed by genetic analysis using quantitative RT-PCR. However, this method takes about 3h. In this study, we attempted to develop a more efficient method for the intraoperative genetic detection of lymph node metastasis in HNSCC. MATERIALS AND METHODS: A total of 312 lymph nodes (65 patients) were diagnosed by the one-step nucleic acid amplification (OSNA) method using GD-100. OSNA consists of a short homogenization step followed by amplification of cytokeratin 19 (CK19) mRNA directly from the lysate. Each lymph node was divided into two to diagnose metastasis. One half was used for the OSNA assay, and the other was subjected to semi-serial sectioning, sliced at 200-µm intervals and examined by H&E and cytokeratin AE1/AE3 immunohistochemical staining. The accuracy of OSNA assay was evaluated based on histopathological diagnosis. RESULTS: Sixty-one of 312 lymph nodes were pathologically metastasis-positive. The overall concordance rate between the OSNA assay using breast cancer criteria and histopathology was 94.2%. The optimal cut-off for the copy number of CK19 mRNA in assessing lymph node metastasis of HNSCC was 300 copies/µl, which had the highest diagnostic accuracy (95.2%). The OSNA assay can be completed within 30 min. CONCLUSION: The OSNA assay, which shows high sensitivity and specificity, suggests the possibility to be used as a novel tool for the genetic detection of lymph node metastasis in HNSCC patients.

Lectin binding pattern of gastric mucosa of pacific white-sided dolphin, Lagenorhynchus obliquidens.

The stomach of the Pacific white-sided dolphin is divided into three parts: forestomach, proper gastric gland portion, and pyloric chamber. The histological features of the dolphin stomach are similar to those of terrestrial mammal stomachs, although the distribution of glycoconjugates in mucosal cells of the dolphin stomach is unknown. To learn about glycoconjugates in cetacean gastric mucosa, the glycoconjugate distribution in the mucous epithelium of the Pacific white-sided dolphin was studied using 21 lectins. Among the lectins tested, GSL-I and DBA specifically labelled the superficial layer of the forestomach epithelium. GSL-I, SBA, RCA-I, VVA, GSL-II, DSL, LEL, STL, s-WGA, WGA, PNA, and Jacalin labelled the luminal surface of the chief cells in the proper gastric gland. GSL-I, SBA, RCA-I, DSL, LEL, STL, s-WGA, PNA, and LCA labelled tubular structures in the cytoplasm of parietal cells. The surface portion of the pits in the pyloric chamber strongly reacted with RCA-I, GSL-II, WGA, PNA, LCA, PHA-L, and UEA-I, whereas the neck portion reacted weakly. Although lining one tubular portion, individual secretory cells in the pyloric gland displayed a heterogeneous reaction. This is the first report on the lectin histochemistry of a cetacean stomach and reveals GSL-I and DBA as specific marker lectins for the cornified stratified squamous epithelium cells of the Pacific white-sided dolphin. The stomachs of cetaceans and terrestrial mammals have similar histological features and mucous glycoconjugate content.

Sensory tract abnormality in the chick model of spina bifida.

Spina bifida aperta (SBA) is an open neural tube defect that occurs during the embryonic period. We created SBA chicks by incising the roof plate of the neural tube in the embryo. The area of the dorsal funiculus was smaller in the SBA chicks than in the normal controls. Additionally, the SBA group had fewer nerve fibres in the dorsal funiculus than the normal controls. The pathway of the ascending sensory nerves was revealed by tracing the degenerated nerve fibres using osmification. We cut the sciatic nerve (L5) of the control and SBA chicks at the central end of the dorsal root ganglion 1 day after hatching and fixed the tissue 3 days later. Degenerated sensory nerve fibres were observed in the ipsilateral dorsal funiculus in the control chicks. In contrast, degenerated sensory nerve fibres were observed in the ipsilateral and contralateral dorsal, ventral and lateral funiculi of the spinal cord in the SBA chicks. Consequently, fewer sensory nerve fibres ascended to the thoracic dorsal funiculus in the SBA chicks than in the normal controls. This is the first report of abnormal changes in the ascending sensory nerve fibres in SBA.

Lectin histochemistry of respiratory mucosa in the Pacific white-sided dolphin.

Sugars in the glycocalyx play an important role in the attachment of infectious agents to the respiratory mucosa. We examined the histochemistry of 23 lectins to survey the sugar expression in the glycocalyx of the respiratory mucosa of the Pacific white-sided dolphin, Lagenorhynchus obliquidens. The ciliated and basal cells were positive for all of the lectins studied. SBA, WFA, GSL-II, STL, S-WGA, and PNA staining in the cytoplasm showed different intensities between basal cells and ciliated cells. These results suggest that multiple terminal glycosylation occurs on ciliated and basal cells, such as GalNAc, GlcNAc, NeuNAc, galactose, glucose/mannose, oligosaccharide, and fucose, and that sugar residue expression changes during cell differentiation. The Pacific white-sided dolphin respiratory mucosa might express multiple sugar residues in the glycocalyx, to prevent the attachment and colonisation of infectious agents.

Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity.

We investigated the effects of Rho-associated kinase (ROCK) on migration and cytoskeletal organization in primary human osteoblasts and Saos-2 human osteosarcoma cells. Both cell types were exposed to two different ROCK inhibitors, Y-27632 and HA-1077. In the improved motility assay used in the present study, Y-27632 and HA-1077 significantly increased the migration of both osteoblasts and osteosarcoma cells on plastic in a dose-dependent and reversible manner. Fluorescent images showed that cells of both types cultured with Y-27632 or HA-1077 exhibited a stellate appearance, with poor assembly of stress fibers and focal contacts. Western blotting showed that ROCK inhibitors reduced myosin light chain (MLC) phosphorylation within 5 min without affecting overall myosin light-chain protein levels. Inhibition of ROCK activity is thought to enhance the migration of human osteoblasts through reorganization of the actin cytoskeleton and regulation of myosin activity. ROCK inhibitors may be potentially useful as anabolic agents to enhance the biocompatibility of bone and joint prostheses.

Incidence of long-term ipsilateral and contralateral ototoxicity following radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: To characterize the long-term adverse effects of radiotherapy on the ears in patients with nasopharyngeal carcinoma (NPC), we investigated ipsilateral and contralateral ototoxicities in the external, middle, and inner ear. METHODS: The records of 48 ears in 24 radiotherapy-treated NPC patients were retrospectively analyzed. Radiotherapy doses varied between 60 and 70 Gy in 2-Gy fractions at 5 fractions/week. Ototoxicities were identified by otoscope and pure-tone audiograms conducted at 2-3 month intervals for ≥12 months. The relationship between radiation dosage and sensorineural threshold deterioration was statistically compared using the Mann-Whitney U-test. RESULTS: Post-radiotherapy, 50% of all ears (3 of 6) that developed severe otitis externa were on the contralateral side. There was a post-radiotherapy increase in contralateral otitis media with effusion (OME) (1-7 ears), but a decrease in ipsilateral cases (16-12 ears), with 2 ears on either side subsequently developing chronic otitis media (COM). All ears that showed sensorineural hearing loss (SNHL) before radiotherapy exhibited a further threshold deterioration of more than 15 dB. No statistically significant difference (p=0.086) in average radiation dose was seen between ears with sensorineural threshold deterioration (50.0 Gy) and those without (48.2 Gy). CONCLUSION: Long-term ototoxicity following radiotherapy for NPC can occur in either the ipsilateral or contralateral ears. Pathophysiology varies between and within each side. The post-therapy increase in OME on the contralateral side was thought to be due to radiotherapy-induced Eustachian tube damage, and the sensorineural threshold deterioration in at least 4 ears was thought to be due to chronic cochlea damage secondary to COM.

Clinical features and outcomes of four patients with invasive fungal sinusitis.

OBJECTIVE: The frequency of invasive fungal sinusitis (IFS) has increased in recent years with the use of steroids, onset of diabetes mellitus, and the administration of antibacterial agents. We report on the clinical features and outcomes of four patients with IFS involving the cavernous sinus and orbit. Prognostic factors facilitating an early diagnosis are described, and the usefulness of combination therapy involving systemic administration of antifungal agents and surgical intervention is discussed. METHODS: We treated four patients with IFS between March 2003 and November 2007 at Ehime University Hospital. Patients were two males and two females, aged from 61 to 74 years (mean 67.8 years). RESULTS: With regard to clinical symptoms, headache was observed in all patients, and cranial nerve paralysis (visual disturbance, blindness, cheek paresthesia) was seen in 3 patients. ß-D-Glucan levels in four patients were high compared with normal values. Aspergillus was histopathologically identified from biopsy specimens in all patients. One patient was complicated with Candida in addition to the Aspergillus infection. Orbital exenteration and ESS were performed in 2 patients as surgical debridement. In all patients, systemic administration of antifungal agents was initiated after surgery. CONCLUSIONS: All patients received strategic treatment with surgery and systemic administration of anti-fungal agents. The single fatality was due to brain infarction caused by the spread of Aspergillus, and the remaining three patients are still alive. Our observations in these patients suggest that early diagnosis and strategic treatment may improve the prognosis of IFS.

Facial synkinesis after experimental compression of the facial nerve comparing intratemporal and extratemporal lesions.

OBJECTIVES/HYPOTHESIS: The anatomical configuration of the facial nerve differs greatly between the intratemporal and extratemporal portions. The purpose of this study was to investigate the incidence of facial synkinesis and misdirection on clamping the facial nerve at the intratemporal or extratemporal portion of the facial nerve in guinea pigs. STUDY DESIGN: Experimental study. METHODS: In 16 guinea pigs, the facial nerve was clamped with microsurgical needle forceps at either the extratemporal (group A) or intratemporal (group B) segment. Facial nerve function was evaluated 1 week postoperatively using electroneurography (ENoG), and the incidence of facial synkinesis was evaluated 15 weeks postoperatively using an evoked blink reflex test. Fifteen weeks postoperatively, two retrograde fluorescent tracers (Dil [1-1'-dioctodecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate] and True Blue) were injected into the facial muscles to observe reorganization of the facial nucleus. RESULTS: No significant difference in the ENoG threshold was observed between groups A and B. In group A, none of the animals developed facial synkinesis and the somatotopic organization of the facial nucleus was not disturbed. In contrast, synkinesis occurred and the somatotopic organization was disturbed in group B. CONCLUSIONS: A lack of funicular structure within the intratemporal facial nerve increases the possibility of misdirected regenerating axons and synkinesis.